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. [pro... See more...

Aliases for CNNM4 Gene

Aliases for CNNM4 Gene

  • Cyclin And CBS Domain Divalent Metal Cation Transport Mediator 4 2 3 5
  • Ancient Conserved Domain-Containing Protein 4 3 4
  • Metal Transporter CNNM4 3 4
  • Cyclin-M4 3 4
  • ACDP4 3 4
  • Ancient Conserved Domain Protein 4 3
  • Cyclin M4 2
  • KIAA1592 4

External Ids for CNNM4 Gene

Previous HGNC Symbols for CNNM4 Gene

  • ACDP4

Previous GeneCards Identifiers for CNNM4 Gene

  • GC02P095298
  • GC02P095882
  • GC02P096894
  • GC02P096911
  • GC02P096848
  • GC02P097426
  • GC02P091387

Summaries for CNNM4 Gene

Entrez Gene Summary for CNNM4 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 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]

GeneCards Summary for CNNM4 Gene

CNNM4 (Cyclin And CBS Domain Divalent Metal Cation Transport Mediator 4) is a Protein Coding gene. Diseases associated with CNNM4 include Jalili Syndrome and Amelogenesis Imperfecta. Gene Ontology (GO) annotations related to this gene include adenyl nucleotide binding. An important paralog of this gene is CNNM2.

UniProtKB/Swiss-Prot Summary for CNNM4 Gene

  • Probable metal transporter. The interaction with the metal ion chaperone COX11 suggests that it may play a role in sensory neuron functions (By similarity). May play a role in biomineralization and retinal function.

Additional gene information for CNNM4 Gene

No data available for CIViC Summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for CNNM4 Gene

Genomics for CNNM4 Gene

GeneHancer (GH) Regulatory Elements for CNNM4 Gene

Promoters and enhancers for CNNM4 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH02J096759 Promoter/Enhancer 2.3 EPDnew Ensembl ENCODE CraniofacialAtlas dbSUPER 750.6 +1.2 1179 5.8 ZNF785 SP1 ZBTB40 CTCF ZBTB6 MLX POLR2A ZNF362 MAX L3MBTL2 CNNM4 NCAPH SNRNP200 ZAP70 LMAN2L STARD7-AS1 RF00017-3268
GH02J096535 Promoter/Enhancer 2.1 EPDnew Ensembl ENCODE CraniofacialAtlas dbSUPER 10.1 -223.2 -223150 4.3 SP1 SIX5 ZBTB6 RBPJ SMARCE1 POLR2A HDAC2 ATF1 CREB1 HCFC1 ARID5A SNRNP200 KANSL3 ITPRIPL1 CIAO1 CNNM3 ANKRD36 LMAN2L STARD7-AS1 CNNM4
GH02J096615 Promoter/Enhancer 1.2 Ensembl ENCODE 10.9 -143.5 -143489 4.8 POLR2A NR2F1 NR2F6 RAD21 ELF3 SP1 RXRA GATAD2A RXRB CEBPB CNNM3 ARID5A FER1L5 KANSL3 LOC105373496 LMAN2L CNNM4 ITPRIPL1 SNRNP200 lnc-NEURL3-5
GH02J096663 Enhancer 1.2 FANTOM5 Ensembl ENCODE 11.1 -95.6 -95590 4.6 DACH1 PRDM1 CEBPA PRDM10 SMARCC1 SMARCC2 BRCA1 ZNF7 PKNOX1 CEBPB LMAN2L CNNM4 ITPRIPL1 CNNM3 ARID5A CIAO1 SNRNP200 KANSL3 GPAT2 TMEM127
GH02J096800 Enhancer 1 ENCODE dbSUPER 12.2 +40.2 40220 0.8 CTCF RBPJ RAD21 MNT BCL6B ELF3 MLLT1 MYC GLIS2 ZIC2 LMAN2L SNRNP200 KANSL3 CNNM4 SEMA4C ANKRD36B ANKRD36 MIR3127 piR-47638
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around CNNM4 on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the CNNM4 gene promoter:
  • AML1a
  • COUP
  • COUP-TF
  • COUP-TF1
  • HNF-4alpha1
  • HNF-4alpha2
  • HTF
  • N-Myc
  • RP58

Genomic Locations for CNNM4 Gene

Genomic Locations for CNNM4 Gene
chr2:96,760,902-96,811,891
(GRCh38/hg38)
Size:
50,990 bases
Orientation:
Plus strand
chr2:97,426,639-97,477,628
(GRCh37/hg19)
Size:
50,990 bases
Orientation:
Plus strand

Genomic View for CNNM4 Gene

Genes around CNNM4 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
CNNM4 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for CNNM4 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for CNNM4 Gene

Proteins for CNNM4 Gene

  • Protein details for CNNM4 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q6P4Q7-CNNM4_HUMAN
    Recommended name:
    Metal transporter CNNM4
    Protein Accession:
    Q6P4Q7
    Secondary Accessions:
    • B7Z1U0
    • C7SQM3
    • C7SQM4
    • C7SQM5
    • Q53RE5
    • Q9H9G3
    • Q9HCI0
    • Q9NRN1

    Protein attributes for CNNM4 Gene

    Size:
    775 amino acids
    Molecular mass:
    86607 Da
    Quaternary structure:
    • Interacts with COX11.
    Miscellaneous:
    • Shares weak sequence similarity with the cyclin family, explaining its name. However, it has no cyclin-like function in vivo.
    SequenceCaution:
    • Sequence=AAF86370.1; Type=Frameshift; Positions=108, 120; Evidence={ECO:0000305}; Sequence=AAY14963.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305}; Sequence=BAB14266.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305};

    Three dimensional structures from OCA and Proteopedia for CNNM4 Gene

    Alternative splice isoforms for CNNM4 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for CNNM4 Gene

Post-translational modifications for CNNM4 Gene

  • Glycosylation at Asn85, Asn122, and Asn127
  • Modification sites at PhosphoSitePlus
  • Glycosylation from GlyConnect
    • CNNM4_HUMAN (1504)

Other Protein References for CNNM4 Gene

No data available for DME Specific Peptides for CNNM4 Gene

Domains & Families for CNNM4 Gene

Gene Families for CNNM4 Gene

HGNC:
Human Protein Atlas (HPA):
  • Disease related genes
  • Potential drug targets
  • Predicted membrane proteins
  • Transporters

Protein Domains for CNNM4 Gene

Suggested Antigen Peptide Sequences for CNNM4 Gene

GenScript: Design optimal peptide antigens:
  • cDNA FLJ58754, highly similar to Homo sapiens cyclin M4 (CNNM4), mRNA (B7Z1U0_HUMAN)
  • Truncated cyclin M4 (C7SQM3_HUMAN)
  • Cyclin M4 (C7SQM4_HUMAN)
  • Cyclin M4 (C7SQM5_HUMAN)
  • Cyclin-M4 (CNNM4_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q6P4Q7

UniProtKB/Swiss-Prot:

CNNM4_HUMAN :
  • Belongs to the ACDP family.
Family:
  • Belongs to the ACDP family.
genes like me logo Genes that share domains with CNNM4: view

Function for CNNM4 Gene

Molecular function for CNNM4 Gene

UniProtKB/Swiss-Prot Function:
Probable metal transporter. The interaction with the metal ion chaperone COX11 suggests that it may play a role in sensory neuron functions (By similarity). May play a role in biomineralization and retinal function.

Phenotypes From GWAS Catalog for CNNM4 Gene

Gene Ontology (GO) - Molecular Function for CNNM4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005515 protein binding IPI 15840172
GO:0015081 sodium ion transmembrane transporter activity IBA,IEA 21873635
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 CNNM4: view
genes like me logo Genes that share phenotypes with CNNM4: view

Human Phenotype Ontology for CNNM4 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for CNNM4 Gene

MGI Knock Outs for CNNM4:
  • Cnnm4 Cnnm4<tm1a(EUCOMM)Wtsi>

Animal Model Products

CRISPR Products

miRNA for CNNM4 Gene

miRTarBase miRNAs that target CNNM4

Clone Products

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targets and HOMER Transcription for CNNM4 Gene

Localization for CNNM4 Gene

Subcellular locations from UniProtKB/Swiss-Prot for CNNM4 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 CNNM4 gene
Compartment Confidence
plasma membrane 4
cytoskeleton 2
endoplasmic reticulum 1
cytosol 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Plasma membrane (3)
  • Actin filaments (1)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for CNNM4 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 IEA --
GO:0030425 dendrite IEA --
genes like me logo Genes that share ontologies with CNNM4: view

Pathways & Interactions for CNNM4 Gene

PathCards logo

SuperPathways for CNNM4 Gene

No Data Available

Pathways by source for CNNM4 Gene

1 GeneTex pathway for CNNM4 Gene

Gene Ontology (GO) - Biological Process for CNNM4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006810 transport IBA 21873635
GO:0006811 ion transport IEA --
GO:0007601 visual perception IEA --
GO:0010960 magnesium ion homeostasis IBA 21873635
GO:0015693 magnesium ion transport IBA,IEA 21873635
genes like me logo Genes that share ontologies with CNNM4: view

No data available for SIGNOR curated interactions for CNNM4 Gene

Drugs & Compounds for CNNM4 Gene

No Compound Related Data Available

Transcripts for CNNM4 Gene

mRNA/cDNA for CNNM4 Gene

CRISPR Products

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for CNNM4 Gene

No ASD Table

Relevant External Links for CNNM4 Gene

GeneLoc Exon Structure for
CNNM4
ECgene alternative splicing isoforms for
CNNM4

Expression for CNNM4 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for CNNM4 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for CNNM4 Gene

This gene is overexpressed in Colon - Transverse (x4.6).

Protein differential expression in normal tissues from HIPED for CNNM4 Gene

This gene is overexpressed in Breast (22.7), Stomach (15.6), and Retina (12.4).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for CNNM4 Gene



Protein tissue co-expression partners for CNNM4 Gene

NURSA nuclear receptor signaling pathways regulating expression of CNNM4 Gene:

CNNM4

SOURCE GeneReport for Unigene cluster for CNNM4 Gene:

Hs.175043

mRNA Expression by UniProt/SwissProt for CNNM4 Gene:

Q6P4Q7-CNNM4_HUMAN
Tissue specificity: Widely expressed. Highly expressed in heart.

Evidence on tissue expression from TISSUES for CNNM4 Gene

  • Nervous system(4.2)

Phenotype-based relationships between genes and organs from Gene ORGANizer for CNNM4 Gene

Germ Layers:
  • ectoderm
  • mesoderm
Systems:
  • nervous
  • skeleton
Regions:
Head and neck:
  • brain
  • cranial nerve
  • eye
  • eyelid
  • head
  • jaw
  • mandible
  • maxilla
  • mouth
  • skull
  • tooth
General:
  • peripheral nervous system
genes like me logo Genes that share expression patterns with CNNM4: view

Orthologs for CNNM4 Gene

This gene was present in the common ancestor of animals and fungi.

Orthologs for CNNM4 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia CNNM4 33
  • 98 (a)
OneToOne
dog
(Canis familiaris)
Mammalia CNNM4 33 32
  • 90.33 (n)
OneToOne
cow
(Bos Taurus)
Mammalia CNNM4 33 32
  • 87.75 (n)
OneToOne
rat
(Rattus norvegicus)
Mammalia Cnnm4 32
  • 87.68 (n)
mouse
(Mus musculus)
Mammalia Cnnm4 17 33 32
  • 87.1 (n)
platypus
(Ornithorhynchus anatinus)
Mammalia CNNM4 33
  • 72 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia CNNM4 33
  • 72 (a)
OneToOne
chicken
(Gallus gallus)
Aves LOC425706 32
  • 72.32 (n)
CNNM4 33
  • 70 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia -- 33
  • 66 (a)
OneToMany
-- 33
  • 58 (a)
OneToMany
tropical clawed frog
(Silurana tropicalis)
Amphibia cnnm2 32
  • 66.9 (n)
zebrafish
(Danio rerio)
Actinopterygii LOC100329789 32
  • 67.9 (n)
CNNM4 33
  • 43 (a)
OneToOne
fruit fly
(Drosophila melanogaster)
Insecta uex 33
  • 39 (a)
OneToMany
worm
(Caenorhabditis elegans)
Secernentea C33D12.2 34
  • 46 (a)
C52D10.12 34
  • 34 (a)
R04E5.2 34
  • 34 (a)
C01H6.6 33
  • 25 (a)
OneToOne
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes MAM3 33
  • 24 (a)
OneToMany
Species where no ortholog for CNNM4 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • 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 (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for CNNM4 Gene

ENSEMBL:
Gene Tree for CNNM4 (if available)
TreeFam:
Gene Tree for CNNM4 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for CNNM4: view image

Paralogs for CNNM4 Gene

Paralogs for CNNM4 Gene

(4) SIMAP similar genes for CNNM4 Gene using alignment to 5 proteins:

  • CNNM4_HUMAN
  • B7Z1U0_HUMAN
  • C7SQM3_HUMAN
  • C7SQM4_HUMAN
  • C7SQM5_HUMAN
genes like me logo Genes that share paralogs with CNNM4: view

Variants for CNNM4 Gene

Sequence variations from dbSNP and Humsavar for CNNM4 Gene

SNP ID Clin Chr 02 pos Variation AA Info Type
rs10172803 likely-benign, Cone-rod dystrophy amelogenesis imperfecta 96,810,999(+) C/T 3_prime_UTR_variant, genic_downstream_transcript_variant
rs116742732 likely-benign, Cone-rod dystrophy amelogenesis imperfecta 96,811,033(+) C/T 3_prime_UTR_variant, genic_downstream_transcript_variant
rs12846 benign, Cone-rod dystrophy amelogenesis imperfecta 96,811,637(+) C/A/T 3_prime_UTR_variant, genic_downstream_transcript_variant
rs138445233 uncertain-significance, Cone-rod dystrophy amelogenesis imperfecta 96,809,343(+) C/T coding_sequence_variant, genic_downstream_transcript_variant, missense_variant, synonymous_variant
rs138690324 uncertain-significance, Cone-rod dystrophy amelogenesis imperfecta 96,761,252(+) A/G coding_sequence_variant, genic_upstream_transcript_variant, missense_variant

Structural Variations from Database of Genomic Variants (DGV) for CNNM4 Gene

Variant ID Type Subtype PubMed ID
dgv607e201 CNV deletion 23290073
esv2677477 CNV deletion 23128226
esv2720413 CNV deletion 23290073
esv2720414 CNV deletion 23290073
esv3365153 CNV duplication 20981092
esv3387574 CNV duplication 20981092
esv3425717 CNV duplication 20981092
esv3591693 CNV loss 21293372
esv5003 OTHER complex 18987735
nsv1135873 CNV deletion 24896259
nsv526313 CNV loss 19592680
nsv834307 CNV loss 17160897

Variation tolerance for CNNM4 Gene

Residual Variation Intolerance Score: 3.07% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 1.33; 26.38% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for CNNM4 Gene

Human Gene Mutation Database (HGMD)
CNNM4
SNPedia medical, phenotypic, and genealogical associations of SNPs for
CNNM4

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for CNNM4 Gene

Disorders for CNNM4 Gene

MalaCards: The human disease database

(7) MalaCards diseases for CNNM4 Gene - From: HGMD, OMIM, ClinVar, GTR, Orphanet, DISEASES, and GeneCards

Disorder Aliases PubMed IDs
jalili syndrome
  • cone-rod dystrophy and amelogenesis imperfecta
amelogenesis imperfecta
  • ai
urofacial syndrome 1
  • ufs1
achromatopsia
  • achromatopsia 2
teeth hard tissue disease
- elite association - COSMIC cancer census association via MalaCards
Search CNNM4 in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

CNNM4_HUMAN
  • Jalili syndrome (JALIS) [MIM:217080]: A syndrome characterized by the association of cone-rod dystrophy and amelogenesis imperfecta. {ECO:0000269 PubMed:19200525, ECO:0000269 PubMed:19200527}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Additional Disease Information for CNNM4

genes like me logo Genes that share disorders with CNNM4: view

No data available for Genatlas for CNNM4 Gene

Publications for CNNM4 Gene

  1. Dental phenotype in Jalili syndrome due to a c.1312 dupC homozygous mutation in the CNNM4 gene. (PMID: 24194943) Luder HU … Schorderet DF (PloS one 2013) 2 3 56
  2. Purification, crystallization and preliminary crystallographic analysis of the CBS pair of the human metal transporter CNNM4. (PMID: 21393841) Gómez García I … Martínez-Cruz LA (Acta crystallographica. Section F, Structural biology and crystallization communications 2011) 2 3 56
  3. Mutations in CNNM4 cause Jalili syndrome, consisting of autosomal-recessive cone-rod dystrophy and amelogenesis imperfecta. (PMID: 19200525) Parry DA … Inglehearn CF (American journal of human genetics 2009) 3 4 56
  4. Mutations in CNNM4 cause recessive cone-rod dystrophy with amelogenesis imperfecta. (PMID: 19200527) Polok B … Schorderet DF (American journal of human genetics 2009) 3 4 56
  5. Physical interaction and functional coupling between ACDP4 and the intracellular ion chaperone COX11, an implication of the role of ACDP4 in essential metal ion transport and homeostasis. (PMID: 15840172) Guo D … Wang CY (Molecular pain 2005) 3 4 56

Products for CNNM4 Gene

Sources for CNNM4 Gene