ACTN2 Gene

HGNC Family	EF-hand domain containing
Name	actinin, alpha 2
Description	Alpha actinins belong to the spectrin gene superfamily which represents a diverse group of cytoskeletal proteins, including the alpha and beta spectrins and dystrophins. Alpha actinin is an actin-binding protein with multiple roles in different cell types. In nonmuscle cells, the cytoskeletal isoform is found along microfilament bundles and adherens-type junctions, where it is involved in binding actin to the membrane. In contrast, skeletal, cardiac, and smooth muscle isoforms are localized to the Z-disc and analogous dense bodies, where they help anchor the myofibrillar actin filaments. This gene encodes a muscle-specific, alpha actinin isoform that is expressed in both skeletal and cardiac muscles. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2013]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Alpha‐actinin‑2 (ACTN2) is a multifunctional, actin‐crosslinking protein that plays a central role in organizing the contractile apparatus of striated muscles as well as in coordinating signaling complexes in non‐muscle cells. In the Z‐disc of both skeletal and cardiac myofibers, ACTN2 crosslinks actin filaments and serves as a scaffold for other structural proteins such as titin, thereby ensuring sarcomeric integrity and optimal force transmission (see."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " ACTN2 also functions in a compensatory capacity; for example, when the fast fiber–specific isoform α‐actinin‑3 is absent due to a common stop‐codon polymorphism, ACTN2 substitutes to maintain the structural and functional properties of the myofibril (see."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}, {"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond its structural role, ACTN2 is intimately involved in intracellular signaling. It interacts with key enzymes and ion channels—such as calcineurin and components of the Ca<sup>2+</sup> signaling machinery—to modulate hypertrophic responses and excitation–contraction coupling in cardiomyocytes (see."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " In neurons, ACTN2 contributes to the stabilization of signaling complexes by binding to kinases like CaMKII and other postsynaptic density proteins, which is critical for maintaining synaptic architecture and function (see."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " Moreover, mutations in the ACTN2 gene can disrupt these diverse functional interactions, leading to cardiomyopathies such as hypertrophic cardiomyopathy, underscoring its importance in normal cardiac physiology (see."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Euripedes de Almeida Ribeiro, Nikos Pinotsis, Andrea Ghisleni, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The structure and regulation of human muscle α-actinin."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cell.2014.10.056"}], "href": "https://doi.org/10.1016/j.cell.2014.10.056"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25433700"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25433700"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Barbara Norman, Mona Esbjörnsson, Håkan Rundqvist, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Strength, power, fiber types, and mRNA expression in trained men and women with different ACTN3 R577X genotypes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Appl Physiol (1985) (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/japplphysiol.91435.2008"}], "href": "https://doi.org/10.1152/japplphysiol.91435.2008"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19150855"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19150855"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Nan Yang, Daniel G MacArthur, Jason P Gulbin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ACTN3 genotype is associated with human elite athletic performance."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1086/377590"}], "href": "https://doi.org/10.1086/377590"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12879365"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12879365"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Hui-Hua Li, Vishram Kedar, Chunlian Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Atrogin-1/muscle atrophy F-box inhibits calcineurin-dependent cardiac hypertrophy by participating in an SCF ubiquitin ligase complex."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Invest (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1172/JCI22220"}], "href": "https://doi.org/10.1172/JCI22220"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15489953"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15489953"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Ling Lu, Qian Zhang, Valeriy Timofeyev, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Molecular coupling of a Ca2+-activated K+ channel to L-type Ca2+ channels via alpha-actinin2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Circ Res (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1161/01.RES.0000253095.44186.72"}], "href": "https://doi.org/10.1161/01.RES.0000253095.44186.72"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17110593"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17110593"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "A J Robison, Martha A Bass, Yuxia Jiao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Multivalent interactions of calcium/calmodulin-dependent protein kinase II with the postsynaptic density proteins NR2B, densin-180, and alpha-actinin-2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M502191200"}], "href": "https://doi.org/10.1074/jbc.M502191200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16120608"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16120608"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Jill A Morris, Geeta Kandpal, Lei Ma, et al. "}, {"type": "b", "children": [{"type": "t", "text": "DISC1 (Disrupted-In-Schizophrenia 1) is a centrosome-associated protein that interacts with MAP1A, MIPT3, ATF4/5 and NUDEL: regulation and loss of interaction with mutation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddg162"}], "href": "https://doi.org/10.1093/hmg/ddg162"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12812986"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12812986"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Christine Chiu, Richard D Bagnall, Jodie Ingles, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mutations in alpha-actinin-2 cause hypertrophic cardiomyopathy: a genome-wide analysis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Am Coll Cardiol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jacc.2009.11.016"}], "href": "https://doi.org/10.1016/j.jacc.2009.11.016"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20022194"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20022194"}]}]}]}
Synonyms	CMH23, CMD1AA
Proteins	ACTN2_HUMAN
NCBI Gene ID	88
API
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

ACTN2 has 6,995 functional associations with biological entities spanning 9 categories (molecular profile, organism, functional term, phrase or reference, chemical, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 136 datasets.

Click the + buttons to view associations for ACTN2 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

ACTN2 Gene

Functional Associations

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

	Dataset	Summary
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of ACTN2 gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of ACTN2 gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles	tissue samples with high or low expression of ACTN2 gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of ACTN2 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 ACTN2 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 ACTN2 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	Biocarta Pathways	pathways involving ACTN2 protein from the Biocarta Pathways dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of ACTN2 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 ACTN2 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 ACTN2 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	Carcinogenome Chemical Perturbation Carcinogenicity Signatures	small molecule perturbations changing expression of ACTN2 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of ACTN2 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 ACTN2 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with ACTN2 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 ACTN2 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of ACTN2 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 ACTN2 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 ACTN2 gene from the curated ClinVar Gene-Phenotype Associations dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with ACTN2 gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CM4AI KOLF21J CRISPRi Gene Perturbation Atlas	gene perturbations changing expression of ACTN2 gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of ACTN2 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing ACTN2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing ACTN2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing ACTN2 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 ACTN2 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 ACTN2 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 ACTN2 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 ACTN2 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with ACTN2 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with ACTN2 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with ACTN2 gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with ACTN2 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 ACTN2 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 ACTN2 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores	diseases involving ACTN2 gene from the DISEASES Curated Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving ACTN2 gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with ACTN2 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 ACTN2 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 ACTN2 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 ACTN2 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.