COL4A1 collagen type IV alpha 1 chain [Homo sapiens (human)] - Gene

Summary

Official Symbol: COL4A1provided by HGNC
Official Full Name: collagen type IV alpha 1 chainprovided by HGNC
Primary source: HGNC:HGNC:2202
See related: Ensembl:ENSG00000187498 MIM:120130; AllianceGenome:HGNC:2202
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: BSVD; BSVD1; RATOR; PADMAL; COL4A1s
Summary: This gene encodes a type IV collagen alpha protein. Type IV collagen proteins are integral components of basement membranes. This gene shares a bidirectional promoter with a paralogous gene on the opposite strand. The protein consists of an amino-terminal 7S domain, a triple-helix forming collagenous domain, and a carboxy-terminal non-collagenous domain. It functions as part of a heterotrimer and interacts with other extracellular matrix components such as perlecans, proteoglycans, and laminins. In addition, proteolytic cleavage of the non-collagenous carboxy-terminal domain results in a biologically active fragment known as arresten, which has anti-angiogenic and tumor suppressor properties. Mutations in this gene cause porencephaly, cerebrovascular disease, and renal and muscular defects. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2014]
Expression: Biased expression in placenta (RPKM 204.1), fat (RPKM 72.2) and 9 other tissues See more
Orthologs: mouse all
NEW: Try the new Gene table
Try the new Transcript table

Genomic context

Location:: 13q34

Exon count:: 53

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	13	NC_000013.11 (110148963..110307157, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	13	NC_060937.1 (109377773..109536621, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	13	NC_000013.10 (110801310..110959504, complement)

Chromosome 13 - NC_000013.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

Go to the top of the page Help

Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

Go to the top of the page Help

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

Go to the top of the page Help

GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Collagen IV deficiency causes hypertrophic remodeling and endothelium-dependent hyperpolarization in small vessel disease with intracerebral hemorrhage.
Title: Collagen IV deficiency causes hypertrophic remodeling and endothelium-dependent hyperpolarization in small vessel disease with intracerebral hemorrhage.
Identification of seven variants in the col4a1 gene that alter RNA splicing by minigene assay.
Title: Identification of seven variants in the col4a1 gene that alter RNA splicing by minigene assay.
An AluYa5 Insertion in the 3'UTR of COL4A1 and Cerebral Small Vessel Disease.
Title: An AluYa5 Insertion in the 3'UTR of COL4A1 and Cerebral Small Vessel Disease.
Collagen type IV alpha 1 chain (COL4A1) expression in the developing human lung.
Title: Collagen type IV alpha 1 chain (COL4A1) expression in the developing human lung.
Potential risks associated with laparoscopic gastrostomy in patients with the COL4A1 variant: Two case reports.
Title: Potential risks associated with laparoscopic gastrostomy in patients with the COL4A1 variant: Two case reports.
Genotypic Analysis of COL4A1 Gene in Diabetic Nephropathy and Type 2 Diabetes Mellitus Patients: A Comparative Genetic Study.
Title: Genotypic Analysis of COL4A1 Gene in Diabetic Nephropathy and Type 2 Diabetes Mellitus Patients: A Comparative Genetic Study.
Collagen IV and Podocyte-Related Gene Variants in Patients with Concurrent IgA Nephropathy and Thin Basement Membrane Nephropathy.
Title: Collagen IV and Podocyte-Related Gene Variants in Patients with Concurrent IgA Nephropathy and Thin Basement Membrane Nephropathy.
Lysyl hydroxylase 3-mediated post-translational modifications are required for proper biosynthesis of collagen alpha1alpha1alpha2(IV).
Title: Lysyl hydroxylase 3-mediated post-translational modifications are required for proper biosynthesis of collagen α1α1α2(IV).
Next-generation sequencing in a large pedigree segregating visceral artery aneurysms suggests potential role of COL4A1/COL4A2 in disease etiology.
Title: Next-generation sequencing in a large pedigree segregating visceral artery aneurysms suggests potential role of COL4A1/COL4A2 in disease etiology.
The ETS1-LINC00278 negative feedback loop plays a role in COL4A1/COL4A2 regulation in laryngeal squamous cell carcinoma.
Title: The ETS1-LINC00278 negative feedback loop plays a role in COL4A1/COL4A2 regulation in laryngeal squamous cell carcinoma.

Submit: New GeneRIF Correction See all GeneRIFs (147)

Phenotypes

Go to the top of the page Help

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
Autosomal dominant familial hematuria-retinal arteriolar tortuosity-contractures syndrome MedGen: C2673195 OMIM: 611773 GeneReviews: COL4A1-Related Disorders	not available
Brain small vessel disease 1 with or without ocular anomalies MedGen: C4551998 OMIM: 175780 GeneReviews: COL4A1-Related Disorders	not available
Hemorrhage, intracerebral, susceptibility to MedGen: C3281105 OMIM: 614519 GeneReviews: Not available	not available
Microangiopathy and leukoencephalopathy, pontine, autosomal dominant MedGen: C5231411 OMIM: 618564 GeneReviews: Not available	not available
Retinal arterial tortuosity MedGen: C0423401 OMIM: 180000 GeneReviews: Not available	not available

EBI GWAS Catalog

Description
COL4A1 is associated with arterial stiffness by genome-wide association scan. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study for coronary artery calcification with follow-up in myocardial infarction. EBI GWAS Catalog EBI GWAS CatalogPubMed
Large-scale association analysis identifies 13 new susceptibility loci for coronary artery disease. EBI GWAS Catalog EBI GWAS CatalogPubMed
Meta-analysis of genome-wide association studies in multiethnic Asians identifies two loci for age-related nuclear cataract. EBI GWAS Catalog EBI GWAS CatalogPubMed
Novel genetic loci identified for the pathophysiology of childhood obesity in the Hispanic population. EBI GWAS Catalog EBI GWAS CatalogPubMed
Shared genetic susceptibility to ischemic stroke and coronary artery disease: a genome-wide analysis of common variants. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

Go to the top of the page Help

See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

Go to the top of the page Help

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

Go to the top of the page Help

Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

Go to the top of the page Help

Markers

073WE5 (e-PCR)
- UniSTS:43530

D13S1440 (e-PCR)
- UniSTS:22043

SHGC-52407 (e-PCR)
- UniSTS:12319

Col4a1 (e-PCR), detects polymorphism
- UniSTS:496710

WI-16856 (e-PCR)
- UniSTS:64599

D13S148 (e-PCR)
- UniSTS:10617

COL4A1__1176 (e-PCR)
- UniSTS:277116

SHGC-147331 (e-PCR)
- UniSTS:175747

G32294 (e-PCR)
- UniSTS:116890

A005V07 (e-PCR)
- UniSTS:57514

D13S1449 (e-PCR)
- UniSTS:82630

D12S2121 (e-PCR)
- UniSTS:71885

WI-14843 (e-PCR)
- UniSTS:14310

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	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	IMP Inferred from Mutant Phenotype more info	PubMed
enables extracellular matrix structural constituent conferring tensile strength	RCA inferred from Reviewed Computational Analysis more info	PubMed
enables platelet-derived growth factor binding	IDA Inferred from Direct Assay more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in basement membrane organization	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in blood vessel morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in brain development	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in branching involved in blood vessel morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cellular response to amino acid stimulus	IEA Inferred from Electronic Annotation more info
involved_in collagen-activated tyrosine kinase receptor signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in epithelial cell differentiation	IEA Inferred from Electronic Annotation more info
involved_in extracellular matrix organization	IBA Inferred from Biological aspect of Ancestor more info
involved_in neuromuscular junction development	IEA Inferred from Electronic Annotation more info
involved_in renal tubule morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in retinal blood vessel morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
located_in basement membrane	IC Inferred by Curator more info	PubMed
part_of collagen type IV trimer	IMP Inferred from Mutant Phenotype more info	PubMed
located_in collagen-containing extracellular matrix	HDA more info	PubMed
is_active_in collagen-containing extracellular matrix	IBA Inferred from Biological aspect of Ancestor more info
colocalizes_with collagen-containing extracellular matrix	ISS Inferred from Sequence or Structural Similarity more info	PubMed
located_in endoplasmic reticulum lumen	TAS Traceable Author Statement more info
located_in extracellular region	NAS Non-traceable Author Statement more info	PubMed
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

Go to the top of the page Help

Preferred Names: collagen alpha-1(IV) chain

Names: COL4A1 NC1 domain; arresten; collagen IV, alpha-1 polypeptide; collagen of basement membrane, alpha-1 chain

NCBI Reference Sequences (RefSeq)

Go to the top of the page Help

NEW Try the new Transcript table

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_011544.2 RefSeqGene

Range

4993..163187

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_1116

mRNA and Protein(s)

NM_001303110.2 → NP_001290039.1 collagen alpha-1(IV) chain isoform 2 precursor

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks alternate exons in the 3' region and contains an alternate 3' terminal exon, resulting in a distinct 3' coding region and 3' UTR compared to variant 1. The encoded isoform (2) has a distinct and shorter C-terminus compared to isoform 1.

Source sequence(s)

AL161773, AL390755, BC142626, X05561

Consensus CDS

CCDS76649.1

UniProtKB/TrEMBL

A5PKV2

Related

ENSP00000443348.1, ENST00000543140.6

Conserved Domains (2) summary

PTZ00449
Location:231 → 310

PTZ00449; 104 kDa microneme/rhoptry antigen; Provisional

pfam01391
Location:275 → 325

Collagen; Collagen triple helix repeat (20 copies)
NM_001845.6 → NP_001836.3 collagen alpha-1(IV) chain isoform 1 preproprotein

See identical proteins and their annotated locations for NP_001836.3

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).

Source sequence(s)

AA678474, AL161773, AL390755, BC047305, BC151220, X05561, Y00706

Consensus CDS

CCDS9511.1

UniProtKB/Swiss-Prot

A7E2W4, B1AM70, F5H5K0, P02462, Q1P9S9, Q5VWF6, Q86X41, Q8NF88, Q9NYC5

UniProtKB/TrEMBL

A0A3B3ISV3

Related

ENSP00000364979.4, ENST00000375820.10

Conserved Domains (2) summary

pfam01391
Location:975 → 1033

Collagen; Collagen triple helix repeat (20 copies)

pfam01413
Location:1556 → 1666

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