COL8A2

Chr 1

collagen type VIII alpha 2 chain

Also known as: FECD, FECD1, PPCD, PPCD2

NCBI Gene: 1296 ENSG00000171812 UniProt: P25067

This gene encodes the alpha 2 chain of type VIII collagen, which is a major component of Descemet's membrane (the basement membrane of corneal endothelial cells) and forms homo- or heterotrimers with alpha 1 type VIII collagen chains. Mutations cause Fuchs endothelial corneal dystrophy and posterior polymorphous corneal dystrophy type 2, both inherited in an autosomal dominant pattern. These corneal dystrophies primarily affect the eye and can lead to vision impairment due to corneal endothelial dysfunction.

ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes the alpha 2 chain of type VIII collagen. This protein is a major component of the basement membrane of the corneal endothelium and forms homo- or heterotrimers with alpha 1 (VIII) type collagens. Defects in this gene are associated with Fuchs endothelial corneal dystrophy and posterior polymorphous corneal dystrophy type 2. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2014]

ResearchGenerating clinical summary…

DNmechanismLOEUF 0.66

Clinical Summary— COL8A2

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.29) despite low pLI — interpret in context.

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ClinVar Variants

3 unique Pathogenic / Likely Pathogenic· 129 VUS of 197 total submissions

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.66LOEUF

pLI 0.118

Z-score 2.45

OE 0.29 (0.14–0.66)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.57Z-score

OE missense 0.78 (0.71–0.85)

304 obs / 391.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.29 (0.14–0.66)

0≤0.351.4

Missense OE?0.78 (0.71–0.85)

0≤0.61.4

Synonymous OE?1.11

0≤1.21.6

LoF obs/exp: 4 / 13.8Missense obs/exp: 304 / 391.3Syn Z: -1.14

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

strongCOL8A2-related corneal dystrophy, Fuchs endothelialOTHERAD

This gene — mechanism propensity

0.78top 25%

GOF

0.5856th %ile

LOF

0.4331th %ile

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

197 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic3

VUS129

Likely Benign31

Benign29

Conflicting1

Pathogenic

129

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	3	0	0	3
Likely Pathogenic	0	0	0	0	0
VUS	3	125	1	0	129
Likely Benign	0	8	5	18	31
Benign	0	5	10	14	29
Conflicting	—				1
Total	3	141	16	32	193

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

View in ClinVar →

8 pathogenic / likely-pathogenic (of 14) ClinVar copy-number / structural variants overlap COL8A2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →