Collagen alpha-1(VI) chain (COL6A1) (COL6A1)

Collagen alpha-1(VI) chain (COL6A1) is a vital structural protein that contributes to the formation of type VI collagen, which organizes the extracellular matrix (ECM) and anchors the basement membrane of muscle fibers to the surrounding connective tissue (UniProt P12109). Mutations in the COL6A1 gene are the underlying cause of Collagen VI-related dystrophies (COL6-RD), a spectrum of muscle disorders ranging from the severe Ullrich congenital muscular dystrophy to the milder Bethlem myopathy (OMIM 120220). Many of these mutations act through a dominant-negative mechanism, where the presence of a single mutant allele disrupts the assembly of the collagen VI heterotrimer, leading to ECM instability and progressive muscle degeneration. Consequently, COL6A1 mutant alleles have emerged as a primary therapeutic target for precision medicine. Current drug development strategies focus on allele-specific silencing using antisense oligonucleotides (ASOs) or small interfering RNAs (siRNAs) to selectively degrade mutant mRNA while sparing the wild-type transcript (PMID: 24532271). Experimental gene-editing approaches, such as CRISPR/Cas9, are also being investigated to permanently disrupt the mutant allele in patient-derived cells (PMID: 28820136). By reducing the burden of defective collagen chains, these therapies aim to restore functional ECM architecture and improve muscle strength in affected patients.

Other names

Collagen type VI alpha 1 chainBTHLM1UCMD1OPLLAlpha-1 type VI collagen

Allele-specific silencing of mutant mRNA transcripts to prevent dominant-negative interference with collagen VI heterotrimer assembly.