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

    Gene ID: 54805, updated on 10-Dec-2024

    Summary

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    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

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    See CNNM2 in Genome Data Viewer
    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_000010.11Genomic Context describing neighboring genes Neighboring gene BORCS7-ASMT readthrough (NMD candidate) Neighboring gene uncharacterized LOC124902567 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr10:104657816-104658316 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr10:104658317-104658817 Neighboring gene uncharacterized LOC107984265 Neighboring gene arsenite methyltransferase Neighboring gene ribosomal protein L22 pseudogene 17 Neighboring gene Sharpr-MPRA regulatory region 3077 Neighboring gene H3K27ac hESC enhancer GRCh37_chr10:104677691-104678377 Neighboring gene H3K27ac hESC enhancer GRCh37_chr10:104677004-104677690 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 2775 Neighboring gene MPRA-validated peak1082 silencer Neighboring gene Sharpr-MPRA regulatory region 2614 Neighboring gene 5'-nucleotidase, cytosolic II Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3953 Neighboring gene ribosomal protein S15a pseudogene 29 Neighboring gene MARCKS like 1 pseudogene 1

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • 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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    Related articles in PubMed

    1. Hypomagnesaemia with varying degrees of extrarenal symptoms as a consequence of heterozygous CNNM2 variants. Bosman W, et al. Sci Rep, 2024 Mar 22. PMID 38519529, Free PMC Article
    2. Decreased CNNM2 expression in prefrontal cortex affects sensorimotor gating function, cognition, dendritic spine morphogenesis and risk of schizophrenia. Zhou DY, et al. Neuropsychopharmacology, 2024 Jan. PMID 37715107,
    3. Splice-variant 1 of the ancient domain protein 2 (ACDP2) complements the magnesium-deficient growth phenotype of Salmonella enterica sv. typhimurium strain MM281. Sponder G, et al. Magnes Res, 2010 Jun. PMID 20519162
    4. Purification, crystallization and preliminary crystallographic analysis of the CBS-domain pair of cyclin M2 (CNNM2). Gómez-García I, et al. Acta Crystallogr Sect F Struct Biol Cryst Commun, 2012 Oct 1. PMID 23027747, Free PMC Article
    5. The impact of the genome-wide supported variant in the cyclin M2 gene on gray matter morphology in schizophrenia. Ohi K, et al. Behav Brain Funct, 2013 Oct 25. PMID 24160291, Free PMC Article

    See all (61) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. 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.
    2. 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.
    3. 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).
    4. Novel variant in the CNNM2 gene associated with dominant hypomagnesemia.
      Title: Novel variant in the CNNM2 gene associated with dominant hypomagnesemia.
    5. 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.
    6. 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.
    7. 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.
    8. 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.
    9. Sensitivity of CNNM2 expression to extracellular Mg(2+) depletion depends on cell type.
      Title: Human CNNM2 is not a Mg(2+) transporter per se.
    10. 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
    		not available
    Renal hypomagnesemia 6
    MedGen: C3151295 OMIM: 613882 GeneReviews: Not available
    		not available

    EBI GWAS Catalog

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

    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

    Homology

    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

    1. NG_031932.2 RefSeqGene

      Range
      5002..176930
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. 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

    2. 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

    3. 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

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000010.11 Reference GRCh38.p14 Primary Assembly

      Range
      102918294..103090222
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060934.1 Alternate T2T-CHM13v2.0

      Range
      103804071..103976463
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q9H8M5.2 GenPept UniProtKB/Swiss-Prot:Q9H8M5

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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