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GeneE
10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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COL9A3
collagen type IX alpha 3 chain
Chromosome 20 · 20q13.33
NCBI Gene: 1299Ensembl: ENSG00000092758.19HGNC: HGNC:2219UniProt: Q14050
60PubMed Papers
23Diseases
0Drugs
54Pathogenic Variants
RESEARCH IMPACT
Variant-Rich
CLINICAL
OMIM Disease Gene
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
extracellular matrixcollagen type IX trimerprotein homodimerization activityextracellular matrix organizationepiphyseal dysplasia, multiple, 3Stickler syndromeStickler syndrome, type 6lumbar disc degeneration
✦AI Summary

COL9A3 encodes the α3 chain of type IX collagen, a structural component of hyaline cartilage and the vitreous of the eye that contributes to extracellular matrix organization and tensile strength 1. This collagen is integrated into the interior structure of intervertebral discs 2. COL9A3 mutations cause autosomal recessive Stickler syndrome, a connective tissue disorder characterized by sensorineural hearing loss, high myopia, vitreoretinal degeneration, and skeletal abnormalities including early-onset arthropathy and spondyloepiphyseal dysplasia 341. Both homozygous and compound heterozygous pathogenic variants have been identified 1. Retinal detachment occurs in approximately 18% of cases with type IX collagen variants 1. COL9A3 mutations also contribute to pseudoachondroplasia severity; notably, combined COMP and Col9A3 mutations were found in 61% of pseudoachondroplasia cases, with some Col9A3 variants producing particularly severe phenotypes 5. Regarding intervertebral disc degeneration, meta-analyses found that the COL9A3 Trp3 polymorphism (rs61734651) alone was not significantly associated with disease risk 26. However, gene-environment interaction studies demonstrated that the Trp3 allele acts synergistically with persistent obesity to increase disc degeneration risk, with 45-71% of degeneration cases attributable to this interaction 7. COL9A3 mutations have also been implicated in skeletal dysplasias presenting with short stature 8.

Sources cited
1
COL9A3 variants cause autosomal recessive Stickler syndrome with high myopia, sensorineural hearing loss, and retinal detachment in ~18% of cases
PMID: 35885918
2
COL9A3 Trp3 polymorphism alone is not significantly associated with intervertebral disc degeneration
PMID: 30342505
3
COL9A3 Trp3 allele acts synergistically with persistent obesity to increase intervertebral disc degeneration risk
PMID: 12461395
4
COL9A3 mutations cause autosomal recessive Stickler syndrome with severe sensorineural hearing loss, myopia, vitreoretinal degeneration, and arthropathy
PMID: 33570243
5
Homozygous COL9A3 loss-of-function mutations cause autosomal recessive Stickler syndrome with hearing loss, high myopia, and skeletal abnormalities
PMID: 30450842
6
COL9A3 gene polymorphism rs61734651 is not significantly associated with lumbar disc degeneration
PMID: 29506578
7
COL9A3 mutations contribute to pseudoachondroplasia phenotype; COMP+Col9A3 mutations found in 61% of cases, with some variants producing severe phenotypes
PMID: 21042783
8
COL9A3 mutations associated with short stature and skeletal dysplasias in collagenopathies
PMID: 35250876
Disease Associationsⓘ23
epiphyseal dysplasia, multiple, 3Open Targets
0.71Strong
Stickler syndromeOpen Targets
0.70Strong
Stickler syndrome, type 6Open Targets
0.61Moderate
lumbar disc degenerationOpen Targets
0.46Moderate
Abnormality of the skeletal systemOpen Targets
0.45Moderate
Stickler syndrom, recessiveOpen Targets
0.43Moderate
genetic disorderOpen Targets
0.42Moderate
multiple epiphyseal dysplasiaOpen Targets
0.37Weak
multiple epiphyseal dysplasia due to collagen 9 anomalyOpen Targets
0.37Weak
connective tissue diseaseOpen Targets
0.36Weak
age-related hearing impairmentOpen Targets
0.36Weak
