Col4a3 is a gene encoding a component of type IV collagen, a key structural protein in the extracellular matrix, especially in basement membranes such as those in the glomeruli of the kidneys, cochlear, and ocular tissues [1,3]. It is crucial for maintaining the integrity and function of these basement membranes. Mutations in Col4a3 can disrupt the formation of normal collagen IV heterotrimers, which are essential for the proper function of these tissues.

Mutations in Col4a3 are associated with autosomal recessive Alport syndrome. In a study of 40 individuals with autosomal recessive inheritance indicated by two mutations, 20 mutation pairs (50%) affected Col4a3. Many of the identified variants led to a stop codon, and those with early onset renal failure often had at least one such mutation [1]. In a transgenic mouse model with a Col4a3 p.G799R mutation, the mutation caused a decrease in intracellular and secreted collagen IV α3α4α5 heterotrimers, with the mutant collagen IV α3 chains accumulating in the endoplasmic reticulum and showing defective secretion. This led to persistent endoplasmic reticulum stress in vivo and in vitro. Treatment with tauroursodeoxycholic acid, an endoplasmic reticulum stress inhibitor, improved kidney function [2].

In conclusion, Col4a3 is essential for the normal structure and function of basement membranes in multiple tissues. Research using mouse models has revealed the pathophysiological mechanisms associated with Col4a3 mutations, especially in relation to Alport syndrome. Understanding Col4a3's function and the effects of its mutations provides insights into the development of this genetic kidney disease and potential treatment strategies [1,2].