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 rena... See more...

Aliases for CNNM2 Gene

Aliases for CNNM2 Gene

  • Cyclin And CBS Domain Divalent Metal Cation Transport Mediator 2 2 3 5
  • Ancient Conserved Domain-Containing Protein 2 3 4
  • Metal Transporter CNNM2 3 4
  • Cyclin M2 2 3
  • ACDP2 3 4
  • Cyclin-M2 4
  • HOMGSMR 3
  • HOMG6 3
  • CNNM2 5

External Ids for CNNM2 Gene

Previous HGNC Symbols for CNNM2 Gene

  • ACDP2

Previous GeneCards Identifiers for CNNM2 Gene

  • GC10P103571
  • GC10P103911
  • GC10P104809
  • GC10P104342
  • GC10P104668
  • GC10P098313

Summaries for CNNM2 Gene

Entrez Gene Summary for CNNM2 Gene

  • 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]

GeneCards Summary for CNNM2 Gene

CNNM2 (Cyclin And CBS Domain Divalent Metal Cation Transport Mediator 2) is a Protein Coding gene. Diseases associated with CNNM2 include Hypomagnesemia, Seizures, And Mental Retardation 1 and Hypomagnesemia 6, Renal. Gene Ontology (GO) annotations related to this gene include adenyl nucleotide binding. An important paralog of this gene is CNNM4.

UniProtKB/Swiss-Prot Summary for CNNM2 Gene

  • Divalent metal cation transporter. Mediates transport of divalent metal cations in an order of Mg(2+) > Co(2+) > Mn(2+) > Sr(2+) > Ba(2+) > Cu(2+) > Fe(2+) (By similarity).

No data available for CIViC Summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for CNNM2 Gene

Genomics for CNNM2 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for CNNM2 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around CNNM2 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for CNNM2

Top Transcription factor binding sites by QIAGEN in the CNNM2 gene promoter:
  • AhR
  • CREB
  • CUTL1
  • Hlf
  • p53
  • PPAR-alpha
  • SEF-1 (1)
  • Sp1
  • YY1

Genomic Locations for CNNM2 Gene

Latest Assembly
chr10:102,918,293-103,090,222
(GRCh38/hg38)
Size:
171,930 bases
Orientation:
Plus strand

Previous Assembly
chr10:104,678,051-104,849,979
(GRCh37/hg19 by Entrez Gene)
Size:
171,929 bases
Orientation:
Plus strand

chr10:104,678,050-104,849,978
(GRCh37/hg19 by Ensembl)
Size:
171,929 bases
Orientation:
Plus strand

Genomic View for CNNM2 Gene

Genes around CNNM2 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
CNNM2 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for CNNM2 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for CNNM2 Gene

Proteins for CNNM2 Gene

  • Protein details for CNNM2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9H8M5-CNNM2_HUMAN
    Recommended name:
    Metal transporter CNNM2
    Protein Accession:
    Q9H8M5
    Secondary Accessions:
    • Q5T569
    • Q5T570
    • Q8WU59
    • Q9H952
    • Q9NRK5
    • Q9NXT4

    Protein attributes for CNNM2 Gene

    Size:
    875 amino acids
    Molecular mass:
    96623 Da
    Quaternary structure:
    No Data Available
    SequenceCaution:
    • Sequence=AAF86374.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; Sequence=BAA90926.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; Sequence=BAB14386.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
    Miscellaneous:
    • Shares weak sequence similarity with the cyclin family, hence its name. However, it has no cyclin-like function in vivo.

    Three dimensional structures from OCA and Proteopedia for CNNM2 Gene

    Alternative splice isoforms for CNNM2 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for CNNM2 Gene

Post-translational modifications for CNNM2 Gene

  • Glycosylation at Asn112
  • Ubiquitination at Lys413
  • Modification sites at PhosphoSitePlus

Antibodies for research

  • Abcam antibodies for CNNM2
  • Boster Bio Antibodies for CNNM2

No data available for DME Specific Peptides for CNNM2 Gene

Domains & Families for CNNM2 Gene

Gene Families for CNNM2 Gene

HGNC:
Human Protein Atlas (HPA):
  • Disease related genes
  • Predicted membrane proteins

Protein Domains for CNNM2 Gene

InterPro:
Blocks:
  • CBS domain
  • CBS
ProtoNet:

Suggested Antigen Peptide Sequences for CNNM2 Gene

GenScript: Design optimal peptide antigens:
  • Cyclin-M2 (CNNM2_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q9H8M5

UniProtKB/Swiss-Prot:

CNNM2_HUMAN :
  • Belongs to the ACDP family.
Family:
  • Belongs to the ACDP family.
genes like me logo Genes that share domains with CNNM2: view

Function for CNNM2 Gene

Molecular function for CNNM2 Gene

UniProtKB/Swiss-Prot Function:
Divalent metal cation transporter. Mediates transport of divalent metal cations in an order of Mg(2+) > Co(2+) > Mn(2+) > Sr(2+) > Ba(2+) > Cu(2+) > Fe(2+) (By similarity).

Phenotypes From GWAS Catalog for CNNM2 Gene

Gene Ontology (GO) - Molecular Function for CNNM2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005524 ATP binding IEA --
GO:0015095 magnesium ion transmembrane transporter activity IBA 21873635
GO:0022857 transmembrane transporter activity IBA 21873635
genes like me logo Genes that share ontologies with CNNM2: view
genes like me logo Genes that share phenotypes with CNNM2: view

Human Phenotype Ontology for CNNM2 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for CNNM2 Gene

MGI Knock Outs for CNNM2:
  • Cnnm2 Cnnm2<tm1.1(KOMP)Vlcg>

miRNA for CNNM2 Gene

miRTarBase miRNAs that target CNNM2

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for CNNM2

Clone products for research

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targets and HOMER Transcription for CNNM2 Gene

Localization for CNNM2 Gene

Subcellular locations from UniProtKB/Swiss-Prot for CNNM2 Gene

Cell membrane. Multi-pass membrane protein.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for CNNM2 gene
Compartment Confidence
plasma membrane 5
extracellular 1
cytoskeleton 1
mitochondrion 1
nucleus 1
endoplasmic reticulum 1
cytosol 1
peroxisome 0

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for CNNM2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005886 plasma membrane IBA 21873635
GO:0016020 membrane IEA --
GO:0016021 integral component of membrane IEA --
GO:0016323 basolateral plasma membrane IMP 21397062
GO:0043231 intracellular membrane-bounded organelle IBA,IDA --
genes like me logo Genes that share ontologies with CNNM2: view

Pathways & Interactions for CNNM2 Gene

PathCards logo

SuperPathways for CNNM2 Gene

No Data Available

Gene Ontology (GO) - Biological Process for CNNM2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006810 transport IBA 21873635
GO:0006811 ion transport IEA --
GO:0010960 magnesium ion homeostasis IMP 21397062
GO:0015693 magnesium ion transport IEA --
GO:0055085 transmembrane transport IEA --
genes like me logo Genes that share ontologies with CNNM2: view

No data available for Pathways by source and SIGNOR curated interactions for CNNM2 Gene

Drugs & Compounds for CNNM2 Gene

(1) Drugs for CNNM2 Gene - From: DrugBank

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Magnesium carbonate Approved, Investigational Pharma Transporter, substrate 0
genes like me logo Genes that share compounds with CNNM2: view

Transcripts for CNNM2 Gene

mRNA/cDNA for CNNM2 Gene

3 REFSEQ mRNAs :
8 NCBI additional mRNA sequence :
4 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for CNNM2

Clone products for research

Alternative Splicing Database (ASD) splice patterns (SP) for CNNM2 Gene

ExUns: 1a · 1b ^ 2 ^ 3 ^ 4 ^ 5 ^ 6a · 6b ^ 7 ^ 8a · 8b ^ 9a · 9b
SP1: - -
SP2: - - -
SP3: -
SP4:

Relevant External Links for CNNM2 Gene

GeneLoc Exon Structure for
CNNM2

Expression for CNNM2 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for CNNM2 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for CNNM2 Gene

This gene is overexpressed in Serum (68.7).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for CNNM2 Gene



Protein tissue co-expression partners for CNNM2 Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for CNNM2

SOURCE GeneReport for Unigene cluster for CNNM2 Gene:

Hs.643509

mRNA Expression by UniProt/SwissProt for CNNM2 Gene:

Q9H8M5-CNNM2_HUMAN
Tissue specificity: Widely expressed. Expressed at higher level in brain, kidney and placenta, while it is weakly expressed in skeletal muscle. In the kidney, it is expressed in the distal convoluted tubule and the thick ascending limb of Henle loop.

Evidence on tissue expression from TISSUES for CNNM2 Gene

  • Intestine(4.4)
  • Kidney(2.5)
  • Nervous system(2.5)

Phenotype-based relationships between genes and organs from Gene ORGANizer for CNNM2 Gene

Germ Layers:
  • ectoderm
  • endoderm
  • mesoderm
Systems:
  • cardiovascular
  • endocrine
  • nervous
  • skeletal muscle
  • skeleton
  • urinary
Regions:
Head and neck:
  • brain
  • ear
  • head
  • meninges
  • neck
  • parathyroid
  • skull
  • thyroid
Thorax:
  • heart
Abdomen:
  • kidney
  • pancreas
General:
  • blood vessel
  • peripheral nerve
  • peripheral nervous system
genes like me logo Genes that share expression patterns with CNNM2: view

Primer products for research

No data available for mRNA differential expression in normal tissues for CNNM2 Gene

Orthologs for CNNM2 Gene

This gene was present in the common ancestor of eukaryotes.

Orthologs for CNNM2 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia CNNM2 30 31
  • 99.7 (n)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia CNNM2 31
  • 97 (a)
OneToOne
Dog
(Canis familiaris)
Mammalia CNNM2 30 31
  • 94.7 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia CNNM2 30 31
  • 93.63 (n)
OneToOne
Oppossum
(Monodelphis domestica)
Mammalia CNNM2 31
  • 93 (a)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Cnnm2 30
  • 91.96 (n)
Mouse
(Mus musculus)
Mammalia Cnnm2 30 17 31
  • 91.66 (n)
OneToOne
Chicken
(Gallus gallus)
Aves CNNM2 30 31
  • 87.66 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia CNNM2 31
  • 84 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia cnnm4 30
  • 81.36 (n)
Zebrafish
(Danio rerio)
Actinopterygii cnnm2a 31
  • 81 (a)
OneToMany
CNNM2 (2 of 2) 31
  • 80 (a)
OneToMany
LOC565702 30
  • 76.66 (n)
Fruit Fly
(Drosophila melanogaster)
Insecta uex 30 31
  • 55.62 (n)
OneToMany
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP002094 30
  • 54.9 (n)
Worm
(Caenorhabditis elegans)
Secernentea CELE_C52D10.12 30
  • 48.91 (n)
C33D12.2 32
  • 44 (a)
C52D10.12 31 32
  • 32 (a)
ManyToMany
R04E5.2 31 32
  • 30 (a)
ManyToMany
Baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes MAM3 31
  • 25 (a)
OneToMany
Thale Cress
(Arabidopsis thaliana)
eudicotyledons AT4G14230 30
  • 46.8 (n)
Rice
(Oryza sativa)
Liliopsida Os05g0395300 30
  • 48.97 (n)
Species where no ortholog for CNNM2 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Squirt (Ciona savignyi)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)

Evolution for CNNM2 Gene

ENSEMBL:
Gene Tree for CNNM2 (if available)
TreeFam:
Gene Tree for CNNM2 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for CNNM2: view image

Paralogs for CNNM2 Gene

Paralogs for CNNM2 Gene

(4) SIMAP similar genes for CNNM2 Gene using alignment to 1 proteins:

  • CNNM2_HUMAN
genes like me logo Genes that share paralogs with CNNM2: view

Variants for CNNM2 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for CNNM2 Gene

SNP ID Clinical significance and condition Chr 10 pos Variation AA Info Type
864795 Uncertain Significance: Spastic paraplegia 45, autosomal recessive 103,089,830(+) T/G
NM_001351169.2(NT5C2):c.1528A>C (p.Thr510Pro)
MISSENSE_VARIANT,THREE_PRIME_UTR
871141 Uncertain Significance: not provided 102,918,686(+) A/G
NM_017649.5(CNNM2):c.206A>G (p.Asn69Ser)
MISSENSE
877907 Uncertain Significance: Hypomagnesemia 6, renal 103,076,252(+) G/A
NM_017649.5(CNNM2):c.2400G>A (p.Ser800=)
SYNONYMOUS
877908 Uncertain Significance: Hypomagnesemia 6, renal 103,076,982(+) G/T
NM_017649.5(CNNM2):c.2430G>T (p.Gln810His)
MISSENSE
877909 Benign: Hypomagnesemia 6, renal 103,077,214(+) C/T
NM_017649.5(CNNM2):c.*34C>T
THREE_PRIME_UTR

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for CNNM2 Gene

All consequence types are included: molecular consequences (e.g. missense, synonymous), and location-based (e.g. intron, upstream).

Structural Variations from Database of Genomic Variants (DGV) for CNNM2 Gene

Variant ID Type Subtype PubMed ID
esv2449517 CNV insertion 19546169
nsv1048637 CNV gain 25217958
nsv7528 CNV deletion 18451855

Variation tolerance for CNNM2 Gene

Residual Variation Intolerance Score: 8.57% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 3.50; 55.33% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for CNNM2 Gene

Human Gene Mutation Database (HGMD)
CNNM2
SNPedia medical, phenotypic, and genealogical associations of SNPs for
CNNM2

SNP Genotyping and Copy Number Assays for research

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for CNNM2 Gene

Disorders for CNNM2 Gene

MalaCards: The human disease database

(12) MalaCards diseases for CNNM2 Gene - From: OMI, CVR, GTR, ORP, SWI, COP, and GCD

UniProtKB/Swiss-Prot

CNNM2_HUMAN
  • Hypomagnesemia 6 (HOMG6) [MIM:613882]: A renal disease characterized by severely lowered serum magnesium levels in the absence of other electrolyte disturbances. Affected individuals show an inappropriately normal urinary magnesium excretion, demonstrating a defect in tubular reabsorption. Age of clinical onset is highly variable and some affected individuals are asymptomatic. {ECO:0000269 PubMed:21397062}. Note=The disease is caused by variants affecting the gene represented in this entry.
  • Hypomagnesemia, seizures, and mental retardation 1 (HOMGSMR1) [MIM:616418]: A disease characterized by renal wasting of magnesium, low serum magnesium, seizures, and variable degrees of delayed psychomotor development. {ECO:0000269 PubMed:24699222}. Note=The disease is caused by variants affecting the gene represented in this entry.

Additional Disease Information for CNNM2

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
Atlas
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
Open Targets Platform
genes like me logo Genes that share disorders with CNNM2: view

No data available for Genatlas for CNNM2 Gene

Publications for CNNM2 Gene

  1. CNNM2 mutations cause impaired brain development and seizures in patients with hypomagnesemia. (PMID: 24699222) Arjona FJ … Hoenderop JG (PLoS genetics 2014) 2 3 4 74
  2. CNNM2, encoding a basolateral protein required for renal Mg2+ handling, is mutated in dominant hypomagnesemia. (PMID: 21397062) Stuiver M … Müller D (American journal of human genetics 2011) 3 4 74
  3. Large-scale association analysis identifies 13 new susceptibility loci for coronary artery disease. (PMID: 21378990) Schunkert H … Samani NJ (Nature genetics 2011) 3 41
  4. A genome-wide association study in Europeans and South Asians identifies five new loci for coronary artery disease. (PMID: 21378988) Coronary Artery Disease (C4D) Genetics Consortium (Nature genetics 2011) 3 41
  5. Genome-wide association study identifies five new schizophrenia loci. (PMID: 21926974) Schizophrenia Psychiatric Genome-Wide Association Study (GWAS) Consortium (Nature genetics 2011) 3 41

Products for CNNM2 Gene

Sources for CNNM2 Gene