Types I (COL1s), II (COL2s), and III (COL3s) collagen, the so-called interstitial collagens, are in many ways distinct from basement membrane collagen (COL4s). Type IV collagen (COL4s) does not form ordered fibrillar structures; rather, a meshwork is formed by 4 molecules held together at the ends.
Both disulfide and typical lysyl-derived collagen crosslinks are involved. Type IV procollagen contains 2 distinct chains. The collagen IV molecule (COL4s) is a heterotrimer of 2 alpha-1 chains (COL4A1) and 1 alpha-2 chain. The alpha-2 chain is encoded at a distinct locus (COL4A2) (MIM.120090).
Pathology
germline mutations in
- HANAC syndrome (autosomal dominant hereditary angiopathy with nephropathy, aneurysms, and muscle cramps)
- familial porencephaly (MIM.175780)
- brain small vessel disease with hemorrhage (MIM.607595)
- brain small vessel disease associated with Axenfeld-Rieger anomalies (MIM.607595)
COL4A1 may be a candidate gene in unexplained familial syndromes with autosomal dominant hematuria, cystic kidney disease, intracranial aneurysms, and muscle cramps.
See also
COL4A3, COL4A4, and COL4A5 are other collagen genes that have been implicated in inherited nephropathies in humans.
References
Plaisier E, Gribouval O, Alamowitch S, Mougenot B, Prost C, Verpont MC, Marro B, Desmettre T, Cohen SY, Roullet E, Dracon M, Fardeau M, Van Agtmael T, Kerjaschki D, Antignac C, Ronco P. COL4A1 mutations and hereditary angiopathy, nephropathy, aneurysms, and muscle cramps. N Engl J Med. 2007 Dec 27;357(26):2687-95. PMID: 18160688