KCNQ4 (P56696) variants and mutations
KCNQ4 (also known as P56696) is a human protein-coding gene encoding a potassium voltage-gated channel subfamily KQT member 4 protein. Its potassium conductance is crucial for electrical homeostasis in cochlear outer hair cells and auditory pathways. Dominant pathogenic variants are a well-established cause of progressive nonsyndromic sensorineural hearing loss, classically DFNA2. This analysis covers 1,332 KCNQ4 variants and mutations. Of these, 92% have computational variant effect predictions. Disease context includes autosomal dominant nonsyndromic hearing loss 2A, multiple sclerosis, and nonsyndromic genetic hearing loss. Example KCNQ4 variants include A2P, A2T, and A2S.
Variant analysis overview
- Gene: KCNQ4
- Protein: P56696
- UniProt accession: P56696
- Organism: Homo sapiens
- Variants analyzed: 1332
- Variant scope: all variants
- Completed: 2026-08-18
Variant and mutation evidence
- Variant composition: 943 unspecified-consequence records; 231 missense variants; 7 in-frame deletions; 92 synonymous variants; 8 stop-gained variants; 42 frameshift variants; 1 in-frame insertions; 8 substitution
- Prediction scores: 1,231 variants have prediction scores (92% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: autosomal dominant nonsyndromic hearing loss 2A, multiple sclerosis, nonsyndromic genetic hearing loss, Lambert-Eaton myasthenic syndrome, myasthenia gravis, epilepsy, Rare genetic deafness, Congenital myasthenic syndromes, congenital myasthenic syndrome, Seizure, Muscle weakness, hereditary disease.
Protein structure and variant hotspots
- Protein features: 6 transmembrane segments; 9 binding sites.
- Structural context: 170 variants have structural context.
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 KCNQ4 variants
Examples include A2P, A2T, A2S, A2V, A2D, A2G, A2A, E3K. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- A2P (p.Ala2Pro), TOPMed rs1359438636, REVEL 0.39, MetaLR 0.80
- A2T (p.Ala2Thr), TOPMed rs1359438636, REVEL 0.37, MetaLR 0.77
- A2S (p.Ala2Ser), gnomAD 1-40784097-G-T, REVEL 0.31, MetaLR 0.80
- A2V (p.Ala2Val), gnomAD 1-40784098-C-T, REVEL 0.32, MetaLR 0.80
- A2D (p.Ala2Asp), gnomAD 1-40784098-C-A, REVEL 0.37, MetaLR 0.73
- A2G (p.Ala2Gly), gnomAD 1-40784098-C-G, REVEL 0.28, MetaLR 0.80
- A2A (p.Ala2Ala), rs1417838891, gnomAD 1-40784099-C-T, CADD 14.60
- E3K (p.Glu3Lys), TOPMed rs1647180074, gnomAD rs1647180074, REVEL 0.31, MetaLR 0.78
