COL8A1

Chr 3

collagen type VIII alpha 1 chain

Also known as: C3orf7

The protein forms one of the two alpha chains of type VIII collagen, which is a major component of the corneal endothelial basement membrane (Descemet's membrane) and blood vessel endothelia. Mutations cause Fuchs endothelial corneal dystrophy and posterior polymorphous corneal dystrophy, both affecting corneal function and vision. These conditions follow autosomal dominant inheritance.

OMIMResearchSummary from RefSeq, UniProt
DNmechanismLOEUF 0.50
Clinical SummaryCOL8A1
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.22) despite low pLI — interpret in context.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.50LOEUF
pLI 0.405
Z-score 3.08
OE 0.22 (0.110.50)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.44Z-score
OE missense 0.80 (0.730.88)
337 obs / 420.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.22 (0.110.50)
00.351.4
Missense OE0.80 (0.730.88)
00.61.4
Synonymous OE0.95
01.21.6
LoF obs/exp: 4 / 18.2Missense obs/exp: 337 / 420.0Syn Z: 0.48
DN
0.75top 25%
GOF
0.5072th %ile
LOF
0.50top 25%

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

DNprediction above median

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.

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

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

COL8A1 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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