COL4A1 gene

COL4A1 (Collagen Type IV Alpha 1 Chain) is a protein coding gene located on chromosome 13q34. The COL4A1 gene encodes a type IV collagen alpha protein. Type IV collagen proteins are integral components of basement membranes. The COL4A1 gene shares a bidirectional promoter with a paralogous gene on the opposite strand.

The encoded protein, collagen type IV, consists of an amino-terminal 7S domain, a triple helix-forming collagenous domain, and a carboxy-terminal non-collagenous domain. It functions as part of a heterotrimer and interacts with other extracellular matrix components such as perlecans, proteoglycans, and laminins.

Proteolytic cleavage of the non-collagenous carboxy-terminal domain results in a biologically active fragment known as "arrests." Arresten, which comprises the C-terminal NC1 domain, inhibits angiogenesis and tumor formation. The C-terminal half is responsible for anti-angiogenic activity. In particular, Arresten inhibits proliferation, migration, and tube formation of endothelial cells.

Type IV collagen forms the main structural component of the glomerular basement membrane (GBM) and together with laminins, proteoglycans and entactin/nidogen forms a type of collagen meshwork.

Diseases associated with mutations in COL4A1 include.

• Porencephaly (a rare (including acquired) cerebral malformation characterized by a fluid-filled intracerebral cyst or cavity with or without a connection between the ventricle and subarachnoid space. Clinical manifestations depend on location and severity and may include hemiparesis, seizures, intellectual developmental deficits, and dystonia.
• Familial retinal arterial tortuosity (OMIM: 120130).
• Angiopathy, Hereditary, With Nephropathy, Aneurysms, And Muscle Cramps.

1. Beyer E (1958) Familial tortuosity of the small retinal arteries with macular hemorrhage. Klin Monatsbl Augenheilkd 132: 532-539.
2. Cagianut B et al. (1968) Familial tortuosity of the small retinal arteries with macular hemorrhage. Klin Monatsbl Augenheilkd 153: 533-542.
3. Clearkin LG et al (1986) Development of retinal arteriolar tortuosity in previously unaffected family members. Trans Ophthal Soc UK 105: 568-574.
4. Meuwissen ME et al (2015) The expanding phenotype of COL4A1 and COL4A2 mutations: clinical data on 13 newly identified families and a review of the literature. Genet Med 17:843-853.