COL8A2

Chr 1AD

collagen type VIII alpha 2 chain

NCBI Gene: 1296ENSG00000171812UniProt: P25067

Macromolecular component of the subendothelium. Major component of the Descemet's membrane (basement membrane) of corneal endothelial cells. Also a component of the endothelia of blood vessels. Necessary for migration and proliferation of vascular smooth muscle cells and thus, has a potential role in the maintenance of vessel wall integrity and structure, in particular in atherogenesis (By similarity)

Primary Disease Associations & Inheritance

Corneal dystrophy, Fuchs endothelial, 1MIM #136800
AD
Corneal dystrophy, posterior polymorphous 2MIM #609140
AD
209
ClinVar variants
0
Pathogenic / LP
0.12
pLI score
0
Active trials
Clinical Summary— COL8A2
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.29) despite low pLI — interpret in context.
📋
ClinVar Variants
209 total variants — no pathogenic classifications of 209 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.66LOEUF
pLI 0.118
Z-score 2.45
OE 0.29 (0.14–0.66)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.57Z-score
OE missense 0.78 (0.71–0.85)
304 obs / 391.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.29 (0.14–0.66)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.78 (0.71–0.85)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.11
0≤1.21.6
LoF obs/exp: 4 / 13.8Missense obs/exp: 304 / 391.3Syn Z: -1.14

ClinVar Variant Classifications

209 submitted variants in ClinVar

ClinVar

Classification Summary

Protein Context — Lollipop Plot

COL8A2 · protein map & ClinVar variants

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

Gene2Phenotype Curations

COL8A2-related corneal dystrophy, Fuchs endothelial

strong
ADUndeterminedAltered Gene Product Structure
Eye
G2P ↗
missense variantinframe deletioninframe insertion

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Corneal dystrophy, Fuchs endothelial, 1

MIM #136800

Molecular basis of disorder known

Autosomal dominant

Corneal dystrophy, posterior polymorphous 2

MIM #609140

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Identification of COL8A2, MICAL2, and TNFSF10 as potential biomarkers associated with both exercise response and osteoarthritis: a multi-omics integration study.
Wang H et al.·3 Biotech
2026
Early Transcriptomic and Pathologic Changes of Col8a2 Mutant Fuchs Endothelial Corneal Dystrophy.
Zhao X et al.·Invest Ophthalmol Vis Sci
2026🔓 Open Access
COL8A2 activation enhances function of corneal endothelial cells through HIPPO signaling/mitochondria pathway.
Ryu Y et al.·Matrix Biol
2024
Descemet membrane endothelial keratoplasty in eyes with COL8A2-associated corneal dystrophy.
Dzhaber D et al.·Am J Ophthalmol Case Rep
2022🔓 Open Access
Collagen type VIII alpha 2 chain (COL8A2), an important component of the basement membrane of the corneal endothelium, facilitates the malignant development of glioblastoma cells via inducing EMT.
Cheng YX et al.·J Bioenerg Biomembr
2021
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

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External Resources

Links to major genomics databases and tools