Collagen alpha-1(III) chain

Collagen alpha-1(III) chain (COL3A1) is a structural protein that comprises a major component of soft connective tissues, typically co-localized with type I collagen (UniProt: P02461). Beyond its classical extracellular matrix role, COL3A1 functions as a ligand for ADGRG1 in the developing brain, where it regulates cortical development by inhibiting neuronal migration and activating RhoA signaling through GNA13 and GNA12 coupling.

COL3A1 is distributed across connective tissues throughout the body and is associated with Ehlers-Danlos syndrome, vascular type (EDSVASC; MIM 130050) and polymicrogyria with vascular-type Ehlers-Danlos syndrome (PMGEDSV; MIM 618343), both reflecting its critical role in tissue integrity and neurodevelopment (UniProt: P02461).

In Alzheimer's disease, COL3A1 is upregulated in post-mortem AD brain tissue relative to age-matched controls (Chaparral AD proteomics). The protein showed a mean log2 fold-change of 0.37 across subcellular fractions in a TMT-labeled quantitative proteomics study of human brain, suggesting increased collagen III accumulation may accompany AD pathology.