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

    Gene ID: 1288, updated on 10-Dec-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
    mouse all
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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_2024_08 current GRCh38.p14 (GCF_000001405.40) X NC_000023.11 (108155614..108439458, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) X NC_060947.1 (106593205..106877000, complement)
    RS_2024_09 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. 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
    2. 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
    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. 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
    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 (72) 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
    		Compare labs

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    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
    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 
    is_active_in collagen-containing extracellular matrix IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    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_2024_08

    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

      UniProtKB/TrEMBL
      B7ZMM7

    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

      UniProtKB/TrEMBL
      B7ZMM7

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

      UniProtKB/TrEMBL
      B7ZMM7

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

      UniProtKB/TrEMBL
      B7ZMM7

    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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