KCNT1 (Q5JUK3) variants and mutations
KCNT1 (also known as Q5JUK3) is a human protein-coding gene encoding a potassium channel subfamily T member 1 protein. Its sodium-activated potassium current helps shape repetitive neuronal firing and adaptation. Gain-of-function variants are a well-established cause of severe early-onset epilepsies, including epilepsy of infancy with migrating focal seizures and autosomal dominant sleep-related hypermotor epilepsy. This analysis covers 1,847 KCNT1 variants and mutations. Of these, 52% have computational variant effect predictions. Disease context includes developmental and epileptic encephalopathy, 14, autosomal dominant nocturnal frontal lobe epilepsy 5, and autosomal dominant nocturnal frontal lobe epilepsy. Example KCNT1 variants include R3Q, A4T, and A4G.
Variant analysis overview
- Gene: KCNT1
- Protein: Q5JUK3
- UniProt accession: Q5JUK3
- Organism: Homo sapiens
- Variants analyzed: 1847
- Variant scope: all variants
- Completed: 2026-08-19
Variant and mutation evidence
- Variant composition: 1,606 unspecified-consequence records; 161 missense variants; 28 frameshift variants; 37 synonymous variants; 5 in-frame deletions; 4 stop-gained variants; 1 in-frame insertions; 5 substitution
- Prediction scores: 959 variants have prediction scores (52% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: developmental and epileptic encephalopathy, 14, autosomal dominant nocturnal frontal lobe epilepsy 5, autosomal dominant nocturnal frontal lobe epilepsy, malignant migrating partial seizures of infancy, Seizure, hereditary disease, epilepsy, childhood-onset epilepsy syndrome, sleep-related hypermotor epilepsy, familial sleep-related hypermotor epilepsy, epilepsy of infancy with migrating focal seizures, infantile spasms.
Protein structure and variant hotspots
- Protein features: 6 transmembrane segments; 2 domains; 25 binding sites; 2 post-translational modification sites.
- Structural context: 524 variants have structural context.
- PTM context: 2 variants overlap post-translational modification sites.
Data sources
Evidence in this analysis draws on EBI Proteins Variation, UniProt, gnomAD v4, EuropePMC, 3D Hotspot Analysis, Interaction Network Analysis, Protein Data Bank, AlphaFold DB, gnomAD constraint, Open Targets, MaveDB, LitVar.
Notable KCNT1 variants
Examples include R3Q, A4T, A4G, A4S, A4E, A4V, K5E, K5Q. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- R3Q (p.Arg3Gln), TOPMed rs1483705202, gnomAD rs1483705202, CADD 17.70
