1gr3

Structural highlights

Disease

[COAA1_HUMAN] Defects in COL10A1 are the cause of Schmid type metaphyseal chondrodysplasia (SMCD) [MIM:156500]. SMCD is a dominantly inherited disorder of the osseous skeleton. The cardinal features of the phenotype are mild short stature, coxa vara and a waddling gait. Radiography usually shows sclerosis of the ribs, flaring of the metaphyses, and a wide irregular growth plate, especially of the knees. A variant form of SMCD is spondylometaphyseal dysplasia Japanese type. It is characterized by spinal involvement comprising mild platyspondyly, vertebral body abnormalities, and end-plate irregularity.^{[1] [2] [3] [4] [5] [6] [7] [8]}

Function

[COAA1_HUMAN] Type X collagen is a product of hypertrophic chondrocytes and has been localized to presumptive mineralization zones of hyaline cartilage.

Evolutionary Conservation

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

References

1. ↑ Wallis GA, Rash B, Sweetman WA, Thomas JT, Super M, Evans G, Grant ME, Boot-Handford RP. Amino acid substitutions of conserved residues in the carboxyl-terminal domain of the alpha 1(X) chain of type X collagen occur in two unrelated families with metaphyseal chondrodysplasia type Schmid. Am J Hum Genet. 1994 Feb;54(2):169-78. PMID:8304336
2. ↑ McIntosh I, Abbott MH, Warman ML, Olsen BR, Francomano CA. Additional mutations of type X collagen confirm COL10A1 as the Schmid metaphyseal chondrodysplasia locus. Hum Mol Genet. 1994 Feb;3(2):303-7. PMID:8004099
3. ↑ Chan D, Cole WG, Rogers JG, Bateman JF. Type X collagen multimer assembly in vitro is prevented by a Gly618 to Val mutation in the alpha 1(X) NC1 domain resulting in Schmid metaphyseal chondrodysplasia. J Biol Chem. 1995 Mar 3;270(9):4558-62. PMID:7876225
4. ↑ Bonaventure J, Chaminade F, Maroteaux P. Mutations in three subdomains of the carboxy-terminal region of collagen type X account for most of the Schmid metaphyseal dysplasias. Hum Genet. 1995 Jul;96(1):58-64. PMID:7607655
5. ↑ Wallis GA, Rash B, Sykes B, Bonaventure J, Maroteaux P, Zabel B, Wynne-Davies R, Grant ME, Boot-Handford RP. Mutations within the gene encoding the alpha 1 (X) chain of type X collagen (COL10A1) cause metaphyseal chondrodysplasia type Schmid but not several other forms of metaphyseal chondrodysplasia. J Med Genet. 1996 Jun;33(6):450-7. PMID:8782043
6. ↑ Ikegawa S, Nakamura K, Nagano A, Haga N, Nakamura Y. Mutations in the N-terminal globular domain of the type X collagen gene (COL10A1) in patients with Schmid metaphyseal chondrodysplasia. Hum Mutat. 1997;9(2):131-5. PMID:9067753 doi:<131::AID-HUMU5>3.0.CO;2-C 10.1002/(SICI)1098-1004(1997)9:2<131::AID-HUMU5>3.0.CO;2-C
7. ↑ Sawai H, Ida A, Nakata Y, Koyama K. Novel missense mutation resulting in the substitution of tyrosine by cysteine at codon 597 of the type X collagen gene associated with Schmid metaphyseal chondrodysplasia. J Hum Genet. 1998;43(4):259-61. PMID:9852679 doi:10.1007/s100380050085
8. ↑ Bateman JF, Wilson R, Freddi S, Lamande SR, Savarirayan R. Mutations of COL10A1 in Schmid metaphyseal chondrodysplasia. Hum Mutat. 2005 Jun;25(6):525-34. PMID:15880705 doi:10.1002/humu.20183
9. ↑ Bogin O, Kvansakul M, Rom E, Singer J, Yayon A, Hohenester E. Insight into Schmid metaphyseal chondrodysplasia from the crystal structure of the collagen X NC1 domain trimer. Structure. 2002 Feb;10(2):165-73. PMID:11839302