retinal detachmentOpen Targets
0.35Weak
retinal perforationOpen Targets
0.34Weak
Lattice retinal degenerationOpen Targets
0.32Weak
schizophreniaOpen Targets
0.27Weak
lumbar disk degenerative disorderOpen Targets
0.19Weak
Hearing impairmentOpen Targets
0.16Weak
multiple epiphyseal dysplasia, Beighton typeOpen Targets
0.16Weak
disorder of earOpen Targets
0.14Weak
sensorineural hearing lossOpen Targets
0.13Weak
Intervertebral disc diseaseUniProt
Multiple epiphyseal dysplasia 3UniProt
Stickler syndrome 6UniProt
Pathogenic Variants54
NM_001853.4(COL9A3):c.1739dup (p.Gly581fs)Pathogenic
not provided
★★☆☆2026→ Residue 581
NM_001853.4(COL9A3):c.528dup (p.Ile177fs)Pathogenic
Connective tissue disorder|not provided
★★☆☆2025→ Residue 177
NM_001853.4(COL9A3):c.1729C>T (p.Arg577Ter)Pathogenic
Stickler syndrome|Stickler syndrome, type 6|not provided|Epiphyseal dysplasia, multiple, 3;Intervertebral disc disorder
★★☆☆2025→ Residue 577
NM_001853.4(COL9A3):c.268C>T (p.Arg90Ter)Pathogenic
Stickler syndrome|Stickler syndrome, type 6|not provided
★★☆☆2025→ Residue 90
NM_001853.4(COL9A3):c.148-1G>APathogenic
Epiphyseal dysplasia, multiple, 3, with myopathy|not provided|Epiphyseal dysplasia, multiple, 3|COL9A3-related disorder
★★☆☆2024
NM_001853.4(COL9A3):c.1411C>T (p.Arg471Ter)Pathogenic
Inborn genetic diseases|Stickler syndrome, type 6|not provided
★★☆☆2022→ Residue 471
NM_001853.4(COL9A3):c.416del (p.Gly139fs)Pathogenic
not provided
★☆☆☆2025→ Residue 139
NM_001853.4(COL9A3):c.102dup (p.Gly35fs)Pathogenic
not provided
★☆☆☆2025→ Residue 35
NM_001853.4(COL9A3):c.1280del (p.Gly427fs)Pathogenic
not provided
★☆☆☆2025→ Residue 427
NM_001853.4(COL9A3):c.469G>T (p.Gly157Ter)Pathogenic
not provided
★☆☆☆2025→ Residue 157
NM_001853.4(COL9A3):c.865G>T (p.Gly289Ter)Pathogenic
not provided
★☆☆☆2025→ Residue 289
NM_001853.4(COL9A3):c.808_809del (p.Arg270fs)Pathogenic
not provided
★☆☆☆2025→ Residue 270
NM_001853.4(COL9A3):c.422dup (p.Pro143fs)Pathogenic
not provided
★☆☆☆2025→ Residue 143
NM_001853.4(COL9A3):c.1A>G (p.Met1Val)Likely pathogenic
Stickler syndrome, type 6
★☆☆☆2025→ Residue 1
NM_001853.4(COL9A3):c.1204C>T (p.Arg402Ter)Pathogenic
Stickler syndrome, type 6|not provided
★☆☆☆2025→ Residue 402
NM_001853.4(COL9A3):c.1267C>T (p.Arg423Ter)Pathogenic
not provided
★☆☆☆2025→ Residue 423
NM_001853.4(COL9A3):c.183+1G>CLikely pathogenic
not provided
★☆☆☆2025
NM_001853.4(COL9A3):c.181_182dup (p.Gly62fs)Pathogenic
not provided
★☆☆☆2025→ Residue 62
NM_001853.4(COL9A3):c.1740delinsCC (p.Gly581fs)Pathogenic
Epiphyseal dysplasia, multiple, 3
★☆☆☆2025→ Residue 581
NM_001853.4(COL9A3):c.395dup (p.Gly133fs)Pathogenic
not provided
★☆☆☆2025→ Residue 133
View on ClinVar ↗
Related Genes
ADAMTSL5Shared pathway100%COL6A5Shared pathway100%COL24A1Shared pathway100%COL22A1Shared pathway100%COL6A6Shared pathway100%ADAMTSL1Shared pathway100%
Tissue Expression6 tissues
Bone Marrow
100%
Brain
41%
Liver
17%
Heart
12%
Ovary
10%
Lung
2%
Gene Interaction Network
Click a node to explore
COL9A3ADAMTSL5COL6A5COL24A1COL22A1COL6A6ADAMTSL1
PROTEIN STRUCTURE
Preparing viewer…
PDB5CTD · 1.60 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.03LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.86 [0.72–1.03]
RankingsWhere COL9A3 stands among ~20K protein-coding genes
  • #7,645of 20,598
    Most Researched60
  • #1,265of 5,498
    Most Pathogenic Variants54 · top quartile
  • #10,116of 17,882
    Most Constrained (LOEUF)1.03
Genes detectedCOL9A3
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
PMID: 20301479
1.00
2
Autosomal Recessive Stickler Syndrome.
PMID: 35885918
Genes (Basel) · 2022
0.90
3
Clinical Characteristics of Short-Stature Patients With Collagen Gene Mutation and the Therapeutic Response to rhGH.
PMID: 35250876
Front Endocrinol (Lausanne) · 2022
0.80
4
Association of COL9A3 trp3 polymorphism with intervertebral disk degeneration: a meta-analysis.
PMID: 30342505
BMC Musculoskelet Disord · 2018
0.70
5
PMID: 20301302
0.60