COL8A1

Chr 3

collagen type VIII alpha 1 chain

Also known as: C3orf7

NCBI Gene: 1295 ENSG00000144810 UniProt: P27658 OMIM: 120251

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.

OMIM ResearchSummary from RefSeq, UniProt

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]

OMIM ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.50

LOEUF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.50LOEUF

pLI 0.405

Z-score 3.08

OE 0.22 (0.11–0.50)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.44Z-score

OE missense 0.80 (0.73–0.88)

337 obs / 420.0 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.22 (0.11–0.50)

0≤0.351.4

Missense OE?0.80 (0.73–0.88)

0≤0.61.4

Synonymous OE?0.95

0≤1.21.6

LoF obs/exp: 4 / 18.2Missense obs/exp: 337 / 420.0Syn Z: 0.48

Background carrier burden — how many people carry a rare variant somewhere in COL8A1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 73

858 rare PASS variants

Rare truncating (LoF)

1 in 3,500

75 rare PASS variants

Rare synonymous (reference)

1 in 110

393 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for COL8A1. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 110	1 in 4,100
South Asian	~43k	1 in 85	1 in 1,400
Remaining (unassigned)	~30k	1 in 73	1 in 6,000
European (Finnish)	~27k	1 in 270	1 in 4,300
Admixed American	~22k	1 in 81	≈ 1 in 7,500
African / African American	~21k	1 in 86	1 in 3,200
East Asian	~20k	1 in 98	≈ 1 in 20,000
Ashkenazi Jewish	~13k	1 in 380	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 130	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 2 coding exons well covered in gnomAD exomes and genomes.? see exons ↓