COL9A2

Chr 1ARAD

collagen type IX alpha 2 chain

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

NCBI Gene: 1298 ENSG00000049089 UniProt: Q14055 OMIM: 120260

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.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes one of the three alpha chains of type IX collagen, the major collagen component of hyaline cartilage. Type IX collagen, a heterotrimeric molecule, is usually found in tissues containing type II collagen, a fibrillar collagen. This chain is unusual in that, unlike the other two type IX alpha chains, it contains a covalently attached glycosaminoglycan side chain. Mutations in this gene are associated with multiple epiphyseal dysplasia. [provided by RefSeq, Jul 2008]

GeneReviews OMIM ResearchGenerating clinical summary…

MultiplemechanismAR/ADLOEUF 0.642 OMIM phenotypes

Clinical Summary— COL9A2

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Gene-Disease Validity (ClinGen)

Stickler syndrome · ARLimited

Limited evidence — not for standalone diagnostic reporting

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

60 unique Pathogenic / Likely Pathogenic· 578 VUS of 1327 total submissions

Explore recent and relevant literature in Research Assistant →

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GeneReview available — COL9A2

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.64LOEUF

pLI 0.000

Z-score 3.61

OE 0.45 (0.32–0.64)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.34Z-score

OE missense 0.82 (0.75–0.89)

354 obs / 432.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.45 (0.32–0.64)

0≤0.351.4

Missense OE?0.82 (0.75–0.89)

0≤0.61.4

Synonymous OE?0.91

0≤1.21.6

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

This gene — mechanism propensity

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

1327 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic35

Likely Pathogenic25

VUS578

Likely Benign548

Benign74

Conflicting53

Pathogenic

Likely Pathogenic

578

VUS

548

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	32	0	2	1	35
Likely Pathogenic	21	2	1	1	25
VUS	27	486	49	16	578
Likely Benign	1	10	338	199	548
Benign	0	3	68	3	74
Conflicting	—				53
Total	81	501	458	220	1,313

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

View in ClinVar →

8 pathogenic / likely-pathogenic (of 18) ClinVar copy-number / structural variants overlap COL9A2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →