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COL4A6 collagen type IV alpha 6 chain [ Homo sapiens (human) ]

Gene ID: 1288, updated on 3-Mar-2019

Summary

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Official Symbol
COL4A6provided by HGNC
Official Full Name
collagen type IV alpha 6 chainprovided by HGNC
Primary source
HGNC:HGNC:2208
See related
Ensembl:ENSG00000197565 MIM:303631
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
DFNX6; DELXq22.3; CXDELq22.3
Summary
This gene encodes one of the six subunits of type IV collagen, the major structural component of basement membranes. Like the other members of the type IV collagen gene family, this gene is organized in a head-to-head conformation with another type IV collagen gene, alpha 5 type IV collagen, so that the gene pair shares a common promoter. Deletions in the alpha 5 gene that extend into the alpha 6 gene result in diffuse leiomyomatosis accompanying the X-linked Alport syndrome caused by the deletion in the alpha 5 gene. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2013]
Expression
Broad expression in endometrium (RPKM 9.0), gall bladder (RPKM 7.4) and 16 other tissues See more
Orthologs
mouse all

Genomic context

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See COL4A6 in Genome Data Viewer
Location:
Xq22.3
Exon count:
49
Annotation release Status Assembly Chr Location
109 current GRCh38.p12 (GCF_000001405.38) X NC_000023.11 (108155607..108439497, complement)
105 previous assembly GRCh37.p13 (GCF_000001405.25) X NC_000023.10 (107398837..107682704, complement)

Chromosome X - NC_000023.11Genomic Context describing neighboring genes Neighboring gene proteasome 26S subunit, non-ATPase 10 Neighboring gene autophagy related 4A cysteine peptidase Neighboring gene collagen type IV alpha 5 chain Neighboring gene uncharacterized LOC101928358 Neighboring gene insulin receptor substrate 4

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. Type IV collagen alpha6 chain-derived noncollagenous domain 1 (alpha6(IV)NC1) inhibits angiogenesis and tumor growth. Mundel TM, et al. Int J Cancer, 2008 Apr 15. PMID 18074349
  2. The expression of type IV collagen alpha6 chain is related to the prognosis in patients with esophageal squamous cell carcinoma. Baba Y, et al. Ann Surg Oncol, 2008 Feb. PMID 17955302
  3. Structure of the human type IV collagen COL4A6 gene, which is mutated in Alport syndrome-associated leiomyomatosis. Zhang X, et al. Genomics, 1996 May 1. PMID 8661006
  4. Complete primary structure of the sixth chain of human basement membrane collagen, alpha 6(IV). Isolation of the cDNAs for alpha 6(IV) and comparison with five other type IV collagen chains. Zhou J, et al. J Biol Chem, 1994 May 6. PMID 8175748
  5. Identification of a new collagen IV chain, alpha 6(IV), by cDNA isolation and assignment of the gene to chromosome Xq22, which is the same locus for COL4A5. Oohashi T, et al. J Biol Chem, 1994 Mar 11. PMID 8125972

See all (65) citations in PubMed

See citations in PubMed for homologs of this gene provided by HomoloGene

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

  1. although alpha5 and alpha6 (IV) chains are induced in the glomerular basement membrane in autosomal recessive Alport syndrome, their induction does not seem to play a major compensatory role
    Title: COL4A6 is dispensable for autosomal recessive Alport syndrome.
  2. deletion breakpoints in five Alport syndrome-diffuse leiomyomatosis patients and show a contiguous COL4A6/COL4A5 deletion in each case, were characterized.
    Title: Characterization of contiguous gene deletions in COL4A6 and COL4A5 in Alport syndrome-diffuse leiomyomatosis.
  3. Mutation in COL4A6 gene is associated with gastric cancer peritoneal carcinomatosis.
    Title: Genetic alterations and their clinical implications in gastric cancer peritoneal carcinomatosis revealed by whole-exome sequencing of malignant ascites.
  4. The expression of collagen type IV and its alpha chains (alpha1-6) was investigated in different endothelial cell culture systems in vitro qualitatively and quantitatively.
    Title: Angiogenesis and collagen type IV expression in different endothelial cell culture systems.
  5. New deletion in COL4A6/COL4A5 related to diffuse esophageal leiomyomatosis associated with Alport syndrome in a Chinese family.
    Title: Chinese family with diffuse oesophageal leiomyomatosis: a new COL4A5/COL4A6 deletion and a case of gonosomal mosaicism.
  6. COL4A6 is associated with X-linked nonsyndromic hearing loss.
    Title: Novel form of X-linked nonsyndromic hearing loss with cochlear malformation caused by a mutation in the type IV collagen gene COL4A6.
  7. We showed that TPM2, CLU, and COL4A6 mRNA levels are downregulated in prostate cancer.
    Title: Identification of new genes downregulated in prostate cancer and investigation of their effects on prognosis.
  8. In this paper we improve the definition of the COL4A5/COL4A6 deletions in three Alport syndrome with diffuse leiomyomatosis.
    Title: Alport syndrome and leiomyomatosis: the first deletion extending beyond COL4A6 intron 2.
  9. The expression of Col I, Col IV and Fn was closely related to tumor invasion, the regional lymph node metastasis and other pathological features in laryngeal squamous cell carcinoma.
    Title: [Expression and pathobiological significance of Col I, Col IV and Fn in laryngeal squamous cell carcinomas].
  10. expression of collagen type IV alpha6 chain in the smooth muscle BM of the gastrointestinal tract is restricted to the esophagus in humans
    Title: Clonal overgrowth of esophageal smooth muscle cells in diffuse leiomyomatosis-Alport syndrome caused by partial deletion in COL4A5 and COL4A6 genes.
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
Deafness, X-linked 6
MedGen: C3806737 OMIM: 300914 GeneReviews: Not available
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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

HIV-1 interactions

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Protein interactions

Protein Gene Interaction Pubs
Tat tat Treatment with cannabinoids inhibits HIV-1 Tat-enhanced attachment of U937 cells to collagen IV, laminin, or ECM1 proteins, which is linked to the cannabinoid receptor type 2 and the modulation of beta1-integrin and actin distribution PubMed
tat HIV-1 Tat enhances adhesion of human U937 monocyte-like cells to proteins of the extracellular matrix, such as collagen IV, laminin, and ECM1 PubMed

Go to the HIV-1, Human Interaction Database

Pathways from BioSystems

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  • AGE-RAGE signaling pathway in diabetic complications, organism-specific biosystem (from KEGG)
    AGE-RAGE signaling pathway in diabetic complications, organism-specific biosystemAdvanced glycation end products (AGEs) are a complex group of compounds produced through the non-enzymatic glycation and oxidation of proteins, lipids and nucleic acids, primarily due to aging and un...
  • AGE-RAGE signaling pathway in diabetic complications, conserved biosystem (from KEGG)
    AGE-RAGE signaling pathway in diabetic complications, conserved biosystemAdvanced glycation end products (AGEs) are a complex group of compounds produced through the non-enzymatic glycation and oxidation of proteins, lipids and nucleic acids, primarily due to aging and un...
  • Amoebiasis, organism-specific biosystem (from KEGG)
    Amoebiasis, organism-specific biosystemEntamoeba histolytica, an extracellular protozoan parasite is a human pathogen that invades the intestinal epithelium. Infection occurs on ingestion of contaminated water and food. The pathogenesis o...
  • Amoebiasis, conserved biosystem (from KEGG)
    Amoebiasis, conserved biosystemEntamoeba histolytica, an extracellular protozoan parasite is a human pathogen that invades the intestinal epithelium. Infection occurs on ingestion of contaminated water and food. The pathogenesis o...
  • Assembly of collagen fibrils and other multimeric structures, organism-specific biosystem (from REACTOME)
    Assembly of collagen fibrils and other multimeric structures, organism-specific biosystemCollagen trimers in triple-helical form, referred to as procollagen or collagen molecules, are exported from the ER and trafficked through the Golgi network before secretion into the extracellular sp...
  • Collagen biosynthesis and modifying enzymes, organism-specific biosystem (from REACTOME)
    Collagen biosynthesis and modifying enzymes, organism-specific biosystemThe biosynthesis of collagen is a multistep process. Collagen propeptides are cotranslationally translocated into the ER lumen. Propeptides undergo a number of post-translational modifications. Proli...
  • Collagen chain trimerization, organism-specific biosystem (from REACTOME)
    Collagen chain trimerization, organism-specific biosystemThe C-propeptides of collagen propeptide chains are essential for the association of three peptide chains into a trimeric but non-helical procollagen. This initial binding event determines the compo...
  • Collagen formation, organism-specific biosystem (from REACTOME)
    Collagen formation, organism-specific biosystemCollagen is a family of at least 29 structural proteins derived from over 40 human genes (Myllyharju & Kivirikko 2004). It is the main component of connective tissue, and the most abundant protein in...
  • ECM-receptor interaction, organism-specific biosystem (from KEGG)
    ECM-receptor interaction, organism-specific biosystemThe extracellular matrix (ECM) consists of a complex mixture of structural and functional macromolecules and serves an important role in tissue and organ morphogenesis and in the maintenance of cell ...
  • ECM-receptor interaction, conserved biosystem (from KEGG)
    ECM-receptor interaction, conserved biosystemThe extracellular matrix (ECM) consists of a complex mixture of structural and functional macromolecules and serves an important role in tissue and organ morphogenesis and in the maintenance of cell ...
  • Extracellular matrix organization, organism-specific biosystem (from REACTOME)
    Extracellular matrix organization, organism-specific biosystemThe extracellular matrix is a component of all mammalian tissues, a network consisting largely of the fibrous proteins collagen, elastin and associated-microfibrils, fibronectin and laminins embedded...
  • Focal Adhesion, organism-specific biosystem (from WikiPathways)
    Focal Adhesion, organism-specific biosystemCell-matrix adhesions play essential roles in important biological processes including cell motility, cell proliferation, cell differentiation, regulation of gene expression and cell survival. At the...
  • Focal adhesion, organism-specific biosystem (from KEGG)
    Focal adhesion, organism-specific biosystemCell-matrix adhesions play essential roles in important biological processes including cell motility, cell proliferation, cell differentiation, regulation of gene expression and cell survival. At the...
  • Focal adhesion, conserved biosystem (from KEGG)
    Focal adhesion, conserved biosystemCell-matrix adhesions play essential roles in important biological processes including cell motility, cell proliferation, cell differentiation, regulation of gene expression and cell survival. At the...
  • PI3K-Akt signaling pathway, organism-specific biosystem (from KEGG)
    PI3K-Akt signaling pathway, organism-specific biosystemThe phosphatidylinositol 3' -kinase(PI3K)-Akt signaling pathway is activated by many types of cellular stimuli or toxic insults and regulates fundamental cellular functions such as transcription, tra...
  • PI3K-Akt signaling pathway, conserved biosystem (from KEGG)
    PI3K-Akt signaling pathway, conserved biosystemThe phosphatidylinositol 3' -kinase(PI3K)-Akt signaling pathway is activated by many types of cellular stimuli or toxic insults and regulates fundamental cellular functions such as transcription, tra...
  • Pathways in cancer, organism-specific biosystem (from KEGG)
    Pathways in cancer, organism-specific biosystem
    Pathways in cancer
  • Protein digestion and absorption, organism-specific biosystem (from KEGG)
    Protein digestion and absorption, organism-specific biosystemProtein is a dietary component essential for nutritional homeostasis in humans. Normally, ingested protein undergoes a complex series of degradative processes following the action of gastric, pancrea...
  • Protein digestion and absorption, conserved biosystem (from KEGG)
    Protein digestion and absorption, conserved biosystemProtein is a dietary component essential for nutritional homeostasis in humans. Normally, ingested protein undergoes a complex series of degradative processes following the action of gastric, pancrea...
  • Small cell lung cancer, organism-specific biosystem (from KEGG)
    Small cell lung cancer, organism-specific biosystemLung cancer is a leading cause of cancer death among men and women in industrialized countries. Small cell lung carcinoma (SCLC) is a highly aggressive neoplasm, which accounts for approximately 25% ...
  • Small cell lung cancer, conserved biosystem (from KEGG)
    Small cell lung cancer, conserved biosystemLung cancer is a leading cause of cancer death among men and women in industrialized countries. Small cell lung carcinoma (SCLC) is a highly aggressive neoplasm, which accounts for approximately 25% ...

Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Clone Names

  • MGC88184

Gene Ontology Provided by GOA

Function Evidence Code Pubs
extracellular matrix structural constituent IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
extracellular matrix structural constituent conferring tensile strength IEA
Inferred from Electronic Annotation
more info
 PubMed 
extracellular matrix structural constituent conferring tensile strength RCA
inferred from Reviewed Computational Analysis
more info
 PubMed 
Process Evidence Code Pubs
cell adhesion IEA
Inferred from Electronic Annotation
more info
  
collagen-activated tyrosine kinase receptor signaling pathway IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
extracellular matrix organization IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
extracellular matrix organization TAS
Traceable Author Statement
more info
  
Component Evidence Code Pubs
collagen type IV trimer IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
collagen type IV trimer NAS
Non-traceable Author Statement
more info
 PubMed 
collagen-containing extracellular matrix HDA PubMed 
endoplasmic reticulum lumen TAS
Traceable Author Statement
more info
  
extracellular matrix IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
extracellular region TAS
Traceable Author Statement
more info
  
extracellular space IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 

General protein information

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Preferred Names
collagen alpha-6(IV) chain
Names
collagen IV, alpha-6 polypeptide
collagen of basement membrane, alpha-6
collagen, type IV, alpha 6
dJ889N15.4 (Collagen Alpha 6(IV))

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_012059.2 RefSeqGene

    Range
    5001..288868
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001287758.1 → NP_001274687.1  collagen alpha-6(IV) chain isoform 3 precursor

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) represents the longest transcript and encodes the longest protein (isoform 3).
    Source sequence(s)
    AL031177, AL034369, AL136080, AW082083, BG680578, CA396616, CA489342, CB050016, CN313332, CN313341, CN313343, CN313347, CN313351, CX872164, DA748513
    Consensus CDS
    CCDS76010.1
    UniProtKB/TrEMBL
    A8MXH5
    Related
    ENSP00000378340.3, ENST00000394872.6
    Conserved Domains (2) summary
    pfam01391
    Location:680 → 739
    Collagen; Collagen triple helix repeat (20 copies)
    pfam01413
    Location:1592 → 1704
    C4; C-terminal tandem repeated domain in type 4 procollagen

  2. NM_001287759.1 → NP_001274688.1  collagen alpha-6(IV) chain isoform 4 precursor

    Status: REVIEWED

    Description
    Transcript Variant: This variant (4) lacks several alternate in-frame exons compared to variant 3. The resulting protein (isoform 4) is shorter compared to isoform 3.
    Source sequence(s)
    AL034369, AL136080, BC000874, BC144669, CB050016, CN313332, CN313347, DB260304, EU182215
    Consensus CDS
    CCDS76009.1
    UniProtKB/TrEMBL
    A0A087WZY5, A8VPY0, B7ZMM7
    Related
    ENSP00000482970.1, ENST00000621266.4
    Conserved Domains (2) summary
    pfam01391
    Location:663 → 722
    Collagen; Collagen triple helix repeat (20 copies)
    pfam01413
    Location:1551 → 1663
    C4; C-terminal tandem repeated domain in type 4 procollagen

  3. NM_001287760.1 → NP_001274689.1  collagen alpha-6(IV) chain isoform 5 precursor

    Status: REVIEWED

    Description
    Transcript Variant: This variant (5) lacks several alternate in-frame exons compared to variant 3. The resulting protein (isoform 5) is shorter compared to isoform 3.
    Source sequence(s)
    AL034369, AL136080, BC000874, BC140855, CB050016, DB260304, U04845
    Consensus CDS
    CCDS76008.1
    UniProtKB/Swiss-Prot
    Q14031
    UniProtKB/TrEMBL
    B2RTX6, F5H3Q5
    Related
    ENSP00000445236.1, ENST00000538570.5
    Conserved Domains (2) summary
    pfam01391
    Location:663 → 722
    Collagen; Collagen triple helix repeat (20 copies)
    pfam01413
    Location:1518 → 1630
    C4; C-terminal tandem repeated domain in type 4 procollagen

  4. NM_001847.3 → NP_001838.2  collagen alpha-6(IV) chain isoform A precursor

    See identical proteins and their annotated locations for NP_001838.2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (A) utilizes a different alternative exon in the 5' UTR and coding region, exon 1A, which results in use of an alternate upstream translation start, compared to variant 3. The resulting protein (isoform A) has a distinct and shorter N-terminus, compared to isoform 3.
    Source sequence(s)
    AL031177, AL034369, AL136080, CB050016, U04845
    Consensus CDS
    CCDS14541.1
    UniProtKB/Swiss-Prot
    Q14031
    Related
    ENSP00000361290.4, ENST00000372216.8
    Conserved Domains (2) summary
    pfam01391
    Location:664 → 723
    Collagen; Collagen triple helix repeat (20 copies)
    pfam01413
    Location:1576 → 1688
    C4; C-terminal tandem repeated domain in type 4 procollagen

  5. NM_033641.3 → NP_378667.1  collagen alpha-6(IV) chain isoform B precursor

    See identical proteins and their annotated locations for NP_378667.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (B) utilizes the same 5' exon as variant 3 (exon 1B) but lacks several alternate in-frame exons. The resulting protein (isoform B) is shorter compared to isoform 3.
    Source sequence(s)
    AL034369, AL136080, BF726518, BQ331638, CB050016, CN313347, D21337, U04845
    Consensus CDS
    CCDS14542.1
    UniProtKB/Swiss-Prot
    Q14031
    Related
    ENSP00000334733.7, ENST00000334504.11
    Conserved Domains (2) summary
    pfam01391
    Location:663 → 722
    Collagen; Collagen triple helix repeat (20 copies)
    pfam01413
    Location:1575 → 1687
    C4; C-terminal tandem repeated domain in type 4 procollagen

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109

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

Reference GRCh38.p12 Primary Assembly

Genomic

  1. NC_000023.11 Reference GRCh38.p12 Primary Assembly

    Range
    108155607..108439497 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_006724617.3 → XP_006724680.1  collagen alpha-6(IV) chain isoform X1

    Conserved Domains (2) summary
    pfam01391
    Location:681 → 740
    Collagen; Collagen triple helix repeat (20 copies)
    pfam01413
    Location:1593 → 1705
    C4; C-terminal tandem repeated domain in type 4 procollagen

  2. XM_011530852.2 → XP_011529154.1  collagen alpha-6(IV) chain isoform X2

    Conserved Domains (2) summary
    pfam01391
    Location:681 → 740
    Collagen; Collagen triple helix repeat (20 copies)
    pfam01413
    Location:1569 → 1681
    C4; C-terminal tandem repeated domain in type 4 procollagen

  3. XM_011530853.3 → XP_011529155.1  collagen alpha-6(IV) chain isoform X3

    Conserved Domains (2) summary
    pfam01391
    Location:653 → 712
    Collagen; Collagen triple helix repeat (20 copies)
    pfam01413
    Location:1565 → 1677
    C4; C-terminal tandem repeated domain in type 4 procollagen

  4. XM_011530854.2 → XP_011529156.1  collagen alpha-6(IV) chain isoform X4

    Conserved Domains (1) summary
    pfam01391
    Location:681 → 740
    Collagen; Collagen triple helix repeat (20 copies)

RNA

  1. XR_001755650.1 RNA Sequence

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q14031.3 GenPept UniProtKB/Swiss-Prot:Q14031

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