COL4A2

Chr 13ADAR

collagen type IV alpha 2 chain

Also known as: BSVD2, BSVD2A, BSVD2B, ICH, POREN2

NCBI Gene: 1284 ENSG00000134871 UniProt: P08572 OMIM: 120090

The protein is a subunit of type IV collagen, the major structural component of basement membranes including those in blood vessels and glomeruli. Mutations cause brain small vessel disease with intracerebral hemorrhage susceptibility, inherited in either autosomal dominant or autosomal recessive patterns depending on the specific variant. This gene is highly constrained against loss-of-function variants, indicating that such mutations are likely to be pathogenic.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes one of the six subunits of type IV collagen, the major structural component of basement membranes. The C-terminal portion of the protein, known as canstatin, is an inhibitor of angiogenesis and tumor growth. 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, Jul 2008]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

{Hemorrhage, intracerebral, susceptibility to}MIM #614519

Brain small vessel disease 2A, autosomal dominantMIM #614483

Brain small vessel disease 2B, autosomal recessiveMIM #621414

UniProtIntracerebral hemorrhage

Clinical highlights

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

112

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.58

LOEUF

Mechanism· G2P