COL4A3 collagen type IV alpha 3 chain [Homo sapiens (human)] - Gene

Summary

Official Symbol: COL4A3provided by HGNC
Official Full Name: collagen type IV alpha 3 chainprovided by HGNC
Primary source: HGNC:HGNC:2204
See related: Ensembl:ENSG00000169031 MIM:120070; AllianceGenome:HGNC:2204
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: ATS2; ATS3; BFH2; ATS3A; ATS3B
Summary: Type IV collagen, the major structural component of basement membranes, is a multimeric protein composed of 3 alpha subunits. These subunits are encoded by 6 different genes, alpha 1 through alpha 6, each of which can form a triple helix structure with 2 other subunits to form type IV collagen. This gene encodes alpha 3. In the Goodpasture syndrome, autoantibodies bind to the collagen molecules in the basement membranes of alveoli and glomeruli. The epitopes that elicit these autoantibodies are localized largely to the non-collagenous C-terminal domain of the protein. A specific kinase phosphorylates amino acids in this same C-terminal region and the expression of this kinase is upregulated during pathogenesis. This gene is also linked to an autosomal recessive form of Alport syndrome. The mutations contributing to this syndrome are also located within the exons that encode this C-terminal region. 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. [provided by RefSeq, Jun 2010]
Expression: Biased expression in kidney (RPKM 8.1), lung (RPKM 7.4) and 12 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 2q36.3

Exon count:: 54

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	2	NC_000002.12 (227164624..227314792)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	2	NC_060926.1 (227647382..227797471)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	2	NC_000002.11 (228029340..228179508)

Chromosome 2 - NC_000002.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Genetic diagnosis of Alport syndrome in 16 Chinese families.
Title: Genetic diagnosis of Alport syndrome in 16 Chinese families.
Pregnancy in women with autosomal recessive Alport syndrome caused by novel compound heterozygous mutations of COL4A3 gene: Two cases reports.
Title: Pregnancy in women with autosomal recessive Alport syndrome caused by novel compound heterozygous mutations of COL4A3 gene: Two cases reports.
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?
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.
Clinical and histopathological characteristics of COL4A3 c.2881+1G>A variant causing Alport spectrum disorders in Croatian population.
Title: Clinical and histopathological characteristics of COL4A3 c.2881+1G>A variant causing Alport spectrum disorders in Croatian population.
Variants in genes coding for collagen type IV alpha-chains are frequent causes of persistent, isolated hematuria during childhood.
Title: Variants in genes coding for collagen type IV α-chains are frequent causes of persistent, isolated hematuria during childhood.
Heterozygous COL4A3/COL4A4 mutations: the hidden part of the iceberg?
Title: Heterozygous COL4A3/COL4A4 mutations: the hidden part of the iceberg?
Association between COL4A3 variant rs55703767 and susceptibility to diabetic kidney disease in patients with type 2 diabetes mellitus: results from the INDEED cohort study.
Title: Association between COL4A3 variant rs55703767 and susceptibility to diabetic kidney disease in patients with type 2 diabetes mellitus: results from the INDEED cohort study.
Pseudodominant Alport syndrome caused by pathogenic homozygous and compound heterozygous COL4A3 splicing variants.
Title: Pseudodominant Alport syndrome caused by pathogenic homozygous and compound heterozygous COL4A3 splicing variants.
Genetic heterogeneity in GJB2, COL4A3, ATP6V1B1 and EDNRB variants detected among hearing impaired families in Morocco.
Title: Genetic heterogeneity in GJB2, COL4A3, ATP6V1B1 and EDNRB variants detected among hearing impaired families in Morocco.

Submit: New GeneRIF Correction See all GeneRIFs (105)

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
Alport syndrome 3b, autosomal recessive MedGen: CN375559 OMIM: 620536 GeneReviews: Alport Syndrome	not available
Autosomal dominant Alport syndrome MedGen: C4746547 OMIM: 104200 GeneReviews: Alport Syndrome	Compare labs
Hematuria, benign familial, 2 MedGen: C5830421 OMIM: 620320 GeneReviews: Not available	not available

EBI GWAS Catalog

Description
Genome-wide association analyses identify multiple loci associated with central corneal thickness and keratoconus. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study of monoamine metabolite levels in human cerebrospinal fluid. EBI GWAS Catalog EBI GWAS CatalogPubMed

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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Replication interactions

Interaction	Pubs
Knockdown of collagen, type IV, alpha 3 (COL4A3) by siRNA enhances the early stages of HIV-1 replication in HeLa-CD4 cells infected with viral pseudotypes HIV89.6R and HIV8.2N	PubMed

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	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

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

SHGC-9488 (e-PCR)
- UniSTS:43531

D2S2158 (e-PCR)
- UniSTS:14096

COL4A3 (e-PCR)
- UniSTS:480029

RH92131 (e-PCR)
- UniSTS:89117

RH79227 (e-PCR)
- UniSTS:33623

SHGC-154740 (e-PCR)
- UniSTS:183389

D2S2555 (e-PCR)
- UniSTS:22382

GDB:304589 (e-PCR)
- UniSTS:156405

G10620 (e-PCR)
- UniSTS:19705

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables extracellular matrix structural constituent conferring tensile strength	HDA 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 integrin binding	IDA Inferred from Direct Assay more info	PubMed
enables integrin binding	TAS Traceable Author Statement more info	PubMed
enables metalloendopeptidase inhibitor activity	NAS Non-traceable Author Statement more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables structural molecule activity	NAS Non-traceable Author Statement more info	PubMed

