COL9A2

Chr 1ARAD

collagen type IX alpha 2 chain

Also known as: DJ39G22.4, EDM2, MED, STL5

The protein is a structural component of hyaline cartilage and vitreous of the eye, forming one of three alpha chains of type IX collagen. Mutations cause multiple epiphyseal dysplasia and Stickler syndrome type V, affecting skeletal development and potentially vision. The gene shows both autosomal recessive and autosomal dominant inheritance patterns and is moderately constrained against loss-of-function variants.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
MultiplemechanismAR/ADLOEUF 0.642 OMIM phenotypes
Clinical SummaryCOL9A2
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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.
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GeneReview available — COL9A2
Authoritative clinical overview · Recommended first read
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.64LOEUF
pLI 0.000
Z-score 3.61
OE 0.45 (0.320.64)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.34Z-score
OE missense 0.82 (0.750.89)
354 obs / 432.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.45 (0.320.64)
00.351.4
Missense OE0.82 (0.750.89)
00.61.4
Synonymous OE0.91
01.21.6
LoF obs/exp: 22 / 49.4Missense obs/exp: 354 / 432.4Syn Z: 0.93
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveCOL9A2-related Stickler syndromeLOFAR
definitiveCOL9A2-related multiple epiphyseal dysplasiaDNAD
DN
0.84top 10%
GOF
0.6053th %ile
LOF
0.3259th %ile

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

DNprediction above median

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.

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

ClinVar Variant Classifications

0 submitted variants 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.

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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Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