ATP1A3 (P13637) variants and mutations
ATP1A3 (also known as P13637) is a human protein-coding gene encoding a sodium/potassium-transporting ATPase subunit alpha-3 protein. It rapidly restores neuronal sodium and potassium gradients after repetitive firing, making it particularly important in highly active neurons. Pathogenic variants cause overlapping syndromes including alternating hemiplegia of childhood, rapid-onset dystonia-parkinsonism, and CAPOS syndrome. This analysis covers 827 ATP1A3 variants and mutations. Of these, 74% have computational variant effect predictions. Disease context includes alternating hemiplegia of childhood 2, dystonia 12, and Cerebellar ataxia - areflexia - pes cavus - optic atrophy - sensorineural hearin. Example ATP1A3 variants include G2A, G2R, and G2V.
Variant analysis overview
- Gene: ATP1A3
- Protein: P13637
- UniProt accession: P13637
- Organism: Homo sapiens
- Variants analyzed: 827
- Variant scope: all variants
- Completed: 2026-08-18
Variant and mutation evidence
- Variant composition: 758 unspecified-consequence records; 2 stop lost; 20 synonymous variants; 5 stop-gained variants; 24 missense variants; 2 splice-region variants; 4 frameshift variants; 12 substitution
- Prediction scores: 615 variants have prediction scores (74% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: alternating hemiplegia of childhood 2, dystonia 12, Cerebellar ataxia - areflexia - pes cavus - optic atrophy - sensorineural hearin, developmental and epileptic encephalopathy 99, cerebellar ataxia-areflexia-pes cavus-optic atrophy-sensorineural hearing loss s, alternating hemiplegia of childhood, Rapid-onset dystonia-parkinsonism, ATP1A3-associated neurological disorder, congestive heart failure, atrial fibrillation, heart failure, cardiovascular disorder.
Protein structure and variant hotspots
- Protein features: 10 transmembrane segments; 12 binding sites; 7 post-translational modification sites.
- Structural context: 216 variants have structural context.
- PTM context: 6 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 ATP1A3 variants
Examples include G2A, G2R, G2V, G2W, D3G, K5E, D6E, D7E. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- G2A (p.Gly2Ala), ExAC rs782342530, TOPMed rs782342530, gnomAD rs782342530, CADD 22.70, PolyPhen-2 0.00
- G2R (p.Gly2Arg), rs2145995411, ClinGen CA406059985, ClinVar RCV002038907, 1000Genomes rs2145995411, CADD 12.90, Uncertain significance, Dystonia 12
- G2V (p.Gly2Val), ExAC rs782342530, TOPMed rs782342530, gnomAD rs782342530, CADD 23.10, PolyPhen-2 0.00
- G2W (p.Gly2Trp), 1000Genomes rs2145995411, CADD 26.40, PolyPhen-2 0.06, Uncertain significance
- D3G (p.Asp3Gly), rs1555866352, ClinGen CA406058082, ClinVar RCV003121704, gnomAD rs1555866352, CADD 25.30, PolyPhen-2 0.96, Uncertain significance, Dystonia 12
- K5E (p.Lys5Glu), rs2145984238, ClinGen CA406058051, ClinVar RCV001885552, Ensembl rs2145984238, AlphaMissense 0.13, MetaLR 0.56, Uncertain significance, Dystonia 12
- D6E (p.Asp6Glu), ExAC rs782107485, gnomAD rs782107485, CADD 20.40, PolyPhen-2 0.00, Likely benign