- A4T (p.Ala4Thr), gnomAD 9-135702277-G-A, REVEL 0.02, CADD 17.10
- A4G (p.Ala4Gly), rs757568103, gnomAD 9-135702277-GC-G, CADD 18.50
- A4S (p.Ala4Ser), rs1835062307, gnomAD 9-135702277-G-T, REVEL 0.02, CADD 11.50
- A4E (p.Ala4Glu), rs1044336128, gnomAD 9-135702278-C-A, REVEL 0.03, CADD 11.50
- A4V (p.Ala4Val), rs1044336128, gnomAD 9-135702278-C-T, REVEL 0.04, CADD 12.20
- K5E (p.Lys5Glu), TOPMed rs1830353289, gnomAD rs1830353289, CADD 18.70
- K5Q (p.Lys5Gln), TOPMed rs1830353289, gnomAD rs1830353289
- L6P (p.Leu6Pro), gnomAD 9-135702264-ACT-A, CADD 19.10
- L6V (p.Leu6Val), gnomAD 9-135702265-C-G, REVEL 0.04, CADD 8.20
- L6F (p.Leu6Phe), gnomAD 9-135702265-C-T, REVEL 0.06, CADD 10.80
- L6I (p.Leu6Ile), gnomAD 9-135702265-C-A, REVEL 0.04, CADD 14.20
- L6L (p.Leu6Leu), rs768423949, gnomAD 9-135702267-C-T, CADD 1.84
- P7L (p.Pro7Leu), gnomAD rs1257974015, CADD 16.90
- P7S (p.Pro7Ser), TOPMed rs1188876343, gnomAD rs1188876343, CADD 17.80
- P7T (p.Pro7Thr), gnomAD 9-135702262-C-A, REVEL 0.04, CADD 13.30
- P7A (p.Pro7Ala), rs748898708, gnomAD 9-135702262-C-G, REVEL 0.05, CADD 12.40
- P7Q (p.Pro7Gln), gnomAD 9-135702263-C-A, REVEL 0.01, CADD 14.50
- P7R (p.Pro7Arg), rs747733979, gnomAD 9-135702269-C-G, REVEL 0.02, CADD 13.70
- P7H (p.Pro7His), rs747733979, gnomAD 9-135702269-C-A, REVEL 0.04, CADD 13.30
- P7P (p.Pro7Pro), rs1236737169, gnomAD 9-135702270-T-C, AlphaMissense 0.75, MetaLR 0.20
- R8C (p.Arg8Cys), NCI-TCGA TCGA novel, CADD 17.60, Variant assessed as somatic; moderate impact.
- R8W (p.Arg8Trp), rs747457929, gnomAD 9-135702280-C-T, REVEL 0.04, CADD 17.00
- R8G (p.Arg8Gly), rs747457929, gnomAD 9-135702280-C-G, REVEL 0.02, CADD 10.30
- R8Q (p.Arg8Gln), gnomAD 9-135702281-G-A, REVEL 0.04, CADD 6.36
- R8R (p.Arg8Arg), gnomAD 9-135702282-G-A, CADD 4.07
- R8L (p.Arg8Leu), rs373446490, gnomAD 9-135702302-G-T, REVEL 0.01, CADD 3.48
- R8P (p.Arg8Pro), gnomAD 9-135702311-G-C, REVEL 0.06, CADD 13.10
- R8H (p.Arg8His), rs753714293, gnomAD 9-135702311-G-A, REVEL 0.02, CADD 12.50
- S9L (p.Ser9Leu), TOPMed rs1830353920, CADD 17.50
- S9T (p.Ser9Thr), Ensembl rs1830353790, CADD 18.10
- P10L (p.Pro10Leu), TOPMed rs1281442772, gnomAD rs1281442772, REVEL 0.04, CADD 9.37
- P10R (p.Pro10Arg), TOPMed rs1281442772, gnomAD rs1281442772, CADD 17.00
- P10S (p.Pro10Ser), rs1174574288, gnomAD 9-135702286-C-T, REVEL 0.04, CADD 14.50
- P10P (p.Pro10Pro), rs139034501, gnomAD 9-135702288-G-C, CADD 1.57
- E12K (p.Glu12Lys), TOPMed rs1315899184, gnomAD rs1315899184, CADD 17.40
- E12G (p.Glu12Gly), gnomAD 9-135702301-CGG-C, CADD 13.80
- E12V (p.Glu12Val), rs755980218, gnomAD 9-135702305-A-T, REVEL 0.03, CADD 7.84
- E12E (p.Glu12Glu), rs1564304686, gnomAD 9-135702306-G-A, AlphaMissense 0.19, MetaLR 0.31
- G13S (p.Gly13Ser), Ensembl rs1564332184
- G13R (p.Gly13Arg), rs773874266, gnomAD 9-135702274-G-C, REVEL 0.12, CADD 16.00
- G13W (p.Gly13Trp), gnomAD 9-135702274-G-T, REVEL 0.18, CADD 21.20
- G13V (p.Gly13Val), gnomAD 9-135702275-G-T, REVEL 0.12, CADD 20.20
- G13A (p.Gly13Ala), gnomAD 9-135702287-CG-C, CADD 10.40
- G13E (p.Gly13Glu), rs1003586835, gnomAD 9-135702290-G-A, REVEL 0.01, CADD 0.82
- G13C (p.Gly13Cys), gnomAD 9-135702292-G-T, REVEL 0.05, CADD 18.10
- G13D (p.Gly13Asp), rs763055585, gnomAD 9-135702293-G-A, REVEL 0.03, CADD 9.55
- G13G (p.Gly13Gly), rs1442852201, gnomAD 9-135702294-C-T, CADD 5.27
- A15R (p.Ala15Arg), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- A15V (p.Ala15Val), rs377687237, gnomAD 9-135702308-C-T, REVEL 0.01, CADD 4.55
- A15A (p.Ala15Ala), gnomAD 9-135702309-G-C, CADD 6.55
- G16V (p.Gly16Val), TOPMed rs1830355117, gnomAD rs1830355117, CADD 18.20
- P17R (p.Pro17Arg), cosmic curated COSV53704
- G18V (p.Gly18Val), TOPMed rs1303158281, gnomAD rs1303158281, CADD 16.90
- G18W (p.Gly18Trp), TOPMed rs1410153884, gnomAD rs1410153884, CADD 17.70
- G19D (p.Gly19Asp), Ensembl rs1830355785, REVEL 0.04, CADD 10.60
- G19S (p.Gly19Ser), TOPMed rs1034344762, gnomAD rs1034344762, REVEL 0.03, CADD 2.91, Likely benign, Inborn genetic diseases; Autosomal dominant nocturnal frontal lobe epilepsy 5; D
- G19R (p.Gly19Arg), rs781519720, gnomAD 9-135702306-GGC-G, CADD 16.10
- p.Gly20 Tyr22del, gnomAD 9-135702314-GCGGG, CADD 10.30
- G19G (p.Gly19Gly), gnomAD 9-135702315-C-G, AlphaMissense 0.16, MetaLR 0.28
- G19E (p.Gly19Glu), rs146292575, gnomAD 9-135702317-G-A, REVEL 0.03, CADD 9.08
- G19A (p.Gly19Ala), rs146292575, gnomAD 9-135702317-G-C, REVEL 0.05, CADD 7.73
- A20G (p.Ala20Gly), Ensembl rs1830355992
- A20P (p.Ala20Pro), TOPMed rs1161445367, gnomAD rs1161445367, CADD 13.20
- A20T (p.Ala20Thr), TOPMed rs1161445367, gnomAD rs1161445367, CADD 13.60
- P21S (p.Pro21Ser), Ensembl rs2131373109, CADD 12.80
- G23D (p.Gly23Asp), TOPMed rs1830356246, gnomAD rs1830356246, CADD 13.20
- A24T (p.Ala24Thr), TOPMed rs1174802265, gnomAD rs1174802265, CADD 12.10
- A25G (p.Ala25Gly), Ensembl rs113539839
- A25T (p.Ala25Thr), TOPMed rs1257317780, gnomAD rs1257317780, CADD 11.80
- A25V (p.Ala25Val), Ensembl rs113539839, CADD 14.50
- A26V (p.Ala26Val), Ensembl rs1830356847, CADD 11.10
- P27R (p.Pro27Arg), TOPMed rs1014352531, gnomAD rs1014352531, CADD 13.10
- P27S (p.Pro27Ser), gnomAD rs1356883613, CADD 13.70
- E28del (p.Glu28del), rs1321537618, gnomAD 9-135702339-CGAG-, CADD 14.90
- E28K (p.Glu28Lys), gnomAD 9-135702340-G-A, REVEL 0.02, CADD 16.00
- E28Q (p.Glu28Gln), rs1564304784, gnomAD 9-135702340-G-C, REVEL 0.02, AlphaMissense 0.15
- E28E (p.Glu28Glu), gnomAD 9-135702342-G-A, CADD 6.48
- E28D (p.Glu28Asp), gnomAD 9-135702342-G-C, REVEL 0.05, CADD 15.90
- G32W (p.Gly32Trp), TOPMed rs1830357346, CADD 15.10
- G32C (p.Gly32Cys), rs754823810, gnomAD 9-135702352-G-T, REVEL 0.05, CADD 15.50
- G32S (p.Gly32Ser), rs754823810, gnomAD 9-135702352-G-A, REVEL 0.03, CADD 14.70
- G32V (p.Gly32Val), rs1588238987, gnomAD 9-135702353-G-T, REVEL 0.03, CADD 17.00
- G32G (p.Gly32Gly), gnomAD 9-135702354-C-A, CADD 5.50
- S34R (p.Ser34Arg), TOPMed rs1210099687, gnomAD rs1210099687, CADD 14.10
- P35T (p.Pro35Thr), TOPMed rs967976864, gnomAD rs967976864, CADD 15.50
- P36del (p.Pro36del), rs745979475, gnomAD 9-135702361-GCCC-, CADD 10.50
- P35L (p.Pro35Leu), rs746315219, gnomAD 9-135702365-C-T, REVEL 0.04, CADD 9.03
- L36Q (p.Leu36Gln), Ensembl rs1830357854, CADD 16.50
- P38L (p.Pro38Leu), 1000Genomes rs547964274, TOPMed rs547964274, gnomAD rs547964274, CADD 16.60
- P38Q (p.Pro38Gln), 1000Genomes rs547964274, TOPMed rs547964274, gnomAD rs547964274, CADD 16.20
- P38S (p.Pro38Ser), TOPMed rs1231396213, CADD 16.60
- P38A (p.Pro38Ala), gnomAD 9-135714581-C-G, REVEL 0.03, CADD 13.00
- P38T (p.Pro38Thr), gnomAD 9-135714581-C-A, REVEL 0.04, CADD 8.03
- P38H (p.Pro38His), gnomAD 9-135714582-C-A, REVEL 0.02, CADD 16.10
- P38P (p.Pro38Pro), rs1349195051, gnomAD 9-135714583-C-T, CADD 8.25
- A39T (p.Ala39Thr), rs751166469, gnomAD 9-135702361-G-A, REVEL 0.03, CADD 3.33
- A39S (p.Ala39Ser), rs751166469, gnomAD 9-135702361-G-T, REVEL 0.01, AlphaMissense 0.07
- A39D (p.Ala39Asp), rs772080195, gnomAD 9-135702362-C-A, REVEL 0.02, AlphaMissense 0.35
- A39V (p.Ala39Val), rs772080195, gnomAD 9-135702362-C-T, REVEL 0.01, CADD 11.50
- A39A (p.Ala39Ala), rs1835067925, gnomAD 9-135702363-C-T, CADD 6.73
- A39G (p.Ala39Gly), rs1238908622, gnomAD 9-135714584-TGC-T, CADD 22.00
- A39E (p.Ala39Glu), gnomAD 9-135714588-C-A, REVEL 0.06, CADD 9.88
- A39P (p.Ala39Pro), gnomAD 9-135714599-G-C, REVEL 0.08, CADD 11.70
- R40C (p.Arg40Cys), TOPMed rs1313241319, CADD 17.00
- R40R (p.Arg40Arg), rs775807509, gnomAD 9-135702331-C-A, CADD 4.59
- R40W (p.Arg40Trp), rs775807509, gnomAD 9-135702331-C-T, REVEL 0.08, CADD 16.50
- R40Q (p.Arg40Gln), gnomAD 9-135702332-G-A, REVEL 0.03, CADD 12.30
- R40L (p.Arg40Leu), gnomAD 9-135702332-G-T, REVEL 0.05, CADD 15.40
- R40P (p.Arg40Pro), rs764163914, gnomAD 9-135702332-G-C, REVEL 0.03, CADD 13.80
- R40G (p.Arg40Gly), gnomAD 9-135702361-GC-G, CADD 19.30
- R40K (p.Arg40Lys), gnomAD 9-135702368-G-A, REVEL 0.10, CADD 34.00
- R40S (p.Arg40Ser), gnomAD 9-135714577-G-T, REVEL 0.07, CADD 24.60
- G41S (p.Gly41Ser), Ensembl rs1381425419, CADD 16.10
- G42E (p.Gly42Glu), TOPMed rs1830358681, REVEL 0.04, CADD 19.20
- G42R (p.Gly42Arg), TOPMed rs1830358561, REVEL 0.10, CADD 17.20, Uncertain significance, Autosomal dominant nocturnal frontal lobe epilepsy 5; Developmental and epilepti
- G42W (p.Gly42Trp), rs772192320, gnomAD 9-135714590-G-T, REVEL 0.05, CADD 22.40
- G42V (p.Gly42Val), gnomAD 9-135714591-G-T, REVEL 0.03, CADD 19.20
- G42G (p.Gly42Gly), rs1278186698, gnomAD 9-135714592-G-A, CADD 8.13
- G43D (p.Gly43Asp), gnomAD rs1830358796, CADD 18.00
- G43V (p.Gly43Val), gnomAD rs1830358796, CADD 17.60
- G43C (p.Gly43Cys), rs773228285, gnomAD 9-135714596-G-T, REVEL 0.09, CADD 22.30
- G43S (p.Gly43Ser), rs773228285, gnomAD 9-135714596-G-A, REVEL 0.14, CADD 17.00
- G43R (p.Gly43Arg), rs773228285, gnomAD 9-135714596-G-C, REVEL 0.14, CADD 21.50
- G43A (p.Gly43Ala), gnomAD 9-135714597-G-C, REVEL 0.09, CADD 9.97
- G43G (p.Gly43Gly), rs1835643705, gnomAD 9-135714598-C-T, CADD 9.73
- S44P (p.Ser44Pro), Ensembl rs1830359066, CADD 18.40
- V45L (p.Val45Leu), Ensembl rs2131373264, CADD 16.00
- V45R (p.Val45Arg), rs1835063072, gnomAD 9-135702287-C-CG, CADD 17.40
- V45I (p.Val45Ile), rs1433663811, gnomAD 9-135702295-G-A, REVEL 0.03, CADD 5.26
- V45G (p.Val45Gly), gnomAD 9-135702296-T-G, REVEL 0.03, CADD 15.80
- V45A (p.Val45Ala), rs764111643, gnomAD 9-135702296-T-C, REVEL 0.03, CADD 15.10
- S47G (p.Ser47Gly), TOPMed rs1290818493, CADD 19.60
- D48* (p.Asp48Ter), gnomAD 9-135702265-C-CT, CADD 19.10
- D48H (p.Asp48His), gnomAD 9-135702271-G-C, REVEL 0.08, CADD 14.30
- D48D (p.Asp48Asp), rs771669111, gnomAD 9-135702273-C-T, CADD 4.13
- D48E (p.Asp48Glu), gnomAD 9-135702273-C-G, REVEL 0.07, CADD 18.30
- D48G (p.Asp48Gly), gnomAD 9-135702347-A-G, REVEL 0.01, CADD 21.00
- D48N (p.Asp48Asn), rs766377529, gnomAD 9-135702349-G-A, REVEL 0.08, CADD 20.20
- D48Y (p.Asp48Tyr), rs766377529, gnomAD 9-135702349-G-T, REVEL 0.06, AlphaMissense 0.07
- D48T (p.Asp48Thr), gnomAD 9-135714588-CG-C, CADD 0.12
- D48V (p.Asp48Val), rs762875063, gnomAD 9-135714609-A-T, REVEL 0.04, CADD 20.80
- V49A (p.Val49Ala), TOPMed rs1830359617
