CNNM2 cyclin and CBS domain divalent metal cation transport mediator 2 [Homo sapiens (human)] - Gene

Summary

Official Symbol: CNNM2provided by HGNC
Official Full Name: cyclin and CBS domain divalent metal cation transport mediator 2provided by HGNC
Primary source: HGNC:HGNC:103
See related: Ensembl:ENSG00000148842 MIM:607803; AllianceGenome:HGNC:103
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: ACDP2; HOMG6; HOMGSMR
Summary: This gene encodes a member of the ancient conserved domain containing protein family. Members of this protein family contain a cyclin box motif and have structural similarity to the cyclins. The encoded protein may play an important role in magnesium homeostasis by mediating the epithelial transport and renal reabsorption of Mg2+. Mutations in this gene are associated with renal hypomagnesemia. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2011]
Expression: Ubiquitous expression in kidney (RPKM 2.4), placenta (RPKM 1.9) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 10q24.32

Exon count:: 9

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	10	NC_000010.11 (102918294..103090222)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	10	NC_060934.1 (103804071..103976463)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	10	NC_000010.10 (104678051..104849979)

Chromosome 10 - NC_000010.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Hypomagnesaemia with varying degrees of extrarenal symptoms as a consequence of heterozygous CNNM2 variants.
Title: Hypomagnesaemia with varying degrees of extrarenal symptoms as a consequence of heterozygous CNNM2 variants.
Decreased CNNM2 expression in prefrontal cortex affects sensorimotor gating function, cognition, dendritic spine morphogenesis and risk of schizophrenia.
Title: Decreased CNNM2 expression in prefrontal cortex affects sensorimotor gating function, cognition, dendritic spine morphogenesis and risk of schizophrenia.
The phenotypic and genetic spectrum of patients with heterozygous mutations in cyclin M2 (CNNM2).
Title: The phenotypic and genetic spectrum of patients with heterozygous mutations in cyclin M2 (CNNM2).
Novel variant in the CNNM2 gene associated with dominant hypomagnesemia.
Title: Novel variant in the CNNM2 gene associated with dominant hypomagnesemia.
This study determined the first crystal structures of the cyclic nucleotide-binding homology (CNBH) domain domains of CNNM2 and CNNM3 at 2.6 and 1.9 A resolutions.
Title: The cyclic nucleotide-binding homology domain of the integral membrane protein CNNM mediates dimerization and is required for Mg(2+) efflux activity.
CNNM2 single nucleotide polymorphisms association with the risk of hypertension in Chinese Han population.
Title: Associations between polymorphisms of the CXCL12 and CNNM2 gene and hypertension risk: A case-control study.
In this large-scale, Han Chinese population-based genetic association study for genetic susceptibility to schizophrenia of a three-gene cluster region, AS3MT-CNNM2-NT5C2, two SNPs with independent effects, rs11191419 and rs11191514, were identified. Rs11191419 is located on the 5' (potential promoter) region of AS3MT, while rs11191514 is located in one of the introns of CNNM2.
Title: Two-stage replication of previous genome-wide association studies of AS3MT-CNNM2-NT5C2 gene cluster region in a large schizophrenia case-control sample from Han Chinese population.
this study implicates altered neural expression of BORCS7, AS3MT, and NT5C2 in susceptibility to schizophrenia arising from genetic variation at the chromosome 10q24 locus
Title: Genome-wide significant schizophrenia risk variation on chromosome 10q24 is associated with altered cis-regulation of BORCS7, AS3MT, and NT5C2 in the human brain.
Sensitivity of CNNM2 expression to extracellular Mg(2+) depletion depends on cell type.
Title: Human CNNM2 is not a Mg(2+) transporter per se.
meta-analysis of two Caucasian cohorts did not show an association between five aneurysm associated loci and sporadic brain Arteriovenous malformations.
Title: Evaluation of genetic risk loci for intracranial aneurysms in sporadic arteriovenous malformations of the brain.

Submit: New GeneRIF Correction See all GeneRIFs (20)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Hypomagnesemia, seizures, and intellectual disability 1 MedGen: C4225333 OMIM: 616418 GeneReviews: Not available	Compare labs
Renal hypomagnesemia 6 MedGen: C3151295 OMIM: 613882 GeneReviews: Not available	Compare labs

EBI GWAS Catalog

Description
A comprehensive family-based replication study of schizophrenia genes. EBI GWAS Catalog EBI GWAS CatalogPubMed
A genome-wide association study in Europeans and South Asians identifies five new loci for coronary artery disease. EBI GWAS Catalog EBI GWAS CatalogPubMed
Biological insights from 108 schizophrenia-associated genetic loci. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association analysis identifies 13 new risk loci for schizophrenia. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study identifies chromosome 10q24.32 variants associated with arsenic metabolism and toxicity phenotypes in Bangladesh. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study identifies eight loci associated with blood pressure. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study identifies five new schizophrenia loci. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study in a Swedish population yields support for greater CNV and MHC involvement in schizophrenia compared with bipolar disorder. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study of intracranial aneurysm identifies three new risk loci. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study reveals genetic risk underlying Parkinson's disease. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide meta-analysis identifies new susceptibility loci for migraine. EBI GWAS Catalog EBI GWAS CatalogPubMed
Identification of 23 new prostate cancer susceptibility loci using the iCOGS custom genotyping array. EBI GWAS Catalog EBI GWAS CatalogPubMed
Identification of risk loci with shared effects on five major psychiatric disorders: a genome-wide analysis. EBI GWAS Catalog EBI GWAS CatalogPubMed
Large-scale association analysis identifies 13 new susceptibility loci for coronary artery disease. EBI GWAS Catalog EBI GWAS CatalogPubMed
Meta-analysis of genome-wide association studies identifies common variants associated with blood pressure variation in east Asians. EBI GWAS Catalog EBI GWAS CatalogPubMed
Shared genetic susceptibility to ischemic stroke and coronary artery disease: a genome-wide analysis of common variants. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH77757 (e-PCR)
- UniSTS:5670

D10S284 (e-PCR)
- UniSTS:148006

D10S287 (e-PCR)
- UniSTS:148009

A006S48 (e-PCR)
- UniSTS:22828

D10S304 (e-PCR)
- UniSTS:148025

CNNM2_9820 (e-PCR)
- UniSTS:468348

D10S1738 (e-PCR), detects polymorphism
- UniSTS:54923

GDB:335751 (e-PCR)
- UniSTS:156601

D15S1390 (e-PCR)
- UniSTS:474340

FB7B11 (e-PCR)
- UniSTS:74478

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables ATP binding	IEA Inferred from Electronic Annotation more info
enables magnesium ion transmembrane transporter activity	IBA Inferred from Biological aspect of Ancestor more info

Process	Evidence Code	Pubs
involved_in magnesium ion homeostasis	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within magnesium ion homeostasis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in magnesium ion transmembrane transport	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
located_in basolateral plasma membrane	IMP Inferred from Mutant Phenotype more info	PubMed
located_in glutamatergic synapse	IEA Inferred from Electronic Annotation more info
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info

General protein information

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Preferred Names: metal transporter CNNM2

Names: ancient conserved domain-containing protein 2; cyclin M2

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_031932.2 RefSeqGene

Range

5002..176930

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_017649.5 → NP_060119.3 metal transporter CNNM2 isoform 1

See identical proteins and their annotated locations for NP_060119.3

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).

Source sequence(s)

AK023066, AL139817, AL356608, BC021222, BU621540, BX113753

Consensus CDS

CCDS44474.1

UniProtKB/Swiss-Prot

Q5T569, Q5T570, Q8WU59, Q9H8M5, Q9H952, Q9NRK5, Q9NXT4

Related

ENSP00000358894.3, ENST00000369878.9

Conserved Domains (1) summary

cl27264
Location:256 → 586

CorC_HlyC; Transporter associated domain
NM_199076.3 → NP_951058.1 metal transporter CNNM2 isoform 2

See identical proteins and their annotated locations for NP_951058.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks an exon in the 3' coding region, but maintains the reading frame, compared to variant 1. The encoded isoform (2) is shorter than isoform 1.

Source sequence(s)

AK023066, AK023479, AL139817, AL356608, BC021222, BU621540, BX113753

Consensus CDS

CCDS44475.1

UniProtKB/Swiss-Prot

Q9H8M5

Related

ENSP00000392875.2, ENST00000433628.2

Conserved Domains (1) summary

cl27264
Location:256 → 586

CorC_HlyC; Transporter associated domain
NM_199077.3 → NP_951059.1 metal transporter CNNM2 isoform 3

See identical proteins and their annotated locations for NP_951059.1

Status: REVIEWED

Description

Transcript Variant: This variant (3) uses an alternate terminal exon and lacks a large portion of the 3' coding region, compared to variant 1. The encoded isoform (3) is shorter and has a distinct C-terminus, compared to isoform 1.

Source sequence(s)

AL356608, BC021222

Consensus CDS

CCDS7543.1

UniProtKB/Swiss-Prot

Q9H8M5

Related

ENSP00000358891.3, ENST00000369875.3

Conserved Domains (1) summary

cl27264
Location:256 → 543

CorC_HlyC; Transporter associated domain