COL9A2

Chr 1ARAD

collagen type IX alpha 2 chain

NCBI Gene: 1298ENSG00000049089UniProt: Q14055

Structural component of hyaline cartilage and vitreous of the eye

Primary Disease Associations & Inheritance

?Stickler syndrome, type VMIM #614284
AR
Epiphyseal dysplasia, multiple, 2MIM #600204
AD
UniProtMultiple epiphyseal dysplasia 2
UniProtIntervertebral disc disease
UniProtStickler syndrome 5
625
ClinVar variants
40
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— COL9A2
🧬
Gene-Disease Validity (ClinGen)
Stickler syndrome · ARLimited

Limited evidence — not for standalone diagnostic reporting

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
40 Pathogenic / Likely Pathogenic· 254 VUS of 625 total submissions

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.
0.64LOEUF
pLI 0.000
Z-score 3.61
OE 0.45 (0.32–0.64)
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.
1.34Z-score
OE missense 0.82 (0.75–0.89)
354 obs / 432.4 exp
Tolerant

Mild missense constraint

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.0.45 (0.32–0.64)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.82 (0.75–0.89)
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.0.91
0≤1.21.6
LoF obs/exp: 22 / 49.4Missense obs/exp: 354 / 432.4Syn Z: 0.93

ClinVar Variant Classifications

625 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic26
Likely Pathogenic14
VUS254
Likely Benign272
Benign44
Conflicting15
26
Pathogenic
14
Likely Pathogenic
254
VUS
272
Likely Benign
44
Benign
15
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
15
0
10
1
26
Likely Pathogenic
10
0
4
0
14
VUS
13
205
33
3
254
Likely Benign
0
3
174
95
272
Benign
0
4
38
2
44
Conflicting
—15
Total38212259101625

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

View in ClinVar →

Protein Context — Lollipop Plot

COL9A2 · protein map & ClinVar variants

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

Gene2Phenotype Curations

COL9A2-related Stickler syndrome

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. DisordersEyeSkeletalEar
G2P ↗

COL9A2-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

?Stickler syndrome, type V

MIM #614284

Molecular basis of disorder known

Autosomal recessive

Epiphyseal dysplasia, multiple, 2

MIM #600204

Molecular basis of disorder known

Autosomal dominant
📖
GeneReview available — COL9A2
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Autosomal Recessive Stickler Syndrome.
Nixon TRW et al.·Genes (Basel)
2022Review
Clinical Characteristics of Short-Stature Patients With Collagen Gene Mutation and the Therapeutic Response to rhGH.
Chen M et al.·Front Endocrinol (Lausanne)
2022Cohort
Multiple epiphyseal dysplasia.
Dahlqvist J et al.·Acta Orthop
2009
Multiomics Identifies Potential Biomarkers in Ankylosing Spondylitis Bone Formation.
Yang L et al.·Hum Mutat
2025
Autosomal recessive Stickler syndrome associated with homozygous mutations in the COL9A2 gene.
Kjellström U et al.·Ophthalmic Genet
2021
Collagen polymorphisms of the intervertebral disc.
Eyre DR et al.·Biochem Soc Trans
2002Review
Pseudoachondroplasia and multiple epiphyseal dysplasia: mutation review, molecular interactions, and genotype to phenotype correlations.
Briggs MD et al.·Hum Mutat
2002Review
Homozygous Type IX collagen variants (COL9A1, COL9A2, and COL9A3) causing recessive Stickler syndrome-Expanding the phenotype.
Nixon TRW et al.·Am J Med Genet A
2019
[Analysis of COL9A2 gene mutations in a Chinese Han population with pathological myopia].
Chen R et al.·Zhonghua Yi Xue Yi Chuan Xue Za Zhi
2014
Collagen IX gene polymorphisms and lumbar disc degeneration: a systematic review and meta-analysis.
Wu H et al.·J Orthop Surg Res
2018Meta-analysis
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
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