SOST

Protein identityUniProt · HPA

UniProt accession

Q9BQB4

Gene

SOST

Ensembl

ENSG00000167941

Chromosome

17

Canonical length

213 aa

Protein class

Disease related genes, FDA approved drug targets, Human disease related genes, Predicted secreted proteins

Secretome location

Secreted to extracellular matrix

OverviewNCBI Gene

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. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

213 residues, UniProt reviewed canonical sequence.

>Q9BQB4|SOST
     1  MQLPLALCLV CLLVHTAFRV VEGQGWQAFK NDATEIIPEL GEYPEPPPEL ENNKTMNRAE
    61  NGGRPPHHPF ETKDVSEYSC RELHFTRYVT DGPCRSAKPV TELVCSGQCG PARLLPNAIG
   121  RGKWWRPSGP DFRCIPDRYR AQRVQLLCPG GEAPRARKVR LVASCKCKRL TRFHNQSELK
   181  DFGTEAARPQ KGRKPRPRAR SAKANQAELE NAY

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against SOST can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Secreted

Secreted

Yes

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.58

Highest tissue expression

67 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about SOST.

Disease | AllUniProt

Conditions SOST is implicated in, by any mechanism.

• Sclerosteosis 1 (SOST1) MIM:269500
• Van Buchem disease (VBCH) MIM:239100
• Craniodiaphyseal dysplasia autosomal dominant (CDD) MIM:122860

Disease | GeneticClinVar

7 pathogenic / likely-pathogenic of 106 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Sclerosteosis 1
• Craniodiaphyseal dysplasia, autosomal dominant
• SOST-related disorder

ReferencesPubMed · IEDB

Publications for SOST from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.45

gnomAD pLI

0.87

gnomAD missense Z

0.84

DepMap mean gene effect

-0.02

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 2% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• BMP signaling pathway
• canonical Wnt signaling pathway
• cellular response to parathyroid hormone stimulus
• negative regulation of BMP signaling pathway
• negative regulation of canonical Wnt signaling pathway
• negative regulation of ossification
• negative regulation of protein-containing complex assembly
• negative regulation of Wnt signaling pathway
• ossification
• positive regulation of DNA-templated transcription
• response to mechanical stimulus

Molecular functions

• BMP binding
• carbohydrate binding
• DNA-binding transcription factor binding
• heparin binding
• molecular function inhibitor activity

Cellular components

• extracellular region
• extracellular space
• Golgi apparatus
• protein-containing complex

Protein domainsUniProt · Pfam · InterPro

• Cystine knot, C-terminal
• Sclerostin/Sclerostin domain-containing protein 1
• Cystine-knot cytokine
• Sclerostin (SOST)

KeywordsUniProt

• Disulfide bond
• Extracellular matrix
• Glycoprotein
• Heparin-binding
• Secreted
• Signal
• Wnt signaling pathway

InteractionsUniProt · HPA

Protein binding partners of SOST in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• LRP4
• LRP5
• LRP6