COL9A3

Chr 20ADAR

collagen type IX alpha 3 chain

ENSG00000092758UniProt: Q14050

Structural component of hyaline cartilage and vitreous of the eye

Primary Disease Associations & Inheritance

{Intervertebral disc disease, susceptibility to}MIM #603932
Epiphyseal dysplasia, multiple, 3, with or without myopathyMIM #600969
AD
Stickler syndrome, type VIMIM #620022
AR
UniProtMultiple epiphyseal dysplasia 3
UniProtStickler syndrome 6
0
ClinVar variants
0
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— COL9A3
🧬
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.
Some data sources returned errors (1)

ncbi: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

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.
0.75LOEUF
pLI 0.000
Z-score 3.00
OE 0.54 (0.40–0.75)
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.
-0.38Z-score
OE missense 1.05 (0.97–1.13)
471 obs / 448.2 exp
Tolerant

Tolerant to missense variation

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.0.54 (0.40–0.75)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.05 (0.97–1.13)
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.1.21
0≤1.21.6
LoF obs/exp: 27 / 49.9Missense obs/exp: 471 / 448.2Syn Z: -2.33

ClinVar Variant Classifications

0 submitted variants in ClinVar

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.

Gene2Phenotype Curations

COL9A3-related Stickler syndrome

limited
ARLoss Of FunctionAbsent Gene Product
Dev. DisordersEyeEar
G2P ↗

COL9A3-related multiple epiphyseal dysplasia

definitive
ADDominant NegativeAltered Gene Product Structure
Dev. DisordersSkeletal
G2P ↗

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

{Intervertebral disc disease, susceptibility to}

MIM #603932

Molecular basis of disorder known

Epiphyseal dysplasia, multiple, 3, with or without myopathy

MIM #600969

Molecular basis of disorder known

Autosomal dominant

Stickler syndrome, type VI

MIM #620022

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Geniposide attenuates astrocyte pyroptosis in depression via long non-coding RNA Six3os1-mediated regulation of the miR-511-3p/COL9A3 axis and MAPK/NLRP3 signaling.
Zou T et al.·J Cell Commun Signal
2025🔓 Open Access
Exome Sequencing Identifies a Novel Splicing Variant in COL9A3 Resulting in Multiple Epiphyseal Dysplasia: A Case Report.
Alnuaimi B et al.·Mol Genet Genomic Med
2025🔓 Open AccessCase report
A novel missense COL9A3 variant in a pedigree with multiple lumbar disc herniation.
Jiang L et al.·J Orthop Surg Res
2024🔓 Open Access
Identification of three novel homozygous variants in COL9A3 causing autosomal recessive Stickler syndrome.
Rad A et al.·Orphanet J Rare Dis
2022🔓 Open Access
USP3 promotes gastric cancer progression and metastasis by deubiquitination-dependent COL9A3/COL6A5 stabilisation.
Wu X et al.·Cell Death Dis
2021🔓 Open Access
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools