2 - Functional consequence phenotyper definition 5 - Submitter 4 - Result 1- Functional effect Functional consequence 3 - Method id Functional effect 6 - Supporting Information rdfs:ID rdfs:SSCID_SCN2A rdfs:functional_effect rdfs:model_system rdfs:phenotype rdfs:synonyms fenix webprotege:R3Kr2TGkTE2Cs3wLLgOUHN A mild-moderate depolarizing shift of voltage dependence of fast inactivation is a depolarizing shift of voltage dependence of fast inactivation (right shift) of a voltage-gated ion channel in which the value of V1/2 is significantly increased by up to 15mV. FENICS:0061 gain-of-function Mild-moderate depolarizing shift of voltage dependence of fast inactivation webprotege:R5vvSMCBavnR4OPfmY6bjk An effect on ion selectivity is a biophysical change in which the specificity of the mutant channel for a single ion type is different from wildtype. FENICS:0079 Effect on ion selectivity webprotege:R6Gg6Rc5Xl21OllEzn2N3h A depolarizing shift of voltage dependence of slow inactivation (right shift) is an effect on shift of voltage dependence of slow inactivation (V1/2) of a voltage-gated ion channel leading to gain of function, in which channels change to the slow inactivated state at significantly more positive potentials. FENICS:0116 Depolarizing shift of voltage dependence of slow inactivation webprotege:R6mSCTdmZqoFcoMx49ADHU Normal persistent current is the absence of an effect on persistent current of a voltage-gated sodium channel, in which no significant difference in persistent current is observed compared to wildtype. FENICS:0044 Normal persistent current webprotege:R72fldK4dv27Jf7NqXalgS5 A moderate increase in peak current is an increase in peak current of a voltage-gated ion channel in which the peak current density of the mutant is significantly increased to 130-200% of that of the wildtype. FENICS:0094 SCN1A, SCN8A, and SCN2A: 1.3-2 fold increase Moderate increase in peak current webprotege:R768x3xvHhzBT7WwmpcMUaP Overall mixed or unclear functional effect due to neuronal network properties is an overall mixed function in which the conflicting effects to the mutant channel's function is observed on systems of multiple neurons. FENICS:0146 Overall mixed or unclear functional effect due to neuronal network properties webprotege:R77VgsjEzz65xAcEUzaZXUt Ramp current, also called ramp current amplitude, is the total amount of current (area under the curve) measured during a steady depolarization over time. An effect on ramp current is a compound biophysical effect in which the ramp current is different in the mutant protein compared to wildtype. FENICS:0128 Effect on ramp current webprotege:R787B5RAMG9oetmadppgGCh A decrease in slope of fast inactivation is an effect on slope of fast inactivation (k) of a voltage-gated ion channel leading to loss of function, in which there is significantly greater steepness of channel inactivation with respect to membrane potential. FENICS:0072 Decrease in slope of fast inactivation webprotege:R7J2tm52qaQH1SwgcywsIqQ Overall normal function with respect of biophysical channel activity is an overall normal function in which the normal function of the mutant channel is concluded from the cumulative effect of the biophysical alterations to the channel. FENICS:0152 Overall normal function with respect of biophysical channel activity webprotege:R7KOr8G1xCnwPzwaON10MTm A hyperpolarizing shift of voltage dependence of fast inactivation (right shift) is an effect on shift of voltage dependence of fast inactivation (V1/2) of a voltage-gated ion channel leading to loss of function, in which channels change to the inactivated state at significantly more negative potentials. FENICS:0065 LOSS-OF-FUNCTION left shift of fast inactivation means that the channels takes "longer" to have 50% of channels available again for activation. Longer is difficult and means "at more negative membrane potentials" loss-of-function mild: up to 7.5 mV shift, moderate 7.5-15 mV shift, severe >15 mV shift Hyperpolarizing shift of voltage dependence of fast inactivation webprotege:R7Q10ohyxQHPdcQsFmhC1Si The overall assessment of ion channel function refers to the experimenters' conclusion regarding the sum total effect of individual parameters on the function of the ion channel. FENICS:0136 Overall assessment of ion channel function webprotege:R7WY7lrtkRqG9NQvD8Fs7Lo A severe decrease in peak current due to reduction in conductance is a severe decrease in peak current of a voltage-gated ion channel which is explained by a significantly reduced single-channel conductance in mutants compared to wildtype. FENICS:0091 Severe decrease in peak current due to reduction in conductance webprotege:R7YvyEoR5sDyyQqL5j9dQoK Persistent current, also called noninactivating current, is the proportion of peak current in voltage-gated sodium channels that remains after the channel changes to the inactivated state. An effect on persistent current (INaP) is an effect on voltage-gated sodium channels in which the amount of persistent current is different in the mutant protein compared to wildtype. FENICS:0038 INaP for sodium channels Important only in Na+ channels, not K+ channels Effect on persistent current webprotege:R7dNr0622a5wBESQGcaLkZg Assessment of single biophysical property on ion channel function is the implied change that an effect on a particular parameter has on the overall behavior of the channel. FENICS:0002 Assessment of single biophysical property on ion channel function webprotege:R7eGXoO3n3Sj7LwciFM7iUY An increase of subthreshold current is an effect on subthreshold current of a voltage-gated ion channel leading to gain-of-function, in which ion flow at membrane potentials below threshold is significantly increased compared to wildtype. FENICS:0125 Increase of subthreshold current webprotege:R7jOR4IAP4IwniBv4AwBnrm An effect on peak current is a biophysical change in which the maximum current density (pA/pF) is different in the mutant protein compared to wildtype. FENICS:0082 a Effect on peak current webprotege:R7rZoUywSrlnsR2QEdxddqS Normal rate of recovery from fast inactivation is an absence of an effect on rate of recovery from fast inactivation of a voltage-gated ion channel, in which no significant difference in time constant (tau) is observed compared to wildtype. FENICS:0054 Normal rate of recovery from fast inactivation webprotege:R7xYGfLUETEAY1cGj6zqYjl Normal slope of fast inactivation is an absence of an effect on slope of fast inactivation (k) of a voltage-gated ion channel in which there is no significant difference observed in slope factor compared to wildtype. FENICS:0074 Normal slope of fast inactivation webprotege:R7z6iE87cbBZePvVnmAKuLf Overall loss-of-function effect with respect to biophysical channel activity is an overall loss-of-function in which the reduction to the mutant channel's function is concluded from the cumulative effect the of biophysical alterations to the channel. FENICS:0144 Overall loss-of-function effect with respect to biophysical channel activity webprotege:R7zJvOsCc8GUzB5y46iKkAM An acceleration of recovery from slow inactivation is an effect on recovery from slow inactivation of a voltage-gated ion channel leading to gain-of-function, in which the time constant (tau) is significantly reduced, corresponding to channels recovering faster compared to wildtype. FENICS:0107 Acceleration of recovery from slow inactivation webprotege:R7zP9gQPx3KzITlYDUOFZfp Normal voltage dependence of slow inactivation is an absence of an effect on shift of voltage dependence of slow inactivation of a voltage-gated ion channel in which no significant difference in V1/2 is observed compared to wildtype. FENICS:0118 Normal voltage dependence of slow inactivation webprotege:R80ryKpw9TZE2fSjbz1ykJ4 A mild slowing of fast inactivation (tau inactivation) is a slowing of fast inactivation of a voltage-gated ion channel in which the mutant has a time constant significantly increased by a factor of up to 2 compared to wildtype. FENICS:0049 Mild (up to 2 fold) Mild slowing of fast inactivation webprotege:R81aXvSVSyOYsrO0hq6JLkY A slowing of slow inactivation is an effect on rate of slow inactivation (tau inactivation) of a voltage-gated ion channel leading to gain-of-function, in which the time constant is significantly increased, corresponding to channels changing to the slow inactivated state slower compared to wildtype. FENICS:0113 Slowing of slow inactivation webprotege:R82G1vBnkSQhiYsTT3hCskW An increase in slope of activation is an effect on slope of activation (k) of a voltage-gated ion channel leading to loss of function, in which there is significantly reduced steepness of channel activation with respect to membrane potential. FENICS:0035 Increase in slope of activation webprotege:R86071iVxOmUgj1ljXI9RwA An overall loss-of-function is an overall assessment of ion channel function in which the experimenters conclude that the activity of the mutant channel is reduced relative to wildtype. FENICS:0141 Overall loss-of-function webprotege:R89pOjwORB6pkvDW9u6hoXN Overall normal function due to neuronal network properties is an overall normal function in which the normal function of the mutant channel is observed on systems of multiple neurons. FENICS:0150 Overall normal function due to neuronal network properties webprotege:R8CM4SZ0Of9GemoYjDN3wjj Overall gain-of-function effect due to single-cell neuronal properties is an overall gain-of-function in which the enhancement to the mutant channel's function is observed at the level of single neuron, e.g. due to firing rates. FENICS:0139 Overall gain-of-function effect due to single-cell neuronal properties webprotege:R8IERLt4CJaeXzaPCOzquSB A severe decrease in peak current due to reduced opening probability is a severe decrease in peak current of a voltage-gated ion channel which is explained by a significantly reduced fraction of open mutant channels compared to wildtype. FENICS:0088 This is rarely measured Severe decrease in peak current due to reduced opening probability webprotege:R8KPCoFR36aEEBnmaUBp1tV An increase in slope of fast inactivation is an effect on slope of fast inactivation (k) of a voltage-gated ion channel leading to gain of function, in which there is significantly reduced steepness of channel inactivation with respect to membrane potential. FENICS:0073 Increase in slope of fast inactivation webprotege:R8KZofOQE10FYr0M6IpoJ72 Overall loss-of-function effect due to single-cell neuronal properties is an overall loss-of-function in which the reduction to the mutant channel's function is observed at the level of single neuron, e.g. due to firing rates. FENICS:0143 Overall loss-of-function effect due to single-cell neuronal properties webprotege:R8KqfFzWrSaU9t4uXABtJRK Resurgent current is current conducted due to voltage-gated ion channels reopening in response to negative voltage changes after a normal transient current. An effect on resurgent current is a biophysical change in which there is a difference in the resurgent current between the mutant protein and wildtype. FENICS:0097 For sodium channel, ‘Resurgent sodium currents’ mechanism is unclear, but present in some cells Effect on resurgent current webprotege:R8Kyj6yec26dDePPO9tgqV2 An effect on ion channel modulation is a biophysical change in which the mutant channel's response to modulators, such as channel blockers or openers, is significantly different compared to wildtype. FENICS:0078 Effect on ion channel modulation webprotege:R8LYDXXexzlysXjoPyjBePm A moderate hyperpolarizing shift of voltage dependence of activation is a hyperpolarizing shift of voltage dependence of activation (left shift) of a voltage-gated ion channel in which the value of V1/2 is significantly decreased by 5-10mV for Na+ channels or 10-20mV for K+ channels. FENICS:0030 Gain-of-function SCN2A and SCN8A moderate: 5-10 mV shift Moderate hyperpolarizing shift of voltage dependence of activation webprotege:R8S5yVPOmxVdhhUOuyW4oyx A severe increase in peak current is an increase in peak current of a voltage-gated ion channel in which the peak current density of the mutant is significantly increased to more than 200% of that of the wildtype. FENICS:0095 SCN1A, SCN8A, and SCN2A: 2 or more fold increase Severe increase in peak current webprotege:R8asTBmmgK6PYqOlvlLtgpz A mild hyperpolarizing shift of voltage dependence of activation is a hyperpolarizing shift of voltage dependence of activation (left shift) of a voltage-gated ion channel in which the value of V1/2 is significantly decreased by up to 5mV for Na+ channels or 10mV for K+ channels. FENICS:0029 Gain-of-function SCN2A and SCN8A mild: up to 5 mV; K+ channels mild: up to 10mV Mild hyperpolarizing shift of voltage dependence of activation webprotege:R8boLFt6478JfJZLRmWETDi A moderate depolarizing shift of voltage dependence of fast inactivation is a depolarizing shift of voltage dependence of fast inactivation (right shift) of a voltage-gated ion channel in which the value of V1/2 is significantly increased by 7.5-15mV. FENICS:0063 7.5 - 15 mV shift gain-of-function Moderate depolarizing shift of voltage dependence of fast inactivation webprotege:R8elYee9oFnTyzGLbmLUaeO Gating-pore current is an alternative, abnormal pathway of ion flow created through the voltage-sensor domain (“omega current”) resulting in abnormal depolarization due to additional cation flow independent of the voltage-gated pore pathway. An effect on gating-pore current is a biophysical change in which gating-pore current is different in the mutant protein compared to wildtype (in which it is absent). FENICS:0075 S4 segment mutations result in gating-pore current independent of the ion channel conductance. Cation flow results in abnormal depolarization. Completely normal pathway of letting ions through. Effect on gating-pore current webprotege:R8fyxz5nx0mgxsMOtEoRmWk A slowing of activation is an effect on rate of activation (tau activation) of a voltage-gated ion channel leading to loss-of-function, in which the time constant is increased, corresponding to channels changing to the activated state significantly slower compared to wildtype. FENICS:0012 measured in ratio. mutant/wildtype mild: up to 1.25 mild to moderate: 1.25-2.0 severe: > 2.00 Slowing of activation webprotege:R8hFpMkdFDIganHQtA3nbJV An effect on rate of activation (tau activation) is an effect on activation of a voltage-gated ion channel in which the affected parameter is the time constant (tau) of activation, which measures how quickly or slowly the channel changes to the activated state with respect to time. FENICS:0009 Effect on rate of activation webprotege:R8iqSYdEKz3pshaN6jwoBjg A mild-moderate slowing of recovery from fast inactivation is a slowing of recovery from fast inactivation of a voltage-gated ion channel, in which the time constant (tau) is significantly increased by a factor of up to 3 compared to wildtype. FENICS:0056 Mild-moderate slowing of recovery from fast inactivation webprotege:R8oN6Lr9gpAWFhWBexO3rhu An effect on shift of voltage dependence of fast inactivation (V1/2) is an effect on voltage dependence of fast inactivation of a voltage-gated ion channel in which the affected parameter is half-maximal voltage (V1/2), the potential at which 50% of channels are in the inactivated state. FENICS:0059 Effect on shift of voltage dependence of fast inactivation webprotege:R8tC7DUKEOwvWvpkJDURZZk An effect on rate of slow inactivation (tau inactivation) is an effect on slow inactivation of a voltage-gated ion channel in which the affected parameter is the time constant (tau) of slow inactivation, which measures how quickly or slowly the channel changes to the slow inactivated state with respect to time. FENICS:0110 Effect on rate of slow inactivation webprotege:R8tp5Ovyd4qcM5Kfw7lDZCs Normal entry into slow inactivation is an absence of an effect on slow inactivation in which no significant difference in time of onset of slow inactivation is observed compared to wildtype. FENICS:0104 Normal entry into slow inactivation webprotege:R918FRlaBUyZMXc8koNdkxQ Hyperpolarizing shift of voltage dependence of activation - A hyperpolarizing shift of voltage dependence of activation (left shift) is an effect on shift of voltage dependence of activation (V1/2) of a voltage-gated ion channel leading to gain of function, in which channels open or change to the activated state at significantly more negative potentials. FENICS:0027 GAIN-OF-FUNCTION SCN2A and SCN8A mild: up to 5 mV; K+ channels mild: up to 10mV SCN2A and SCN8A moderate: 5-10 mV shift SCN2A and SCN8A severe: >10 mV; K+ channels severe: >20mV Hyperpolarizing shift of voltage dependence of activation webprotege:R989oVaOLlRTh0b3roVWMYa A component leading to gain-of-function is an alteration that contributes to overall reduced mutant function compared to wildtype. FENICS:0004 Component leading to Loss-of-Function (LoF) webprotege:R99KATlEV5UUOxmTthHewYy An effect on shift of voltage dependence of activation (V1/2) is an effect on voltage dependence of activation of a voltage-gated ion channel in which the affected parameter is half-maximal voltage (V1/2), the potential at which 50% of channels are in the open state. FENICS:0021 Voltage which half of channels have activated Effect on shift of voltage dependence of activation webprotege:R9GXFE2OawwbLewohMEJYng The presence of abnormal gating pore current denotes abnormal ion channel function wherein ion flow through the voltage-sensing domain is detected. FENICS:0077 Presence of abnormal gating pore current webprotege:R9HYQpAlzBNEVxccrGnZUKO Normal recovery from slow inactivation is an absence of an effect on recovery from slow inactivation, in which no significant difference in time constant (tau) of recovery is observed compared to wildtype. FENICS:0108 Normal recovery from slow inactivation webprotege:R9NOUr9iWj3sPK7GlxuC6dy A mild increase in peak current is an increase in peak current of a voltage-gated ion channel in which the peak current density of the mutant is significantly increased to up to, but less than, 130% of that of the wildtype. FENICS:0093 SCN1A, SCN8A, and SCN2A: up to 1.3 fold increase Mild increase in peak current webprotege:R9SJwUDkFAFc4AoKk8KpfDC Absence of peak current may be referred to as "no whole cell current" and denotes a lack of detectable current through a voltage-gated ion channel, i.e. a peak current of 0, or complete loss-of-function. FENICS:0083 Absence of peak current webprotege:R9SbYpUEIgenr1NAQGsVJLA An effect on voltage dependence of fast inactivation is an effect on fast inactivation of a voltage-gated ion channel in which the affected parameter is the proportion of channels that are in inactivated states after being held at different membrane potentials/voltages. FENICS:0058 Effect on voltage dependence of fast inactivation webprotege:R9Up0isZLT8RDpuQWBovMas A moderate hyperpolarizing shift of voltage dependence of fast inactivation is a hyperpolarizing shift of voltage dependence of fast inactivation (left shift) of a voltage-gated ion channel in which the value of V1/2 is significantly reduced by 7.5-15mV. FENICS:0068 7.5-15 mV shift loss-of-function Moderate hyperpolarizing shift of voltage dependence of fast inactivation webprotege:R9YmpNJrUqHfe8VU8jjemmJ A severe decrease in peak current is a decrease in peak current of a voltage-gated ion channel in which the peak current density of the mutant is significantly reduced to less than 20% of that of the wildtype. FENICS:0087 Severe decrease in peak current, less than 20% of wildtype Severe decrease in peak current webprotege:R9Z6wISzLzKf2jr6s67a677 A moderate slowing of fast inactivation (tau inactivation) is a slowing of fast inactivation of a voltage-gated ion channel in which the mutant has a time constant significantly increased by a factor of 2-4 compared to wildtype. FENICS:0050 Moderate (2-4 fold) Moderate slowing of fast inactivation webprotege:R9ZPhGuiK6bJRYHFi2PqXZJ Normal rate of activation is an absence of an effect on rate of activation (tau activation) of a voltage-gated ion channel in which no significant difference in time constant is observed compared to wildtype. FENICS:0011 Normal rate of activation webprotege:R9ZUbOgKjGPPQ9CPTMGPh9f A severe slowing of recovery from fast inactivation is a slowing of recovery from fast inactivation of a voltage-gated ion channel in which the time constant (tau) is significantly increased by a factor of more than 3 compared to wildtype. FENICS:0057 Severe slowing of recovery from fast inactivation webprotege:R9n9tt9GXmhInThrpajHuKY Normal ramp current is an absence of an effect on ramp current, in which no significant difference is observed compared to wildtype. FENICS:0131 Normal ramp current webprotege:R9sk2fOWBMQbWVog5qqITs7 A depolarizing shift of voltage dependence of fast inactivation (right shift) is an effect on shift of voltage dependence of fast inactivation (V1/2) of a voltage-gated ion channel leading to gain of function, in which channels change to the inactivated state at significantly more positive potentials. FENICS:0060 GAIN-OF-FUNCTION Gain-of-function mild up to 7.5 mV shift, moderate 7.5-15 mV shift, severe > 15 mV shift Depolarizing shift of voltage dependence of fast inactivation webprotege:R9vNK7NGPSBEp5FQ7nMB7Z2 A decrease of subthreshold current is an effect on subthreshold current of a voltage-gated ion channel leading to loss-of-function, in which ion flow at membrane potentials below threshold is significantly reduced compared to wildtype. FENICS:0124 Decrease of subthreshold current webprotege:R9wEM2OxcV4ZL1GcpqWaE52 An overall gain-of-function is an overall assessment of ion channel function in which the experimenters conclude that the activity of the mutant channel is enhanced relative to wildtype. FENICS:0137 Overall gain-of-function webprotege:R9wmRpum1ZjBHKOc0cthMrv A depolarizing shift of voltage dependence of activation (right shift) is an effect on shift of voltage dependence of activation (V1/2) of a voltage-gated ion channel leading to loss of function, in which channels open or change to the activated state at significantly more positive potentials. FENICS:0022 LOSS-OF-FUNCTION SCN2A and SCN8A mild: up to 5 mV; K+ channels mild: up to 10mV SCN2A and SCN8A moderate: 5-10 mV shift SCN2A and SCN8A severe: >10 mV, K+ channels severe: >20mV Depolarizing shift of voltage dependence of activation webprotege:RB39ECWMLncqVLZXtTVSuW3 An effect on slope of slow inactivation (k) is an effect on voltage dependence of slow inactivation of a voltage-gated ion channel in which the affected parameter is slope factor (k), which indicates the steepness of voltage dependence of inactivation when plotted with respect to voltage after fitting to a Boltzmann function. FENICS:0119 Effect on slope of slow inactivation webprotege:RBBfmTmxXmWBRBGEeKe7r0O An effect on rate of recovery from fast inactivation is an effect on fast inactivation of a voltage-gated ion channel in which the affected parameter is the time constant (tau) of recovery from fast inactivation, which measures how quickly or slowly the channel becomes available for activation after return to hyperpolarizing potentials to allow recovery from inactivation, i.e. the channel’s inactivation gate reopens. FENICS:0052 Recovery from fast inactivation is usually after a conditioning step of <1 second. Recovery is fit by one or more exponentials with amplitudes Unlike slow inactivation, channels are recovered usually within 1s, with may recovered within 10 ms Effect on rate of recovery from fast inactivation webprotege:RBH2UZNWWHmsOgLS1XKdf8N Normal resurgent current is the absence of an effect on resurgent current of a voltage-gated ion channel, in which no significant difference is observed compared to wildtype. FENICS:0100 Normal resurgent current webprotege:RBIy27OxlnSdZXc0c2teiZD Normal peak current is an absence of an effect on peak current in which no significant difference in peak current density is observed compared to wildtype. FENICS:0096 Wide range of normal Normal peak current webprotege:RBJ0Krtjy03lvhvCmwvnsjZ An acceleration of activation is an effect on rate of activation (tau activation) of a voltage-gated ion channel leading to gain-of-function, in which the time constant is reduced, corresponding to channels changing to the activated state significantly faster compared to wildtype. FENICS:0010 likely not meaningful as hightest increase would be 1.2 fold Acceleration of activation webprotege:RBJiFsljKf9Ot340DhQvUT An effect on ion channel function involving multiple biophysical properties is an effect on a single measured value which results from distinct biophysical effects but is not readily decomposed into independent parameters. FENICS:0127 Effect on ion channel function involving multiple biophysical properties webprotege:RBKM326sr6YtbqsamE9pEtf Normal rate of fast inactivation (tau inactivation) is an absence of an effect on rate of fast inactivation of a voltage-gated ion channel in which no significant difference in time constant is observed compared to wildtype. FENICS:0047 Normal fast inactivation webprotege:RBNgNEEXTwqRuFYweKcutxe An increase in persistent current is an effect on persistent current of a voltage-gated sodium channel leading to gain of function, in which a significantly greater current is conducted by the channel following fast inactivation. FENICS:0040 Increase in persistent current webprotege:RBOVqte4ccjmqTJAI8jkV44 Normal slope of activation is an absence of an effect on slope of activation (k) of a voltage-gated ion channel in which there is no significant difference in k observed compared to wildtype. FENICS:0036 Normal slope of activation webprotege:RBRr02cNOD5wl0pS44hXqqX A mild-moderate hyperpolarizing shift of voltage dependence of fast inactivation is a hyperpolarizing shift of voltage dependence of fast inactivation (left shift) of a voltage-gated ion channel in which the value of V1/2 is significantly reduced by up to 15mV. FENICS:0066 loss-of-function Mild-moderate hyperpolarizing shift of voltage dependence of fast inactivation webprotege:RBSKgEYTBWMuaYGCUWF6iOv Overall loss-of-function effect due to neuronal network properties is an overall loss-of-function in which the reduction to the mutant channel's function is observed on systems of multiple neurons. FENICS:0142 Overall loss-of-function effect due to neuronal network properties webprotege:RBSg2tM1FbJBOPZrJ3Ipe0G A mild depolarizing shift of voltage dependence of fast inactivation is a depolarizing shift of voltage dependence of fast inactivation (right shift) of a voltage-gated ion channel in which the value of V1/2 is significantly increased by up to 7.5mV. FENICS:0062 gain-of-function up to 7.5 mV shift Mild depolarizing shift of voltage dependence of fast inactivation webprotege:RBWAIKiQem63yDopljeSmcj A component leading to gain-of-function is an alteration that contributes to overall enhanced mutant function compared to wildtype. FENICS:0003 Component leading to Gain-of-Function (GoF) webprotege:RBc0zNLLgdk5NOgtaBohQMX A decrease in ramp current is an effect on ramp current of a voltage-gated ion channel leading to loss of function, in which the current amplitude is significantly reduced compared to wildtype. FENICS:0129 Decrease in ramp current webprotege:RBdbOghIxdzmUv1FRMZcqMy A severe slowing of fast inactivation (tau inactivation) is a slowing of fast inactivation of a voltage-gated ion channel in which the mutant has a time constant significantly increased by a factor of >4 compared to wildtype. FENICS:0051 Severe: more than 4 fold Severe slowing of fast inactivation webprotege:RBeZ7v8FkpfoCRDKvHZD936 A severe decrease in peak current due to reduced trafficking due to phosphorylation is a severe decrease in peak current due to reduced trafficking of a voltage-gated ion channel in which the reduced trafficking is explained by significant changes to the pattern of attachment of phosphoryl groups to specific residues within the channel. FENICS:0090 Severe decrease in peak current due to reduced trafficking due to phosphorylation webprotege:RBijWyJfrgnn2shZrQFKwyM A decrease in peak current is an effect on peak current of a voltage-gated ion channel leading to loss-of-function, in which peak current density is significantly reduced compared to wildtype. FENICS:0084 Decrease in peak current, LOF 50-100% mild 20-50% moderate <20% wild-type - severe Decrease in peak current webprotege:RBjmWtBKwt8nrHDyuxb6Nug Normal voltage dependence of activation is an absence of an effect on shift of voltage dependence of activation of a voltage-gated ion channel in which no significant difference in V1/2 is observed compared to wildtype. FENICS:0032 Helper term in bio-ontology, signified explicit absence of parent term Normal voltage dependence of activation webprotege:RBoUVhAjinxgCZHvQei6QsT A decrease in slope of activation is an effect on slope of activation (k) of a voltage-gated ion channel leading to gain of function, in which there is significantly greater steepness of channel activation with respect to membrane potential. FENICS:0034 Decrease in slope of activation webprotege:RBp4HSri5YtkrPJguFjDAxP A mild increase in persistent current is an increase in persistent current of a voltage-gated sodium channel in which the persistent current is significantly increased by a factor of up to 2 in the mutant compared to wildtype. FENICS:0041 up to 2x increase Mild increase in persistent current webprotege:RBwtVQzCS1UVEiDyo07xcdJ Abnormal ion selectivity is an effect on ion selectivity in which the mutant channel conducts a different type of ion. FENICS:0080 Abnormal ion selectivity webprotege:RBx87cocPenIzmpmFJRAE8E An acceleration of fast inactivation (tau inactivation) is an effect on rate of fast inactivation of a voltage-gated ion channel leading to loss-of-function, in which the time constant is significantly reduced, corresponding to channels changing to the inactivated state faster compared to wildtype. FENICS:0046 No distinct subclasses, less milliseconds, LoF Acceleration of fast inactivation webprotege:RByNptA431wiEbrBZa4Y14U A moderate increase in persistent current is an increase in persistent current of a voltage-gated sodium channel in which the persistent current is signfiicantly increased by a factor of 2-3 in the mutant compared to wildtype. FENICS:0042 2-3x fold increase Moderate increase in persistent current webprotege:RByPM9kRtVogJhkqUM3lsh4 The activated state is when the pore is open and the channel conducts current. An effect on activation is a biophysical change in which one of the parameters of channel changing to the activated state is different in the mutant protein compared to wildtype. FENICS:0008 Effect on activation webprotege:RC3aErf3GasgglmgYMcpS4n An acceleration of recovery from fast inactivation is an effect on rate of recovery from fast inactivation of a voltage-gated ion channel leading to gain-of-function, in which the time constant (tau) is significantly reduced, corresponding to channels recovering from inactivation faster compared to wildtype. FENICS:0053 Acceleration of recovery from fast inactivation webprotege:RC3cyZOGS7bJrI8gBqDaHzo A moderate depolarizing shift of voltage dependence of activation is a depolarizing shift of voltage dependence of activation (right shift) of a voltage-gated ion channel in which the value of V1/2 is significantly increased by 5-10mV for Na+ channels or 10-20mV for K+ channels. FENICS:0025 Loss-of-function SCN2A and SCN8A moderate: 5-10 mV shift Moderate depolarizing shift of voltage dependence of activation webprotege:RC6e65svL8GnahTMiaHjRON The fast inactivated state is when the pore is open but does not conduct current. An effect on fast inactivation is a biophysical change in which one of the parameters of the channel changing to the fast inactivated state is different in the mutant protein compared to wildtype. FENICS:0037 Effect on fast inactivation webprotege:RC7JvpnEA0enGEJxIIdz4c A severe slowing of activation (tau activation) of a voltage-gated ion channel in which the mutant has a time constant significantly increased by a factor of more than 2 compared to wildtype. FENICS:0015 KCNQ2: severe > 2.00 Severe slowing of activation webprotege:RC7UYgJd2o0EeyLF1F20qZG A mild depolarizing shift of voltage dependence of activation is a depolarizing shift of voltage dependence of activation (right shift) of a voltage-gated ion channel in which the value of V1/2 is significantly increased by up to 5mV for Na+ channels or 10mV for K+ channels. FENICS:0024 Loss-of-function SCN2A and SCN8A mild: up to 5 mV; K+ channels mild: up to 10mV Mild depolarizing shift of voltage dependence of activation webprotege:RCCYzTbbm9jGGdBAcyrpQbn An acceleration of entry into slow inactivation is an effect on entry into slow inactivation of a voltage-gated ion channel leading to loss-of-function, in which the time of onset of slow inactivation is significantly reduced. FENICS:0103 measured in milliseconds/seconds Acceleration of entry into slow inactivation webprotege:RCDQDyUZ1O1bMFQkiFtMAZu A component leading to uncertain biophysiological effect is an alteration for which it is unclear whether the contribution is to enhancement or reduction in mutant function compared to wildtype. FENICS:0006 Component leading to uncertain biophysiological effect webprotege:RCEWxMPvxnLPQFI7e1TeyDC An increase in resurgent current is an effect on resurgent current of a voltage-gated ion channel leading to gain-of-function, in which ion flow in mutant channels which reopened following the normal transient current is significantly increased compared to wildtype. FENICS:0099 Increase in resurgent current webprotege:RCJNYSXtzUQaxxxeigBc9rg The absence of abnormal gating pore current denotes normal ion channel function wherein no ion flow through the voltage-sensing domain is detected. FENICS:0076 Absence of abnormal gating pore current webprotege:RCJZXn4sxIYSrwb8TbZJlqg Normal ion selectivity is an absence of an effect on ion selectivity in which no significant difference in ion specificity is observed compared to wildtype. FENICS:0081 Normal ion selectivity webprotege:RCQHSBGZT4JxStSfikvi8js An effect on entry into slow inactivation is an effect on slow inactivation of a voltage-gated ion channel in which the affected parameter is the time it takes for slow inactivation to begin. FENICS:0102 Effect on entry into slow inactivation webprotege:RCQdh0b9O2PwzpekxN1WriE A mild hyperpolarizing shift of voltage dependence of fast inactivation is a hyperpolarizing shift of voltage dependence of fast inactivation (left shift) of a voltage-gated ion channel in which the value of V1/2 is significantly reduced by up to 7.5mV. FENICS:0067 loss-of-function up to 7.5 mV shift Mild hyperpolarizing shift of voltage dependence of fast inactivation webprotege:RCkkho6vZp3kuq92L9UxQ7x A component leading to normal function is an alteration that contributes to no change in mutant function compared to wildtype. FENICS:0005 Component leading to normal ion channel function webprotege:RCvk5iSgbniWz9P4mjJsdlC An overall mixed or unclear function is an overall assessment of ion channel function in which the experimenters conclude that the activity of the mutant channel is neither explicitly enhanced nor reduced relative to wildtype. FENICS:0145 Overall mixed or unclear functional effect not able to be clearly categorized as Gain- or Loss-of-Function webprotege:RCxkRIG6UqWPWVsBL3fvLdo An effect on shift of voltage dependence of slow inactivation (V1/2) is an effect on voltage dependence of slow inactivation of a voltage-gated ion channel in which the affected parameter is the half-maximal voltage (V1/2), the potential at which 50% of channels are in the slow inactivated state. FENICS:0115 Effect on shift of voltage dependence of slow inactivation webprotege:RD0BDIIzgUe4mtGYW27xz6H Overall normal function due to single-cell neuronal properties is an overall normal function in which the normal function of the mutant channel is observed at the level of single neuron, e.g. due to firing rates. FENICS:0151 Overall normal function due to single-cell neuronal properties webprotege:RD13eaB3fwGp3eE77vJf9J7 An increase in peak current is an effect on peak current of a voltage-gated ion channel leading to gain-of-function, in which peak current density is significantly increased compared to wildtype. FENICS:0092 2 fold or higher - severe 1.3-2 fold moderate up to 1.3 fold is mild Increase in peak current webprotege:RD4l3irGmoY9l24tfaycvl An increase of decay in current amplitude in use dependence is an effect on use dependence of a voltage-gated ion channel leading to loss of function, in which the use-dependent attenuation is significantly increased, leading to less current conducted over repeat depolarization. FENICS:0134 Increase of decay in current amplitude in use dependence webprotege:RD8Pi69ieWp9K2OhT9WJEG A decrease of decay in current amplitude in use dependence is an effect on use dependence of a voltage-gated ion channel leading to gain of function, in which the use-dependent attenuation is significantly reduced, leading to more current conducted over repeat depolarization. FENICS:0133 Decrease of decay in current amplitude in use dependence webprotege:RDFDJF4kvghH94F1afcua4w An effect on slope of activation (k) is an effect on voltage dependence of activation of a voltage-gated ion channel in which the affected parameter is the slope factor (k), which indicates the steepness of voltage dependence of activation when plotted with respect to voltage after fitting to a Boltzmann function. FENICS:0033 change in activation for Na+ channels Effect on slope of activation webprotege:RDGPKWNIULbpyxm7b0wIuii A decrease in slope of slow inactivation is an effect on slope of slow inactivation (k) of a voltage-gated ion channel leading to loss of function, in which there is significantly greater steepness of channel inactivation with respect to membrane potential. FENICS:0120 Decrease in slope of slow inactivation webprotege:RDI44zpLiKB8U9OBgFIDIop An effect on slope of fast inactivation (k) is an effect on voltage dependence of fast inactivation of a voltage-gated ion channel in which the affected parameter is slope factor (k), which indicates the steepness of voltage dependence of inactivation when plotted with respect to voltage after fitting to a Boltzmann function. FENICS:0071 Effect on slope of fast inactivation webprotege:RDM0lP4PmjUTUE8TDmx0vhO A mild slowing of activation is a slowing of activation (tau activation) of a voltage-gated ion channel in which the mutant has a time constant increased significantly by a factor of up to 1.25 compared to wildtype. FENICS:0013 KCNQ2: up to 1.25 Mild slowing of activation webprotege:RDN1HidwTo5yxEolQVUN1i2 An acceleration of deactivation is an effect on rate of deactivation (tau deactivation) of a voltage-gated ion channel leading to loss-of-function, in which the time constant is reduced, corresponding to channels closing significantly faster compared to wildtype. FENICS:0017 Acceleration of deactivation webprotege:RDTMAY4Nsd5P8hpcBUUypxU Overall gain-of-function effect due to neuronal network properties is an overall gain-of-function in which the enhancement to the mutant channel's function is observed on systems of multiple neurons. FENICS:0138 Overall gain-of-function effect due to neuronal network properties webprotege:RDXWDoljWFzQfFl2YI7DCtA An effect on voltage dependence of slow inactivation is an effect on slow inactivation of a voltage-gated ion channel in which the affected parameter is the proportion of channels that are in inactivated states after being held at different membrane potentials/voltages. FENICS:0114 Effect on voltage dependence of slow inactivation webprotege:RDcpKlApCB4PPPBO6hjgl6m A severe depolarizing shift of voltage dependence of fast inactivation is a depolarizing shift of voltage dependence of fast inactivation (right shift) of a voltage-gated ion channel in which the value of V1/2 is significantly increased by >15mV. FENICS:0064 > 15 mV shift gain-of-function Severe depolarizing shift of voltage dependence of fast inactivation webprotege:RDnQOos7Y952sZBt7bCl2A An overall normal function is an overall assessment of ion channel function in which the experimenters conclude that the activity of the mutant channel is similar to wildtype. FENICS:0149 Overall normal function webprotege:RDrJoygIdb3JDax6AmGciVY Effect on ion channel function FENICS:0001 Effect on ion channel function webprotege:RDtSd8oWO4IYoQfAWZxQBNy Overall gain-of-function effect with respect to biophysical channel activity is an overall gain-of-function in which the enhancement to the mutant channel's function is concluded from the cumulative effect of the biophysical alterations to the channel. FENICS:0140 Overall gain-of-function effect with respect to biophysical channel activity webprotege:RDuKs2x3U7Ftv1RPSUUW7bG Overall mixed or unclear functional effect with respect to biophysical channel activity is an overall mixed function in which the conflicting effects to the mutant channel's function is concluded from the cumulative effect of the biophysical alterations to the channel. FENICS:0148 Overall mixed or unclear functional effect with respect to biophysical channel activity webprotege:RDufCzpibYChlFwDOguxQBk An acceleration of slow inactivation is an effect on rate of slow inactivation (tau inactivation) of a voltage-gated ion channel leading to loss-of-function, in which the time constant is significantly reduced, corresponding to channels changing to the slow inactivated state faster compared to wildtype. FENICS:0111 Acceleration of slow inactivation webprotege:RDyQ9lJFRvp1SJ8SKR7BkGn An effect on voltage dependence of activation is an effect on activation of a voltage-gated ion channel in which the affected parameter is the proportion of channels that are in activated states after being held at different membrane potentials/voltages. FENICS:0020 Effect on voltage dependence of activation webprotege:RF33PdZrU9lQq5U6wsPKju Normal rate of deactivation is an absence of an effect on rate of deactivation (tau deactivation) of a voltage-gated ion channel in which no significant difference in time constant is observed compared to wildtype. FENICS:0018 Normal rate of deactivation webprotege:RFM4zJvoKLRdsir6FY0w37 A severe increase in persistent current is an increase in persistent current of a voltage-gated sodium channel in which the persistent current is significantly increased by a factor of more than 3 in the mutant compared to wildtype. FENICS:0043 Severe increase in persistent current webprotege:RFfobOSwAuTUYKPE2tL5xf Normal slope of slow inactivation is an absence of an effect on slope of slow inactivation (k) in which there is no significant difference in slope factor observed compared to wildtype. FENICS:0122 Normal slope of slow inactivation webprotege:RGZCWQhcAEWq0SY26S5m5e Normal voltage dependence of fast inactivation is an absence of an effect on voltage dependence of fast inactivation in which no significant difference in V1/2 is observed compared to wildtype. FENICS:0070 Normal voltage dependence of fast inactivation webprotege:RHVrokWeLjYhM07ls02sTd An increase in ramp current is an effect on ramp current of a voltage-gated ion channel leading to gain of function, in which the current amplitude is significantly increased compared to wildtype. FENICS:0130 Increase in ramp current webprotege:RM0V7djo7NgfCr6xB32iax A mild decrease in peak current is a decrease in peak current of a voltage-gated ion channel in which peak current density in the mutant is significantly reduced to 50-100% of that of the wildtype. FENICS:0085 50-100% of wildtype Mild decrease in peak current webprotege:RMPJkbO62zkkObPHsJZpnf A decrease in persistent current is an effect on persistent current of a voltage-gated sodium channel leading to loss of function, in which a significantly reduced current is conducted by the channel following fast inactivation. FENICS:0039 Reduced persistent current is an outlier SCN11a and SCN10a: technically can have reduced persistent current Decrease in persistent current webprotege:RMxVquE9c2j3gk6Vbhg9TW An increase in slope of slow inactivation is an effect on slope of slow inactivation (k) of a voltage-gated ion channel leading to gain of function, in which there is significantly reduced steepness of channel inactivation with respect to membrane potential. FENICS:0121 Increase in slope of slow inactivation webprotege:RNbTxYjtlhgiWW8okEMzyj Normal current amplitude in use dependence is an absence of effect on use dependence of a voltage-gated ion channel, in which no significant difference is observed compared to wildtype. FENICS:0135 Normal current amplitude in use dependence webprotege:ROWM5cmXNzjTPBn7ogKyII A severe decrease in peak current due to reduced trafficking is a severe decrease in peak current of a voltage-gated ion channel which is explained by a significantly reduced fraction of mutant channels being trafficked to the plasma membrane compared to wildtype. FENICS:0089 Severe decrease in peak current due to reduced trafficking webprotege:RPGjvHXaR7w0A4dKjNGhVc A slowing of fast inactivation (tau inactivation) is an effect on rate of fast inactivation of a voltage-gated ion channel leading to gain-of-function, in which the time constant is significantly increased, corresponding to channels changing to the inactivated state more slowly than wildtype channels. FENICS:0048 Mild (up to 2 fold) Moderate (2-4 fold) Severe: more than 4 fold more milliseconds, GoF Slowing of fast inactivation webprotege:RQNDbYiHvI4VNvMipjKcIZ A slowing of recovery from slow inactivation is an effect on recovery from slow inactivation of a voltage-gated ion channel leading to loss-of-function, in which the time constant (tau) is significantly increased, corresponding to channels recovering slower compared to wildtype. FENICS:0109 Slowing of recovery from slow inactivation webprotege:RQjP2MguDr8OzKDeceZJ46 A mild-moderate depolarizing shift of voltage dependence of activation is a depolarizing shift of voltage dependence of activation (right shift) of a voltage-gated ion channel in which the value of V1/2 is significantly increased by up to 10mV for Na+ channels or 20mV for K+ channels. FENICS:0023 Loss-of-function Mild-moderate depolarizing shift of voltage dependence of activation webprotege:RTJTAlmpfiiOAckMP7C8xY A slowing of deactivation is an effect on rate of deactivation (tau deactivation) of a voltage-gated ion channel leading to gain-of-function, in which the time constant is increased, corresponding to channels closing significantly slower compared to wildtype. FENICS:0019 Slowing of deactivation webprotege:RVDcHrv1yHMY8q3VkhEV9W A decrease in resurgent current is an effect on resurgent current of a voltage-gated ion channel leading to loss-of-function, in which ion flow in mutant channels which reopened following the normal transient current is significantly reduced compared to wildtype. FENICS:0098 Decrease in resurgent current webprotege:RW0QrBvuBOwHBYFFJMntlo A slowing of entry into slow inactivation is an effect on entry into slow inactivation of a voltage-gated ion channel leading to gain-of-function, in which the time of onset of slow inactivation is significantly increased. FENICS:0105 Slowing of entry into slow inactivation webprotege:RWsIdPK9ef5X7RMzIebmPQ Use dependence refers to the attenuation of current conducted by a voltage-gated ion channel in response to repeated depolarization. An effect on use dependence is a compound biophysical effect in which this use-dependent decay in current amplitude is different in the mutant protein compared to wildtype. FENICS:0132 amplitude goes down after repeat impulses, not biophysical property of channel itself Effect on use dependence webprotege:RXhKs55YyYQdgiLKwckPRg A slowing of recovery from fast inactivation is an effect on rate of recovery from fast inactivation of a voltage-gated ion channel leading to loss-of-function, in which the time constant (tau) is significantly increased, corresponding to channels recovering more slowly compared to wildtype. FENICS:0055 Slowing of recovery from fast inactivation webprotege:RYWQSm4huaAno89B4WFQZH A moderate decrease in peak current is a decrease in peak current of a voltage-gated ion channel in which the peak current density of the mutant is significantly reduced to 20-49% of that of the wildtype. FENICS:0086 20-50% of wildtype Moderate decrease in peak current webprotege:Rbfc13foQ6CEHIWiXh434p An effect on rate of fast inactivation (tau inactivation) is an effect on fast inactivation of a voltage-gated ion channel in which the affected parameter is the time constant (tau) of fast inactivation, which measures how quickly or slowly the open channel changes to the inactivated state with respect to time. FENICS:0045 Effect on rate of fast inactivation webprotege:RbjgdQVqMBklwux9sWTACl A severe depolarizing shift of voltage dependence of activation is a depolarizing shift of voltage dependence of activation (right shift) of a voltage-gated ion channel in which the value of V1/2 is significantly increased by >5mV for Na+ channels or >10mV for K+ channels. FENICS:0026 Loss-of-function SCN2A and SCN8A severe: >10 mV, K+ channels severe: >20mV Severe depolarizing shift of voltage dependence of activation webprotege:RfJRsrblTGfIJ44dw2SyYJ A severe hyperpolarizing shift of voltage dependence of fast inactivation is a hyperpolarizing shift of voltage dependence of fast inactivation (left shift) of a voltage-gated ion channel in which the value of V1/2 is significantly reduced by >15mV. FENICS:0069 loss-of-function more than 15 mV shift Severe hyperpolarizing shift of voltage dependence of fast inactivation webprotege:RgGuZhqK1D3ro0nNhiBoXw Normal subthreshold current is an absence of an effect on subthreshold current, in which no significant difference is observed compared to wildtype. FENICS:0126 Normal subthreshold current webprotege:RiK8rUNBcWv8Rw4Rq5MIQX A mild to moderate slowing of activation is a slowing of activation (tau activation) of a voltage-gated ion channel in which the mutant has a time constant significantly increased by a factor of 1.25-2 compared to wildtype. FENICS:0014 KCNQ2: 1.25-2.0 Moderate slowing of activation webprotege:Rkesu9uJL9z5Q6W38xiAhQ A severe hyperpolarizing shift of voltage dependence of activation is a hyperpolarizing shift of voltage dependence of activation (left shift) of a voltage-gated ion channel in which the value of V1/2 is significantly decreased by >10mV for Na+ channels or >20mV for K+ channels. FENICS:0031 Gain-of-function SCN2A and SCN8A severe: >10 mV; K+ channels severe: >20mV Severe hyperpolarizing shift of voltage dependence of activation webprotege:Rl7K1Hgqs34BVxM4PNtn4w A