ANK2 (Ankyrin-2) variants and mutations
ANK2 (also known as Ankyrin-2) is a human protein-coding gene encoding an ankyrin-2 protein. It organizes membrane proteins and ion-handling complexes by linking them to the cytoskeleton, with especially important roles in cardiomyocytes and neurons. Pathogenic variants can disrupt cardiac electrical organization and cause ankyrin-B syndrome, including sinus-node dysfunction, arrhythmias, and variable QT abnormalities. This analysis covers 6,887 ANK2 variants and mutations. Of these, 51% have computational variant effect predictions. Disease context includes Romano-Ward syndrome, neurodevelopmental disorder, and Prolonged QT interval. Example ANK2 variants include M2V, M2K, and M2I.
Variant analysis overview
- Gene: ANK2
- Protein: Ankyrin-2
- UniProt accession: Q01484
- Organism: Homo sapiens
- Variants analyzed: 6887
- Variant scope: all variants
- Completed: 2026-08-19
Variant and mutation evidence
- Variant composition: 6,729 unspecified-consequence records; 107 missense variants; 30 synonymous variants; 10 frameshift variants; 5 stop-gained variants; 1 protein altering variant; 3 in-frame deletions; 1 splice-region variants; 1 substitution
- Prediction scores: 3,536 variants have prediction scores (51% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: Romano-Ward syndrome, neurodevelopmental disorder, Prolonged QT interval, Abnormality of the cardiovascular system, complex neurodevelopmental disorder, hereditary disease, epilepsy, autism spectrum disorder, Brugada syndrome, myocardial ischemia, Proptosis, placental retention.
Protein structure and variant hotspots
- Protein features: 4 domains; 50 post-translational modification sites.
- Structural context: 1,191 variants have structural context.
- PTM context: 80 variants overlap post-translational modification sites.
- Experimental data: 78 protein positions have experimental scores. Source: ANK2 Death domain domainome 1.0.
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, ClinGen, MaveDB, LitVar.
Notable ANK2 variants
Examples include M2V, M2K, M2I, M2L, M2T, N3K, N3N, N3T. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- M2V (p.Met2Val), rs929854524, ClinGen CA104483597, ClinVar RCV002343030, TOPMed rs929854524, REVEL 0.20, CADD 23.20, Uncertain significance, Cardiovascular phenotype
- M2K (p.Met2Lys), gnomAD 4-112904504-T-A, CADD 23.50
- M2I (p.Met2Ile), gnomAD 4-112904505-G-A, CADD 23.10
- M2L (p.Met2Leu), gnomAD 4-113049732-A-T, REVEL 0.21, CADD 23.80
- M2T (p.Met2Thr), rs116338686, gnomAD 4-113145933-T-C, CADD 16.60
- N3K (p.Asn3Lys), cosmic curated COSV10805, NCI-TCGA TCGA novel, CADD 16.00, Variant assessed as somatic; moderate impact.
- N3N (p.Asn3Asn), gnomAD 4-113049737-C-T, CADD 12.50
- N3T (p.Asn3Thr), rs1374538922, gnomAD 4-113145876-A-C, CADD 21.10
- E4K (p.Glu4Lys), 1000Genomes rs535919946, ExAC rs535919946, gnomAD rs535919946, REVEL 0.28, CADD 32.00, Uncertain significance, not provided
- E4* (p.Glu4Ter), gnomAD 4-113049738-G-T, CADD 37.00
- p.Glu4delinsAspSer, gnomAD 4-113049739-A-ACT, CADD 27.30
- D5G (p.Asp5Gly), Ensembl rs1433952417, REVEL 0.11, CADD 25.90
- D5N (p.Asp5Asn), ExAC rs748654930, gnomAD rs748654930, REVEL 0.11, CADD 26.00, Uncertain significance
- D5Y (p.Asp5Tyr), rs748654930, ClinGen CA357992657, ClinVar RCV000498439, ExAC rs748654930, REVEL 0.23, CADD 31.00, Uncertain significance, not provided
- D5V (p.Asp5Val), gnomAD 4-113049742-A-T, REVEL 0.19, CADD 29.20
- p.Asp5 Ala6delinsGlu, gnomAD 4-113049742-ATGC-, CADD 20.40
- A6S (p.Ala6Ser), NCI-TCGA Cosmic COSV5216, cosmic curated COSV52165, Variant assessed as somatic; moderate impact.
- A6T (p.Ala6Thr), rs1335618863, gnomAD 4-113117293-G-A, CADD 18.90
- A6P (p.Ala6Pro), gnomAD 4-113117293-G-C, CADD 18.60
- A6V (p.Ala6Val), rs1450203225, gnomAD 4-113117294-C-T, CADD 18.40
- A6D (p.Ala6Asp), rs2154369290, gnomAD 4-113117303-C-A, CADD 18.10
- A6A (p.Ala6Ala), gnomAD 4-113145883-C-A, CADD 13.00
- A7D (p.Ala7Asp), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- A7T (p.Ala7Thr), gnomAD 4-113117329-G-A, CADD 18.10
- A7V (p.Ala7Val), rs75050054, gnomAD 4-113145903-C-T, CADD 14.50
- A7E (p.Ala7Glu), rs75050054, gnomAD 4-113145903-C-A, CADD 14.10
- A7A (p.Ala7Ala), rs920309443, gnomAD 4-113145904-G-A, CADD 3.29
- Q8K (p.Gln8Lys), gnomAD 4-112904509-C-A, CADD 15.90
- Q8* (p.Gln8Ter), gnomAD 4-112904509-C-T, CADD 38.00
- Q8L (p.Gln8Leu), gnomAD 4-112904510-A-T, CADD 22.60
- Q8R (p.Gln8Arg), rs2084530006, gnomAD 4-112904510-A-G, CADD 19.30
- Q8Q (p.Gln8Gln), gnomAD 4-112904511-A-G, CADD 9.09
- Q8P (p.Gln8Pro), gnomAD 4-113049751-A-C, REVEL 0.19, CADD 24.50
- Q8H (p.Gln8His), gnomAD 4-113049752-G-T, REVEL 0.12, CADD 26.40
- K9S (p.Lys9Ser), gnomAD 4-112904509-CA-C, CADD 28.90
- K9E (p.Lys9Glu), gnomAD 4-112904512-A-G, CADD 23.90
- K9M (p.Lys9Met), gnomAD 4-112904513-A-T, CADD 32.00
- K9R (p.Lys9Arg), gnomAD 4-112904513-A-G, CADD 23.90
- K9N (p.Lys9Asn), gnomAD 4-112904514-G-T, CADD 34.00
- S10G (p.Ser10Gly), gnomAD rs1440598505, REVEL 0.07, CADD 24.10, Uncertain significance, not provided
- S10N (p.Ser10Asn), gnomAD 4-113049757-G-A, REVEL 0.09, CADD 25.50
- S10E (p.Ser10Glu), rs2154367173, gnomAD 4-113113728-T-TGT, CADD 11.40
- S10Y (p.Ser10Tyr), rs1460940236, gnomAD 4-113117309-C-A, CADD 18.00
- p.Ser8 Ser9del, rs1299464401, gnomAD 4-113145889-CTCTT, CADD 17.20
- S10C (p.Ser10Cys), gnomAD 4-113145891-C-G, CADD 18.10
- S10A (p.Ser10Ala), rs2096812314, gnomAD 4-113145893-T-G, CADD 16.40
- S10S (p.Ser10Ser), rs921558493, gnomAD 4-113145895-T-C, CADD 8.81
- D11N (p.Asp11Asn), NCI-TCGA TCGA novel, REVEL 0.19, CADD 29.90, Variant assessed as somatic; moderate impact.
- D11G (p.Asp11Gly), gnomAD 4-113049760-A-G, REVEL 0.25, CADD 25.70
- D11D (p.Asp11Asp), rs2066071736, gnomAD 4-113049761-C-T, CADD 14.90
- D11H (p.Asp11His), rs901459994, gnomAD 4-113117338-G-C, CADD 18.40
- D11Y (p.Asp11Tyr), rs901459994, gnomAD 4-113117338-G-T, CADD 18.30
- D11V (p.Asp11Val), rs1205644528, gnomAD 4-113145906-A-T, CADD 14.90
- S12G (p.Ser12Gly), ExAC rs778450160, gnomAD rs778450160, REVEL 0.07, CADD 22.50
- S12I (p.Ser12Ile), rs1428896596, ClinGen CA357992711, ClinVar RCV001768310, TOPMed rs1428896596, REVEL 0.15, CADD 26.90, Uncertain significance, not provided
- S12S (p.Ser12Ser), rs2066075615, gnomAD 4-113049764-T-C, CADD 13.40
- S12N (p.Ser12Asn), gnomAD 4-113145912-G-A, CADD 19.80
- G13E (p.Gly13Glu), cosmic curated COSV10438, ExAC rs771799732, gnomAD rs771799732, REVEL 0.26, CADD 27.30
- G13R (p.Gly13Arg), ExAC rs745356870, TOPMed rs745356870, gnomAD rs745356870, REVEL 0.28, CADD 32.00
- G13G (p.Gly13Gly), rs1282818023, gnomAD 4-113049767-A-G, CADD 7.92
- G13A (p.Gly13Ala), gnomAD 4-113145873-G-C, CADD 20.30
- E14* (p.Glu14Ter), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- E14D (p.Glu14Asp), rs983314290, ClinGen CA104483598, ClinVar RCV003112597, TOPMed rs983314290, REVEL 0.12, CADD 25.20, Uncertain significance, Long QT syndrome
- E14Q (p.Glu14Gln), gnomAD 4-113049768-G-C, REVEL 0.20, CADD 27.70
- E14G (p.Glu14Gly), gnomAD 4-113049769-A-G, REVEL 0.20, CADD 32.00
- E14E (p.Glu14Glu), gnomAD 4-113049770-G-A, CADD 13.30
- E14K (p.Glu14Lys), rs1380933071, gnomAD 4-113117326-G-A, CADD 19.10
- E14A (p.Glu14Ala), gnomAD 4-113117360-A-C, CADD 19.40
- E14V (p.Glu14Val), rs1326514629, gnomAD 4-113145939-A-T, CADD 19.40
- K15E (p.Lys15Glu), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- K15del (p.Lys15del), rs1195823103, gnomAD 4-113049768-GAGA-, CADD 21.10
- K15R (p.Lys15Arg), gnomAD 4-113049772-A-G, REVEL 0.04, CADD 24.40
- K15N (p.Lys15Asn), gnomAD 4-113117346-G-C, CADD 17.10
- K15K (p.Lys15Lys), rs1177165569, gnomAD 4-113145910-G-A, CADD 19.80
- F16F (p.Phe16Phe), rs779606672, gnomAD 4-113049776-C-T, CADD 14.40
- N17D (p.Asn17Asp), rs1424055453, ClinGen CA357992742, ClinVar RCV003338989, ClinVar RCV004572941, REVEL 0.18, CADD 27.30, Uncertain significance, Cardiovascular phenotype
- N17N (p.Asn17Asn), rs1489481220, gnomAD 4-113049779-C-T, CADD 8.35
- N17I (p.Asn17Ile), rs1242786445, gnomAD 4-113117347-GA-G, CADD 17.10
- N17K (p.Asn17Lys), rs1242786445, gnomAD 4-113117347-G-GA, CADD 18.10
- N17Y (p.Asn17Tyr), gnomAD 4-113117353-A-T, CADD 17.40
- N17S (p.Asn17Ser), rs1181915642, gnomAD 4-113117354-A-G, CADD 11.90
- N17T (p.Asn17Thr), rs769494048, gnomAD 4-113145927-GA-G, CADD 7.99
- G18D (p.Gly18Asp), rs746628566, NCI-TCGA Cosmic COSV1000, cosmic curated COSV10000, ExAC rs746628566, REVEL 0.24, CADD 28.10, Variant assessed as somatic; moderate impact.
- G18S (p.Gly18Ser), gnomAD 4-113049780-G-A, REVEL 0.11, CADD 26.60
- G18G (p.Gly18Gly), gnomAD 4-113049782-C-G, CADD 12.20
- G18R (p.Gly18Arg), rs752401219, gnomAD 4-113145926-G-A, CADD 20.20
- G18A (p.Gly18Ala), gnomAD 4-113145927-G-C, CADD 18.00
- G18E (p.Gly18Glu), rs532838849, gnomAD 4-113145927-G-A, CADD 18.30
- S19G (p.Ser19Gly), ExAC rs768352926, TOPMed rs768352926, gnomAD rs768352926, REVEL 0.05, CADD 13.30, Uncertain significance, Cardiovascular phenotype
- S19I (p.Ser19Ile), ESP rs369260005, ExAC rs369260005, TOPMed rs369260005, gnomAD rs369260005, REVEL 0.03, CADD 21.40, Likely benign
- S19N (p.Ser19Asn), rs369260005, ClinGen CA3049843, ClinVar RCV000315698, ClinVar RCV001342296, REVEL 0.04, CADD 18.90, Conflicting interpretations, Long QT syndrome; Cardiac arrhythmia, ankyrin-B-related; Cardiovascular phenotyp
- S19R (p.Ser19Arg), NCI-TCGA Cosmic COSV5217, cosmic curated COSV52171, Variant assessed as somatic; moderate impact.
- S20C (p.Ser20Cys), Ensembl rs2154322706
- S20G (p.Ser20Gly), gnomAD 4-113049786-A-G, REVEL 0.04, CADD 21.80
- S20N (p.Ser20Asn), gnomAD 4-113049787-G-A, REVEL 0.04, CADD 22.30
- S20R (p.Ser20Arg), gnomAD 4-113049788-T-A, REVEL 0.09, CADD 22.80
- S20S (p.Ser20Ser), gnomAD 4-113049788-T-C, CADD 11.60
- Q21R (p.Gln21Arg), ESP rs147439862, ExAC rs147439862, REVEL 0.07, CADD 22.50, Uncertain significance, Cardiovascular phenotype
- Q21Q (p.Gln21Gln), rs1060504155, gnomAD 4-113049791-G-A, CADD 11.50
- Q21K (p.Gln21Lys), rs2094913522, gnomAD 4-113117377-C-A, CADD 18.00
- Q21L (p.Gln21Leu), rs2097060413, gnomAD 4-113151093-A-T, CADD 10.20
- Q21H (p.Gln21His), rs2097060526, gnomAD 4-113151094-G-C, CADD 13.20
- R22G (p.Arg22Gly), NCI-TCGA Cosmic COSV5219, cosmic curated COSV52193, Variant assessed as somatic; moderate impact.
- R22K (p.Arg22Lys), TOPMed rs1216511889, gnomAD rs1216511889, REVEL 0.09, CADD 29.10
- R22Q (p.Arg22Gln), rs2094905822, gnomAD 4-113117324-G-A, CADD 19.10
- R22R (p.Arg22Arg), rs552815546, gnomAD 4-113145919-A-G, CADD 12.80
- R22S (p.Arg22Ser), rs552815546, gnomAD 4-113145919-A-C, CADD 12.50
- R23K (p.Arg23Lys), Ensembl rs1580054974, REVEL 0.02, CADD 21.40
- R23T (p.Arg23Thr), gnomAD 4-113049796-G-C, REVEL 0.10, CADD 22.20
- K24R (p.Lys24Arg), TOPMed rs2066097153, REVEL 0.04, CADD 22.80
- K24N (p.Lys24Asn), gnomAD 4-113049800-A-C, REVEL 0.06, CADD 24.00
- R25D (p.Arg25Asp), gnomAD 4-113049796-GA-G, CADD 23.80
- R25G (p.Arg25Gly), gnomAD 4-113049801-A-G, REVEL 0.07, CADD 24.90
- R25I (p.Arg25Ile), gnomAD 4-113049802-G-T, REVEL 0.09, CADD 23.80
- R25S (p.Arg25Ser), gnomAD 4-113117370-A-T, CADD 14.70
- P26L (p.Pro26Leu), TOPMed rs2066098531
- P26H (p.Pro26His), gnomAD 4-113049805-C-A, REVEL 0.17, CADD 26.30
- P26R (p.Pro26Arg), gnomAD 4-113049805-C-G, REVEL 0.15, CADD 24.30
- P26P (p.Pro26Pro), rs928291078, gnomAD 4-113049806-C-T, CADD 14.10
- P26T (p.Pro26Thr), rs1420988261, gnomAD 4-113117389-C-A, CADD 17.80
- P26S (p.Pro26Ser), rs1264843271, gnomAD 4-113145953-C-T, CADD 17.40
- P26A (p.Pro26Ala), gnomAD 4-113145953-C-G, CADD 17.20
- P26Q (p.Pro26Gln), gnomAD 4-113151102-C-A, CADD 9.70
- K27T (p.Lys27Thr), rs769843073, ClinGen CA301003, ClinVar RCV000170724, ClinVar RCV000228758, REVEL 0.08, CADD 23.00, Uncertain significance, not provided; Long QT syndrome; Cardiac arrhythmia, ankyrin-B-related
- K27* (p.Lys27Ter), gnomAD 4-113049807-A-T, CADD 37.00
- K27R (p.Lys27Arg), gnomAD 4-113049808-A-G, REVEL 0.06, CADD 18.50
- K27E (p.Lys27Glu), rs1439079045, gnomAD 4-113145947-A-G, CADD 16.30
- K27N (p.Lys27Asn), gnomAD 4-113145949-A-C, CADD 14.40
- K28E (p.Lys28Glu), gnomAD 4-113049810-A-G, REVEL 0.21, CADD 25.40
- K28K (p.Lys28Lys), rs139765650, gnomAD 4-113049812-G-A, CADD 26.10
- K28N (p.Lys28Asn), gnomAD 4-113049812-G-T, REVEL 0.17, CADD 35.00
- K28R (p.Lys28Arg), rs1208770308, gnomAD 4-113117372-A-G, CADD 19.70
- S29=, NCI-TCGA TCGA novel, Variant assessed as somatic; low impact.
- S29C (p.Ser29Cys), Ensembl rs969646633
- D30E (p.Asp30Glu), NCI-TCGA Cosmic COSV5215, cosmic curated COSV52157, CADD 17.00, Variant assessed as somatic; moderate impact.
- D30N (p.Asp30Asn), rs1333554820, gnomAD 4-113117365-G-A, CADD 19.10
- D30V (p.Asp30Val), gnomAD 4-113117366-A-T, CADD 19.60
- D30G (p.Asp30Gly), gnomAD 4-113145957-A-G, CADD 21.40
- D30D (p.Asp30Asp), gnomAD 4-113145958-C-T, CADD 17.40
- N32K (p.Asn32Lys), ExAC rs758379675, TOPMed rs758379675, gnomAD rs758379675, Likely benign
- N32S (p.Asn32Ser), gnomAD rs1250640997, REVEL 0.28, CADD 25.40
- N32N (p.Asn32Asn), gnomAD 4-113145973-C-T, CADD 16.60
- A33T (p.Ala33Thr), gnomAD rs1193481066, REVEL 0.14, CADD 23.70
- S34I (p.Ser34Ile), gnomAD 4-113145975-G-T, CADD 19.30
- L36F (p.Leu36Phe), rs1373936514, ClinGen CA357992881, ClinVar RCV003531596, gnomAD rs1373936514, REVEL 0.38, CADD 25.10, Uncertain significance, Long QT syndrome
- L36M (p.Leu36Met), gnomAD 4-112904506-T-A, CADD 23.30
- L36L (p.Leu36Leu), gnomAD 4-112904506-T-C, CADD 7.87
- L36S (p.Leu36Ser), gnomAD 4-112904507-T-C, CADD 24.30
- L36V (p.Leu36Val), rs1018403093, gnomAD 4-113117335-C-G, CADD 15.10
- L36* (p.Leu36Ter), rs1235765606, gnomAD 4-113145939-AACTG, CADD 18.60
- L36P (p.Leu36Pro), rs1372457839, gnomAD 4-113145942-T-C, CADD 16.80
- R37C (p.Arg37Cys), rs369877280, ClinGen CA3049937, ClinVar RCV001545260, ClinVar RCV001824994, CADD 18.10, Uncertain significance, not provided
- R37H (p.Arg37His), gnomAD rs2098115966, CADD 18.50, Uncertain significance, ANK2-related disorder
- R37I (p.Arg37Ile), gnomAD 4-113117393-G-T, CADD 18.50
- R37S (p.Arg37Ser), rs1017475184, gnomAD 4-113117394-A-C, CADD 15.90
- A38V (p.Ala38Val), rs2098116035, ClinGen CA357992903, ClinVar RCV002223351, ClinVar RCV002454589, AlphaMissense 0.94, MetaLR 0.68, Uncertain significance, Long QT syndrome; Cardiovascular phenotype; not provided
- A38T (p.Ala38Thr), rs1419809451, gnomAD 4-113151107-G-A, CADD 10.90
- A38D (p.Ala38Asp), rs1474161198, gnomAD 4-113151108-C-A, CADD 14.20
- A38A (p.Ala38Ala), rs1056901729, gnomAD 4-113151109-C-A, CADD 13.20
- A39S (p.Ala39Ser), rs1463855073, ClinGen CA357992906, cosmic curated COSV52178, ClinVar RCV000816171, CADD 6.28, Uncertain significance, not provided; Long QT syndrome
- A39T (p.Ala39Thr), rs868182830, gnomAD 4-113151110-G-A, CADD 6.24
- A39V (p.Ala39Val), gnomAD 4-113151111-C-T, CADD 7.15
- A39A (p.Ala39Ala), gnomAD 4-113151112-C-T, CADD 14.10
- R40R (p.Arg40Arg), rs1021398367, gnomAD 4-113117407-C-A, CADD 16.70
- R40* (p.Arg40Ter), gnomAD 4-113117407-C-T, CADD 17.10
- R40Q (p.Arg40Gln), rs2094919857, gnomAD 4-113117408-G-A, CADD 18.90
- R40I (p.Arg40Ile), gnomAD 4-113117414-G-T, CADD 18.50
- A41E (p.Ala41Glu), Ensembl rs2098116234
- A41T (p.Ala41Thr), rs1085307623, ClinGen CA357992917, ClinVar RCV000490229, ClinVar RCV003409672, REVEL 0.27, CADD 27.20, Uncertain significance, ANK2-related disorder; not provided
- G42S (p.Gly42Ser), gnomAD 4-113145965-G-A, CADD 20.60
- G42G (p.Gly42Gly), gnomAD 4-113145967-C-T, CADD 19.30
- G42R (p.Gly42Arg), gnomAD 4-113145995-G-A, CADD 16.00
- G42V (p.Gly42Val), rs775485891, gnomAD 4-113145996-G-T, CADD 12.70
- N43D (p.Asn43Asp), rs2153225129, ClinGen CA357992930, ClinVar RCV002037500, Ensembl rs2153225129, AlphaMissense 0.78, MetaLR 0.34, Uncertain significance, Long QT syndrome
- N43S (p.Asn43Ser), cosmic curated COSV52164, gnomAD rs1169068254, REVEL 0.47, CADD 25.80
- N43H (p.Asn43His), gnomAD 4-113151113-A-C, CADD 13.90
- L44P (p.Leu44Pro), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- L44V (p.Leu44Val), rs145272651, ClinGen CA3049938, cosmic curated COSV10000, ClinVar RCV000250584, REVEL 0.19, CADD 19.40, Benign/Likely benign, Cardiovascular phenotype; not provided; Long QT syndrome
- D45G (p.Asp45Gly), TOPMed rs1047496087, gnomAD rs1047496087, REVEL 0.61, CADD 31.00
- D45N (p.Asp45Asn), rs531912509, gnomAD 4-113145980-G-A, CADD 20.20
Public ANK2 analysis runs
- ANK2 analysis run — ANK2 (6,887 variants) — completed 2026-08-19