COL1A2: Collagen Type I Alpha 2 Chain Gene
Genetic insights into collagen-related disorders and connective tissue biology
Gene Information Card
| Symbol | COL1A2 |
|---|---|
| Full Name | Collagen Type I Alpha 2 Chain |
| Gene Type | Protein coding |
| Chromosomal Location | 7q21.3 |
| NCBI Gene ID | 1278 ncbi.nlm.nih.gov/gene/1278 |
| Ensembl ID | ENSG00000164692 |
| UniProt ID | P08123 |
| OMIM ID | 120160 |
| HGNC ID | 2198 |
| Aliases | OI4, EDSCV, EDSARTH, EDSRDB, collagen alpha-2(I) chain |
Description
The COL1A2 gene encodes the alpha-2 chain of type I collagen, the most abundant collagen in the human body. Type I collagen is a triple-helical protein composed of two alpha-1 chains and one alpha-2 chain, providing structural support to bone, skin, tendons, and other connective tissues. Mutations in COL1A2 can lead to a spectrum of disorders, including osteogenesis imperfecta (brittle bone disease) and various forms of Ehlers-Danlos syndrome, characterized by skeletal fragility, joint hypermobility, and skin abnormalities.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Osteogenesis Imperfecta (OI) | Mutations disrupt collagen triple helix formation, leading to abnormal bone matrix and increased fragility. | ClinVar, OMIM |
| Ehlers-Danlos Syndrome, Cardiac Valvular Type | Deficiency of alpha-2(I) collagen results in joint hypermobility, skin hyperextensibility, and cardiac valve defects. | OMIM, ClinVar |
| Ehlers-Danlos Syndrome, Arthrochalasia Type | Mutations affecting the N-terminal propeptide cleavage site impair collagen processing, causing severe joint laxity and congenital hip dislocation. | OMIM, ClinVar |
| Osteoporosis | Polymorphisms in COL1A2 may influence bone mineral density and fracture risk. | NCBI, PubMed (via OMIM) |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Bone | High | Major site of type I collagen synthesis |
| Skin | High | Dermal collagen production |
| Tendon | High | Structural component |
| Lung | Medium | Pulmonary connective tissue |
| Artery | Medium | Vascular wall integrity |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Osteoblasts | High | Bone-forming cells |
| Fibroblasts | High | Connective tissue cells |
| Chondrocytes | Low | Cartilage cells (type I collagen minor) |
| Smooth muscle cells | Medium | Vascular and visceral smooth muscle |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1170+1G>A | Splice site | Rare | Exon skipping leading to frameshift and premature termination; associated with OI type II/III |
| p.Gly256Val | Missense | Rare | Disrupts Gly-X-Y repeat, destabilizes triple helix; causes OI type IV |
| p.Gly565Ser | Missense | Rare | Substitution in collagen triple helix; leads to EDS arthrochalasia type |
| c.2010delC | Frameshift | Rare | Premature stop codon; results in haploinsufficiency and mild OI phenotype |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations (e.g., frameshift, nonsense) reduce alpha-2(I) chain production, leading to haploinsufficiency and milder forms of osteogenesis imperfecta.
Gain of Function (GOF)
Gain-of-function mutations are not typical for COL1A2; most pathogenic variants act through dominant-negative effects.
Dominant Negative (DN)
Dominant-negative mutations (e.g., glycine substitutions) incorporate mutant chains into the collagen triple helix, causing structural disruption and severe phenotypes like OI type II/III.
View complete mutation data：
Gene Ontology (GO)
| • extracellular matrix structural constituent | • collagen binding |
| • integrin binding | • platelet-derived growth factor binding |
| • identical protein binding | • extracellular matrix organization |
| • collagen fibril organization | • skeletal system development |
| • response to mechanical stimulus |
Pathways
• Collagen biosynthesis and modifying enzymes
• ECM-receptor interaction
• Protein digestion and absorption
• Focal adhesion
• PI3K-Akt signaling pathway
Protein Summary
The COL1A2 protein (UniProt P08123) is a 1366-amino-acid precursor that undergoes post-translational modifications, including hydroxylation and glycosylation, before forming a triple helix with two alpha-1(I) chains. The mature alpha-2(I) chain contains a long triple-helical domain with repeating Gly-X-Y motifs, essential for collagen stability. Mutations in this domain often lead to connective tissue disorders. The protein is secreted into the extracellular matrix where it self-assembles into fibrils, providing tensile strength to tissues.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| COL1A2 Knockout HEK293 Cell Line | EDJ-KQ1321 | Human | 1278 | Details Get a Quote |
| COL1A2 Knockout HeLa Cell Line | EDJ-KQ22057 | Human | 1278 | Details Get a Quote |
| COL1A2 Knockout A-549 Cell Line | EDJ-KQ61414 | Human | 1278 | Details Get a Quote |
| COL1A2 Knockout HCT 116 Cell Line | EDJ-KQ69909 | Human | 1278 | Details Get a Quote |
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