COL25A1

Chr 4AR

collagen type XXV alpha 1 chain

Also known as: AMY, CFEOM5, CLAC, CLAC-P, CLACP

This gene encodes a brain-specific membrane associated collagen. A product of proteolytic processing of the encoded protein, CLAC (collagenous Alzheimer amyloid plaque component), binds to amyloid beta-peptides found in Alzheimer amyloid plaques but CLAC inhibits rather than facilitates amyloid fibril elongation (PMID: 16300410). A study of over-expression of this collagen in mice, however, found changes in pathology and behavior suggesting that the encoded protein may promote amyloid plaque formation (PMID: 19548013). Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]

OMIMResearchGenerating clinical summary…
LOFmechanismARLOEUF 0.881 OMIM phenotype
Clinical SummaryCOL25A1
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
11 unique Pathogenic / Likely Pathogenic· 91 VUS of 160 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint?
0.88LOEUF
pLI 0.000
Z-score 2.30
OE 0.67 (0.510.88)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?
1.45Z-score
OE missense 0.79 (0.720.87)
301 obs / 380.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.67 (0.510.88)
00.351.4
Missense OE?0.79 (0.720.87)
00.61.4
Synonymous OE?1.00
01.21.6
LoF obs/exp: 37 / 55.5Missense obs/exp: 301 / 380.5Syn Z: 0.04
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongCOL25A1-related fibrosis of extraocular muscles, congenitalLOFAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.84top 10%
GOF
0.5563th %ile
LOF
0.4528th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

160 submitted variants in ClinVar

Classification Summary

Pathogenic5
Likely Pathogenic6
VUS91
Likely Benign33
Benign9
5
Pathogenic
6
Likely Pathogenic
91
VUS
33
Likely Benign
9
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
3
1
1
0
5
Likely Pathogenic
4
2
0
0
6
VUS
0
88
3
0
91
Likely Benign
0
4
12
17
33
Benign
0
2
3
4
9
Total7971921144

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

View in ClinVar →

14 pathogenic / likely-pathogenic (of 21) ClinVar copy-number / structural variants overlap COL25A1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →

Protein Context — Lollipop Plot

COL25A1 · 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 →