COL4A1

Chr 13

collagen type IV alpha 1 chain

Also known as: BSVD, BSVD1, COL4A1s, PADMAL, RATOR

NCBI Gene: 1282 ENSG00000187498 UniProt: P02462

The encoded type IV collagen alpha protein functions as part of a heterotrimer that forms integral components of basement membranes and interacts with other extracellular matrix components including perlecans, proteoglycans, and laminins. Mutations cause autosomal dominant conditions including hereditary angiopathy with nephropathy, aneurysms and muscle cramps, brain small vessel disease with or without ocular anomalies, and pontine microangiopathy with leukoencephalopathy. The pathogenic mechanism involves loss of function, leading to compromised basement membrane integrity in cerebrovascular and other tissues.

ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

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]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtHereditary angiopathy with nephropathy aneurysms and muscle cramps

UniProtBrain small vessel disease 1 with or without ocular anomalies

UniProtIntracerebral hemorrhage

UniProtTortuosity of retinal arteries

Clinical highlights

Gene-disease validity (ClinGen)

COL4A1-related disorder · ADDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

A dominant-negative effect is the curated mechanism (Gene2Phenotype), so a variant that simply removes the protein may not be the pathogenic class here — missense variants in functional domains often carry more weight.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

212

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.13

LOEUF· LoF intol.

DN*

Mechanism· G2P

Some data sources returned errors (1)