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10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
ANK2
ankyrin 2
Chromosome 4 Β· 4q25-q26
NCBI Gene: 287Ensembl: ENSG00000145362.21HGNC: HGNC:493UniProt: A0A5F9ZGS5
137PubMed Papers
21Diseases
0Drugs
90Pathogenic Variants
FUNCTIONAL ROLE
Highly ConstrainedHub GeneTransporter
RESEARCH IMPACT
Variant-Rich
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
enzyme bindingprotein kinase bindingregulation of release of sequestered calcium ion into cytosolpositive regulation of potassium ion import across plasma membraneRomano-Ward syndromeNeurodevelopmental disorderAbnormality of the cardiovascular systemProlonged QT interval
✦AI Summary

ANK2 (ankyrin 2) is a critical membrane scaffolding protein that stabilizes ion transporters and channels in multiple cell types, particularly in cardiac and neuronal tissues. In cardiomyocytes, ANK2 coordinates the assembly of key proteins including Na/Ca exchangers, Na/K ATPases, and calcium channels at specialized membrane sites 1. The protein plays essential roles in neuronal function, where loss-of-function variants cause neurodevelopmental disorders characterized by autism spectrum disorders, epilepsy, and intellectual disability 23. ANK2-deficient neurons exhibit hyperactive and desynchronized network activity with impaired axon initial segment plasticity, contributing to the neurological phenotypes observed in patients 2. In cardiac contexts, ANK2 variants have been associated with hypertrophic cardiomyopathy, where patients show increased wall thickness, though its classification as a definitive long QT syndrome gene remains disputed with only limited evidence supporting this association 14. ANK2 also participates in cellular processes beyond ion channel regulation, including endocytosis and protein trafficking through interactions with the cytoskeleton 5. The protein's dysfunction appears to converge with other autism-associated genes in neuronal networks, highlighting its importance in neurodevelopmental pathways.

Sources cited
1
ANK2 variants associated with hypertrophic cardiomyopathy and increased cardiac wall thickness
PMID: 25351510
2
ANK2 loss-of-function variants cause epilepsy and neurodevelopmental disorders with hyperactive neuronal networks and impaired axon initial segment plasticity
PMID: 37195288
3
ANK2 mutations cause autism spectrum disorders, epilepsy, intellectual disability and developmental delays
PMID: 40035441
4
ANK2 has limited evidence as a long QT syndrome-causative gene
PMID: 31983240
5
ANK2 participates in protein-protein interaction networks relevant to autism spectrum disorders in human neurons
PMID: 36950384
Disease Associationsβ“˜21
Romano-Ward syndromeOpen Targets
0.74Strong
Neurodevelopmental disorderOpen Targets
0.61Moderate
Abnormality of the cardiovascular systemOpen Targets
0.54Moderate
Prolonged QT intervalOpen Targets
0.54Moderate
complex neurodevelopmental disorderOpen Targets
0.50Moderate
genetic disorderOpen Targets
0.48Moderate
epilepsyOpen Targets
0.39Weak
autism spectrum disorderOpen Targets
0.38Weak
Brugada syndromeOpen Targets
0.35Weak
Myocardial IschemiaOpen Targets
0.33Weak
ProptosisOpen Targets
0.33Weak
catecholaminergic polymorphic ventricular tachycardia 1Open Targets
0.30Weak
placental retentionOpen Targets
0.30Weak
rheumatic diseaseOpen Targets
0.28Weak
contractureOpen Targets
0.28Weak
joint diseaseOpen Targets
0.26Weak
skin diseaseOpen Targets
0.23Weak
congenital anomaly of cardiovascular systemOpen Targets
0.22Weak
systemic lupus erythematosusOpen Targets
0.22Weak
atrial fibrillationOpen Targets
0.20Weak
Long QT syndrome 4UniProt
Pathogenic Variants90
NM_001148.6(ANK2):c.11760_11761delinsTT (p.Gln3921Ter)Pathogenic
Cardiovascular phenotype|Long QT syndrome
β˜…β˜…β˜†β˜†2025β†’ Residue 3921
NM_001148.6(ANK2):c.9337C>T (p.Arg3113Ter)Pathogenic
Cardiovascular phenotype|Long QT syndrome
β˜…β˜…β˜†β˜†2025β†’ Residue 3113
NM_001148.6(ANK2):c.2683C>T (p.Arg895Ter)Pathogenic
not provided|Cardiovascular phenotype
β˜…β˜…β˜†β˜†2025β†’ Residue 895
NM_001148.6(ANK2):c.2662C>T (p.Arg888Ter)Pathogenic
not provided|ANK2-related epilepsy
β˜…β˜…β˜†β˜†2025β†’ Residue 888
NM_001148.6(ANK2):c.6757_6761del (p.Lys2252_Lys2253insTer)Pathogenic
not provided|Cardiovascular phenotype
β˜…β˜…β˜†β˜†2025β†’ Residue 2252
NM_001148.6(ANK2):c.2929C>T (p.Arg977Ter)Pathogenic
not provided|Cardiovascular phenotype
β˜…β˜…β˜†β˜†2024β†’ Residue 977
NM_001148.6(ANK2):c.3019C>T (p.Arg1007Ter)Pathogenic
Inborn genetic diseases|Cardiac arrhythmia, ankyrin-B-related|not provided
β˜…β˜…β˜†β˜†2024β†’ Residue 1007
NM_001148.6(ANK2):c.11761C>T (p.Gln3921Ter)Pathogenic
Cardiac arrhythmia, ankyrin-B-related|not provided|Cardiovascular phenotype
β˜…β˜…β˜†β˜†2024β†’ Residue 3921
NM_001148.6(ANK2):c.2944C>T (p.Arg982Ter)Pathogenic
not provided|Cardiovascular phenotype
β˜…β˜…β˜†β˜†2022β†’ Residue 982
NM_001148.6(ANK2):c.5450_5451del (p.Arg1817fs)Pathogenic
ANK2-associated seizure disorder
β˜…β˜†β˜†β˜†2025β†’ Residue 1817
NM_001148.6(ANK2):c.9239del (p.Pro3080fs)Pathogenic
Cardiovascular phenotype
β˜…β˜†β˜†β˜†2025β†’ Residue 3080
NM_001148.6(ANK2):c.9220C>T (p.Gln3074Ter)Pathogenic
Cardiovascular phenotype
β˜…β˜†β˜†β˜†2025β†’ Residue 3074
NM_001148.6(ANK2):c.11137T>G (p.Ser3713Ala)Likely pathogenic
Cardiac arrhythmia, ankyrin-B-related
β˜…β˜†β˜†β˜†2025β†’ Residue 3713
NM_001148.6(ANK2):c.3224+1G>ALikely pathogenic
not provided
β˜…β˜†β˜†β˜†2025
NM_001148.6(ANK2):c.10573G>T (p.Glu3525Ter)Pathogenic
Long QT syndrome
β˜…β˜†β˜†β˜†2025β†’ Residue 3525
NM_001148.6(ANK2):c.4846T>C (p.Cys1616Arg)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 1616
NM_001148.6(ANK2):c.4212dup (p.Ala1405fs)Pathogenic
Long QT syndrome
β˜…β˜†β˜†β˜†2025β†’ Residue 1405
NM_001148.6(ANK2):c.3271del (p.Glu1091fs)Pathogenic
Long QT syndrome
β˜…β˜†β˜†β˜†2025β†’ Residue 1091
NM_001148.6(ANK2):c.10264G>T (p.Glu3422Ter)Pathogenic
Cardiovascular phenotype
β˜…β˜†β˜†β˜†2025β†’ Residue 3422
NM_001148.6(ANK2):c.4279C>T (p.Arg1427Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 1427
View on ClinVar β†—
Related Genes
CUL1Protein interaction100%SPTBProtein interaction100%OBSCNProtein interaction99%NFASCProtein interaction99%ITPR3Protein interaction98%TTNProtein interaction98%
Tissue Expression6 tissues
Heart
100%
Brain
63%
Ovary
16%
Lung
2%
Liver
1%
Bone Marrow
0%
Gene Interaction Network
Click a node to explore
ANK2CUL1SPTBOBSCNNFASCITPR3TTN
PROTEIN STRUCTURE
Preparing viewer…
PDB6KZJ Β· 1.50 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.27Highly Constrained
pLIβ“˜
1.00Intolerant
Observed/Expected LoF0.23 [0.19–0.27]
RankingsWhere ANK2 stands among ~20K protein-coding genes
  • #3,364of 20,598
    Most Researched137 Β· top quartile
  • #846of 5,498
    Most Pathogenic Variants90 Β· top quartile
  • #914of 17,882
    Most Constrained (LOEUF)0.27 Β· top 10%
Genes detectedANK2
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
In vivo Perturb-Seq reveals neuronal and glial abnormalities associated with autism risk genes.
PMID: 33243861
Science Β· 2020
1.00
2
Novel genotype-phenotype associations demonstrated by high-throughput sequencing in patients with hypertrophic cardiomyopathy.
PMID: 25351510
Heart Β· 2015
0.90
3
A Mutation in the ANK2 Gene Causing ASD and a Review of the Literature.
PMID: 40035441
Mol Genet Genomic Med Β· 2025
0.80
4
ANK2 loss-of-function variants are associated with epilepsy, and lead to impaired axon initial segment plasticity and hyperactive network activity in hiPSC-derived neuronal networks.
PMID: 37195288
Hum Mol Genet Β· 2023
0.70
5
An International, Multicentered, Evidence-Based Reappraisal of Genes Reported to Cause Congenital Long QT Syndrome.
PMID: 31983240
Circulation Β· 2020
0.60