CNNM3 Gene

Name	cyclin and CBS domain divalent metal cation transport mediator 3
Description	Predicted to enable transmembrane transporter activity. Predicted to be involved in magnesium ion homeostasis. Located in membrane. [provided by Alliance of Genome Resources, Mar 2025]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Recent studies have uncovered a multifaceted role for CNNM3—a member of the cyclin M family—in both cellular magnesium homeostasis and cancer biology. Genome‐wide association analyses have identified common variants in CNNM3 that correlate with serum magnesium levels, implicating CNNM3 in the regulation of systemic magnesium balance."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " Functional investigations reveal that CNNM3 acts as a magnesium transporter whose activity is modulated through direct physical interactions with regulatory proteins. In particular, CNNM3 forms a functional complex with the phosphatases of regenerating liver (PRL‐2 and PRL‐3) via its conserved CBS‐pair domain; this interaction is essential for the regulation of intracellular magnesium levels and has been shown to confer oncogenic advantages, as disruption of the complex reduces cancer cell proliferation under magnesium‐deprived conditions."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "2", "end_ref": "4"}]}, {"type": "t", "text": " In addition, CNNM3 has been shown to cooperate with ion channels such as TRPM7 to stimulate divalent cation entry, suggesting that CNNM3 not only promotes magnesium efflux but also contributes to magnesium influx by recruiting other transport machinery."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " Moreover, transcriptional regulation of CNNM3 by upstream kinases such as PDK2 has been implicated in promoting cisplatin resistance and tumor growth in lung adenocarcinoma models, highlighting its emerging role as a mediator of drug resistance in cancer."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " Collectively, these findings suggest that CNNM3 functions as a key regulator of magnesium transport whose interactions and regulatory mechanisms are critically linked to both normal cellular physiology and the pathogenesis of cancer.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Tamra E Meyer, Germaine C Verwoert, Shih-Jen Hwang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genome-wide association studies of serum magnesium, potassium, and sodium concentrations identify six Loci influencing serum magnesium levels."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS Genet (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pgen.1001045"}], "href": "https://doi.org/10.1371/journal.pgen.1001045"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20700443"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20700443"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "S Hardy, N Uetani, N Wong, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The protein tyrosine phosphatase PRL-2 interacts with the magnesium transporter CNNM3 to promote oncogenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/onc.2014.33"}], "href": "https://doi.org/10.1038/onc.2014.33"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24632616"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24632616"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Huizhi Zhang, Guennadi Kozlov, Xinlu Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PRL3 phosphatase active site is required for binding the putative magnesium transporter CNNM3."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41598-017-00147-2"}], "href": "https://doi.org/10.1038/s41598-017-00147-2"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28246390"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28246390"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Elie Kostantin, Serge Hardy, William C Valinsky, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Inhibition of PRL-2·CNNM3 Protein Complex Formation Decreases Breast Cancer Proliferation and Tumor Growth."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M115.705863"}], "href": "https://doi.org/10.1074/jbc.M115.705863"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26969161"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26969161"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Zhiyong Bai, Jianlin Feng, Gijs A C Franken, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CNNM proteins selectively bind to the TRPM7 channel to stimulate divalent cation entry into cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS Biol (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pbio.3001496"}], "href": "https://doi.org/10.1371/journal.pbio.3001496"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34928937"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34928937"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Tinghua Hu, Shuo Yu, Yang Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PDK2 induces cisplatin-resistance in lung adenocarcinoma via transcriptional regulation of CNNM3."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Drug Target (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1080/1061186X.2018.1550648"}], "href": "https://doi.org/10.1080/1061186X.2018.1550648"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30457021"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30457021"}]}]}]}
Synonyms	ACDP3
Proteins	CNNM3_HUMAN
NCBI Gene ID	26505
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

CNNM3 has 5,667 functional associations with biological entities spanning 9 categories (molecular profile, organism, chemical, functional term, phrase or reference, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 112 datasets.

Click the + buttons to view associations for CNNM3 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

CNNM3 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 CNNM3 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 CNNM3 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 CNNM3 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 CNNM3 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 CNNM3 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 CNNM3 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 CNNM3 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 CNNM3 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 CNNM3 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 CNNM3 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of CNNM3 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 CNNM3 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with CNNM3 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with CNNM3 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 CNNM3 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of CNNM3 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 CNNM3 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CM4AI KOLF21J CRISPRi Gene Perturbation Atlas	gene perturbations changing expression of CNNM3 gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing CNNM3 protein from integrated AP-MS and IF data from the CM4AI U2OS Cell Map Protein Localization Assemblies dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of CNNM3 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing CNNM3 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing CNNM3 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with CNNM3 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 CNNM3 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with CNNM3 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with CNNM3 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with CNNM3 gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with CNNM3 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 CNNM3 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with CNNM3 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 CNNM3 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 CNNM3 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with CNNM3 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 CNNM3 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 CNNM3 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of CNNM3 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 CNNM3 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with CNNM3 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GAD High Level Gene-Disease Associations	diseases associated with CNNM3 gene in GWAS and other genetic association datasets from the GAD High Level Gene-Disease Associations dataset.
	GDSC Cell Line Gene Expression Profiles	cell lines with high or low expression of CNNM3 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.