Collagen type VI alpha 3 chain (COL6A3)

Collagen type VI alpha 3 chain (COL6A3) is one of three primary subunits of collagen VI, an extracellular matrix protein ubiquitously expressed in connective and skeletal muscle tissues. It is essential for microfibril formation, providing structural support and stability to tissues including skin, muscle, fat, and joints. The alpha-3 chain is distinctively large and complex, containing multiple von Willebrand factor type A domains, whose alternative splicing generates several variants. In addition to its structural roles, COL6A3 is a precursor for endotrophin, a bioactive fragment that drives tumor progression, fibrosis, chemoresistance, and inflammation. Pathologic loss- or gain-of-function mutations in COL6A3 cause musculoskeletal diseases such as Bethlem myopathy and Ullrich congenital muscular dystrophy. Aberrant expression of COL6A3 and endotrophin is linked to metabolic, fibrotic, and neoplastic disorders, making COL6A3 a significant therapeutic target and a biomarker in oncology and metabolic research.

Other names

Collagen alpha-3(VI) chainCOL6A3Bethlem myopathy 1 (BTHLM1, BTHLM1C)Dystonia 27 (DYT27)Ullrich congenital muscular dystrophy 1 (UCMD1, UCMD1C)Epididymis secretory sperm binding protein

Inhibition of endotrophin: blocks ECM/tumor remodeling, inflammation, and fibrosis Potentially modulates TGF-β pathway activity, reducing epithelial-mesenchymal transition (EMT) and angiogenesis in cancer