This gene belongs to the chemokine-like factor gene superfamily, a novel family that is similar to the chemokine and the transmembrane 4 superfamilies of signaling molecules. This gene is one of several chemokine-like factor genes located in a cluster on chromosome 16. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSe... See more...

Aliases for CMTM4 Gene

Aliases for CMTM4 Gene

  • CKLF Like MARVEL Transmembrane Domain Containing 4 2 3 5
  • CKLF-Like MARVEL Transmembrane Domain-Containing Protein 4 3 4
  • Chemokine-Like Factor Superfamily Member 4 3 4
  • Chemokine-Like Factor Super Family 4 2 3
  • CKLFSF4 3 4
  • CKLF-Like MARVEL Transmembrane Domain Containing 4 2
  • Chemokine-Like Factor Superfamily 4 2
  • CMTM4 5

External Ids for CMTM4 Gene

Previous HGNC Symbols for CMTM4 Gene

  • CKLFSF4

Previous GeneCards Identifiers for CMTM4 Gene

  • GC16M065207
  • GC16M066648
  • GC16M052524
  • GC16M066616

Summaries for CMTM4 Gene

Entrez Gene Summary for CMTM4 Gene

  • This gene belongs to the chemokine-like factor gene superfamily, a novel family that is similar to the chemokine and the transmembrane 4 superfamilies of signaling molecules. This gene is one of several chemokine-like factor genes located in a cluster on chromosome 16. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

GeneCards Summary for CMTM4 Gene

CMTM4 (CKLF Like MARVEL Transmembrane Domain Containing 4) is a Protein Coding gene. Gene Ontology (GO) annotations related to this gene include cytokine activity. An important paralog of this gene is CMTM6.

UniProtKB/Swiss-Prot Summary for CMTM4 Gene

  • Acts as a backup for CMTM6 to regulate plasma membrane expression of PD-L1/CD274, an immune inhibitory ligand critical for immune tolerance to self and antitumor immunity. May protect PD-L1/CD274 from being polyubiquitinated and targeted for degradation.

No data available for CIViC Summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for CMTM4 Gene

Genomics for CMTM4 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for CMTM4 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 CMTM4 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for CMTM4

Top Transcription factor binding sites by QIAGEN in the CMTM4 gene promoter:
  • AP-2gamma
  • Cdc5
  • HOXA5
  • Ik-2
  • LyF-1
  • NRSF form 1
  • NRSF form 2
  • Pax-4a
  • POU2F1
  • POU2F1a

Genomic Locations for CMTM4 Gene

Genomic Locations for CMTM4 Gene
chr16:66,598,178-66,696,743
(GRCh38/hg38)
Size:
98,566 bases
Orientation:
Minus strand
chr16:66,648,653-66,730,610
(GRCh37/hg19)
Size:
81,958 bases
Orientation:
Minus strand

Genomic View for CMTM4 Gene

Genes around CMTM4 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
CMTM4 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for CMTM4 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for CMTM4 Gene

Proteins for CMTM4 Gene

  • Protein details for CMTM4 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q8IZR5-CKLF4_HUMAN
    Recommended name:
    CKLF-like MARVEL transmembrane domain-containing protein 4
    Protein Accession:
    Q8IZR5
    Secondary Accessions:
    • Q52M40
    • Q8IZR4
    • Q8IZV1

    Protein attributes for CMTM4 Gene

    Size:
    234 amino acids
    Molecular mass:
    25828 Da
    Quaternary structure:
    • Interacts with PD-L1/CD274 and CMTM6.

    Alternative splice isoforms for CMTM4 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for CMTM4 Gene

Post-translational modifications for CMTM4 Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for CMTM4 Gene

No data available for DME Specific Peptides for CMTM4 Gene

Domains & Families for CMTM4 Gene

Gene Families for CMTM4 Gene

Protein Domains for CMTM4 Gene

InterPro:
Blocks:
  • Marvel
ProtoNet:

Suggested Antigen Peptide Sequences for CMTM4 Gene

GenScript: Design optimal peptide antigens:
  • Chemokine-like factor superfamily member 4 (CKLF4_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q8IZR5

UniProtKB/Swiss-Prot:

CKLF4_HUMAN :
  • Belongs to the chemokine-like factor family.
Family:
  • Belongs to the chemokine-like factor family.
genes like me logo Genes that share domains with CMTM4: view

Function for CMTM4 Gene

Molecular function for CMTM4 Gene

UniProtKB/Swiss-Prot Function:
Acts as a backup for CMTM6 to regulate plasma membrane expression of PD-L1/CD274, an immune inhibitory ligand critical for immune tolerance to self and antitumor immunity. May protect PD-L1/CD274 from being polyubiquitinated and targeted for degradation.

Phenotypes From GWAS Catalog for CMTM4 Gene

Gene Ontology (GO) - Molecular Function for CMTM4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005515 protein binding IPI 28813410
genes like me logo Genes that share ontologies with CMTM4: view
genes like me logo Genes that share phenotypes with CMTM4: view

Animal Model Products

  • Taconic Biosciences Mouse Models for CMTM4

CRISPR Products

miRNA for CMTM4 Gene

miRTarBase miRNAs that target CMTM4

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for CMTM4

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Animal Models , Transcription Factor Targets and HOMER Transcription for CMTM4 Gene

Localization for CMTM4 Gene

Subcellular locations from UniProtKB/Swiss-Prot for CMTM4 Gene

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 CMTM4 gene
Compartment Confidence
plasma membrane 4
golgi apparatus 2
extracellular 1
cytoskeleton 1
nucleus 1
endoplasmic reticulum 1
endosome 1
cytosol 1
lysosome 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Golgi apparatus (2)
  • Plasma membrane (2)
  • Vesicles (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for CMTM4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0016020 membrane IEA --
GO:0016021 integral component of membrane IBA 21873635
genes like me logo Genes that share ontologies with CMTM4: view

Pathways & Interactions for CMTM4 Gene

PathCards logo

SuperPathways for CMTM4 Gene

No Data Available

Gene Ontology (GO) - Biological Process for CMTM4 Gene

None

No data available for Pathways by source and SIGNOR curated interactions for CMTM4 Gene

Drugs & Compounds for CMTM4 Gene

No Compound Related Data Available

Transcripts for CMTM4 Gene

mRNA/cDNA for CMTM4 Gene

2 REFSEQ mRNAs :
9 NCBI additional mRNA sequence :
5 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for CMTM4

Alternative Splicing Database (ASD) splice patterns (SP) for CMTM4 Gene

ExUns: 1a · 1b ^ 2 ^ 3 ^ 4a · 4b ^ 5
SP1: -
SP2: -
SP3:

Relevant External Links for CMTM4 Gene

GeneLoc Exon Structure for
CMTM4

Expression for CMTM4 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for CMTM4 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for CMTM4 Gene

This gene is overexpressed in Spleen (22.5), Lung (17.4), and Retina (7.2).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for CMTM4 Gene



Protein tissue co-expression partners for CMTM4 Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for CMTM4

SOURCE GeneReport for Unigene cluster for CMTM4 Gene:

Hs.643961

mRNA Expression by UniProt/SwissProt for CMTM4 Gene:

Q8IZR5-CKLF4_HUMAN
Tissue specificity: Highly expressed in testis and prostate.

Evidence on tissue expression from TISSUES for CMTM4 Gene

  • Kidney(4.4)
  • Spleen(4.3)
  • Liver(4.2)
  • Nervous system(3.1)
  • Intestine(2.5)
genes like me logo Genes that share expression patterns with CMTM4: view

No data available for mRNA differential expression in normal tissues and Phenotype-based relationships between genes and organs from Gene ORGANizer for CMTM4 Gene

Orthologs for CMTM4 Gene

This gene was present in the common ancestor of chordates.

Orthologs for CMTM4 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia CMTM4 30 31
  • 99.86 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia CMTM4 30 31
  • 94.55 (n)
OneToOne
Mouse
(Mus musculus)
Mammalia Cmtm4 30 17 31
  • 92.31 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Cmtm4 30
  • 91.83 (n)
Oppossum
(Monodelphis domestica)
Mammalia CMTM4 31
  • 89 (a)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia CMTM4 31
  • 87 (a)
OneToOne
Dog
(Canis familiaris)
Mammalia CMTM4 31
  • 71 (a)
OneToOne
Chicken
(Gallus gallus)
Aves CMTM4 30 31
  • 80.68 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia CMTM4 31
  • 78 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia LOC100498042 30
  • 69.65 (n)
Zebrafish
(Danio rerio)
Actinopterygii cmtm4 30 31
  • 67.97 (n)
OneToOne
Sea Squirt
(Ciona savignyi)
Ascidiacea CSA.2454 31
  • 26 (a)
OneToMany
Species where no ortholog for CMTM4 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium 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)
  • Baker's yeast (Saccharomyces cerevisiae)
  • 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)
  • Fruit Fly (Drosophila melanogaster)
  • 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 Vase (Ciona intestinalis)
  • 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)
  • Worm (Caenorhabditis elegans)

Evolution for CMTM4 Gene

ENSEMBL:
Gene Tree for CMTM4 (if available)
TreeFam:
Gene Tree for CMTM4 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for CMTM4: view image

Paralogs for CMTM4 Gene

(2) SIMAP similar genes for CMTM4 Gene using alignment to 2 proteins:

  • CKLF4_HUMAN
  • J3QRP2_HUMAN
genes like me logo Genes that share paralogs with CMTM4: view

Variants for CMTM4 Gene

Additional dbSNP identifiers (rs#s) for CMTM4 Gene

Structural Variations from Database of Genomic Variants (DGV) for CMTM4 Gene

Variant ID Type Subtype PubMed ID
nsv1071337 CNV deletion 25765185

Variation tolerance for CMTM4 Gene

Residual Variation Intolerance Score: 63.2% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 0.69; 14.70% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for CMTM4 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
CMTM4

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot and Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for CMTM4 Gene

Disorders for CMTM4 Gene

No disorders were found for CMTM4 Gene.

No data available for MalaCards , UniProtKB/Swiss-Prot and Genatlas for CMTM4 Gene

Publications for CMTM4 Gene

  1. Identification of eight genes encoding chemokine-like factor superfamily members 1-8 (CKLFSF1-8) by in silico cloning and experimental validation. (PMID: 12782130) Han W … Ma D (Genomics 2003) 2 3 4
  2. Identification of CMTM6 and CMTM4 as PD-L1 protein regulators. (PMID: 28813410) Mezzadra R … Schumacher TNM (Nature 2017) 3 4
  3. A reference map of the human binary protein interactome. (PMID: 32296183) Luck K … Calderwood MA (Nature 2020) 3
  4. LMBR1L regulates lymphopoiesis through Wnt/β-catenin signaling. (PMID: 31073040) Choi JH … Beutler B (Science (New York, N.Y.) 2019) 3
  5. CMTM4 regulates angiogenesis by promoting cell surface recycling of VE-cadherin to endothelial adherens junctions. (PMID: 30097810) Chrifi I … Cheng C (Angiogenesis 2019) 3

Products for CMTM4 Gene

Sources for CMTM4 Gene