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COL4A4 collagen type IV alpha 4 chain [ Homo sapiens (human) ]

Gene ID: 1286, updated on 16-Apr-2024

Summary

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Official Symbol
COL4A4provided by HGNC
Official Full Name
collagen type IV alpha 4 chainprovided by HGNC
Primary source
HGNC:HGNC:2206
See related
Ensembl:ENSG00000081052 MIM:120131; AllianceGenome:HGNC:2206
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
BFH; ATS2; BFH1; CA44
Summary
This gene encodes one of the six subunits of type IV collagen, the major structural component of basement membranes. This particular collagen IV subunit, however, is only found in a subset 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 so that each gene pair shares a common promoter. Mutations in this gene are associated with type II autosomal recessive Alport syndrome (hereditary glomerulonephropathy) and with familial benign hematuria (thin basement membrane disease). Two transcripts, differing only in their transcription start sites, have been identified for this gene and, as is common for collagen genes, multiple polyadenylation sites are found in the 3' UTR. [provided by RefSeq, Jul 2008]
Expression
Broad expression in kidney (RPKM 5.3), thyroid (RPKM 4.9) and 18 other tissues See more
Orthologs
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Genomic context

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Location:
2q36.3
Exon count:
57
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 2 NC_000002.12 (226967360..227164488, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 2 NC_060926.1 (227431447..227647252, complement)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 2 NC_000002.11 (227867430..228028921, complement)

Chromosome 2 - NC_000002.12Genomic Context describing neighboring genes Neighboring gene MPRA-validated peak4064 silencer Neighboring gene MPRA-validated peak4065 silencer Neighboring gene microRNA 5702 Neighboring gene Sharpr-MPRA regulatory region 3334 Neighboring gene MPRA-validated peak4066 silencer Neighboring gene Sharpr-MPRA regulatory region 11623 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 12389 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr2:227661675-227662624 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 12390 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 12391 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 12392 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 12393 Neighboring gene insulin receptor substrate 1 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr2:227677874-227678445 Neighboring gene Sharpr-MPRA regulatory region 3963 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 12394 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 17195 Neighboring gene rhomboid domain containing 1 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 12395 Neighboring gene MPRA-validated peak4067 silencer Neighboring gene small nucleolar RNA SNORA48 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 17196 Neighboring gene P300/CBP strongly-dependent group 1 enhancer GRCh37_chr2:227859794-227860993 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr2:227929821-227930408 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:228028248-228029149 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 12397 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr2:228050272-228050810 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr2:228055439-228056638 Neighboring gene collagen type IV alpha 3 chain Neighboring gene MFF divergent transcript Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr2:228185522-228186050 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 17198 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 12398 Neighboring gene stress induced phosphoprotein 1 pseudogene 2 Neighboring gene mitochondrial fission factor

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. A COL4A4-G394S Variant and Impaired Collagen IV Trimerization in a Patient with Mild Alport Syndrome. Kohler J, et al. Kidney360, 2022 Nov 24. PMID 36514391, Free PMC Article
  2. COL4A4 variant recently identified: lessons learned in variant interpretation-a case report. Cocorpus J, et al. BMC Nephrol, 2022 Jul 16. PMID 35842573, Free PMC Article
  3. Clinical and pathohistological characteristics of Alport spectrum disorder caused by COL4A4 mutation c.193-2A>C: a case series. Šenjug P, et al. Croat Med J, 2021 Jun 30. PMID 34212557, Free PMC Article
  4. Population-based studies reveal an additive role of type IV collagen variants in hematuria and albuminuria. Barua M, et al. Pediatr Nephrol, 2022 Feb. PMID 33635378
  5. A novel heterozygous variant of the COL4A4 gene in a Chinese family with hematuria and proteinuria leads to focal segmental glomerulosclerosis and chronic kidney disease. Fan LL, et al. Mol Genet Genomic Med, 2020 Dec. PMID 33159707, Free PMC Article

See all (115) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Genetic diagnosis of Alport syndrome in 16 Chinese families.
    Title: Genetic diagnosis of Alport syndrome in 16 Chinese families.
  2. Is there a dominant-negative effect in individuals with heterozygous disease-causing variants in COL4A3/COL4A4?
    Title: Is there a dominant-negative effect in individuals with heterozygous disease-causing variants in COL4A3/COL4A4?
  3. Potential Founder Variants in COL4A4 Identified in Bukharian Jews Linked to Autosomal Dominant and Autosomal Recessive Alport Syndrome.
    Title: Potential Founder Variants in COL4A4 Identified in Bukharian Jews Linked to Autosomal Dominant and Autosomal Recessive Alport Syndrome.
  4. COL4A gene variants are common in children with hematuria and a family history of kidney disease.
    Title: COL4A gene variants are common in children with hematuria and a family history of kidney disease.
  5. Genetic Variants of the COL4A3 , COL4A4 , and COL4A5 Genes Contribute to Thinned Glomerular Basement Membrane Lesions in Sporadic IgA Nephropathy Patients.
    Title: Genetic Variants of the COL4A3 , COL4A4 , and COL4A5 Genes Contribute to Thinned Glomerular Basement Membrane Lesions in Sporadic IgA Nephropathy Patients.
  6. A COL4A4-G394S Variant and Impaired Collagen IV Trimerization in a Patient with Mild Alport Syndrome.
    Title: A COL4A4-G394S Variant and Impaired Collagen IV Trimerization in a Patient with Mild Alport Syndrome.
  7. Heterozygous COL4A3/COL4A4 mutations: the hidden part of the iceberg?
    Title: Heterozygous COL4A3/COL4A4 mutations: the hidden part of the iceberg?
  8. COL4A4 variant recently identified: lessons learned in variant interpretation-a case report.
    Title: COL4A4 variant recently identified: lessons learned in variant interpretation-a case report.
  9. Population-based studies reveal an additive role of type IV collagen variants in hematuria and albuminuria.
    Title: Population-based studies reveal an additive role of type IV collagen variants in hematuria and albuminuria.
  10. Heterozygous Urinary Abnormality-Causing Variants of COL4A3 and COL4A4 Affect Severity of Autosomal Recessive Alport Syndrome.
    Title: Heterozygous Urinary Abnormality-Causing Variants of COL4A3 and COL4A4 Affect Severity of Autosomal Recessive Alport Syndrome.
Submit: New GeneRIF Correction See all GeneRIFs (67)

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
Alport syndrome
MedGen: C1567741 GeneReviews: Not available
Compare labs
Autosomal recessive Alport syndrome
MedGen: C4746745 OMIM: 203780 GeneReviews: Alport Syndrome
Compare labs
Hematuria, benign familial, 1
MedGen: CN376803 OMIM: 141200 GeneReviews: Not available
not available

EBI GWAS Catalog

Description
Genome-wide analysis of polymorphisms associated with cytokine responses in smallpox vaccine recipients.
EBI GWAS Catalog

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
Envelope surface glycoprotein gp160, precursor env HIV-1 gp160 and serum-free macrophage supernatant (MSP) enhance synthesis of type IV collagen by mesangial cells; anti-TGF-beta antibodies attenuate this gp160/MSP-induced collagen synthesis PubMed
Tat 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
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

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

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables extracellular matrix structural constituent IMP
Inferred from Mutant Phenotype
more info
 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 molecular adaptor activity EXP
Inferred from Experiment
more info
 PubMed 
Process Evidence Code Pubs
involved_in glomerular basement membrane development IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in glomerular basement membrane development IMP
Inferred from Mutant Phenotype
more info
 PubMed 
Component Evidence Code Pubs
located_in basement membrane IDA
Inferred from Direct Assay
more info
 PubMed 
part_of collagen type IV trimer IBA
Inferred from Biological aspect of Ancestor
more info
  
part_of collagen type IV trimer IDA
Inferred from Direct Assay
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-4(IV) chain
Names
Collagen IV, alpha-4 polypeptide
collagen of basement membrane, alpha-4 chain
collagen, type IV, alpha 4

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_011592.1 RefSeqGene

    Range
    5001..166849
    Download
    GenBank, FASTA, Sequence Viewer (Graphics), LRG_231

mRNA and Protein(s)

  1. NM_000092.5 → NP_000083.3  collagen alpha-4(IV) chain precursor

    See identical proteins and their annotated locations for NP_000083.3

    Status: REVIEWED

    Source sequence(s)
    AC073149, AC079235, BX094848, X81053
    Consensus CDS
    CCDS42828.1
    UniProtKB/Swiss-Prot
    A8MTZ1, P53420, Q53RW9, Q53S42, Q53WR1
    Related
    ENSP00000379866.3, ENST00000396625.5
    Conserved Domains (2) summary
    pfam01391
    Location:829 → 880
    Collagen; Collagen triple helix repeat (20 copies)
    pfam01413
    Location:1466 → 1570
    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_000002.12 Reference GRCh38.p14 Primary Assembly

    Range
    226967360..227164488 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_011510565.3 → XP_011508867.1  collagen alpha-4(IV) chain isoform X10

    Conserved Domains (1) summary
    pfam01391
    Location:829 → 880
    Collagen; Collagen triple helix repeat (20 copies)

  2. XM_011510570.3 → XP_011508872.1  collagen alpha-4(IV) chain isoform X13

    See identical proteins and their annotated locations for XP_011508872.1

    Conserved Domains (1) summary
    pfam01391
    Location:829 → 880
    Collagen; Collagen triple helix repeat (20 copies)

  3. XM_011510562.3 → XP_011508864.1  collagen alpha-4(IV) chain isoform X7

    See identical proteins and their annotated locations for XP_011508864.1

    Conserved Domains (3) summary
    pfam01391
    Location:829 → 880
    Collagen; Collagen triple helix repeat (20 copies)
    pfam01413
    Location:1466 → 1570
    C4; C-terminal tandem repeated domain in type 4 procollagen
    cl02467
    Location:1574 → 1607
    C4; C-terminal tandem repeated domain in type 4 procollagen

  4. XM_047443250.1 → XP_047299206.1  collagen alpha-4(IV) chain isoform X13

  5. XM_047443245.1 → XP_047299201.1  collagen alpha-4(IV) chain isoform X7

  6. XM_011510569.3 → XP_011508871.1  collagen alpha-4(IV) chain isoform X13

    See identical proteins and their annotated locations for XP_011508871.1

    Conserved Domains (1) summary
    pfam01391
    Location:829 → 880
    Collagen; Collagen triple helix repeat (20 copies)

  7. XM_011510567.3 → XP_011508869.1  collagen alpha-4(IV) chain isoform X11

    See identical proteins and their annotated locations for XP_011508869.1

    Conserved Domains (1) summary
    pfam01391
    Location:829 → 880
    Collagen; Collagen triple helix repeat (20 copies)

  8. XM_047443249.1 → XP_047299205.1  collagen alpha-4(IV) chain isoform X11

  9. XM_011510566.3 → XP_011508868.1  collagen alpha-4(IV) chain isoform X11

    See identical proteins and their annotated locations for XP_011508868.1

    Conserved Domains (1) summary
    pfam01391
    Location:829 → 880
    Collagen; Collagen triple helix repeat (20 copies)

  10. XM_047443248.1 → XP_047299204.1  collagen alpha-4(IV) chain isoform X11

  11. XM_011510561.3 → XP_011508863.1  collagen alpha-4(IV) chain isoform X7

    See identical proteins and their annotated locations for XP_011508863.1

    Conserved Domains (3) summary
    pfam01391
    Location:829 → 880
    Collagen; Collagen triple helix repeat (20 copies)
    pfam01413
    Location:1466 → 1570
    C4; C-terminal tandem repeated domain in type 4 procollagen
    cl02467
    Location:1574 → 1607
    C4; C-terminal tandem repeated domain in type 4 procollagen

  12. XM_011510560.3 → XP_011508862.1  collagen alpha-4(IV) chain isoform X6

    See identical proteins and their annotated locations for XP_011508862.1

    Conserved Domains (3) summary
    pfam01391
    Location:829 → 880
    Collagen; Collagen triple helix repeat (20 copies)
    pfam01413
    Location:1466 → 1570
    C4; C-terminal tandem repeated domain in type 4 procollagen
    cl02467
    Location:1574 → 1605
    C4; C-terminal tandem repeated domain in type 4 procollagen

  13. XM_047443242.1 → XP_047299198.1  collagen alpha-4(IV) chain isoform X6

  14. XM_011510559.3 → XP_011508861.1  collagen alpha-4(IV) chain isoform X6

    See identical proteins and their annotated locations for XP_011508861.1

    Conserved Domains (3) summary
    pfam01391
    Location:829 → 880
    Collagen; Collagen triple helix repeat (20 copies)
    pfam01413
    Location:1466 → 1570
    C4; C-terminal tandem repeated domain in type 4 procollagen
    cl02467
    Location:1574 → 1605
    C4; C-terminal tandem repeated domain in type 4 procollagen

  15. XM_047443241.1 → XP_047299197.1  collagen alpha-4(IV) chain isoform X6

  16. XM_047443228.1 → XP_047299184.1  collagen alpha-4(IV) chain isoform X1

    UniProtKB/Swiss-Prot
    A8MTZ1, P53420, Q53RW9, Q53S42, Q53WR1

  17. XM_005246281.4 → XP_005246338.1  collagen alpha-4(IV) chain isoform X1

    See identical proteins and their annotated locations for XP_005246338.1

    UniProtKB/Swiss-Prot
    A8MTZ1, P53420, Q53RW9, Q53S42, Q53WR1
    Conserved Domains (2) summary
    pfam01391
    Location:829 → 880
    Collagen; Collagen triple helix repeat (20 copies)
    pfam01413
    Location:1466 → 1570
    C4; C-terminal tandem repeated domain in type 4 procollagen

  18. XM_005246282.4 → XP_005246339.1  collagen alpha-4(IV) chain isoform X8

    Conserved Domains (2) summary
    pfam01391
    Location:644 → 695
    Collagen; Collagen triple helix repeat (20 copies)
    pfam01413
    Location:1281 → 1385
    C4; C-terminal tandem repeated domain in type 4 procollagen

  19. XM_011510558.3 → XP_011508860.1  collagen alpha-4(IV) chain isoform X3

    Conserved Domains (2) summary
    pfam01391
    Location:793 → 844
    Collagen; Collagen triple helix repeat (20 copies)
    pfam01413
    Location:1430 → 1534
    C4; C-terminal tandem repeated domain in type 4 procollagen

  20. XM_011510557.3 → XP_011508859.1  collagen alpha-4(IV) chain isoform X2

    Conserved Domains (2) summary
    pfam01391
    Location:829 → 880
    Collagen; Collagen triple helix repeat (20 copies)
    pfam01413
    Location:1439 → 1543
    C4; C-terminal tandem repeated domain in type 4 procollagen

  21. XM_017003297.2 → XP_016858786.1  collagen alpha-4(IV) chain isoform X4

  22. XM_006712246.4 → XP_006712309.1  collagen alpha-4(IV) chain isoform X5

    Conserved Domains (3) summary
    pfam01391
    Location:829 → 880
    Collagen; Collagen triple helix repeat (20 copies)
    pfam01413
    Location:1511 → 1623
    C4; C-terminal tandem repeated domain in type 4 procollagen
    cl02467
    Location:1445 → 1507
    C4; C-terminal tandem repeated domain in type 4 procollagen

  23. XM_011510572.4 → XP_011508874.1  collagen alpha-4(IV) chain isoform X14

    Conserved Domains (2) summary
    pfam01391
    Location:271 → 322
    Collagen; Collagen triple helix repeat (20 copies)
    pfam01413
    Location:908 → 1012
    C4; C-terminal tandem repeated domain in type 4 procollagen

  24. XM_047443246.1 → XP_047299202.1  collagen alpha-4(IV) chain isoform X9

  25. XM_011510568.3 → XP_011508870.1  collagen alpha-4(IV) chain isoform X12

    Conserved Domains (1) summary
    pfam01391
    Location:829 → 880
    Collagen; Collagen triple helix repeat (20 copies)

RNA

  1. XR_922837.3 RNA Sequence

  2. XR_001738602.2 RNA Sequence

  3. XR_007069255.1 RNA Sequence

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060926.1 Alternate T2T-CHM13v2.0

    Range
    227431447..227647252 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054340451.1 → XP_054196426.1  collagen alpha-4(IV) chain isoform X10

  2. XM_054340458.1 → XP_054196433.1  collagen alpha-4(IV) chain isoform X13

  3. XM_054340447.1 → XP_054196422.1  collagen alpha-4(IV) chain isoform X7

  4. XM_054340455.1 → XP_054196430.1  collagen alpha-4(IV) chain isoform X11

  5. XM_054340453.1 → XP_054196428.1  collagen alpha-4(IV) chain isoform X11

  6. XM_054340454.1 → XP_054196429.1  collagen alpha-4(IV) chain isoform X11

  7. XM_054340452.1 → XP_054196427.1  collagen alpha-4(IV) chain isoform X11

  8. XM_054340457.1 → XP_054196432.1  collagen alpha-4(IV) chain isoform X13

  9. XM_054340448.1 → XP_054196423.1  collagen alpha-4(IV) chain isoform X7

  10. XM_054340446.1 → XP_054196421.1  collagen alpha-4(IV) chain isoform X6

  11. XM_054340444.1 → XP_054196419.1  collagen alpha-4(IV) chain isoform X6

  12. XM_054340445.1 → XP_054196420.1  collagen alpha-4(IV) chain isoform X6

  13. XM_054340443.1 → XP_054196418.1  collagen alpha-4(IV) chain isoform X6

  14. XM_054340437.1 → XP_054196412.1  collagen alpha-4(IV) chain isoform X1

  15. XM_054340438.1 → XP_054196413.1  collagen alpha-4(IV) chain isoform X1

  16. XM_054340449.1 → XP_054196424.1  collagen alpha-4(IV) chain isoform X8

  17. XM_054340440.1 → XP_054196415.1  collagen alpha-4(IV) chain isoform X3

  18. XM_054340439.1 → XP_054196414.1  collagen alpha-4(IV) chain isoform X2

  19. XM_054340441.1 → XP_054196416.1  collagen alpha-4(IV) chain isoform X4

  20. XM_054340442.1 → XP_054196417.1  collagen alpha-4(IV) chain isoform X5

  21. XM_054340459.1 → XP_054196434.1  collagen alpha-4(IV) chain isoform X14

  22. XM_054340450.1 → XP_054196425.1  collagen alpha-4(IV) chain isoform X9

  23. XM_054340456.1 → XP_054196431.1  collagen alpha-4(IV) chain isoform X12

RNA

  1. XR_008486265.1 RNA Sequence

  2. XR_008486264.1 RNA Sequence

  3. XR_008486263.1 RNA Sequence

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
P53420.3 GenPept UniProtKB/Swiss-Prot:P53420

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