Collagen alpha-3(IV) chain (COL4A3)

Collagen alpha-3(IV) chain (COL4A3) is a structural protein encoded by the COL4A3 gene, essential for the formation of type IV collagen networks that constitute the basement membranes of various tissues, especially in the kidney, inner ear, and eye. This protein forms triple-helical protomers with alpha-4 and alpha-5(IV) chains, creating a unique α345(IV) collagen network that is crucial for the filtration function of the glomerular basement membrane. The non-collagenous (NC1) domain of the alpha-3(IV) chain is the primary autoantigen in Goodpasture’s disease, where pathogenic antibodies cause severe renal and pulmonary symptoms by binding and initiating inflammation. Mutations in COL4A3 disrupt collagen IV network assembly, leading to genetic renal diseases such as Alport syndrome, which is characterized by progressive kidney failure, hearing loss, and ocular abnormalities; milder mutations can result in thin basement membrane nephropathy presenting with isolated hematuria. The tumstatin fragment, derived from the C-terminal domain, is known to have anti-angiogenic properties. COL4A3 is not a direct target for approved drugs but is an important disease biomarker and autoantigen in rare autoimmune and hereditary nephropathies.

Other names

Collagen type IV alpha 3 chainCollagen alpha-3(IV) chainTumstatinGoodpasture antigenCollagen IV, alpha-3 polypeptideCollagen, type IV, alpha 3 (Goodpasture antigen)ATS2ATS3ATS3AATS3BBFH2

Not a direct therapeutic target; pathogenic mechanism in Goodpasture’s disease is antibody-mediated binding to the non-collagenous C-terminal domain (α3NC1 domain) leading to inflammation and tissue damage. In Alport syndrome, mutations cause loss-of-function (defective network assembly), leading to disease via structural deficiency.