- D7E (p.Asp7Glu), ExAC rs782337626, gnomAD rs782337626
- D7G (p.Asp7Gly), Ensembl rs2145984213, Uncertain significance, Dystonia 12
- D7N (p.Asp7Asn), ExAC rs781962237, gnomAD rs781962237, CADD 23.70, PolyPhen-2 0.03, Uncertain significance, not provided
- K8N (p.Lys8Asn), rs2145984204, ClinGen CA406057978, ClinVar RCV003628372, Uncertain significance, Dystonia 12
- D9E (p.Asp9Glu), ExAC rs781919964, gnomAD rs781919964, CADD 13.30, PolyPhen-2 0.00
- D9G (p.Asp9Gly), ExAC rs782065058, gnomAD rs782065058, CADD 16.30, PolyPhen-2 0.00, Uncertain significance, Dystonia 12
- D9N (p.Asp9Asn), TOPMed rs2075307477, CADD 15.80, PolyPhen-2 0.00
- S10* (p.Ser10Ter), rs2514086772, ClinGen CA406057952, ClinVar RCV003318142, NCI-TCGA TCGA novel, Uncertain significance
- S10L (p.Ser10Leu), rs2514086772, ClinGen CA406057943, ClinVar RCV003990080, Uncertain significance, Alternating hemiplegia of childhood 2
- P11A (p.Pro11Ala), ExAC rs782419036, gnomAD rs782419036, CADD 22.50, PolyPhen-2 0.96
- K13E (p.Lys13Glu), Ensembl rs2075307275
- K13T (p.Lys13Thr), rs782280535, ClinGen CA9467980, NCI-TCGA Cosmic COSV1001, cosmic curated COSV10013, AlphaMissense 0.30, MetaLR 0.80, Uncertain significance, not provided
- N14K (p.Asn14Lys), rs1247855214, TOPMed rs1247855214, gnomAD rs1247855214, ClinGen CA406057890, CADD 9.31, PolyPhen-2 0.00, Uncertain significance, Inborn genetic diseases; Dystonia 12
- N14S (p.Asn14Ser), TOPMed rs2075307222, gnomAD rs2075307222, CADD 5.66, PolyPhen-2 0.00
- G16S (p.Gly16Ser), rs559227917, ClinGen CA9467979, ClinVar RCV001373837, ClinVar RCV002550180, CADD 19.50, PolyPhen-2 0.01, Uncertain significance, Inborn genetic diseases; Dystonia 12
- K17R (p.Lys17Arg), gnomAD rs1555866312, CADD 24.30, PolyPhen-2 0.78
- E18D (p.Glu18Asp), rs541121307, ClinGen CA406057824, ClinVar RCV001350323, 1000Genomes rs541121307, CADD 13.00, PolyPhen-2 0.02, Uncertain significance, Dystonia 12
- R19C (p.Arg19Cys), rs782229302, ClinGen CA9467977, NCI-TCGA Cosmic COSV5748, cosmic curated COSV57487, CADD 28.70, PolyPhen-2 0.28, Conflicting interpretations, Inborn genetic diseases; not specified; not provided
- R19H (p.Arg19His), rs782596240, ClinGen CA9467976, cosmic curated COSV57492, ClinVar RCV001252419, AlphaMissense 0.20, MetaLR 0.58, Uncertain significance, not provided
- R19L (p.Arg19Leu), ExAC rs782596240, TOPMed rs782596240, gnomAD rs782596240, Likely benign
- R19P (p.Arg19Pro), rs782596240, ClinGen CA406057814, ClinVar RCV003415259, AlphaMissense 0.20, MetaLR 0.58, Uncertain significance, not provided
- R19S (p.Arg19Ser), rs782229302, ClinGen CA406057818, ClinVar RCV003628428, CADD 24.00, PolyPhen-2 0.00, Uncertain significance, Dystonia 12
- R20G (p.Arg20Gly), ExAC rs782461379, TOPMed rs782461379, gnomAD rs782461379, CADD 22.60, PolyPhen-2 0.04, Uncertain significance, Dystonia 12
- R20Q (p.Arg20Gln), rs949169436, ClinGen CA308599532, ClinVar RCV000690433, TOPMed rs949169436, CADD 22.40, PolyPhen-2 0.00, Likely benign, Dystonia 12
- R20W (p.Arg20Trp), rs782461379, ClinGen CA406057806, ClinVar RCV003514060, ExAC rs782461379, CADD 26.10, PolyPhen-2 0.46, Uncertain significance, Dystonia 12
- V29A (p.Val29Ala), ExAC rs782688554, TOPMed rs782688554, gnomAD rs782688554, CADD 26.10, PolyPhen-2 0.28
- M31T (p.Met31Thr), rs1461631461, ClinGen CA406057628, ClinVar RCV002942921, ClinVar RCV006275136, AlphaMissense 0.82, MetaLR 0.59, Uncertain significance, not provided; Dystonia 12
- E33D (p.Glu33Asp), TOPMed rs35429923, gnomAD rs35429923, Likely benign
- K35M (p.Lys35Met), TOPMed rs1168671489, gnomAD rs1168671489, CADD 26.20
- K35N (p.Lys35Asn), gnomAD rs1555866213, CADD 26.30
- K35R (p.Lys35Arg), TOPMed rs1168671489, gnomAD rs1168671489, CADD 23.10, PolyPhen-2 0.03
- M36I (p.Met36Ile), rs1599725994, ClinGen CA406057431, ClinVar RCV000990224, NCI-TCGA TCGA novel, CADD 19.90, PolyPhen-2 0.00, Uncertain significance, Dystonia 12
- V38A (p.Val38Ala), rs886044790, ClinGen CA10604150, ClinVar RCV000341137, ClinVar RCV003514344, CADD 23.30, PolyPhen-2 0.01, Uncertain significance, not provided; Dystonia 12
- C42R (p.Cys42Arg), rs2075305399, ClinGen CA406057330, ClinVar RCV001198824, Ensembl rs2075305399, AlphaMissense 0.95, MetaLR 0.34, Uncertain significance, Dystonia 12
- R43Q (p.Arg43Gln), rs782453913, ClinGen CA9467949, cosmic curated COSV10511, ClinVar RCV001048072, CADD 22.70, PolyPhen-2 0.01, Conflicting interpretations, not provided; Inborn genetic diseases; Dystonia 12
- R43W (p.Arg43Trp), rs781898188, ClinGen CA9467950, ClinVar RCV003834022, ExAC rs781898188, CADD 26.30, PolyPhen-2 0.85, Uncertain significance, Dystonia 12
- A58V (p.Ala58Val), cosmic curated COSV10964, TOPMed rs2075303386, Uncertain significance, not provided; Dystonia 12
- E60K (p.Glu60Lys), cosmic curated COSV57489, Ensembl rs868970134
- I61L (p.Ile61Leu), gnomAD rs1555866078, CADD 19.30, PolyPhen-2 0.02
- L62V (p.Leu62Val), TOPMed rs2075303291
- A63P (p.Ala63Pro), gnomAD rs1555866076, CADD 20.30
- R64Q (p.Arg64Gln), rs201573515, ClinGen CA9467926, cosmic curated COSV57487, ClinVar RCV000560382, CADD 22.70, PolyPhen-2 0.03, Conflicting interpretations, not provided; Dystonia 12; not specified
- R64W (p.Arg64Trp), rs1203339638, ClinGen CA406056817, NCI-TCGA Cosmic COSV5748, cosmic curated COSV57487, CADD 25.80, PolyPhen-2 0.95, Uncertain significance, Dystonia 12
- D65N (p.Asp65Asn), cosmic curated COSV57487, Ensembl rs868908863
- G66R (p.Gly66Arg), rs2145983320, ClinGen CA406056791, ClinVar RCV001904674, Ensembl rs2145983320, AlphaMissense 1.00, MetaLR 0.96, Uncertain significance, Dystonia 12
- P67R (p.Pro67Arg), NCI-TCGA Cosmic COSV5749, TOPMed rs2075303051, gnomAD rs2075303051, CADD 24.30, PolyPhen-2 0.99, Variant assessed as somatic; moderate impact.
- P67S (p.Pro67Ser), rs2514084918, ClinGen CA406056772, ClinVar RCV003129495, Uncertain significance, not provided
- A69V (p.Ala69Val), Ensembl rs2145983292, Uncertain significance, not provided; Dystonia 12
- P72S (p.Pro72Ser), ExAC rs782292182, TOPMed rs782292182, gnomAD rs782292182, CADD 25.00, PolyPhen-2 1.00
- P72T (p.Pro72Thr), ExAC rs782292182, TOPMed rs782292182, gnomAD rs782292182
- P73L (p.Pro73Leu), rs1161880070, ClinGen CA406056658, NCI-TCGA Cosmic COSV5748, cosmic curated COSV57485, CADD 27.50, PolyPhen-2 0.93, Uncertain significance, not provided
- T76I (p.Thr76Ile), rs2145983246, ClinGen CA406056628, ClinVar RCV001955386, Ensembl rs2145983246, CADD 22.90, PolyPhen-2 0.23, Uncertain significance, Dystonia 12
- P77L (p.Pro77Leu), Ensembl rs987457417
- P77Q (p.Pro77Gln), rs987457417, ClinGen CA406056615, ClinVar RCV003332630, AlphaMissense 0.88, MetaLR 0.85, Uncertain significance, not provided
- V80I (p.Val80Ile), ExAC rs782214312, gnomAD rs782214312, CADD 19.60, PolyPhen-2 0.01
- C83F (p.Cys83Phe), Ensembl rs1555866032
- R84G (p.Arg84Gly), rs1555866028, ClinGen CA406056520, ClinVar RCV000549638, Ensembl rs1555866028, AlphaMissense 0.49, MetaLR 0.45, Likely benign, Dystonia 12
- R84Q (p.Arg84Gln), rs782194114, ClinGen CA9467913, NCI-TCGA Cosmic COSV5749, cosmic curated COSV57490, CADD 25.80, PolyPhen-2 0.06, Uncertain significance, not specified; Dystonia 12
- R84W (p.Arg84Trp), rs1555866028, ClinGen CA406056519, ClinVar RCV001557391, ClinVar RCV006467683, AlphaMissense 0.49, MetaLR 0.45, Uncertain significance, Developmental and epileptic encephalopathy 99; not provided; Dystonia 12
- G88R (p.Gly88Arg), rs2075302447, TOPMed rs2075302447, ClinGen CA406056470, ClinVar RCV003515872, CADD 26.80, PolyPhen-2 0.99, Uncertain significance, Dystonia 12
- G89A (p.Gly89Ala), rs1599725621, ClinGen CA406056451, ClinVar RCV000995500, ClinVar RCV003442137, AlphaMissense 0.90, MetaLR 0.68, Pathogenic/Likely pathogenic, Dystonia 12; Hereditary ataxia; not provided
- G89C (p.Gly89Cys), rs1057522886, ClinGen CA406056455, ClinVar RCV002465433, AlphaMissense 0.83, MetaLR 0.71, Likely pathogenic, Cerebellar ataxia-areflexia-pes cavus-optic atrophy-sensorineural hearing loss s
- G89S (p.Gly89Ser), rs1057522886, ClinGen CA16608263, ClinVar RCV000426824, Ensembl rs1057522886, AlphaMissense 0.83, MetaLR 0.71, Likely pathogenic, not provided
- I92L (p.Ile92Leu), TOPMed rs933392084, gnomAD rs933392084, CADD 19.00, PolyPhen-2 0.00, Uncertain significance
- I92V (p.Ile92Val), rs933392084, ClinGen CA308599033, ClinVar RCV001071677, ClinVar RCV003396729, CADD 20.40, PolyPhen-2 0.00, Uncertain significance, not specified; Dystonia 12
- L94P (p.Leu94Pro), rs2514084596, ClinGen CA406056371, ClinVar RCV002795956, Pathogenic, Dystonia 12
- I99V (p.Ile99Val), rs958239123, ClinGen CA308598991, ClinVar RCV001369659, ClinVar RCV003322887, CADD 19.30, PolyPhen-2 0.00, Uncertain significance, not provided; Dystonia 12
- G106S (p.Gly106Ser), cosmic curated COSV57489, ExAC rs782154879, gnomAD rs782154879, CADD 17.30, PolyPhen-2 0.00
- A109V (p.Ala109Val), rs1568866568, ClinGen CA406056111, NCI-TCGA Cosmic COSV5748, cosmic curated COSV57486, CADD 21.20, PolyPhen-2 0.00, Uncertain significance, not provided; Dystonia 12
- E112K (p.Glu112Lys), cosmic curated COSV10511, Ensembl rs2145983067, Uncertain significance, not specified; Dystonia 12
- D113N (p.Asp113Asn), TOPMed rs2075301845
- D114N (p.Asp114Asn), rs782128088, cosmic curated COSV10942, ExAC rs782128088, gnomAD rs782128088, CADD 20.60, PolyPhen-2 0.00, Variant assessed as somatic; moderate impact.
- P115R (p.Pro115Arg), ExAC rs781955231, CADD 24.90, PolyPhen-2 0.01
- D118V (p.Asp118Val), TOPMed rs2075301704, gnomAD rs2075301704, CADD 25.90
- L126M (p.Leu126Met), rs1167271636, ClinGen CA406055617, ClinVar RCV001267620, TOPMed rs1167271636, AlphaMissense 0.93, MetaLR 0.83, Uncertain significance, Inborn genetic diseases
- A127V (p.Ala127Val), rs2075284959, ClinGen CA406055593, NCI-TCGA Cosmic COSV5749, cosmic curated COSV57491, CADD 20.70, PolyPhen-2 0.49, Likely pathogenic, Developmental and epileptic encephalopathy 99
- V129M (p.Val129Met), rs1555865401, ClinGen CA10602480, ClinVar RCV000225081, ClinVar RCV002274003, AlphaMissense 0.94, MetaLR 0.84, Pathogenic/Likely pathogenic, not provided; Juvenile onset psychosis; Alternating hemiplegia of childhood 2
- V130L (p.Val130Leu), rs1555865397, ClinGen CA406055535, ClinVar RCV001220470, gnomAD rs1555865397, AlphaMissense 0.98, MetaLR 0.71, Uncertain significance, Dystonia 12
- V130M (p.Val130Met), gnomAD rs1555865397, AlphaMissense 0.98, MetaLR 0.71, Uncertain significance
- C135W (p.Cys135Trp), ExAC rs782252241, gnomAD rs782252241, CADD 28.00, PolyPhen-2 0.21
- S137F (p.Ser137Phe), rs542652468, ClinGen CA345998, ClinVar RCV000148303, ClinVar RCV000414799, AlphaMissense 0.92, MetaLR 0.86, Pathogenic, Dystonia 12; not provided; Alternating hemiplegia of childhood 2
- S137T (p.Ser137Thr), rs2514079536, ClinGen CA406055429, ClinVar RCV003223832, Uncertain significance, not provided
- S137Y (p.Ser137Tyr), rs542652468, ClinGen CA345997, ClinVar RCV001206535, UniProt VAR 068936, AlphaMissense 0.92, MetaLR 0.86, Pathogenic, Dystonia 12
- Q140L (p.Gln140Leu), rs606231427, UniProt VAR 068937, Ensembl rs606231427, AlphaMissense 0.94, MetaLR 0.91, Pathogenic, in AHC2
- A142S (p.Ala142Ser), TOPMed rs878853219, CADD 23.20, PolyPhen-2 0.08
- A142T (p.Ala142Thr), TOPMed rs878853219
- M148V (p.Met148Val), 1000Genomes rs544689536
- S150Y (p.Ser150Tyr), rs2514079452, ClinGen CA406055096, ClinVar RCV003227356, Uncertain significance, not provided
- K152R (p.Lys152Arg), gnomAD rs1555865360, CADD 24.90, PolyPhen-2 0.08
- M154T (p.Met154Thr), rs1568865452, ClinGen CA406055002, ClinVar RCV000734309, Ensembl rs1568865452, AlphaMissense 0.99, MetaLR 0.86, Uncertain significance, not provided
- M154V (p.Met154Val), rs1135401821, ClinGen CA406055012, ClinVar RCV000496204, ClinVar RCV005621958, AlphaMissense 0.83, MetaLR 0.76, Likely pathogenic, Intellectual disability; Cerebellar ataxia-areflexia-pes cavus-optic atrophy-sen
- Q158K (p.Gln158Lys), NCI-TCGA TCGA novel, Ensembl rs2075282826, CADD 22.70, PolyPhen-2 0.01, Variant assessed as somatic; moderate impact.
- I162F (p.Ile162Phe), rs2075282776, ClinGen CA406054758, ClinVar RCV003991131, TOPMed rs2075282776, CADD 26.10, PolyPhen-2 0.86, Uncertain significance, Dystonia 12
- R163Q (p.Arg163Gln), rs2514078905, ClinGen CA406054739, ClinVar RCV002907664, ClinVar RCV006546142, CADD 32.00, PolyPhen-2 0.98, Uncertain significance, Dystonia 12; not provided
- R163W (p.Arg163Trp), rs2514078912, ClinGen CA406054745, ClinVar RCV003325843, ClinVar RCV004701036, CADD 31.00, PolyPhen-2 1.00, Uncertain significance, not specified; not provided
- A172T (p.Ala172Thr), ExAC rs782236247, TOPMed rs782236247, gnomAD rs782236247, CADD 24.20, PolyPhen-2 0.05
- G178R (p.Gly178Arg), NCI-TCGA Cosmic COSV1001, cosmic curated COSV10013, NCI-TCGA Cosmic COSV5748, TOPMed rs2075282646, CADD 26.00, PolyPhen-2 1.00, Uncertain significance, not provided
- E182* (p.Glu182Ter), Ensembl rs1555865268
- K184R (p.Lys184Arg), rs372927309, ClinGen CA9467845, ClinVar RCV003515082, ESP rs372927309, CADD 22.90, PolyPhen-2 0.05, Uncertain significance, Dystonia 12
- R188* (p.Arg188Ter), rs2075282510, ClinGen CA406054375, cosmic curated COSV10511, ClinVar RCV001297560, Pathogenic
- R188Q (p.Arg188Gln), cosmic curated COSV57489, TOPMed rs1555865260, gnomAD rs1555865260, CADD 24.70, PolyPhen-2 0.28
- V189A (p.Val189Ala), rs2514078768, ClinGen CA406054362, ClinVar RCV004552405, Uncertain significance, ATP1A3-related disorder
- P190L (p.Pro190Leu), rs1599723609, ClinGen CA406054351, ClinVar RCV000996936, ClinVar RCV002550704, AlphaMissense 0.97, MetaLR 0.96, Conflicting interpretations, not provided; Dystonia 12
- A191S (p.Ala191Ser), rs1568865274, ClinGen CA406054349, ClinVar RCV000703622, Ensembl rs1568865274, AlphaMissense 0.55, MetaLR 0.93, Uncertain significance, Dystonia 12
- R194G (p.Arg194Gly), TOPMed rs1246646193, gnomAD rs1246646193, CADD 26.80, PolyPhen-2 1.00, Uncertain significance
- R194W (p.Arg194Trp), rs1246646193, ClinGen CA406054317, NCI-TCGA Cosmic COSV5749, cosmic curated COSV57490, CADD 28.70, PolyPhen-2 1.00, Uncertain significance, not provided
- I196N (p.Ile196Asn), Ensembl rs1555865247
- A198T (p.Ala198Thr), TOPMed rs2075282168
- H199Q (p.His199Gln), rs139145792, ClinGen CA406054263, ClinVar RCV003627827, Uncertain significance, Dystonia 12
- G200S (p.Gly200Ser), rs1555865238, ClinGen CA406054258, ClinVar RCV001337893, ClinVar RCV006266713, CADD 22.50, PolyPhen-2 0.47, Uncertain significance, not provided; Dystonia 12
- V203L (p.Val203Leu), ExAC rs782613472, gnomAD rs782613472, CADD 33.00, PolyPhen-2 1.00
- N205T (p.Asn205Thr), Ensembl rs1599723127
- S206P (p.Ser206Pro), Ensembl rs1599723121
- S207P (p.Ser207Pro), Ensembl rs1599723111
- E211D (p.Glu211Asp), rs2514076878, ClinGen CA406054141, ClinVar RCV003628145, Uncertain significance, Dystonia 12
- E211K (p.Glu211Lys), cosmic curated COSV57486, Ensembl rs2075277171
- E213K (p.Glu213Lys), rs1420042955, ClinGen CA406054134, ClinVar RCV002918043, ClinVar RCV005495420, AlphaMissense 0.98, MetaLR 0.83, Uncertain significance, Inborn genetic diseases; Dystonia 12
- R217C (p.Arg217Cys), rs782713179, NCI-TCGA Cosmic COSV5748, cosmic curated COSV57488, ExAC rs782713179, CADD 27.90, PolyPhen-2 1.00, Variant assessed as somatic; moderate impact.
- R217H (p.Arg217His), rs1555865039, ClinGen CA406054104, NCI-TCGA Cosmic COSV5748, cosmic curated COSV57487, CADD 25.70, PolyPhen-2 1.00, Uncertain significance, Alternating hemiplegia of childhood 2
- S218T (p.Ser218Thr), rs782150714, ClinGen CA9467819, ClinVar RCV002300953, ClinVar RCV006470463, CADD 19.80, PolyPhen-2 0.01, Uncertain significance, Dystonia 12; not provided
- P219A (p.Pro219Ala), 1000Genomes rs201302324, ExAC rs201302324, gnomAD rs201302324
- P219T (p.Pro219Thr), 1000Genomes rs201302324, ExAC rs201302324, gnomAD rs201302324
- D220A (p.Asp220Ala), rs2145978691, ClinGen CA406054088, ClinVar RCV001563270, Ensembl rs2145978691, AlphaMissense 0.52, MetaLR 0.55, Uncertain significance, not provided
- D220N (p.Asp220Asn), rs1396898460, ClinGen CA406054091, ClinVar RCV001210834, ClinVar RCV001549522, CADD 22.30, PolyPhen-2 0.35, Uncertain significance, not provided; Dystonia 12
- D220V (p.Asp220Val), rs2145978691, ClinGen CA406054086, ClinVar RCV003142317, ClinVar RCV006473654, AlphaMissense 0.52, MetaLR 0.55, Uncertain significance, Cerebellar ataxia-areflexia-pes cavus-optic atrophy-sensorineural hearing loss s
- C221Y (p.Cys221Tyr), rs782125149, ClinGen CA9467816, ClinVar RCV000480352, ExAC rs782125149, CADD 18.10, PolyPhen-2 0.00, Uncertain significance, not provided
- T222I (p.Thr222Ile), cosmic curated COSV10587, Ensembl rs2075276786, CADD 24.20, PolyPhen-2 0.92
- T222M (p.Thr222Met), rs2145978673, ClinGen CA2573156418, ClinVar RCV002001830, Ensembl rs2145978673, Uncertain significance, Dystonia 12
- D224N (p.Asp224Asn), TOPMed rs1271282195, gnomAD rs1271282195, CADD 23.00, PolyPhen-2 0.53, Uncertain significance, Dystonia 12
- R230P (p.Arg230Pro), ExAC rs782657023, gnomAD rs782657023
- R230Q (p.Arg230Gln), ExAC rs782657023, gnomAD rs782657023, CADD 23.20, PolyPhen-2 0.21, Uncertain significance, Dystonia 12
- R230W (p.Arg230Trp), rs782251693, ClinGen CA9467811, ClinVar RCV003115463, ExAC rs782251693, CADD 27.10, PolyPhen-2 0.99, Uncertain significance, Dystonia 12
- I232F (p.Ile232Phe), TOPMed rs2075276386, gnomAD rs2075276386, CADD 24.90
- I232V (p.Ile232Val), TOPMed rs2075276386, gnomAD rs2075276386, CADD 20.50, PolyPhen-2 0.01
- F235L (p.Phe235Leu), rs782230953, ClinGen CA406053346, ClinVar RCV002260434, ClinVar RCV002260435, AlphaMissense 1.00, MetaLR 0.78, Benign, Developmental and epileptic encephalopathy 99; Cerebellar ataxia-areflexia-pes c
- T237A (p.Thr237Ala), rs2514076607, ClinGen CA406053338, ClinVar RCV003515342, Uncertain significance, Dystonia 12
- N238S (p.Asn238Ser), rs782467046, NCI-TCGA Cosmic COSV5748, cosmic curated COSV57486, ExAC rs782467046, CADD 22.40, PolyPhen-2 0.85, Variant assessed as somatic; moderate impact.
- V240A (p.Val240Ala), rs2075276205, ClinGen CA406053315, ClinVar RCV001219501, ClinVar RCV001773492, AlphaMissense 0.92, MetaLR 0.74, Uncertain significance, Dystonia 12; not provided
- G242D (p.Gly242Asp), cosmic curated COSV57489, gnomAD rs1555864935
- G242V (p.Gly242Val), rs1555864935, ClinGen CA406053287, ClinVar RCV003239250, AlphaMissense 1.00, MetaLR 0.96, Uncertain significance, not provided
- T243M (p.Thr243Met), rs2075274884, ClinGen CA406053281, NCI-TCGA Cosmic COSV5748, cosmic curated COSV57487, CADD 26.80, PolyPhen-2 0.78, Uncertain significance, Dystonia 12
- R245P (p.Arg245Pro), gnomAD rs1555864929, CADD 28.00, PolyPhen-2 0.94
- V247M (p.Val247Met), rs782227665, ClinGen CA9467783, ClinVar RCV000502583, ClinVar RCV001857074, CADD 21.90, PolyPhen-2 0.61, Conflicting interpretations, Dystonia 12; Inborn genetic diseases; not specified
- T251M (p.Thr251Met), cosmic curated COSV10013, TOPMed rs1471214305, gnomAD rs1471214305, AlphaMissense 0.64, MetaLR 0.93, Uncertain significance, Dystonia 12
- T251R (p.Thr251Arg), rs1471214305, ClinGen CA406053236, ClinVar RCV003208355, AlphaMissense 0.64, MetaLR 0.93, Uncertain significance, Inborn genetic diseases
- D253N (p.Asp253Asn), rs1057523788, ClinGen CA16608258, ClinVar RCV000435264, ClinVar RCV000624477, CADD 26.20, PolyPhen-2 1.00, Uncertain significance, Inborn genetic diseases; not provided
- R254C (p.Arg254Cys), rs782783739, ClinGen CA9467779, ClinVar RCV002877584, ClinVar RCV003403935, CADD 29.00, PolyPhen-2 0.77, Uncertain significance, not specified; Dystonia 12
- R254H (p.Arg254His), rs1315342682, ClinGen CA406053219, NCI-TCGA Cosmic COSV1001, cosmic curated COSV10013, CADD 22.70, PolyPhen-2 0.00, Uncertain significance, Dystonia 12
- R259C (p.Arg259Cys), rs2145978147, ClinGen CA406053186, NCI-TCGA Cosmic COSV1001, cosmic curated COSV10013, AlphaMissense 0.97, MetaLR 0.90, Uncertain significance, ATP1A3-related disorder; Dystonia 12
- R259H (p.Arg259His), rs1599722721, ClinGen CA406053185, NCI-TCGA Cosmic COSV5748, cosmic curated COSV57487, CADD 27.90, PolyPhen-2 1.00, Uncertain significance, not provided; Alternating hemiplegia of childhood 2
- L263P (p.Leu263Pro), TOPMed rs2075274182
- S265T (p.Ser265Thr), rs2514075842, ClinGen CA406053126, ClinVar RCV003627792, Uncertain significance, Dystonia 12
- G266R (p.Gly266Arg), gnomAD rs2075274098, CADD 24.50
- G266V (p.Gly266Val), rs2514075825, ClinGen CA406053099, ClinVar RCV003514910, ClinVar RCV004775432, Uncertain significance, not provided; Dystonia 12
- V269G (p.Val269Gly), Ensembl rs1599722692
- V269M (p.Val269Met), ExAC rs782749330, gnomAD rs782749330, CADD 23.50, PolyPhen-2 0.04
- G270D (p.Gly270Asp), rs1555864875, ClinGen CA406053036, ClinVar RCV001894190, gnomAD rs1555864875, AlphaMissense 0.84, MetaLR 0.74, Uncertain significance, Dystonia 12
- G270S (p.Gly270Ser), rs2514075769, ClinGen CA406053049, ClinVar RCV003389278, Likely benign, Cerebellar ataxia-areflexia-pes cavus-optic atrophy-sensorineural hearing loss s
- K271E (p.Lys271Glu), TOPMed rs2075273928
- I274F (p.Ile274Phe), rs879975642, ClinGen CA406052972, ClinVar RCV002308727, AlphaMissense 0.52, MetaLR 0.80, Likely pathogenic, ATP1A3-related disorder
- I274N (p.Ile274Asn), rs80356532, ClinGen CA346000, ClinVar RCV000148305, ClinVar RCV005089717, AlphaMissense 0.99, MetaLR 0.88, Pathogenic, Dystonia 12
- I274T (p.Ile274Thr), rs80356532, ClinGen CA341234, ClinVar RCV000013773, UniProt VAR 026735, AlphaMissense 0.99, MetaLR 0.88, Pathogenic, Dystonia 12
- I274V (p.Ile274Val), Ensembl rs879975642
- A275T (p.Ala275Thr), rs868987618, NCI-TCGA Cosmic COSV5748, cosmic curated COSV57485, Ensembl rs868987618, AlphaMissense 0.48, MetaLR 0.72, Uncertain significance, not provided; Dystonia 12
- I276M (p.Ile276Met), ESP rs372952520, ExAC rs372952520, TOPMed rs372952520, gnomAD rs372952520, CADD 6.02, PolyPhen-2 0.01, Likely benign
- E277K (p.Glu277Lys), rs80356533, ClinGen CA341235, cosmic curated COSV57486, ClinVar RCV000013774, AlphaMissense 1.00, MetaLR 0.76, Pathogenic/Likely pathogenic, not provided; Dystonia 12
- E279K (p.Glu279Lys), TOPMed rs1333580568, gnomAD rs1333580568, CADD 24.90
- H280Y (p.His280Tyr), rs2075273663, ClinGen CA406052863, ClinVar RCV001216759, Ensembl rs2075273663, CADD 24.50, PolyPhen-2 0.97, Uncertain significance, Dystonia 12
- F281V (p.Phe281Val), rs2145977959, ClinGen CA406052852, ClinVar RCV001988300, Ensembl rs2145977959, AlphaMissense 0.98, MetaLR 0.82, Uncertain significance, Dystonia 12
- I285L (p.Ile285Leu), rs2075273567, ClinGen CA406052787, ClinVar RCV004425849, ClinVar RCV006444298, CADD 26.50, PolyPhen-2 1.00, Uncertain significance, Paroxysmal central nervous system disorders; Inborn genetic diseases
- T286P (p.Thr286Pro), Ensembl rs2075273515, CADD 26.50, PolyPhen-2 0.99
- G287C (p.Gly287Cys), rs1279680384, ClinGen CA406052739, ClinVar RCV003069252, ClinVar RCV005242300, CADD 23.20, PolyPhen-2 0.98, Uncertain significance, not provided; Dystonia 12
- G287S (p.Gly287Ser), rs1279680384, ClinGen CA406052746, ClinVar RCV003515705, NCI-TCGA TCGA novel, CADD 22.80, PolyPhen-2 0.19, Uncertain significance, Dystonia 12
Public ATP1A3 analysis runs
- ATP1A3 analysis run — ATP1A3 (827 variants) — completed 2026-08-18