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CNNM4 cyclin and CBS domain divalent metal cation transport mediator 4 [ Homo sapiens (human) ]

Gene ID: 26504, updated on 5-Mar-2024

Summary

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Official Symbol
CNNM4provided by HGNC
Official Full Name
cyclin and CBS domain divalent metal cation transport mediator 4provided by HGNC
Primary source
HGNC:HGNC:105
See related
Ensembl:ENSG00000158158 MIM:607805; AllianceGenome:HGNC:105
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
ACDP4
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 a role in metal ion transport. Mutations in this gene are associated with Jalili syndrome which consists of cone-rod dystrophy and amelogenesis imperfecta. [provided by RefSeq, Feb 2010]
Expression
Broad expression in colon (RPKM 26.1), thyroid (RPKM 9.4) and 23 other tissues See more
Orthologs
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Genomic context

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Location:
2q11.2
Exon count:
12
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 2 NC_000002.12 (96760902..96811874)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 2 NC_060926.1 (97267540..97318504)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 2 NC_000002.11 (97426639..97477611)

Chromosome 2 - NC_000002.12Genomic Context describing neighboring genes Neighboring gene fer-1 like family member 5 Neighboring gene H3K27ac hESC enhancer GRCh37_chr2:97326800-97327300 Neighboring gene H3K27ac hESC enhancer GRCh37_chr2:97327301-97327801 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr2:97351655-97352380 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:97359457-97359958 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:97360677-97361221 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:97361222-97361765 Neighboring gene lectin, mannose binding 2 like Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr2:97404177-97405116 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr2:97405117-97406054 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16224 Neighboring gene H3K4me1 hESC enhancers GRCh37_chr2:97426686-97427275 and GRCh37_chr2:97427276-97427864 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 11775 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16226 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16227 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:97435174-97436108 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16228 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16229 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16230 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16231 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16232 Neighboring gene microRNA 3127 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16233 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 11776 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 11777 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 11778 Neighboring gene CNNM3 divergent transcript Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:97494389-97494889 Neighboring gene uncharacterized LOC124907859 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr2:97498033-97499232 Neighboring gene cyclin and CBS domain divalent metal cation transport mediator 3

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. Novel CNNM4 variant and clinical features of Jalili syndrome. Rattanapornsompong K, et al. Clin Genet, 2023 Feb. PMID 36354001
  2. Expanding the genotypic spectrum of Jalili syndrome: Novel CNNM4 variants and uniparental isodisomy in a north American patient cohort. Prasov L, et al. Am J Med Genet A, 2020 Mar. PMID 32022389, Free PMC Article
  3. A novel pathogenic missense variant in CNNM4 underlying Jalili syndrome: Insights from molecular dynamics simulations. Parveen A, et al. Mol Genet Genomic Med, 2019 Sep. PMID 31347285, Free PMC Article
  4. Report of two unrelated families with Jalili syndrome and a novel nonsense heterozygous mutation in CNNM4 gene. Maia CMF, et al. Eur J Med Genet, 2018 Jul. PMID 29421602
  5. Jalili Syndrome: Cross-sectional and Longitudinal Features of Seven Patients With Cone-Rod Dystrophy and Amelogenesis Imperfecta. Hirji N, et al. Am J Ophthalmol, 2018 Apr. PMID 29421294, Free PMC Article