- V49L (p.Val49Leu), 1000Genomes rs926236598, TOPMed rs926236598, gnomAD rs926236598, CADD 16.50
- V49M (p.Val49Met), 1000Genomes rs926236598, TOPMed rs926236598, gnomAD rs926236598, CADD 16.80
- G50D (p.Gly50Asp), TOPMed rs1830359885, CADD 19.30
- G50S (p.Gly50Ser), TOPMed rs1830359742, gnomAD rs1830359742, CADD 17.40
- G50A (p.Gly50Ala), gnomAD 9-135714616-CG-C, CADD 16.10
- G50R (p.Gly50Arg), rs148808978, gnomAD 9-135714617-G-C, REVEL 0.04, CADD 9.82
- G50C (p.Gly50Cys), gnomAD 9-135714617-G-T, REVEL 0.03, CADD 10.60
- G50V (p.Gly50Val), gnomAD 9-135714618-G-T, REVEL 0.09, CADD 18.20
- G50G (p.Gly50Gly), gnomAD 9-135714619-C-A, CADD 11.00
- Q51* (p.Gln51Ter), gnomAD 9-135702355-C-T, CADD 34.00
- Q51R (p.Gln51Arg), rs1214788912, gnomAD 9-135702356-A-G, REVEL 0.04, CADD 0.05
- Q51P (p.Gln51Pro), gnomAD 9-135702356-A-C, REVEL 0.02, CADD 1.95
- Q51H (p.Gln51His), gnomAD 9-135702357-A-C, REVEL 0.04, CADD 6.85
- Q51Q (p.Gln51Gln), rs146152956, gnomAD 9-135702357-A-G, CADD 2.94
- L53I (p.Leu53Ile), gnomAD 9-135714602-C-A, REVEL 0.04, CADD 7.32
- L53F (p.Leu53Phe), rs869312682, gnomAD 9-135714602-C-T, REVEL 0.05, CADD 11.90
- L53V (p.Leu53Val), rs869312682, gnomAD 9-135714602-C-G, REVEL 0.05, CADD 7.60
- L53W (p.Leu53Trp), gnomAD 9-135714603-TC-T, CADD 20.20
- L53P (p.Leu53Pro), gnomAD 9-135714603-T-C, REVEL 0.03, CADD 11.60
- L53L (p.Leu53Leu), gnomAD 9-135714604-C-G, CADD 6.17
- L53M (p.Leu53Met), gnomAD 9-135714605-C-A, REVEL 0.05, CADD 14.50
- L53Q (p.Leu53Gln), gnomAD 9-135714606-T-A, REVEL 0.05, CADD 10.00
- P54S (p.Pro54Ser), TOPMed rs957996086
- P54T (p.Pro54Thr), rs766901520, gnomAD 9-135714653-C-A, REVEL 0.18, MetaLR 0.12
- P54A (p.Pro54Ala), gnomAD 9-135714653-C-G, REVEL 0.17, MetaLR 0.11
- P54R (p.Pro54Arg), gnomAD 9-135714654-C-G, REVEL 0.19, MetaLR 0.20
- P54H (p.Pro54His), gnomAD 9-135714654-C-A, REVEL 0.19, MetaLR 0.21
- P54L (p.Pro54Leu), gnomAD 9-135714654-C-T, REVEL 0.21, MetaLR 0.19
- P54P (p.Pro54Pro), gnomAD 9-135714655-C-A, CADD 12.70
- p.Pro65 Pro66insTrpAlaGlnLeuAlaA, gnomAD 9-135714659-C-CCC, CADD 17.90
- P54W (p.Pro54Trp), gnomAD 9-135714660-C-CCT, CADD 25.20
- P54Q (p.Pro54Gln), gnomAD 9-135714660-C-A, REVEL 0.07, MetaLR 0.09
- P54C (p.Pro54Cys), gnomAD 9-135714660-C-CCT, CADD 25.40
- P54G (p.Pro54Gly), gnomAD 9-135714661-G-GGG, CADD 26.30
- E56* (p.Glu56Ter), TOPMed rs988103241, gnomAD rs988103241
- E56K (p.Glu56Lys), TOPMed rs988103241, gnomAD rs988103241
- E56R (p.Glu56Arg), gnomAD 9-135714641-TC-T, CADD 24.00
Public KCNT1 analysis runs
- KCNT1 analysis run — KCNT1 (1,847 variants) — completed 2026-08-19