COL4A2

Chr 13ADAR

collagen type IV alpha 2 chain

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

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.

OMIMResearchSummary from RefSeq, OMIM, UniProt
DNmechanismAD/ARLOEUF 0.583 OMIM phenotypes
Clinical SummaryCOL4A2
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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Clinical Trials
2 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.58LOEUF
pLI 0.000
Z-score 4.81
OE 0.45 (0.350.58)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
2.19Z-score
OE missense 0.81 (0.760.86)
842 obs / 1040.4 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.45 (0.350.58)
00.351.4
Missense OE0.81 (0.760.86)
00.61.4
Synonymous OE0.95
01.21.6
LoF obs/exp: 40 / 89.0Missense obs/exp: 842 / 1040.4Syn Z: 0.83
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
moderateCOL4A2-related porencephalyDNAD
DN
0.78top 25%
GOF
0.6053th %ile
LOF
0.3452th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median · 1 literature citation

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Literature Evidence

DNTogether, our findings suggest that patients with COL4A1 and COL4A2 mutations may be at elevated risk of retinal hemorrhages and that retinal examinations may be useful for identifying patients with COL4A1 and COL4A2 mutations who are also at elevated risk of hemorrhagic strokes.PMID:26813606

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

COL4A2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold
Clinical Literature
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