See all (57) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Novel CNNM4 variant and clinical features of Jalili syndrome.
    Title: Novel CNNM4 variant and clinical features of Jalili syndrome.
  2. CNNM proteins selectively bind to the TRPM7 channel to stimulate divalent cation entry into cells.
    Title: CNNM proteins selectively bind to the TRPM7 channel to stimulate divalent cation entry into cells.
  3. Expanding the genotypic spectrum of Jalili syndrome: Novel CNNM4 variants and uniparental isodisomy in a north American patient cohort.
    Title: Expanding the genotypic spectrum of Jalili syndrome: Novel CNNM4 variants and uniparental isodisomy in a north American patient cohort.
  4. The novel identified variant in CNNM4 is the first report from the Pakistani population. Sequence analysis of CNNM4 revealed a novel missense variant (c.1220G>T, p.Arg407Leu) in exon-1 encoding cystathionine-beta-synthase (CBS) domain.
    Title: A novel pathogenic missense variant in CNNM4 underlying Jalili syndrome: Insights from molecular dynamics simulations.
  5. Jalili Syndrome is a rare cone-rod dystrophy (CORD) and amelogenesis imperfecta (AI), We have further characterized its ocular phenotype, including describing SD-OCT, FAF, and electrophysiological features; and report several novel disease-causing sequence variants.
    Title: Jalili Syndrome: Cross-sectional and Longitudinal Features of Seven Patients With Cone-Rod Dystrophy and Amelogenesis Imperfecta.
  6. Here, we report the 2 first families with Jalili Syndrome in Brazil. Molecular analysis of the first family identified a previously described homozygous mutation (p.Leu324Pro) in exon 1 of CNNM4 gene. In the second family, affected patients demonstrated a compound heterozygous mutation in CNNM4, the p.Leu324Pro and the novel nonsense mutation p.Tyr581*.
    Title: Report of two unrelated families with Jalili syndrome and a novel nonsense heterozygous mutation in CNNM4 gene.
  7. Results identified linkage at chromosome 2p14-2q14 and found a homozygous mutation in the CNNM4 gene (p.R605X) causing Jalili syndrome. The truncated CNNM4 protein starting at R605 significantly increased the rate of apoptosis, and significantly increased the interaction between CNNM4 and IQCB1. This mutation may cause Jalili syndrome by a nonsense-mediated decay mechanism, affecting the function of IQCB1 and apoptosis.
    Title: Identification of a mutation in CNNM4 by whole exome sequencing in an Amish family and functional link between CNNM4 and IQCB1.
  8. Mutational analysis showed in all three brothers a novel likely pathogenic homozygous missense substitution in exon 1 (c.1076T>C, p.(Leu359Pro)) of CNNM4. Both parents were carriers for the variant.
    Title: Co-occurrence of Jalili syndrome and muscular overgrowth.
  9. We describe three siblings with clinical features of Jalili syndrome with a homozygous missense mutation in exon 4 of CNNM4, c.1781A>G (p.N594S).
    Title: A new familial case of Jalili syndrome caused by a novel mutation in CNNM4.
  10. These results suggest a new role of CNNM4 in sperm Ca(2+) homeostasis.
    Title: The Mg2+ transporter CNNM4 regulates sperm Ca2+ homeostasis and is essential for reproduction.
Submit: New GeneRIF Correction See all GeneRIFs (21)

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
Jalili syndrome
MedGen: C3495589 OMIM: 217080 GeneReviews: Not available
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EBI GWAS Catalog

Description
Large-scale genome-wide association analysis of bipolar disorder identifies a new susceptibility locus near ODZ4.
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)

Genotypes

Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Clone Names

  • FLJ37746, FLJ42791, KIAA1592

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables magnesium ion transmembrane transporter activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables sodium ion transmembrane transporter activity IBA
Inferred from Biological aspect of Ancestor
more info
  
Process Evidence Code Pubs
involved_in enamel mineralization IEA
Inferred from Electronic Annotation
more info
  
involved_in intracellular monoatomic cation homeostasis IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in magnesium ion homeostasis IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in magnesium ion transmembrane transport IEA
Inferred from Electronic Annotation
more info
  
involved_in magnesium ion transport IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in response to stimulus IEA
Inferred from Electronic Annotation
more info
  
involved_in sodium ion transmembrane transport IEA
Inferred from Electronic Annotation
more info
  
involved_in visual perception IEA
Inferred from Electronic Annotation
more info
  
Component Evidence Code Pubs
located_in basolateral plasma membrane IEA
Inferred from Electronic Annotation
more info
  
is_active_in plasma membrane IBA
Inferred from Biological aspect of Ancestor
more info
  
part_of protein-containing complex IDA
Inferred from Direct Assay
more info
 PubMed 

General protein information

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Preferred Names
metal transporter CNNM4
Names
ancient conserved domain protein 4
ancient conserved domain-containing protein 4
cyclin-M4

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_016608.1 RefSeqGene

    Range
    5001..55973
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_020184.4 → NP_064569.3  metal transporter CNNM4 precursor

    See identical proteins and their annotated locations for NP_064569.3

    Status: REVIEWED

    Source sequence(s)
    AB046812, BC063295
    Consensus CDS
    CCDS2024.2
    UniProtKB/Swiss-Prot
    B7Z1U0, C7SQM3, C7SQM4, C7SQM5, Q53RE5, Q6P4Q7, Q9H9G3, Q9HCI0, Q9NRN1
    Related
    ENSP00000366275.2, ENST00000377075.3
    Conserved Domains (3) summary
    COG0517
    Location:373 → 500
    CBS; CBS domain [Signal transduction mechanisms]
    cd04590
    Location:382 → 502
    CBS_pair_CorC_HlyC_assoc; This cd contains two tandem repeats of the cystathionine beta-synthase (CBS pair) domains associated with the CorC_HlyC domain. CorC_HlyC is a transporter associated domain. This small domain is found in Na+/H+ antiporters, in proteins involved in ...
    pfam01595
    Location:196 → 358
    DUF21; Domain of unknown function DUF21

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

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

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000002.12 Reference GRCh38.p14 Primary Assembly

    Range
    96760902..96811874
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_047443911.1 → XP_047299867.1  metal transporter CNNM4 isoform X1

  2. XM_005263914.5 → XP_005263971.1  metal transporter CNNM4 isoform X2

    Conserved Domains (3) summary
    COG0517
    Location:373 → 500
    CBS; CBS domain [Signal transduction mechanisms]
    cd04590
    Location:382 → 502
    CBS_pair_CorC_HlyC_assoc; This cd contains two tandem repeats of the cystathionine beta-synthase (CBS pair) domains associated with the CorC_HlyC domain. CorC_HlyC is a transporter associated domain. This small domain is found in Na+/H+ antiporters, in proteins involved in ...
    pfam01595
    Location:196 → 358
    DUF21; Domain of unknown function DUF21

  3. XM_047443912.1 → XP_047299868.1  metal transporter CNNM4 isoform X4

  4. XM_005263915.5 → XP_005263972.1  metal transporter CNNM4 isoform X3

    Conserved Domains (3) summary
    COG0517
    Location:373 → 500
    CBS; CBS domain [Signal transduction mechanisms]
    cd04590
    Location:382 → 502
    CBS_pair_CorC_HlyC_assoc; This cd contains two tandem repeats of the cystathionine beta-synthase (CBS pair) domains associated with the CorC_HlyC domain. CorC_HlyC is a transporter associated domain. This small domain is found in Na+/H+ antiporters, in proteins involved in ...
    pfam01595
    Location:196 → 358
    DUF21; Domain of unknown function DUF21

  5. XM_011510956.4 → XP_011509258.1  metal transporter CNNM4 isoform X5

    Conserved Domains (2) summary
    pfam01595
    Location:196 → 358
    DUF21; Domain of unknown function DUF21
    cl15354
    Location:382 → 474
    CBS_pair; The CBS domain, named after human CBS, is a small domain originally identified in cystathionine beta-synthase and is subsequently found in a wide range of different proteins. CBS domains usually occur in tandem repeats. They associate to form a so-called ...

  6. XM_017003799.2 → XP_016859288.1  metal transporter CNNM4 isoform X6

RNA

  1. XR_007071513.1 RNA Sequence

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060926.1 Alternate T2T-CHM13v2.0

    Range
    97267540..97318504
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054341363.1 → XP_054197338.1  metal transporter CNNM4 isoform X1

  2. XM_054341364.1 → XP_054197339.1  metal transporter CNNM4 isoform X2

  3. XM_054341366.1 → XP_054197341.1  metal transporter CNNM4 isoform X4

  4. XM_054341365.1 → XP_054197340.1  metal transporter CNNM4 isoform X3

  5. XM_054341367.1 → XP_054197342.1  metal transporter CNNM4 isoform X5

  6. XM_054341368.1 → XP_054197343.1  metal transporter CNNM4 isoform X6

RNA

  1. XR_008486323.1 RNA Sequence

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q6P4Q7.3 GenPept UniProtKB/Swiss-Prot:Q6P4Q7

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