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

Gene ID: 1288, updated on 3-Apr-2024

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; AllianceGenome:HGNC:2208
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
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Genomic context

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See COL4A6 in Genome Data Viewer
Location:
Xq22.3
Exon count:
50
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) X NC_000023.11 (108155614..108439458, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) X NC_060947.1 (106593205..106877000, complement)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) X NC_000023.10 (107398844..107682688, complement)

Chromosome X - NC_000023.11Genomic Context describing neighboring genes Neighboring gene V-set and immunoglobulin domain containing 1 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 29838 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 29839 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chrX:107370111-107370674 Neighboring gene proteasome 26S subunit, non-ATPase 10 Neighboring gene H3K4me1 hESC enhancer GRCh37_chrX:107399852-107400352 Neighboring gene autophagy related 4A cysteine peptidase Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chrX:107421110-107421795 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chrX:107420425-107421109 Neighboring gene NANOG-H3K27ac hESC enhancer GRCh37_chrX:107419738-107420424 Neighboring gene uncharacterized LOC124905205 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chrX:107513459-107514658 Neighboring gene NANOG-H3K27ac hESC enhancer GRCh37_chrX:107596629-107597181 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chrX:107609798-107610337 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chrX:107634248-107634889 Neighboring gene collagen type IV alpha 5 chain Neighboring gene H3K27ac hESC enhancer GRCh37_chrX:107843610-107844540 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chrX:107884720-107885919 Neighboring gene IRS4 antisense RNA 1 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. Confirmation of COL4A6 variants in X-linked nonsyndromic hearing loss and its clinical implications. O'Brien A, et al. Eur J Hum Genet, 2022 Jan. PMID 33840813, Free PMC Article
  2. 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
  3. 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
  4. 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
  5. 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

See all (70) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Confirmation of COL4A6 variants in X-linked nonsyndromic hearing loss and its clinical implications.
    Title: Confirmation of COL4A6 variants in X-linked nonsyndromic hearing loss and its clinical implications.
  2. These findings indicate that alpha112:alpha556 (IV) network, which is the only network that includes the alpha6(IV) chain, is one regulator of KRT10 expression in keratinization of oral mucosal epithelium.
    Title: Type IV collagen α6 chain is a regulator of keratin 10 in keratinization of oral mucosal epithelium.
  3. 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.
  4. 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.
  5. 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.
  6. 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.
  7. 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.
  8. 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.
  9. 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.
  10. 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.
Submit: New GeneRIF Correction See all GeneRIFs (23)

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
Hearing loss, 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 PubChem

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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
enables extracellular matrix structural constituent conferring tensile strength HDA PubMed 
enables extracellular matrix structural constituent conferring tensile strength IBA
Inferred from Biological aspect of Ancestor
more info
  
enables extracellular matrix structural constituent conferring tensile strength RCA
inferred from Reviewed Computational Analysis
more info
 PubMed 
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
Process Evidence Code Pubs
involved_in cell adhesion IEA
Inferred from Electronic Annotation
more info
  
involved_in cellular response to amino acid stimulus IEA
Inferred from Electronic Annotation
more info
  
involved_in collagen-activated tyrosine kinase receptor signaling pathway IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in extracellular matrix organization IBA
Inferred from Biological aspect of Ancestor
more info
  
Component Evidence Code Pubs
is_active_in basement membrane IBA
Inferred from Biological aspect of Ancestor
more info
  
part_of collagen type IV trimer IBA
Inferred from Biological aspect of Ancestor
more info
  
part_of collagen type IV trimer NAS
Non-traceable Author Statement
more info
 PubMed 
located_in collagen-containing extracellular matrix HDA PubMed 
located_in endoplasmic reticulum lumen TAS
Traceable Author Statement
more info
  
located_in extracellular region TAS
Traceable Author Statement
more info
  
is_active_in extracellular space IBA
Inferred from Biological aspect of Ancestor
more info
  

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
    6053..288861
    Download
    GenBank, FASTA, Sequence Viewer (Graphics), LRG_233

mRNA and Protein(s)

  1. NM_001287758.2 → 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, AL136080, AW082083, BG680578, CA396616, CA489342, CB050016, CN313332, CN313341, CN313343, CN313347, CN313351, CX872164, DA748513
    Consensus CDS
    CCDS76010.1
    UniProtKB/TrEMBL
    A8MXH5, B7ZMM7
    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_001287759.2 → 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)
    AL136080, BC000874, BC144669, CB050016, CN313332, CN313347, DB260304, EU182215
    Consensus CDS
    CCDS76009.1
    UniProtKB/TrEMBL
    A0A087WZY5, 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_001287760.2 → 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/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_001847.4 → 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, AL136080, CB050016, U04845
    Consensus CDS
    CCDS14541.1
    UniProtKB/Swiss-Prot
    Q12823, Q14031, Q14053, Q5JYH6, Q5JYH8, Q9NQM5, Q9NTX3, Q9UJ76, Q9UMG6, Q9Y4L4
    UniProtKB/TrEMBL
    B7ZMM7
    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_033641.4 → 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)
    AL136080, BF726518, BQ331638, CB050016, CN313347, D21337, U04845
    Consensus CDS
    CCDS14542.1
    UniProtKB/TrEMBL
    B7ZMM7
    Related
    ENSP00000334733.7, ENST00000334504.12
    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: 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_000023.11 Reference GRCh38.p14 Primary Assembly

    Range
    108155614..108439458 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_047441813.1 → XP_047297769.1  collagen alpha-6(IV) chain isoform X4

  2. XM_011530852.3 → XP_011529154.1  collagen alpha-6(IV) chain isoform X2

    UniProtKB/TrEMBL
    B7ZMM7
    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_006724617.4 → XP_006724680.1  collagen alpha-6(IV) chain isoform X1

    UniProtKB/TrEMBL
    B7ZMM7
    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

  4. XM_011530853.4 → 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

  5. XM_047441818.1 → XP_047297774.1  collagen alpha-6(IV) chain isoform X9

  6. XM_047441816.1 → XP_047297772.1  collagen alpha-6(IV) chain isoform X7

  7. XM_011530854.3 → XP_011529156.1  collagen alpha-6(IV) chain isoform X5

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

  8. XM_047441819.1 → XP_047297775.1  collagen alpha-6(IV) chain isoform X10

  9. XM_047441817.1 → XP_047297773.1  collagen alpha-6(IV) chain isoform X8

  10. XM_047441815.1 → XP_047297771.1  collagen alpha-6(IV) chain isoform X6

RNA

  1. XR_001755650.2 RNA Sequence

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060947.1 Alternate T2T-CHM13v2.0

    Range
    106593205..106877000 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054326445.1 → XP_054182420.1  collagen alpha-6(IV) chain isoform X4

  2. XM_054326443.1 → XP_054182418.1  collagen alpha-6(IV) chain isoform X2

  3. XM_054326442.1 → XP_054182417.1  collagen alpha-6(IV) chain isoform X1

  4. XM_054326444.1 → XP_054182419.1  collagen alpha-6(IV) chain isoform X3

  5. XM_054326450.1 → XP_054182425.1  collagen alpha-6(IV) chain isoform X9

  6. XM_054326448.1 → XP_054182423.1  collagen alpha-6(IV) chain isoform X7

  7. XM_054326446.1 → XP_054182421.1  collagen alpha-6(IV) chain isoform X5

  8. XM_054326451.1 → XP_054182426.1  collagen alpha-6(IV) chain isoform X10

  9. XM_054326449.1 → XP_054182424.1  collagen alpha-6(IV) chain isoform X8

  10. XM_054326447.1 → XP_054182422.1  collagen alpha-6(IV) chain isoform X6

RNA

  1. XR_008485449.1 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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