COL8A1

Chr 3

collagen type VIII alpha 1 chain

Also known as: C3orf7

This gene encodes one of the two alpha chains of type VIII collagen. The gene product is a short chain collagen and a major component of the basement membrane of the corneal endothelium. The type VIII collagen fibril can be either a homo- or a heterotrimer. Alternatively spliced transcript variants encoding the same protein have been observed. [provided by RefSeq, Dec 2011]

OMIMResearchGenerating clinical summary…
DNmechanismLOEUF 0.50
Clinical SummaryCOL8A1
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.22) despite low pLI — interpret in context.
📋
ClinVar Variants
69 VUS of 78 total submissions

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 OE?0.22 (0.110.50)
00.351.4
Missense OE?0.80 (0.730.88)
00.61.4
Synonymous OE?0.95
01.21.6
LoF obs/exp: 4 / 18.2Missense obs/exp: 337 / 420.0Syn Z: 0.48

This gene — mechanism propensity

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

78 submitted variants in ClinVar

Classification Summary

VUS69
Likely Benign6
Benign2
69
VUS
6
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
0
0
0
Likely Pathogenic
0
0
0
0
0
VUS
0
69
0
0
69
Likely Benign
0
3
0
3
6
Benign
0
1
0
1
2
Total0730477

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

10 pathogenic / likely-pathogenic (of 17) ClinVar copy-number / structural variants overlap COL8A1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →

Protein Context — Lollipop Plot

COL8A1 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →