1knt

Structural highlights

Disease

[CO6A3_HUMAN] Defects in COL6A3 are a cause of Bethlem myopathy (BM) [MIM:158810]. BM is a rare autosomal dominant proximal myopathy characterized by early childhood onset (complete penetrance by the age of 5) and joint contractures most frequently affecting the elbows and ankles.^{[1] [2] [3] [4] [5]} Defects in COL6A3 are a cause of Ullrich congenital muscular dystrophy (UCMD) [MIM:254090]; also known as Ullrich scleroatonic muscular dystrophy. UCMD is an autosomal recessive congenital myopathy characterized by muscle weakness and multiple joint contractures, generally noted at birth or early infancy. The clinical course is more severe than in Bethlem myopathy.^{[6] [7]}

Function

[CO6A3_HUMAN] Collagen VI acts as a cell-binding protein.

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

References

1. ↑ Demir E, Sabatelli P, Allamand V, Ferreiro A, Moghadaszadeh B, Makrelouf M, Topaloglu H, Echenne B, Merlini L, Guicheney P. Mutations in COL6A3 cause severe and mild phenotypes of Ullrich congenital muscular dystrophy. Am J Hum Genet. 2002 Jun;70(6):1446-58. Epub 2002 Apr 24. PMID:11992252 doi:S0002-9297(07)60697-1
2. ↑ Pan TC, Zhang RZ, Pericak-Vance MA, Tandan R, Fries T, Stajich JM, Viles K, Vance JM, Chu ML, Speer MC. Missense mutation in a von Willebrand factor type A domain of the alpha 3(VI) collagen gene (COL6A3) in a family with Bethlem myopathy. Hum Mol Genet. 1998 May;7(5):807-12. PMID:9536084
3. ↑ Pepe G, Bertini E, Giusti B, Brunelli T, Comeglio P, Saitta B, Merlini L, Chu ML, Federici G, Abbate R. A novel de novo mutation in the triple helix of the COL6A3 gene in a two-generation Italian family affected by Bethlem myopathy. A diagnostic approach in the mutations' screening of type VI collagen. Neuromuscul Disord. 1999 Jun;9(4):264-71. PMID:10399756
4. ↑ Lampe AK, Dunn DM, von Niederhausern AC, Hamil C, Aoyagi A, Laval SH, Marie SK, Chu ML, Swoboda K, Muntoni F, Bonnemann CG, Flanigan KM, Bushby KM, Weiss RB. Automated genomic sequence analysis of the three collagen VI genes: applications to Ullrich congenital muscular dystrophy and Bethlem myopathy. J Med Genet. 2005 Feb;42(2):108-20. PMID:15689448 doi:42/2/108
5. ↑ Baker NL, Morgelin M, Pace RA, Peat RA, Adams NE, Gardner RJ, Rowland LP, Miller G, De Jonghe P, Ceulemans B, Hannibal MC, Edwards M, Thompson EM, Jacobson R, Quinlivan RC, Aftimos S, Kornberg AJ, North KN, Bateman JF, Lamande SR. Molecular consequences of dominant Bethlem myopathy collagen VI mutations. Ann Neurol. 2007 Oct;62(4):390-405. PMID:17886299 doi:10.1002/ana.21213
6. ↑ Demir E, Sabatelli P, Allamand V, Ferreiro A, Moghadaszadeh B, Makrelouf M, Topaloglu H, Echenne B, Merlini L, Guicheney P. Mutations in COL6A3 cause severe and mild phenotypes of Ullrich congenital muscular dystrophy. Am J Hum Genet. 2002 Jun;70(6):1446-58. Epub 2002 Apr 24. PMID:11992252 doi:S0002-9297(07)60697-1
7. ↑ Lampe AK, Dunn DM, von Niederhausern AC, Hamil C, Aoyagi A, Laval SH, Marie SK, Chu ML, Swoboda K, Muntoni F, Bonnemann CG, Flanigan KM, Bushby KM, Weiss RB. Automated genomic sequence analysis of the three collagen VI genes: applications to Ullrich congenital muscular dystrophy and Bethlem myopathy. J Med Genet. 2005 Feb;42(2):108-20. PMID:15689448 doi:42/2/108
8. ↑ Arnoux B, Merigeau K, Saludjian P, Norris F, Norris K, Bjorn S, Olsen O, Petersen L, Ducruix A. The 1.6 A structure of Kunitz-type domain from the alpha 3 chain of human type VI collagen. J Mol Biol. 1995 Mar 10;246(5):609-17. PMID:7533217