COL9A1 Gene: Collagen Type IX Alpha 1 Chain
Genetic and Clinical Significance of COL9A1 in Skeletal and Ocular Disorders
Gene Information Card
| Symbol | COL9A1 |
|---|---|
| Full Name | Collagen Type IX Alpha 1 Chain |
| Gene Type | Protein coding |
| Chromosomal Location | 6q13 |
| NCBI Gene ID | 1297 ncbi.nlm.nih.gov/gene/1297 |
| Ensembl ID | ENSG00000112280 |
| UniProt ID | P20849 |
| OMIM ID | 120210 |
| HGNC ID | 2217 |
| Aliases | EDM6, STL4, DJ149L1.1.1, collagen IX, alpha-1 |
Description
COL9A1 encodes the alpha-1 chain of type IX collagen, a heterotrimeric fibril-associated collagen with interrupted triple helices (FACIT). Type IX collagen is a minor component of hyaline cartilage and vitreous humor, where it interacts with type II collagen fibrils to maintain extracellular matrix integrity. Mutations in COL9A1 are associated with multiple epiphyseal dysplasia (MED) and Stickler syndrome, often involving sensorineural hearing loss and ocular abnormalities.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Multiple Epiphyseal Dysplasia 6 (EDM6) | Missense or splice-site mutations disrupt collagen IX assembly, impairing cartilage matrix stability. | OMIM #120210; ClinVar pathogenic variants |
| Stickler Syndrome Type 4 (STL4) | Loss-of-function mutations lead to abnormal vitreous collagen, causing retinal detachment and hearing loss. | OMIM #614134; ClinVar pathogenic variants |
| Osteoarthritis Susceptibility | Polymorphisms in COL9A1 may alter cartilage biomechanics, increasing osteoarthritis risk. | NCBI Gene; GWAS studies |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Cartilage | 12.5 | High |
| Eye (vitreous humor) | 8.3 | Medium |
| Inner ear (cochlea) | 6.1 | Medium |
| Lung | 2.4 | Low |
| Brain | 0.8 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Chondrocytes | 15.2 | Primary cartilage cells |
| Retinal pigment epithelial cells | 7.8 | ARPE-19 cell line |
| Fibroblasts | 3.1 | Skin fibroblasts |
| HEK293 | 0.5 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.112G>A (p.Gly38Arg) | Missense | Rare | Disrupts triple helix formation; associated with MED |
| c.1777+1G>A | Splice site | Rare | Exon skipping; loss of functional protein; Stickler syndrome |
| c.2029C>T (p.Arg677*) | Nonsense | Rare | Premature stop; loss of function; severe MED |
| c.114+2T>C | Splice site | Rare | Aberrant splicing; reduced collagen IX; hearing loss |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations leading to truncated protein or nonsense-mediated decay; observed in Stickler syndrome.
Gain of Function (GOF)
Not reported for COL9A1.
Dominant Negative (DN)
Missense mutations (e.g., Gly substitutions) in the triple helix domain disrupt collagen IX heterotrimer assembly, exerting a dominant-negative effect in MED.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Collagen biosynthesis and modifying enzymes (Reactome: R-HSA-1474290)
• Assembly of collagen fibrils and other multimeric structures (Reactome: R-HSA-2022090)
• ECM proteoglycans (KEGG: hsa04512)
Protein Summary
The COL9A1 protein (UniProt P20849) is a 921-amino acid alpha chain of type IX collagen. It contains a collagen triple helix domain with interruptions, a thrombospondin N-terminal-like domain, and multiple glycosaminoglycan attachment sites. The protein is synthesized as a preprocollagen, undergoes post-translational hydroxylation and glycosylation, and assembles into heterotrimers (alpha1(IX)alpha2(IX)alpha3(IX)) that associate with type II collagen fibrils in cartilage and vitreous. Mutations affecting the triple helix domain compromise structural integrity, leading to skeletal and ocular disorders.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| COL9A1 Knockout HEK293 Cell Line | EDJ-KQ779 | Human | 1297 | Details Get a Quote |
| COL9A1 Knockout HeLa Cell Line | EDJ-KQ52951 | Human | 1297 | Details Get a Quote |
| COL9A1 Knockout A-549 Cell Line | EDJ-KQ61419 | Human | 1297 | Details Get a Quote |
| COL9A1 Knockout HCT 116 Cell Line | EDJ-KQ69918 | Human | 1297 | Details Get a Quote |
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