CAMK2D Gene

Name	calcium/calmodulin-dependent protein kinase II delta
Description	The product of this gene belongs to the serine/threonine protein kinase family and to the Ca(2+)/calmodulin-dependent protein kinase subfamily. Calcium signaling is crucial for several aspects of plasticity at glutamatergic synapses. In mammalian cells, the enzyme is composed of four different chains: alpha, beta, gamma, and delta. The product of this gene is a delta chain. Alternative splicing results in multiple transcript variants encoding distinct isoforms. Distinct isoforms of this chain have different expression patterns.[provided by RefSeq, Nov 2008]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Calcium/calmodulin‐dependent protein kinase II delta (CAMK2D) has emerged as a multifunctional regulator in diverse tissues, with particularly critical roles in the heart, vasculature, cartilage, and brain. In cardiomyocytes, CAMK2D isoforms—especially the delta B variant—mediate hypertrophic signaling by phosphorylating substrates such as histone deacetylase 4 (HDAC4), which in turn relieves repression of transcription factors (for example, MEF2) and promotes the expression of fetal cardiac genes. Such signaling is central to regulating excitation–contraction coupling and adapting the myocardium under stress, as seen in conditions that lead to dilated cardiomyopathy ["}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": "]. Furthermore, aberrant splicing of CAMK2D—observed in settings of RBM20 mutations and loss of splicing regulators such as hnRNP U—has been linked to disturbed calcium handling and an increased propensity for arrhythmias in cardiomyopathy patients ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "]. In addition to its role in regulating contractile and mechanical properties (for example, via phosphorylation of titin’s N2B-unique sequence to modulate myocyte passive tension), CAMK2D has also been identified within networks associated with inflammatory and stress responses. It is part of a functional gene network linked to Kawasaki disease susceptibility, thereby connecting it to mechanisms of inflammation and cardiovascular pathology ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "]. During certain viral infections, such as those caused by SARS coronavirus, CAMK2D participates in intracellular pathways that impact host protein stability and immune responses ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "]. Outside the heart, CAMK2D is targeted by microRNAs—for instance, miR-146a in articular chondrocytes—to influence cartilage homeostasis and may contribute to the pathogenesis of osteoarthritis ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "]. Recent studies have also linked a long noncoding RNA, C2dat2, to CAMK2D in the context of cerebral ischemia–reperfusion injury, suggesting that CAMK2D-related signaling pathways may modulate neuronal stress responses ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "]. Finally, specific endothelial isoforms of CaMKIIδ, such as CaMKIIδ(6), have been shown to regulate RhoA activation and cytoskeletal rearrangements, thereby affecting vascular permeability under conditions of thrombin stimulation ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "]. Collectively, these findings underscore a central role for CAMK2D in coordinating kinase signaling that governs not only cardiac contractility and hypertrophy but also inflammation, tissue remodeling, and cellular responses to stress.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Gillian H Little, Yan Bai, Tyisha Williams, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Nuclear calcium/calmodulin-dependent protein kinase IIdelta preferentially transmits signals to histone deacetylase 4 in cardiac cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M604281200"}], "href": "https://doi.org/10.1074/jbc.M604281200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17179159"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17179159"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Carla J Aguiar, João A Rocha-Franco, Pedro A Sousa, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Succinate causes pathological cardiomyocyte hypertrophy through GPR91 activation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Commun Signal (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s12964-014-0078-2"}], "href": "https://doi.org/10.1186/s12964-014-0078-2"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25539979"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25539979"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "John Perkin, Rebecca Slater, Giorgia Del Favero, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Phosphorylating Titin's Cardiac N2B Element by ERK2 or CaMKIIδ Lowers the Single Molecule and Cardiac Muscle Force."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biophys J (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bpj.2015.11.002"}], "href": "https://doi.org/10.1016/j.bpj.2015.11.002"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26682816"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26682816"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Saranya P Wyles, Xing Li, Sybil C Hrstka, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Modeling structural and functional deficiencies of RBM20 familial dilated cardiomyopathy using human induced pluripotent stem cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddv468"}], "href": "https://doi.org/10.1093/hmg/ddv468"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26604136"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26604136"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Junqiang Ye, Nadine Beetz, Sean O'Keeffe, et al. "}, {"type": "b", "children": [{"type": "t", "text": "hnRNP U protein is required for normal pre-mRNA splicing and postnatal heart development and function."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1508461112"}], "href": "https://doi.org/10.1073/pnas.1508461112"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26039991"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26039991"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "David Burgner, Sonia Davila, Willemijn B Breunis, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A genome-wide association study identifies novel and functionally related susceptibility Loci for Kawasaki disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS Genet (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pgen.1000319"}], "href": "https://doi.org/10.1371/journal.pgen.1000319"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19132087"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19132087"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Yue Ma-Lauer, Javier Carbajo-Lozoya, Marco Y Hein, et al. "}, {"type": "b", "children": [{"type": "t", "text": "p53 down-regulates SARS coronavirus replication and is targeted by the SARS-unique domain and PLpro via E3 ubiquitin ligase RCHY1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1603435113"}], "href": "https://doi.org/10.1073/pnas.1603435113"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27519799"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27519799"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Xudong Zhang, Chuandong Wang, Jingyu Zhao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "miR-146a facilitates osteoarthritis by regulating cartilage homeostasis via targeting Camk2d and Ppp3r2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Death Dis (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/cddis.2017.146"}], "href": "https://doi.org/10.1038/cddis.2017.146"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28383548"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28383548"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Qian Xu, Ma Guohui, Dandan Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "lncRNA C2dat2 facilitates autophagy and apoptosis via the miR-30d-5p/DDIT4/mTOR axis in cerebral ischemia-reperfusion injury."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Aging (Albany NY) (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.18632/aging.202824"}], "href": "https://doi.org/10.18632/aging.202824"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33833132"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33833132"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Zhen Wang, Roman Ginnan, Iskandar F Abdullaev, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Calcium/Calmodulin-dependent protein kinase II delta 6 (CaMKIIdelta6) and RhoA involvement in thrombin-induced endothelial barrier dysfunction."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M110.120790"}], "href": "https://doi.org/10.1074/jbc.M110.120790"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20442409"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20442409"}]}]}]}
Synonyms	CAMKD
Proteins	KCC2D_HUMAN
NCBI Gene ID	817
API
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

CAMK2D has 9,567 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 133 datasets.

Click the + buttons to view associations for CAMK2D from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

CAMK2D 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 CAMK2D 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 CAMK2D 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 CAMK2D 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 CAMK2D 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 CAMK2D 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 CAMK2D gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	Biocarta Pathways	pathways involving CAMK2D protein from the Biocarta Pathways dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of CAMK2D 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 CAMK2D 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 CAMK2D 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 CAMK2D gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Gene Mutation Profiles	cell lines with CAMK2D gene mutations from the CCLE Cell Line Gene Mutation Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with CAMK2D protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with CAMK2D 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 CAMK2D gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of CAMK2D 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 CAMK2D gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing CAMK2D protein from integrated AP-MS and IF data from the CM4AI U2OS Cell Map Protein Localization Assemblies dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing CAMK2D protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing CAMK2D protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with CAMK2D 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 CAMK2D protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	CORUM Protein Complexes	protein complexs containing CAMK2D protein from the CORUM Protein Complexes dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of CAMK2D gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with CAMK2D gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with CAMK2D gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with CAMK2D gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with CAMK2D gene in GWAS and other genetic association datasets from the dbGAP Gene-Trait Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by CAMK2D gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with CAMK2D 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 CAMK2D 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 CAMK2D 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 CAMK2D gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with CAMK2D gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	DrugBank Drug Targets	interacting drugs for CAMK2D protein from the curated DrugBank Drug Targets dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at CAMK2D 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 CAMK2D gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of CAMK2D gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
	ESCAPE Omics Signatures of Genes and Proteins for Stem Cells	PubMedIDs of publications reporting gene signatures containing CAMK2D from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with CAMK2D gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.