COL9A1

Chr 6ADAR

collagen type IX alpha 1 chain

NCBI Gene: 1297ENSG00000112280UniProt: P20849

Structural component of hyaline cartilage and vitreous of the eye

Primary Disease Associations & Inheritance

?Epiphyseal dysplasia, multiple, 6MIM #614135
AD
Stickler syndrome, type IVMIM #614134
AR
UniProtMultiple epiphyseal dysplasia 6
UniProtStickler syndrome 4
596
ClinVar variants
48
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— COL9A1
🧬
Gene-Disease Validity (ClinGen)
Stickler syndrome, type 4 · 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.
📋
ClinVar Variants
48 Pathogenic / Likely Pathogenic· 204 VUS of 596 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.
0.81LOEUF
pLI 0.000
Z-score 2.78
OE 0.63 (0.48–0.81)
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.
0.19Z-score
OE missense 0.98 (0.91–1.05)
514 obs / 526.0 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.0.63 (0.48–0.81)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.98 (0.91–1.05)
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.1.25
0≤1.21.6
LoF obs/exp: 40 / 64.0Missense obs/exp: 514 / 526.0Syn Z: -2.58

ClinVar Variant Classifications

596 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic27
Likely Pathogenic21
VUS204
Likely Benign337
Benign3
Conflicting4
27
Pathogenic
21
Likely Pathogenic
204
VUS
337
Likely Benign
3
Benign
4
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
17
0
10
0
27
Likely Pathogenic
20
0
1
0
21
VUS
4
179
17
4
204
Likely Benign
0
6
203
128
337
Benign
0
0
3
0
3
Conflicting
—4
Total41185234132596

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

View in ClinVar →

Protein Context — Lollipop Plot

COL9A1 · protein map & ClinVar variants

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

Gene2Phenotype Curations

COL9A1-related Stickler syndrome

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. DisordersEyeSkeletalEar
G2P ↗

COL9A1-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

?Epiphyseal dysplasia, multiple, 6

MIM #614135

Molecular basis of disorder known

Autosomal dominant

Stickler syndrome, type IV

MIM #614134

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — COL9A1
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Plasma Proteomic Profiles Predict Individual Future Osteoarthritis Risk.
Kang Z et al.·Arthritis Rheumatol
2025
Data-driven identification of predictive risk biomarkers for subgroups of osteoarthritis using interpretable machine learning.
Nielsen RL et al.·Nat Commun
2024
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
A thorough analysis of data on the correlation between COL9A1 polymorphisms and the susceptibility to congenital talipes equinovarus: a meta-analysis.
Golshan-Tafti M et al.·J Orthop Surg Res
2024Meta-analysis
Leveraging Proteomics and Proteogenomics for Understanding Osteoporosis and Other Musculoskeletal Diseases.
Hasebe M et al.·Curr Osteoporos Rep
2025Review
COL9A1-related disorder with pectus carinatum, without epiphyseal dysplasia: case report and review of literature.
Olarewaju BA et al.·Skeletal Radiol
2025Review
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
Variants in FAT1 and COL9A1 genes in male population with or without substance use to assess the risk factors for oral malignancy.
Chung CM et al.·PLoS One
2019
Inherited Retinal Diseases with High Myopia: A Review.
Liu C et al.·Genes (Basel)
2025Review
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