COL9A3

Chr 20ADAR

collagen type IX alpha 3 chain

Also known as: DJ885L7.4.1, EDM3, IDD, MED, STL6

This gene encodes the alpha-3 chain of type IX collagen, a structural component of hyaline cartilage and vitreous of the eye that forms heterotrimeric molecules typically found alongside type II collagen. Mutations cause multiple epiphyseal dysplasia type 3 (with or without myopathy), Stickler syndrome type VI, and susceptibility to intervertebral disc disease, affecting skeletal and ocular systems. The gene shows both autosomal dominant and autosomal recessive inheritance patterns and is not highly constrained against loss-of-function variants.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
MultiplemechanismAD/ARLOEUF 0.753 OMIM phenotypes
Clinical SummaryCOL9A3
🧬
Gene-Disease Validity (ClinGen)
Stickler syndrome · 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.
📖
GeneReview available — COL9A3
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.75LOEUF
pLI 0.000
Z-score 3.00
OE 0.54 (0.400.75)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
-0.38Z-score
OE missense 1.05 (0.971.13)
471 obs / 448.2 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.54 (0.400.75)
00.351.4
Missense OE1.05 (0.971.13)
00.61.4
Synonymous OE1.21
01.21.6
LoF obs/exp: 27 / 49.9Missense obs/exp: 471 / 448.2Syn Z: -2.33
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
limitedCOL9A3-related Stickler syndromeLOFAR
definitiveCOL9A3-related multiple epiphyseal dysplasiaDNAD
DN
0.86top 5%
GOF
0.6149th %ile
LOF
0.3164th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median · 1 literature citation

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.

Literature Evidence

DNThe novel phenotype of MED and mild myopathy is likely caused by a dominant-negative effect of the exon 3-skipping mutation in the COL9A3 gene.PMID:10655510

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

COL9A3 · 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.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC