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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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CNNM1
cyclin and CBS domain divalent metal cation transport mediator 1
Chromosome 10 · 10q24.2
NCBI Gene: 26507Ensembl: ENSG00000119946.12HGNC: HGNC:102UniProt: A0A8Q3SIV9
22PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Transporter
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingtransmembrane transporter activitymagnesium ion homeostasisplasma membraneplacenta praeviatooth diseasebenign prostatic hyperplasiaadolescent idiopathic scoliosis
✦AI Summary

CNNM1 (cyclin and CBS domain divalent metal cation transport mediator 1) is a transmembrane protein that functions as a probable metal transporter involved in magnesium ion homeostasis 1. The protein contains a transmembrane domain, CBS-domain pair, and a CNBH domain that collectively mediate its function 2. CNNM1 plays a regulatory role in ion channel function by selectively binding and modulating TRPM7, an ion channel-kinase, with the CBS-pair and CNBH domains providing critical contact points for channel and kinase activity modulation 2. Post-translational modifications, specifically complex N-glycosylation mediated by ARL15 interaction, regulate CNNM1's magnesium transport capacity 3. Clinically, CNNM1 has emerged as a significant player in cancer pathogenesis. The gene harbors recurrent mutations in pulmonary carcinoid tumors affecting cancer-relevant pathways 4 and is implicated in prostate cancer angiogenesis, where elevated CNNM1 expression promotes vascular growth through upregulation of angiogenic markers 5. In hepatocellular carcinoma, CNNM1 is a target of miR-9-5p and is upregulated through sequestration by the long noncoding RNA SNHG7, promoting cancer cell proliferation 6. Additionally, CNNM1 mutations are associated with invasion and metastasis in acral melanoma 7 and contribute to diagnostic and prognostic signatures in glioma and epilepsy 8.

Sources cited
1
CNNM proteins maintain cellular and body magnesium homeostasis and contain CBS-domain pairs
PMID: 23027747
2
CNNM family proteins selectively bind and regulate TRPM7 channel; CBS-pair and CNBH domains modulate channel and kinase activities
PMID: 40962059
3
ARL15 regulates CNNM magnesium transport through promotion of complex N-glycosylation
PMID: 34089346
4
CNNM1 harbors recurrent mutations in pulmonary carcinoid tumors involved in cancer-relevant biological processes
PMID: 29351916
5
CNNM1 expression regulates angiogenesis in prostate cancer through CD31, VEGF, and PDGF expression
PMID: 30486934
6
CNNM1 is upregulated in hepatocellular carcinoma through miR-9-5p sequestration by SNHG7, promoting proliferation
PMID: 32397799
7
CNNM1 mutations are associated with invasion and metastasis in acral melanoma
PMID: 33890690
8
CNNM1 is a hub gene in diagnostic and prognostic models for glioma and epilepsy
PMID: 37192718
Disease Associationsⓘ20
placenta praeviaOpen Targets
0.35Weak
benign prostatic hyperplasiaOpen Targets
0.32Weak
tooth diseaseOpen Targets
0.32Weak
adolescent idiopathic scoliosisOpen Targets
0.30Weak
Abnormality of the skeletal systemOpen Targets
0.25Weak
glomerulonephritisOpen Targets
0.24Weak
breast ductal adenocarcinomaOpen Targets
0.11Weak
cervical carcinomaOpen Targets
0.05Suggestive
central nervous system cancerOpen Targets
0.04Suggestive
ovarian dysfunctionOpen Targets
0.03Suggestive
eye injuryOpen Targets
0.03Suggestive
Chronic Obstructive AsthmaOpen Targets
0.03Suggestive
joint diseaseOpen Targets
0.03Suggestive
HeadacheOpen Targets
0.03Suggestive
multinodular goiterOpen Targets
0.03Suggestive
medulloblastomaOpen Targets
0.02Suggestive
PainOpen Targets
0.02Suggestive
headache disorderOpen Targets
0.02Suggestive
migraine disorderOpen Targets
0.02Suggestive
atypical teratoid rhabdoid tumorOpen Targets
0.02Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
CNNM3Shared pathway100%CBSProtein interaction91%PTP4A2Protein interaction79%PTP4A1Protein interaction73%COX11Protein interaction70%TRPM6Protein interaction70%
Tissue Expression6 tissues
Brain
100%
Ovary
75%
Bone Marrow
18%
Liver
7%
Lung
3%
Heart
2%
Gene Interaction Network
Click a node to explore
CNNM1CNNM3CBSPTP4A2PTP4A1COX11TRPM6
PROTEIN STRUCTURE
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AlphaFoldAI-predicted · UniProt Q9NRU3
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.62LoF Tolerant
pLIⓘ
0.04Tolerant
Observed/Expected LoF0.44 [0.32–0.62]
RankingsWhere CNNM1 stands among ~20K protein-coding genes
  • #13,629of 20,598
    Most Researched22
  • #4,315of 17,882
    Most Constrained (LOEUF)0.62 · top quartile
Genes detectedCNNM1
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Pathways Impacted by Genomic Alterations in Pulmonary Carcinoid Tumors.
PMID: 29351916
Clin Cancer Res · 2018
1.00
2
Ginsenoside Rh2 Inhibits Angiogenesis in Prostate Cancer by Targeting CNNM1.
PMID: 30486934
J Nanosci Nanotechnol · 2019
0.90
3
Insight on the hub gene associated signatures and potential therapeutic agents in epilepsy and glioma.
PMID: 37192718
Brain Res Bull · 2023
0.80
4
The cytoplasmic domains of the CNNM family of transmembrane proteins modulate the ion channel-kinase TRPM7.
PMID: 40962059
J Biol Chem · 2025
0.70
5
ARL15 modulates magnesium homeostasis through N-glycosylation of CNNMs.
PMID: 34089346
Cell Mol Life Sci · 2021
0.60