mild-moderate hyperpolarizing shift of voltage dependence of activation is a hyperpolarizing shift of voltage dependence of activation (left shift) of a voltage-gated ion channel in which the value of V1/2 is significantly decreased by up to 10mV for Na+ channels or 20mV for K+ channels. FENICS:0028 Gain-of-function Mild-moderate hyperpolarizing shift of voltage dependence of activation webprotege:RoMCTYJPjBEU5d6aaVUh44 A hyperpolarizing shift of voltage dependence of slow inactivation (left shift) is an effect on shift of voltage dependence of slow inactivation (V1/2) of a voltage-gated ion channel leading to loss of function, in which channels change to the slow inactivated state at significantly more negative potentials. FENICS:0117 Hyperpolarizing shift of voltage dependence of slow inactivation webprotege:RobShQwofhZsmj29NgnSGj Slow inactivation is the process by which voltage-gated sodium channels change to an inactivated state following long (seconds) or high frequency depolarizations, reducing the proportion of channels available for opening. An effect on slow inactivation is a biophysical change of sodium channels in which there is a difference in the parameters of slow inactivation in the mutant protein compared to wildtype. FENICS:0101 Effect on slow inactivation webprotege:Rsw2n4guhiNupAT5yaAXtb Subthreshold current is continuous low-level conduction of ions by voltage-gated ion channels. An effect on subthreshold current is a biophysical change in which this flow is different in the mutant protein compared to wildtype. FENICS:0123 Subthreshold, for example for sodium channels ‘low threshold sodium current’ sometimes designated INaP in papers Effect on subthreshold current webprotege:RwQyQ1jQlK4mhCi3frcbsW An effect on ion channel biophysical properties is an alteration to an experimental measurement corresponding to a specific biophysical parameter of ion channel function. FENICS:0007 Effect on ion channel biophysical properties webprotege:RwcubAXCIcP10yoVjk9JVf An effect on rate of recovery from slow inactivation is an effect on slow inactivation of a voltage-gated ion channel in which the affected parameter is the time constant (tau) of recovery from slow inactivation, which measures how quickly or slowly the channel becomes available for activation after return to hyperpolarizing potentials to allow recovery from inactivation, i.e. the channel’s inactivation gate reopens. FENICS:0106 Effect on rate of recovery from slow inactivation webprotege:Rwd2Okf7Sd1xsETaBGsjeS Deactivation is the changing of the channel from the open state to the closed state in which the pore is closed and does not conduct current. An effect on rate of deactivation (tau deactivation) is an effect on activation of a voltage-gated ion channel in which the affected parameter is the time constant (tau) of deactivation, which measures how quickly or slowly the channel closes upon repolarization with respect to time. FENICS:0016 Effect on rate of deactivation webprotege:Rzl8n5oqmxsKFuEQoGs7ys Normal rate of slow inactivation is an absence of an effect on rate of slow inactivation (tau inactivation) in which no significant difference in time constant is observed compared to wildtype. FENICS:0112 Normal rate of slow inactivation webprotege:RzxAghzfGsgvWX3Ibm1dzr Overall mixed or unclear functional effect due to single-cell neuronal properties is an overall mixed function in which the conflicting effects to the mutant channel's function is observed at the level of single neuron, e.g. due to firing rates. FENICS:0147 Overall mixed or unclear functional effect due to single-cell neuronal properties owl:Thing Epilepsia, 54(9):e117–e121, 2013 doi: 10.1111/epi.12241 Lauxmann/Bosselmann 31/AUG/2020 SCN2A_Y1589C_tsA201 CB BFNIS ss PMID: 32090326 DOI: 10.1111/epi.16438 Same site as SCN1A_R944H SCN2A_R937H_index1016_Brunklaus2020 ASD Cells that expressed both b-subunits were used for electrophysiological recording experiments SCN1A_R859H_HEK_ab SCN1A_R964H Denis 2019 SCN8A_L267V_index277_Brunklaus2020 DEE ss Same site as SCN8A_R1872Q original paper Wolf et al., 2017 DOI: 10.1093/brain/awx054 SCN2A_R1882Q_index2042_Brunklaus2020 DEE ss PMID: 32090326 DOI: 10.1111/epi.16438 Same site as SCN1A_R946C SCN2A_R937C_index1016_Brunklaus2020 ASD SCN2A_K1422E SCN8A_G964R_index1051_Brunklaus2020 NDD without epilepsy SCN3A_I875T SCN1A_E788K_HEK_ss Also Rhodes SCN1A_G979R_index1051_Brunklaus2020 Dravet SCN8A_G964R EF HEK-293T cells PMID: 32515017 SCN3A_L855P_index925_Zaman2020 non-neonatal isoform, make sure "order" is correct SCN2A_M1879T KCNQ2 mutant with KCNQ2 wt and KCNQ3 (1:1:2), not KCNQ3, CHO cells, https://hal-amu.archives-ouvertes.fr/hal-01664283/file/2015_KCNQ2_A294V%20-%20biffe%CC%81.pdf KCNQ2_A294V_Abidi2015_exp1 ss SSCID_SCN2A Same site as SCN1A_R1657C doi: 10.1111/epi.16438 original paper Wengert 2019 doi: 10.1111/j.1460-9568.2011.07826.x. SCN8A_R1638C_index1807_Brunklaus2020 NDD without epilepsy test4 Christian's test Denis 2019 SCN8A_Q1470K_index1637_Brunklaus2020 DEE HEK293T cells PMID: 31402610 SCN8A_N374K_Zaman2019 EF HEK-293T cells PMID: 32515017 SCN3A_P1333L_Zaman2020 KCNA2_P405L_Syrbe2015 SCN1A_R1657C_HEK_ab ss PMID: 32090326 DOI: 10.1111/epi.16438 same site as SCN2A_R937C_Brunklaus2000 SCN1A_R946C_index1016_Brunklaus2020 Dravet EF HEK-293T cells PMID: 32515017 SCN3A_I1468R_Zaman2020 Wolff 2017 SCN2A_P1622S_index1782_Brunklaus2020 ASD and Sz KCNA2_R294H_Helbig2016 KCNA2_R297Q_Syrbe2015 oocytes, expression with wt KCNQ3 and KCNQ2 mutation 1:1 (homozygous) KCNQ2_R333Q_homozygous https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6004444/ This functional profile would be impossible to intuit from voltage clamp analysis of the L1563V variant given the relatively small but opposing changes of the activation and inactivation curves and an enhanced recovery from fast inactivation compared with wild-type, highlighting a strength of the dynamic action potential-clamp method in providing meaningful frameworks for understanding variant functional mechanisms. SCN2A_L1563V_CHO CHO EF HEK-293T cells PMID: 32515017 SCN3A_I875T_Zaman2020 PMID:31402610 SCN8A_M139I_Zamaan2019 SCN2A_R1882Q_HEK not performed KCNQ2_R333Q_heterozygous_hypothetical Same site as SCN2A_R1882 SCN8A_R1872W_index2042_Zaman2019 SCN2A_R853Q_oocytes xenopus oocytes ss SCN1A_L263V_index277_Brunklaus2020 FHM3 Rhodes 2005 SCN1A_P1632S_index1782_Brunklaus2020 Dravet VARIO_1, VARIO_2, VARIO_3, see below XYZ TBD Fulltext of functional result TBD XYZ test_variant HEK293T cells PMID: 31402610 SCN8A_M139I_Zaman2019 ss Same site as SCN2A_R1882Q doi: 10.1111/epi.16438 original Wagnon 2015 PMID: 26900580 SCN8A_R1872Q_index2042_Brunklaus2020 DEE SCN2A_R853Q_HEK HEK cells ss Same site as SCN8A_R1638C original paper: Lossin 2003 doi: 10.1523/JNEUROSCI.23-36-11289.2003 SCN1A_R1657C_index1807_Brunklaus2020 GEFS+ P405L disrupts the highly-conserved, KV-specific PVP motif in S6, which is thought to link the gate to the voltage-sensor. KCNA2_P405L_oocytes CB test1 ss PMID: 32090326 DOI: 10.1111/epi.16438 same site as SCN2A_R937H SCN1A_R946H_index1016_Brunklaus2020 Dravet Domain 2, S4 SCN1A_R865G_Brunklaus2019 SCN2A_p.R1312S HEK cells Dravet Syndrome Kahlig 2008, Cestele 2013 SCN1A_Q1489K_index1637_Brunklaus2020 FHM3