COL18A1

Chr 21ADAR

collagen type XVIII alpha 1 chain

Also known as: GLCC, KNO, KNO1, KS

The COL18A1 gene encodes the alpha chain of type XVIII collagen, an extracellular matrix protein that undergoes proteolytic processing to produce endostatin, an antiangiogenic protein, and plays a major role in determining retinal structure and neural tube closure. Mutations cause Knobloch syndrome type 1 (characterized by retinal abnormalities and occipital encephalocele) and primary closed-angle glaucoma, with both autosomal recessive and autosomal dominant inheritance patterns reported. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.535), indicating some tolerance to complete gene disruption.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismAD/ARLOEUF 0.542 OMIM phenotypes
Clinical SummaryCOL18A1
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Gene-Disease Validity (ClinGen)
Knobloch syndrome 1 · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.54LOEUF
pLI 0.000
Z-score 4.94
OE 0.40 (0.300.54)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
-0.80Z-score
OE missense 1.07 (1.021.13)
1057 obs / 986.5 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.40 (0.300.54)
00.351.4
Missense OE1.07 (1.021.13)
00.61.4
Synonymous OE1.32
01.21.6
LoF obs/exp: 31 / 78.2Missense obs/exp: 1057 / 986.5Syn Z: -5.14
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveCOL18A1-related Knobloch syndromeLOFAR

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

DN
0.6743th %ile
GOF
0.5856th %ile
LOF
0.3550th %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.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

COL18A1 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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