Col4a1, encoding the proα1(IV) chain, is a key gene. Two proα1(IV) chains encoded by Col4a1 form trimers along with a proα2(IV) chain encoded by Col4a2, which are major components of the basement membrane in many tissues [1,2]. Mutations in Col4a1 are associated with a wide range of disorders, and understanding its function is crucial for deciphering the pathogenesis of related diseases.

Mutations in Col4a1 have been linked to hereditary porencephaly, a cerebrovascular disorder, in an autosomal dominant manner [1]. It is also associated with a broader spectrum of cerebrovascular, renal, ophthalmological, cardiac, and muscular abnormalities, collectively known as "COL4A1 mutation-related disorders" [1]. In children, Col4a1 mutations are often found in those with porencephaly or other patterns of parenchymal hemorrhage, with a high de novo mutation rate [1]. Neurologically, childhood-onset focal seizures, often complicated and drug-resistant, are common phenotypes associated with Col4a1/2 mutations [3]. Fetal intraparenchymal hemorrhage is also seen in COL4A1-related disorders, with various patterns on fetal MRI [4].

In conclusion, Col4a1 is essential for the formation of basement membrane components. Research on Col4a1, especially through the study of its mutations, has revealed its significant role in multiple disease areas, mainly cerebrovascular, neurological, and fetal intracranial hemorrhage-related conditions. Understanding Col4a1 contributes to better insights into the pathogenesis and potentially new treatment strategies for these diseases.