Col12a1, encoding collagen type XII α1 chain, is associated with connective tissues and plays a role in various biological processes. It is involved in extracellular matrix organization, which is crucial for the structure and function of tissues. Genetic models are valuable for studying its functions and impacts on health and disease [4].

Mutations in Col12a1 have been associated with Ullrich congenital muscular dystrophy (UCMD) and myopathic Ehlers-Danlos syndrome. A homozygous c.8903C>T (p.Pro2968Leu) missense variant in Col12a1 was found in a UCMD patient with joint hyperlaxity, falls, and skin lesions [4]. Experimental knockout of Col12a1 in intrahepatic cholangiocarcinoma (iCCA) cells inhibited their proliferation, invasiveness, and growth. Promoter hypermethylation-induced downregulation of miR-424-5p led to Col12a1 upregulation in iCCA, suggesting its potential as a druggable target [3]. In osteosarcoma, knockdown of Col12a1 inhibited cell growth, migration, invasion, and promoted apoptosis, while its overexpression activated the FAK/PI3K/AKT/mTOR pathway, enhancing tumor development [2]. In breast cancer, COL12A1 was negatively associated with prognosis, and its knockdown impaired cell proliferation, also affecting M2 macrophage infiltration and immunotherapy response [1]. In pancreatic cancer, COL12A1 was highly expressed in cancer-associated fibroblasts (CAFs). Knocking down COL12A1 decreased CAF proliferation and migration, and reversed the cancer-promoting effect [5].

In conclusion, Col12a1 is essential for connective tissue-related functions. Through gene knockout and related models, its role in multiple diseases has been revealed, including congenital muscular dystrophies and various cancers. Understanding Col12a1 function in these disease areas provides potential targets for diagnosis, prognosis, and treatment.