Process	Evidence Code	Pubs
involved_in activation of cysteine-type endopeptidase activity involved in apoptotic process	IDA Inferred from Direct Assay more info	PubMed
involved_in blood circulation	TAS Traceable Author Statement more info	PubMed
involved_in cell adhesion	IEA Inferred from Electronic Annotation more info
involved_in cell surface receptor signaling pathway	NAS Non-traceable Author Statement more info	PubMed
involved_in collagen-activated tyrosine kinase receptor signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in endothelial cell apoptotic process	IDA Inferred from Direct Assay more info	PubMed
involved_in extracellular matrix organization	IBA Inferred from Biological aspect of Ancestor more info
involved_in glomerular basement membrane development	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of angiogenesis	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of cell population proliferation	TAS Traceable Author Statement more info	PubMed
involved_in negative regulation of vascular endothelial cell proliferation	IDA Inferred from Direct Assay more info	PubMed
involved_in response to glucose	IEA Inferred from Electronic Annotation more info
involved_in sensory perception of sound	TAS Traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
is_active_in basement membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in basement membrane	IDA Inferred from Direct Assay more info	PubMed
part_of collagen type IV trimer	IDA Inferred from Direct Assay more info	PubMed
located_in collagen-containing extracellular matrix	HDA more info	PubMed
located_in endoplasmic reticulum	IDA Inferred from Direct Assay 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
located_in intracellular membrane-bounded organelle	IDA Inferred from Direct Assay more info

General protein information

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Preferred Names: collagen alpha-3(IV) chain

Names: collagen IV, alpha-3 polypeptide; collagen, type IV, alpha 3 (Goodpasture antigen); tumstatin

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

NG_011591.1 RefSeqGene

Range

5001..155228

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_230

mRNA and Protein(s)

NM_000091.5 → NP_000082.2 collagen alpha-3(IV) chain precursor

See identical proteins and their annotated locations for NP_000082.2

Status: REVIEWED

Source sequence(s)

AC097662, AC107069, AU099354, BM670570, BM712932, CD675393, X80031

Consensus CDS

CCDS42829.1

UniProtKB/Swiss-Prot

Q01955, Q53QQ1, Q53R14, Q53RW8, Q9BQT2, Q9NYC4, Q9UDJ9, Q9UDK9, Q9UDL0, Q9UDL1

Related

ENSP00000379823.3, ENST00000396578.8

Conserved Domains (2) summary

pfam01391
Location:67 → 124

Collagen; Collagen triple helix repeat (20 copies)

pfam01413
Location:1446 → 1552

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

NC_000002.12 Reference GRCh38.p14 Primary Assembly

Range

227164624..227314792

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_005246277.4 → XP_005246334.1 collagen alpha-3(IV) chain isoform X1

Conserved Domains (2) summary

pfam01391
Location:67 → 124

Collagen; Collagen triple helix repeat (20 copies)

pfam01413
Location:1411 → 1517

C4; C-terminal tandem repeated domain in type 4 procollagen
XM_011510555.2 → XP_011508857.1 collagen alpha-3(IV) chain isoform X2

Conserved Domains (3) summary

pfam01391
Location:67 → 124

Collagen; Collagen triple helix repeat (20 copies)

pfam01413
Location:1446 → 1552

C4; C-terminal tandem repeated domain in type 4 procollagen

cl02467
Location:1556 → 1586

C4; C-terminal tandem repeated domain in type 4 procollagen
XM_047443224.1 → XP_047299180.1 collagen alpha-3(IV) chain isoform X3
XM_006712245.4 → XP_006712308.1 collagen alpha-3(IV) chain isoform X4

Conserved Domains (1) summary

pfam01391
Location:67 → 124

Collagen; Collagen triple helix repeat (20 copies)
XM_017003295.2 → XP_016858784.1 collagen alpha-3(IV) chain isoform X5
XM_005246280.4 → XP_005246337.1 collagen alpha-3(IV) chain isoform X6

Conserved Domains (1) summary

pfam01391
Location:67 → 124

Collagen; Collagen triple helix repeat (20 copies)

RNA

XR_001738601.2 RNA Sequence

Alternate T2T-CHM13v2.0

Genomic

NC_060926.1 Alternate T2T-CHM13v2.0

Range

227647382..227797471

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054340431.1 → XP_054196406.1 collagen alpha-3(IV) chain isoform X1
XM_054340432.1 → XP_054196407.1 collagen alpha-3(IV) chain isoform X2
XM_054340433.1 → XP_054196408.1 collagen alpha-3(IV) chain isoform X3
XM_054340434.1 → XP_054196409.1 collagen alpha-3(IV) chain isoform X4
XM_054340435.1 → XP_054196410.1 collagen alpha-3(IV) chain isoform X5
XM_054340436.1 → XP_054196411.1 collagen alpha-3(IV) chain isoform X6

RNA

XR_008486262.1 RNA Sequence

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

NM_031362.2: Suppressed sequence

Description

NM_031362.2: This RefSeq was permanently suppressed because currently there is insufficient support for the transcript and the protein.
NM_031363.1: Suppressed sequence

Description

NM_031363.1: This RefSeq was permanently suppressed because it is a nonsense-mediated decay (NMD) candidate.
NM_031364.1: Suppressed sequence

Description

NM_031364.1: This RefSeq was permanently suppressed because it is a nonsense-mediated decay (NMD) candidate.
NM_031365.2: Suppressed sequence

Description

NM_031365.2: This RefSeq was permanently suppressed because currently there is insufficient support for the transcript and the protein.
NM_031366.2: Suppressed sequence

Description

NM_031366.2: This RefSeq was permanently suppressed because currently there is insufficient support for the transcript and the protein.