COL9A2 Gene: Function, Mutations, and Associated Diseases | NCBI, UniProt, OMIM

COL9A2 encodes the alpha-2 chain of type IX collagen, a heterotrimeric fibril-associated collagen with interrupted triple helices (FACIT). Type IX collagen is a major component of cartilage extracellular matrix, where it associates with type II collagen fibrils and contributes to the structural integrity and biomechanical properties of cartilage. The protein is also expressed in the inner ear, where it is essential for normal hearing. Mutations in COL9A2 cause multiple epiphyseal dysplasia type 2 (EDM2) and are associated with sensorineural hearing loss.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Collagen biosynthesis and modifying enzymes (Reactome: R-HSA-1650814)

• Assembly of collagen fibrils and other multimeric structures (Reactome: R-HSA-2022090)

• ECM proteoglycans (KEGG: hsa04512)

The COL9A2 protein (alpha-2 chain of type IX collagen) is 689 amino acids long and contains three collagenous domains (COL1–COL3) and four non-collagenous domains (NC1–NC4). It forms a heterotrimer with alpha-1 and alpha-3 chains. The protein is extensively post-translationally modified, including hydroxylation of proline and lysine residues, and glycosylation. It localizes to the extracellular matrix, where it binds to type II collagen fibrils and mediates matrix–cell interactions.