ANK2 Gene

HGNC Family	Ankyrin repeat domain containing (ANKRD)
Name	ankyrin 2, neuronal
Description	This gene encodes a member of the ankyrin family of proteins that link the integral membrane proteins to the underlying spectrin-actin cytoskeleton. Ankyrins play key roles in activities such as cell motility, activation, proliferation, contact and the maintenance of specialized membrane domains. Most ankyrins are typically composed of three structural domains: an amino-terminal domain containing multiple ankyrin repeats; a central region with a highly conserved spectrin binding domain; and a carboxy-terminal regulatory domain which is the least conserved and subject to variation. The protein encoded by this gene is required for targeting and stability of Na/Ca exchanger 1 in cardiomyocytes. Mutations in this gene cause long QT syndrome 4 and cardiac arrhythmia syndrome. Multiple transcript variants encoding different isoforms have been described. [provided by RefSeq, Dec 2011]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Ankyrin‐B, encoded by the ANK2 gene, is emerging as a critical membrane adaptor protein that orchestrates the proper localization and stabilization of key ion channels and transporters in cardiomyocytes. Through direct binding interactions, ankyrin‐B tethers components such as the Na⁺/K⁺ ATPase, Na⁺/Ca²⁺ exchanger, inositol 1,4,5‐trisphosphate receptors, and ryanodine receptors to specialized membrane domains—including T‐tubules and the sinoatrial node—thereby ensuring coordinated Ca²⁺ handling and normal electrical excitability."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " Loss‐of‐function mutations or haploinsufficiency of ANK2 disrupt this multiprotein complex and lead to abnormal channel targeting, altered Ca²⁺ signaling, and consequent arrhythmogenic phenotypes such as prolonged or shortened action potentials, type 4 long‐QT syndrome, and sick sinus syndrome."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}, {"type": "fg_fs", "start_ref": "3", "end_ref": "5"}]}, {"type": "t", "text": " Systematic evaluations of diverse ANK2 variants have revealed a spectrum of cellular dysfunctions—from subtle to severe—correlating with a range of clinical manifestations, which underscores the dosage‐sensitive nature of ankyrin‐B’s role in cardiac electrogenesis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " Moreover, its interaction with beta–spectrin—most notably beta₂–spectrin—further stabilizes these membrane complexes in neonatal cardiomyocytes, highlighting a fundamental cytoskeletal mechanism required for channel targeting and cardiac function."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " Collectively, these findings identify ANK2 as a pivotal regulator of cardiac membrane organization whose disruption contributes to arrhythmias and conduction disorders.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Peter J Mohler, Jean-Jacques Schott, Anthony O Gramolini, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Ankyrin-B mutation causes type 4 long-QT cardiac arrhythmia and sudden cardiac death."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature01335"}], "href": "https://doi.org/10.1038/nature01335"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12571597"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12571597"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Peter J Mohler, Jonathan Q Davis, Vann Bennett "}, {"type": "b", "children": [{"type": "t", "text": "Ankyrin-B coordinates the Na/K ATPase, Na/Ca exchanger, and InsP3 receptor in a cardiac T-tubule/SR microdomain."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS Biol (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pbio.0030423"}], "href": "https://doi.org/10.1371/journal.pbio.0030423"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16292983"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16292983"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Matteo Vatta, Michael J Ackerman, Bin Ye, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mutant caveolin-3 induces persistent late sodium current and is associated with long-QT syndrome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Circulation (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1161/CIRCULATIONAHA.106.635268"}], "href": "https://doi.org/10.1161/CIRCULATIONAHA.106.635268"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17060380"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17060380"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Solena Le Scouarnec, Naina Bhasin, Claude Vieyres, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Dysfunction in ankyrin-B-dependent ion channel and transporter targeting causes human sinus node disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0805500105"}], "href": "https://doi.org/10.1073/pnas.0805500105"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18832177"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18832177"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Shane R Cunha, Thomas J Hund, Seyed Hashemi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Defects in ankyrin-based membrane protein targeting pathways underlie atrial fibrillation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Circulation (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1161/CIRCULATIONAHA.111.023986"}], "href": "https://doi.org/10.1161/CIRCULATIONAHA.111.023986"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21859974"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21859974"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Peter J Mohler, Solena Le Scouarnec, Isabelle Denjoy, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Defining the cellular phenotype of \"ankyrin-B syndrome\" variants: human ANK2 variants associated with clinical phenotypes display a spectrum of activities in cardiomyocytes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Circulation (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1161/CIRCULATIONAHA.106.656512"}], "href": "https://doi.org/10.1161/CIRCULATIONAHA.106.656512"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17242276"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17242276"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Peter J Mohler, Anthony O Gramolini, Vann Bennett "}, {"type": "b", "children": [{"type": "t", "text": "The ankyrin-B C-terminal domain determines activity of ankyrin-B/G chimeras in rescue of abnormal inositol 1,4,5-trisphosphate and ryanodine receptor distribution in ankyrin-B (-/-) neonatal cardiomyocytes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M110958200"}], "href": "https://doi.org/10.1074/jbc.M110958200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11781319"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11781319"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Peter J Mohler, Woohyun Yoon, Vann Bennett "}, {"type": "b", "children": [{"type": "t", "text": "Ankyrin-B targets beta2-spectrin to an intracellular compartment in neonatal cardiomyocytes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M406018200"}], "href": "https://doi.org/10.1074/jbc.M406018200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15262991"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15262991"}]}]}]}
Synonyms	LQT4, ANK-2, BRANK-2
Proteins	ANK2_HUMAN
NCBI Gene ID	287
API
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

ANK2 has 9,150 functional associations with biological entities spanning 9 categories (molecular profile, organism, disease, phenotype or trait, chemical, functional term, phrase or reference, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 126 datasets.

Click the + buttons to view associations for ANK2 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

ANK2 Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Achilles Cell Line Gene Essentiality Profiles	cell lines with fitness changed by ANK2 gene knockdown relative to other cell lines from the Achilles Cell Line Gene Essentiality Profiles dataset.
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of ANK2 gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of ANK2 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of ANK2 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of ANK2 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of ANK2 gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of ANK2 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of ANK2 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of ANK2 gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of ANK2 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with ANK2 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with ANK2 gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of ANK2 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of ANK2 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of ANK2 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	ClinVar Gene-Phenotype Associations	phenotypes associated with ANK2 gene from the curated ClinVar Gene-Phenotype Associations dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of ANK2 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing ANK2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing ANK2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing ANK2 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores 2025	cellular components containing ANK2 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with ANK2 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with ANK2 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of ANK2 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with ANK2 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with ANK2 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with ANK2 gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with ANK2 gene in GWAS and other genetic association datasets from the dbGAP Gene-Trait Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of ANK2 protein relative to other small molecule perturbations from the DeepCoverMOA Drug Mechanisms of Action dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by ANK2 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores	diseases involving ANK2 gene from the DISEASES Curated Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving ANK2 gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with ANK2 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with ANK2 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with ANK2 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with ANK2 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with ANK2 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with ANK2 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at ANK2 gene from the ENCODE Histone Modification Site Profiles dataset.
	ENCODE Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of ANK2 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.