- p.Glu3 Pro15del, gnomAD 1-40784097-GCCGAG, CADD 18.50
- E3* (p.Glu3Ter), gnomAD 1-40784100-G-T, CADD 35.00
- E3V (p.Glu3Val), gnomAD 1-40784101-A-T, REVEL 0.36, MetaLR 0.79
- E3G (p.Glu3Gly), gnomAD 1-40784101-A-G, REVEL 0.21, MetaLR 0.79
- E3D (p.Glu3Asp), gnomAD 1-40784102-G-T, REVEL 0.37, MetaLR 0.78
- E3E (p.Glu3Glu), gnomAD 1-40784102-G-A, CADD 11.90
- A4D (p.Ala4Asp), Ensembl rs1647180092, REVEL 0.30, MetaLR 0.79
- A4T (p.Ala4Thr), 1000Genomes rs2148830514, REVEL 0.28, MetaLR 0.80
- A4P (p.Ala4Pro), gnomAD 1-40784101-AG-A, CADD 23.30
- A4S (p.Ala4Ser), gnomAD 1-40784103-G-T, REVEL 0.26, MetaLR 0.79
- A4G (p.Ala4Gly), gnomAD 1-40784104-C-G, REVEL 0.30, MetaLR 0.74
- A4V (p.Ala4Val), gnomAD 1-40784104-C-T, REVEL 0.24, MetaLR 0.80
- A4A (p.Ala4Ala), rs1288969367, gnomAD 1-40784105-C-A, CADD 14.60
- P5L (p.Pro5Leu), TOPMed rs1422496526, gnomAD rs1422496526, REVEL 0.38, MetaLR 0.83
- P5S (p.Pro5Ser), TOPMed rs1427513839, gnomAD rs1427513839, REVEL 0.31, MetaLR 0.81
- p.Pro5 Gly40del, gnomAD 1-40784104-CCCCCC, CADD 19.20
- P5T (p.Pro5Thr), gnomAD 1-40784106-C-A, REVEL 0.33, MetaLR 0.84
- P5H (p.Pro5His), gnomAD 1-40784107-C-A, REVEL 0.34, MetaLR 0.89
- P5P (p.Pro5Pro), rs891485411, gnomAD 1-40784108-C-A, CADD 13.90
- P6L (p.Pro6Leu), TOPMed rs1478347910, gnomAD rs1478347910, REVEL 0.38, MetaLR 0.79
- P6Q (p.Pro6Gln), TOPMed rs1478347910, gnomAD rs1478347910, REVEL 0.34, MetaLR 0.79
- p.Pro6 Pro19del, gnomAD 1-40784102-GGCCCC, CADD 18.50
- P6R (p.Pro6Arg), gnomAD 1-40784103-GC-G, CADD 23.40
- P6A (p.Pro6Ala), gnomAD 1-40784103-GCC-G, CADD 23.70
- P6S (p.Pro6Ser), gnomAD 1-40784109-C-T, REVEL 0.26, MetaLR 0.82
- P6T (p.Pro6Thr), gnomAD 1-40784109-C-A, REVEL 0.30, MetaLR 0.82
- P6P (p.Pro6Pro), gnomAD 1-40784111-G-C, CADD 14.20
- R7H (p.Arg7His), TOPMed rs1248234130, REVEL 0.30, MetaLR 0.81
- R7A (p.Arg7Ala), rs1296567197, gnomAD 1-40784103-G-GC, CADD 24.10
- R7S (p.Arg7Ser), gnomAD 1-40784112-C-A, REVEL 0.29, MetaLR 0.83
- R7C (p.Arg7Cys), gnomAD 1-40784112-C-T, REVEL 0.35, MetaLR 0.83
- R7P (p.Arg7Pro), gnomAD 1-40784113-G-C, REVEL 0.44, MetaLR 0.79
- R7L (p.Arg7Leu), gnomAD 1-40784113-G-T, REVEL 0.35, MetaLR 0.80
- R7R (p.Arg7Arg), gnomAD 1-40784114-C-A, CADD 14.10
- R8L (p.Arg8Leu), TOPMed rs1647180247, REVEL 0.40, MetaLR 0.82
- R8A (p.Arg8Ala), gnomAD 1-40784103-G-GCC, CADD 24.00
- R8G (p.Arg8Gly), rs1647180136, gnomAD 1-40784104-CCCCCC, CADD 25.50
- R8C (p.Arg8Cys), gnomAD 1-40784115-C-T, REVEL 0.41, MetaLR 0.81
- R8S (p.Arg8Ser), gnomAD 1-40784115-C-A, REVEL 0.39, MetaLR 0.77
- R8H (p.Arg8His), gnomAD 1-40784116-G-A, REVEL 0.35, MetaLR 0.82
- R8R (p.Arg8Arg), gnomAD 1-40784117-C-A, CADD 13.40
- L9P (p.Leu9Pro), gnomAD 1-40784113-GCCGCC, CADD 24.00
- L9A (p.Leu9Ala), gnomAD 1-40784115-CGCCTC, CADD 25.70
- L9I (p.Leu9Ile), gnomAD 1-40784118-C-A, REVEL 0.36, MetaLR 0.87
- L9F (p.Leu9Phe), gnomAD 1-40784118-C-T, REVEL 0.40, MetaLR 0.85
- L9H (p.Leu9His), gnomAD 1-40784119-T-A, REVEL 0.37, MetaLR 0.85
- L9L (p.Leu9Leu), rs1190669660, gnomAD 1-40784120-C-T, CADD 13.30
- G10A (p.Gly10Ala), gnomAD rs1374479325, REVEL 0.36, MetaLR 0.79
- G10C (p.Gly10Cys), TOPMed rs1170668900, gnomAD rs1170668900, REVEL 0.39, MetaLR 0.78, Uncertain significance
- G10R (p.Gly10Arg), TOPMed rs1170668900, gnomAD rs1170668900, REVEL 0.35, MetaLR 0.79, Uncertain significance
- G10S (p.Gly10Ser), rs1170668900, ClinGen CA339884859, ClinVar RCV002872442, ClinVar RCV004065019, REVEL 0.41, MetaLR 0.71, Uncertain significance, Inborn genetic diseases; not provided; Autosomal dominant nonsyndromic hearing l
- p.Gly10 Ala21del, gnomAD 1-40784119-TCGGCC, CADD 18.90
- G10V (p.Gly10Val), gnomAD 1-40784122-G-T, REVEL 0.34, MetaLR 0.81
- G10D (p.Gly10Asp), gnomAD 1-40784122-G-A, REVEL 0.39, MetaLR 0.82
- G10G (p.Gly10Gly), gnomAD 1-40784123-C-T, CADD 14.60
- L11L (p.Leu11Leu), gnomAD 1-40784124-C-T, CADD 13.90
- L11M (p.Leu11Met), gnomAD 1-40784124-C-A, REVEL 0.36, MetaLR 0.94
- L11P (p.Leu11Pro), gnomAD 1-40784125-T-C, REVEL 0.55, MetaLR 0.94
- L11Q (p.Leu11Gln), gnomAD 1-40784125-T-A, REVEL 0.51, MetaLR 0.94
- L11R (p.Leu11Arg), gnomAD 1-40784125-T-G, REVEL 0.56, MetaLR 0.94
- G12D (p.Gly12Asp), ExAC rs777816150, gnomAD rs777816150, REVEL 0.48, MetaLR 0.74
- p.Gly12 Leu47del, gnomAD 1-40784106-CCCCCG, CADD 19.50
- G12S (p.Gly12Ser), gnomAD 1-40784125-TGG-T, CADD 25.30
- G12V (p.Gly12Val), gnomAD 1-40784125-TG-T, CADD 24.50
- G12C (p.Gly12Cys), gnomAD 1-40784127-G-T, REVEL 0.40, MetaLR 0.78
- G12R (p.Gly12Arg), gnomAD 1-40784127-G-C, REVEL 0.38, MetaLR 0.77
- G12A (p.Gly12Ala), gnomAD 1-40784128-G-C, REVEL 0.33, MetaLR 0.65
- G12G (p.Gly12Gly), gnomAD 1-40784129-T-C, CADD 12.20
- P13A (p.Pro13Ala), TOPMed rs1647180417, REVEL 0.37, MetaLR 0.92
- P13T (p.Pro13Thr), TOPMed rs1647180417, REVEL 0.40, MetaLR 0.93
- P13V (p.Pro13Val), gnomAD 1-40784127-G-GGC, CADD 25.40
- P13S (p.Pro13Ser), gnomAD 1-40784130-C-T, REVEL 0.39, MetaLR 0.93
- P13H (p.Pro13His), gnomAD 1-40784131-C-A, REVEL 0.50, MetaLR 0.94
- P13L (p.Pro13Leu), gnomAD 1-40784131-C-T, REVEL 0.48, MetaLR 0.93
- P13P (p.Pro13Pro), gnomAD 1-40784132-C-T, CADD 14.20
- P14L (p.Pro14Leu), Ensembl rs1013934456, REVEL 0.30, MetaLR 0.82
- P14A (p.Pro14Ala), gnomAD 1-40784129-TCC-T, CADD 23.60
- P14R (p.Pro14Arg), gnomAD 1-40784129-TC-T, CADD 23.60
- P14T (p.Pro14Thr), gnomAD 1-40784133-C-A, REVEL 0.34, MetaLR 0.83
- P14S (p.Pro14Ser), gnomAD 1-40784133-C-T, REVEL 0.26, MetaLR 0.82
- P14Q (p.Pro14Gln), gnomAD 1-40784134-C-A, REVEL 0.37, MetaLR 0.83
- P14P (p.Pro14Pro), rs749544977, gnomAD 1-40784135-G-T, CADD 13.60
- P15A (p.Pro15Ala), Ensembl rs1647180470, REVEL 0.47, MetaLR 0.72
- P15L (p.Pro15Leu), TOPMed rs1369988851, gnomAD rs1369988851, REVEL 0.44, MetaLR 0.82
- P15R (p.Pro15Arg), gnomAD 1-40784129-TCCCCC, CADD 25.00
- P15S (p.Pro15Ser), gnomAD 1-40784136-C-T, REVEL 0.38, MetaLR 0.72
- P15T (p.Pro15Thr), gnomAD 1-40784136-C-A, REVEL 0.41, MetaLR 0.78
- P15H (p.Pro15His), gnomAD 1-40784137-C-A, REVEL 0.47, MetaLR 0.82
- P15P (p.Pro15Pro), gnomAD 1-40784138-C-A, CADD 12.60
- G16A (p.Gly16Ala), TOPMed rs1278081268, gnomAD rs1278081268, REVEL 0.36, MetaLR 0.80
- G16R (p.Gly16Arg), Ensembl rs1345793795, REVEL 0.41, MetaLR 0.79
- G16W (p.Gly16Trp), Ensembl rs1345793795, REVEL 0.45, MetaLR 0.90
- G16E (p.Gly16Glu), gnomAD 1-40784140-G-A, REVEL 0.43, MetaLR 0.81
- G16V (p.Gly16Val), gnomAD 1-40784140-G-T, REVEL 0.41, MetaLR 0.84
- G16G (p.Gly16Gly), rs1276675997, gnomAD 1-40784141-G-A, CADD 13.60
- D17A (p.Asp17Ala), rs2148830548, ClinGen CA339884952, ClinVar RCV002763048, Ensembl rs2148830548, Uncertain significance, Inborn genetic diseases
- D17G (p.Asp17Gly), Ensembl rs2148830548, REVEL 0.42, MetaLR 0.86, Uncertain significance
- D17H (p.Asp17His), Ensembl rs1647180556, REVEL 0.41, MetaLR 0.84
- D17T (p.Asp17Thr), gnomAD 1-40784134-CG-C, CADD 23.60
- D17R (p.Asp17Arg), gnomAD 1-40784138-CGG-C, CADD 24.60
- D17N (p.Asp17Asn), gnomAD 1-40784142-G-A, REVEL 0.28, MetaLR 0.82
- D17Y (p.Asp17Tyr), gnomAD 1-40784142-G-T, REVEL 0.37, MetaLR 0.86
- D17V (p.Asp17Val), gnomAD 1-40784143-A-T, REVEL 0.53, MetaLR 0.85
- D17E (p.Asp17Glu), gnomAD 1-40784144-C-A, REVEL 0.28, MetaLR 0.81
- D17D (p.Asp17Asp), rs1175167086, gnomAD 1-40784144-C-T, CADD 13.20
- A18D (p.Ala18Asp), TOPMed rs1347676173, REVEL 0.34, MetaLR 0.77, Uncertain significance
- A18G (p.Ala18Gly), TOPMed rs1347676173, REVEL 0.28, MetaLR 0.75, Uncertain significance
- A18S (p.Ala18Ser), rs2523790198, ClinGen CA2580062739, ClinVar RCV002659386, REVEL 0.34, MetaLR 0.77, Uncertain significance, not provided
- A18V (p.Ala18Val), rs1347676173, ClinGen CA339884961, ClinVar RCV003846644, TOPMed rs1347676173, REVEL 0.32, MetaLR 0.76, Uncertain significance, not provided
- A18P (p.Ala18Pro), gnomAD 1-40784144-CG-C, CADD 23.30
- A18T (p.Ala18Thr), gnomAD 1-40784145-G-A, REVEL 0.26, MetaLR 0.78
- A18A (p.Ala18Ala), gnomAD 1-40784147-C-A, CADD 13.30
- P19S (p.Pro19Ser), TOPMed rs1570792829, REVEL 0.31, MetaLR 0.70
- P19V (p.Pro19Val), gnomAD 1-40784147-C-CGT, CADD 23.40
- P19T (p.Pro19Thr), gnomAD 1-40784148-C-A, REVEL 0.27, MetaLR 0.77
- P19A (p.Pro19Ala), gnomAD 1-40784148-C-G, REVEL 0.28, MetaLR 0.78
- P19H (p.Pro19His), gnomAD 1-40784149-C-A, REVEL 0.34, MetaLR 0.81
- P19L (p.Pro19Leu), gnomAD 1-40784149-C-T, REVEL 0.33, MetaLR 0.79
- P19P (p.Pro19Pro), gnomAD 1-40784150-C-A, CADD 12.80
- R20C (p.Arg20Cys), TOPMed rs1268949306, gnomAD rs1268949306, REVEL 0.38, MetaLR 0.80
- R20G (p.Arg20Gly), TOPMed rs1268949306, gnomAD rs1268949306, REVEL 0.35, MetaLR 0.79
- R20A (p.Arg20Ala), rs754748939, gnomAD 1-40784145-GC-G, CADD 23.60
- R20P (p.Arg20Pro), rs754748939, gnomAD 1-40784145-G-GC, CADD 23.80
- R20S (p.Arg20Ser), gnomAD 1-40784151-C-A, REVEL 0.29, MetaLR 0.84
- R20L (p.Arg20Leu), gnomAD 1-40784152-G-T, REVEL 0.28, MetaLR 0.83
- R20H (p.Arg20His), gnomAD 1-40784152-G-A, REVEL 0.28, MetaLR 0.81
- R20R (p.Arg20Arg), rs1342847028, gnomAD 1-40784153-C-T, CADD 13.00
- A21E (p.Ala21Glu), gnomAD rs1647180690, REVEL 0.35, MetaLR 0.77
- A21P (p.Ala21Pro), Ensembl rs1647180672, MetaLR 0.78, MetaSVM 0.28
- A21G (p.Ala21Gly), gnomAD 1-40784145-GCC-G, CADD 23.60
- A21S (p.Ala21Ser), gnomAD 1-40784154-G-T, REVEL 0.24, MetaLR 0.76
- A21T (p.Ala21Thr), gnomAD 1-40784154-G-A, REVEL 0.26, MetaLR 0.77
- A21V (p.Ala21Val), gnomAD 1-40784155-C-T, REVEL 0.22, MetaLR 0.68
- A21A (p.Ala21Ala), rs1203769615, gnomAD 1-40784156-G-A, CADD 9.27
- E22A (p.Glu22Ala), rs2148830560, ClinGen CA339884986, ClinVar RCV002787300, Uncertain significance, Inborn genetic diseases
- E22G (p.Glu22Gly), Ensembl rs2148830560, REVEL 0.33, MetaLR 0.82
- E22K (p.Glu22Lys), gnomAD 1-40784157-G-A, REVEL 0.32, MetaLR 0.87
- E22Q (p.Glu22Gln), gnomAD 1-40784157-G-C, REVEL 0.31, MetaLR 0.88
- E22* (p.Glu22Ter), gnomAD 1-40784157-G-T, CADD 35.00
- E22V (p.Glu22Val), gnomAD 1-40784158-A-T, REVEL 0.33, MetaLR 0.89
- E22E (p.Glu22Glu), gnomAD 1-40784159-G-A, CADD 12.70
- E22D (p.Glu22Asp), gnomAD 1-40784159-G-T, REVEL 0.34, MetaLR 0.86
- L23I (p.Leu23Ile), TOPMed rs1406640097, gnomAD rs1406640097, REVEL 0.21, MetaLR 0.82
- L23L (p.Leu23Leu), gnomAD 1-40784160-C-T, CADD 12.60
- L23V (p.Leu23Val), gnomAD 1-40784160-C-G, REVEL 0.21, MetaLR 0.82
- L23P (p.Leu23Pro), gnomAD 1-40784161-T-C, REVEL 0.34, MetaLR 0.85
- L23Q (p.Leu23Gln), gnomAD 1-40784161-T-A, REVEL 0.31, MetaLR 0.85
- V24A (p.Val24Ala), gnomAD rs905612913, REVEL 0.37, MetaLR 0.88
- V24L (p.Val24Leu), 1000Genomes rs770609353, ExAC rs770609353, TOPMed rs770609353, gnomAD rs770609353, REVEL 0.42, MetaLR 0.83
- V24M (p.Val24Met), gnomAD 1-40784163-G-A, REVEL 0.39, MetaLR 0.92
- V24E (p.Val24Glu), gnomAD 1-40784164-T-A, REVEL 0.49, MetaLR 0.87
- V24G (p.Val24Gly), gnomAD 1-40784164-T-G, REVEL 0.50, MetaLR 0.88
- V24V (p.Val24Val), gnomAD 1-40784165-G-C, CADD 12.50
- A25E (p.Ala25Glu), Ensembl rs1647180800, REVEL 0.37, MetaLR 0.88
- A25R (p.Ala25Arg), gnomAD 1-40784164-TG-T, CADD 24.80
- A25S (p.Ala25Ser), gnomAD 1-40784166-G-T, REVEL 0.34, MetaLR 0.86
- A25T (p.Ala25Thr), gnomAD 1-40784166-G-A, REVEL 0.33, MetaLR 0.88
- A25P (p.Ala25Pro), gnomAD 1-40784166-G-C, REVEL 0.41, MetaLR 0.87
- A25G (p.Ala25Gly), gnomAD 1-40784167-C-G, REVEL 0.30, MetaLR 0.81
- A25V (p.Ala25Val), gnomAD 1-40784167-C-T, REVEL 0.37, MetaLR 0.86
- A25A (p.Ala25Ala), gnomAD 1-40784168-G-C, CADD 13.70
- L26I (p.Leu26Ile), gnomAD 1-40784169-C-A, REVEL 0.33, MetaLR 0.88
- L26F (p.Leu26Phe), gnomAD 1-40784169-C-T, REVEL 0.31, MetaLR 0.88
- L26V (p.Leu26Val), gnomAD 1-40784169-C-G, REVEL 0.27, MetaLR 0.90
- L26H (p.Leu26His), gnomAD 1-40784170-T-A, REVEL 0.40, MetaLR 0.91
- L26P (p.Leu26Pro), gnomAD 1-40784170-T-C, REVEL 0.43, MetaLR 0.91
- L26L (p.Leu26Leu), gnomAD 1-40784171-C-G, CADD 13.00
- T27R (p.Thr27Arg), rs1001249688, ClinGen CA21089024, ClinVar RCV003881864, ClinVar RCV004987133, REVEL 0.36, MetaLR 0.84, Conflicting interpretations, Inborn genetic diseases; not provided
- T27S (p.Thr27Ser), gnomAD 1-40784172-A-T, REVEL 0.35, MetaLR 0.81
- T27A (p.Thr27Ala), gnomAD 1-40784172-A-G, REVEL 0.28, MetaLR 0.86
- T27K (p.Thr27Lys), gnomAD 1-40784173-C-A, REVEL 0.36, MetaLR 0.81
- T27M (p.Thr27Met), gnomAD 1-40784173-C-T, REVEL 0.36, MetaLR 0.91
Public KCNQ4 analysis runs
- KCNQ4 analysis run — KCNQ4 (1,332 variants) — completed 2026-08-18