COL2A1: The Type II Collagen Gene and Its Role in Skeletal Development and Disease
A comprehensive overview of COL2A1, encoding the alpha-1 chain of type II collagen, including its genomic context, expression, associated disorders, and mutation spectrum.
Gene Information Card
| Symbol | COL2A1 |
|---|---|
| Full Name | Collagen Type II Alpha 1 Chain |
| Gene Type | Protein coding |
| Chromosomal Location | 12q13.11 |
| NCBI Gene ID | 1280 ncbi.nlm.nih.gov/gene/1280 |
| Ensembl ID | ENSG00000139219 |
| UniProt ID | P02458 |
| OMIM ID | 120140 |
| HGNC ID | 2200 |
| Aliases | ANFH, AOM, COL11A3, SEDC, STL1 |
Description
The COL2A1 gene encodes the alpha-1 chain of type II collagen, a homotrimeric fibrillar collagen that is the major structural component of cartilage and vitreous humor. It is essential for endochondral ossification and skeletal development. Mutations in COL2A1 lead to a spectrum of disorders known as type II collagenopathies, ranging from severe perinatal lethal conditions (achondrogenesis type II, hypochondrogenesis) to milder forms such as Stickler syndrome type I and early-onset osteoarthritis. The gene is also implicated in degenerative joint diseases and certain cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Achondrogenesis type II | Loss-of-function or dominant-negative mutations leading to severely disrupted cartilage matrix | OMIM #200610; ClinVar |
| Hypochondrogenesis | Dominant-negative mutations affecting collagen triple helix assembly | OMIM #200610; ClinVar |
| Stickler syndrome type I | Haploinsufficiency due to nonsense or frameshift mutations causing premature termination | OMIM #108300; ClinVar |
| Kniest dysplasia | In-frame deletions or splice-site mutations leading to shortened collagen chains | OMIM #156550; ClinVar |
| Spondyloepiphyseal dysplasia congenita | Missense mutations affecting glycine residues in the triple helix | OMIM #183900; ClinVar |
| Osteoarthritis (susceptibility) | Polymorphisms and somatic mutations in cartilage tissue | ClinVar; COSMIC |
| Melorheostosis (rare) | Somatic mutations in COL2A1 in affected bone lesions | COSMIC; literature |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Cartilage | High | Major site of expression |
| Vitreous humor | High | Eye expression |
| Bone | Moderate | During development |
| Lung | Low | Minimal expression |
| Skin | Low | Minimal expression |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Chondrocytes | High | Primary cell type |
| Mesenchymal stem cells (chondrogenic differentiation) | High | Upregulated during differentiation |
| HeLa | Low | Cancer cell line |
| A549 | Low | Lung carcinoma |
| MCF7 | Low | Breast cancer |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.2010G>A (p.Gly670Ser) | Missense | Rare | Dominant-negative; disrupts triple helix |
| c.1450C>T (p.Arg484Ter) | Nonsense | Rare | Loss-of-function; haploinsufficiency |
| c.2700delG (p.Gly901ValfsTer5) | Frameshift | Rare | Loss-of-function; haploinsufficiency |
| c.3505G>A (p.Gly1169Ser) | Missense | Rare | Dominant-negative; severe phenotype |
| c.2010+1G>A | Splice site | Rare | Exon skipping; dominant-negative |
Mutation functional classification
Loss of Function (LOF)
Nonsense, frameshift, and splice-site mutations that lead to premature termination codons and nonsense-mediated decay, resulting in haploinsufficiency. These are typically associated with milder phenotypes such as Stickler syndrome type I.
Gain of Function (GOF)
Not commonly described; COL2A1 mutations are generally not gain-of-function. However, some missense mutations may exert a dominant-negative effect rather than a true gain of function.
Dominant Negative (DN)
Missense mutations, particularly those affecting glycine residues in the Gly-X-Y repeat, disrupt triple helix assembly and secretion, leading to a dominant-negative effect. These are associated with severe phenotypes like achondrogenesis type II and Kniest dysplasia.
View complete mutation data：
Gene Ontology (GO)
| • extracellular matrix structural constituent | • collagen binding |
| • extracellular matrix organization | • cartilage development |
| • skeletal system development | • endochondral ossification |
| • cell adhesion | • response to mechanical stimulus |
Pathways
• Collagen biosynthesis and modifying enzymes
• Degradation of the extracellular matrix
• Protein digestion and absorption
• Focal adhesion
• PI3K-Akt signaling pathway
• ECM-receptor interaction
Protein Summary
The COL2A1 protein is a 1487-amino acid precursor that undergoes post-translational modifications, including hydroxylation and glycosylation, to form a triple-helical procollagen. After cleavage of N- and C-propeptides, mature type II collagen assembles into fibrils that provide tensile strength to cartilage and vitreous. The protein contains a characteristic Gly-X-Y repeat motif, where X is often proline and Y is hydroxyproline, essential for triple helix stability. Mutations disrupting this motif lead to collagenopathies.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| COL2A1 Knockout HEK293 Cell Line | EDJ-KQ769 | Human | 1280 | Details Get a Quote |
| COL2A1 Knockout HeLa Cell Line | EDJ-KQ52948 | Human | 1280 | Details Get a Quote |
| COL2A1 Knockout A-549 Cell Line | EDJ-KQ61415 | Human | 1280 | Details Get a Quote |
| COL2A1 Knockout HCT 116 Cell Line | EDJ-KQ69910 | Human | 1280 | Details Get a Quote |
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