InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: SOST

Summary

InnateDB Protein

IDBP-52909.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

SOST

Protein Name

sclerostin

Synonyms

Species

Homo sapiens

Ensembl Protein

ENSP00000301691

InnateDB Gene

IDBG-52907 (SOST)

Protein Structure

UniProt Annotation

Function

Negative regulator of bone growth that acts through inhibition of Wnt signaling and bone formation. {ECO:0000269PubMed:15908424}.

Subcellular Localization

Secreted, extracellular space, extracellular matrix {ECO:0000269PubMed:20551380}.

Disease Associations

Sclerosteosis 1 (SOST1) [MIM:269500]: An autosomal recessive sclerosing bone dysplasia characterized by a generalized hyperostosis and sclerosis leading to a markedly thickened skull, with mandible, ribs, clavicles and all long bones also being affected. Due to narrowing of the foramina of the cranial nerves, facial nerve palsy, hearing loss and atrophy of the optic nerves can occur. Sclerosteosis is clinically and radiologically very similar to van Buchem disease, mainly differentiated by hand malformations and a large stature in sclerosteosis patients. {ECO:0000269PubMed:11179006, ECO:0000269PubMed:11181578, ECO:0000269PubMed:20583295}. Note=The disease is caused by mutations affecting the gene represented in this entry.Van Buchem disease (VBCH) [MIM:239100]: VBCH is an autosomal recessive sclerosing bone dysplasia characterized by endosteal hyperostosis of the mandible, skull, ribs, clavicles, and diaphyses of the long bones. Affected patients present a symmetrically increased thickness of bones, most frequently found as an enlarged jawbone, but also an enlargement of the skull, ribs, diaphysis of long bones, as well as tubular bones of hands and feet. The clinical consequence of increased thickness of the skull include facial nerve palsy causing hearing loss, visual problems, neurological pain, and, very rarely, blindness as a consequence of optic atrophy. Serum alkaline phosphatase levels are elevated. {ECO:0000269PubMed:11836356}. Note=The disease is caused by mutations affecting the gene represented in this entry. A 52 kb deletion downstream of SOST results in SOST transcription suppression causing van Buchem disease.Craniodiaphyseal dysplasia autosomal dominant (CDD) [MIM:122860]: A severe bone dysplasia characterized by massive generalized hyperostosis and sclerosis, especially involving the skull and facial bones. The sclerosis is so severe that the resulting facial distortion is referred to as 'leontiasis ossea' (leonine faces) and the bone deposition results in progressive stenosis of craniofacial foramina. Respiratory obstruction due to choanal stenosis compromises the clinical outcomes of affected patients. {ECO:0000269PubMed:21221996}. Note=The disease is caused by mutations affecting the gene represented in this entry. Heterozygous mutations located in the secretion signal of the SOST gene prevent sclerostin secretion and can be responsible for craniodiaphyseal dysplasia.

Tissue Specificity

Widely expressed at low levels with highest levels in bone, cartilage, kidney, liver, bone marrow and primary osteoblasts differentiated for 21 days. Detected in the subendothelial layer of the aortic intima (at protein level). {ECO:0000269PubMed:20551380}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 3 experimentally validated interaction(s) in this database.

Experimentally validated
Total	3 [view]
Protein-Protein	3 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Gene Ontology

Molecular Function

Accession	GO Term
GO:0005515	protein binding
GO:0008134	transcription factor binding
GO:0008201	heparin binding

Biological Process

GO:0001503	ossification
GO:0009612	response to mechanical stimulus
GO:0016055	Wnt signaling pathway
GO:0030178	negative regulation of Wnt signaling pathway
GO:0030279	negative regulation of ossification
GO:0030514	negative regulation of BMP signaling pathway
GO:0031333	negative regulation of protein complex assembly
GO:0045893	positive regulation of transcription, DNA-templated
GO:0071374	cellular response to parathyroid hormone stimulus
GO:0090090	negative regulation of canonical Wnt signaling pathway
GO:2000054	negative regulation of Wnt receptor signaling pathway involved in dorsal/ventral axis specification