Sclerostin (SOST)

VBCH; Sclerosteosis

SPN	T993
HGNC	13771
MGI	1921749
PubMed	19049336
RGD	69358
UniProt	Q9BQB4
Wiki	Sclerostin

Sclerostin is a secreted glycoprotein with a C-terminal cysteine knot-like (CTCK) domain and sequence similarity to the DAN (differential screening-selected gene aberrative in neuroblastoma) family of bone morphogenetic protein (BMP) antagonists. Loss-of-function mutations in this gene are associated with an autosomal-recessive disorder, sclerosteosis, which causes progressive bone overgrowth. A deletion downstream of this gene, which causes reduced sclerostin expression, is associated with a milder form of the disorder called van Buchem disease.Sclerostin is produced by the osteocyte. These cells originate from osteoblasts, the cells that form the bone matrix. Sclerostin has an inhibitory effect on the life time of the osteoblast. Osteoblasts are self limiting by a negative feedback system.

Reference

"Increased bone density in sclerosteosis is due to the deficiency of a novel secreted protein (SOST)."
Hum. Mol. Genet. 10:537-543(2001) [PubMed] [Europe PMC] [Abstract]

"Bone dysplasia sclerosteosis results from loss of the SOST gene product, a novel cystine knot-containing protein."
Am. J. Hum. Genet. 68:577-589(2001) [PubMed] [Europe PMC] [Abstract]

"The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment."
Genome Res. 13:2265-2270(2003) [PubMed] [Europe PMC] [Abstract]

"DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage."
Nature 440:1045-1049(2006) [PubMed] [Europe PMC] [Abstract]

"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]

"Signal peptide prediction based on analysis of experimentally verified cleavage sites."
Protein Sci. 13:2819-2824(2004) [PubMed] [Europe PMC] [Abstract]

"Identification of a 52 kb deletion downstream of the SOST gene in patients with van Buchem disease."
J. Med. Genet. 39:91-97(2002) [PubMed] [Europe PMC] [Abstract]

"SOST is a ligand for LRP5/LRP6 and a Wnt signaling inhibitor."
J. Biol. Chem. 280:26770-26775(2005) [PubMed] [Europe PMC] [Abstract]

"Proteomics characterization of extracellular space components in the human aorta."
Mol. Cell. Proteomics 9:2048-2062(2010) [PubMed] [Europe PMC] [Abstract]

"Identification of signal peptide domain SOST mutations in autosomal dominant craniodiaphyseal dysplasia."
Hum. Genet. 129:497-502(2011) [PubMed] [Europe PMC] [Abstract]

"Bone overgrowth-associated mutations in the LRP4 gene impair sclerostin facilitator function."
J. Biol. Chem. 286:19489-19500(2011) [PubMed] [Europe PMC] [Abstract]

"Characterization of the structural features and interactions of sclerostin: molecular insight into a key regulator of Wnt-mediated bone formation."
J. Biol. Chem. 284:10890-10900(2009) [PubMed] [Europe PMC] [Abstract]

"First missense mutation in the SOST gene causing sclerosteosis by loss of sclerostin function."
Hum. Mutat. 31:E1526-E1543(2010) [PubMed] [Europe PMC] [Abstract]