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 ... See more...

Aliases for SOST Gene

Aliases for SOST Gene

  • Sclerostin 2 3 4 5
  • DAND6 2 3
  • VBCH 2 3
  • Sclerosteosis 2
  • SOST1 3
  • SOST 5
  • CDD 3

External Ids for SOST Gene

Previous GeneCards Identifiers for SOST Gene

  • GC17M041573
  • GC17M044008
  • GC17M041841
  • GC17M042306
  • GC17M039186
  • GC17M037597

Summaries for SOST Gene

Entrez Gene Summary for SOST 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]

GeneCards Summary for SOST Gene

SOST (Sclerostin) is a Protein Coding gene. Diseases associated with SOST include Sclerosteosis 1 and Craniodiaphyseal Dysplasia, Autosomal Dominant. Among its related pathways are Signaling by GPCR and Parathyroid hormone synthesis, secretion and action. Gene Ontology (GO) annotations related to this gene include transcription factor binding and heparin binding. An important paralog of this gene is SOSTDC1.

UniProtKB/Swiss-Prot Summary for SOST Gene

  • Negative regulator of bone growth that acts through inhibition of Wnt signaling and bone formation.

Gene Wiki entry for SOST Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for SOST Gene

Genomics for SOST Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for SOST Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around SOST on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for SOST

Top Transcription factor binding sites by QIAGEN in the SOST gene promoter:
  • AhR
  • aMEF-2
  • Arnt
  • C/EBPalpha
  • MEF-2
  • MEF-2A
  • RSRFC4

Genomic Locations for SOST Gene

Latest Assembly
chr17:43,753,738-43,758,791
(GRCh38/hg38)
Size:
5,054 bases
Orientation:
Minus strand

Previous Assembly
chr17:41,831,106-41,836,159
(GRCh37/hg19 by Entrez Gene)
Size:
5,054 bases
Orientation:
Minus strand

chr17:41,831,099-41,836,156
(GRCh37/hg19 by Ensembl)
Size:
5,058 bases
Orientation:
Minus strand

Genomic View for SOST Gene

Genes around SOST on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
SOST Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for SOST Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for SOST Gene

Proteins for SOST Gene

  • Protein details for SOST Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9BQB4-SOST_HUMAN
    Recommended name:
    Sclerostin
    Protein Accession:
    Q9BQB4
    Secondary Accessions:
    • Q495N9

    Protein attributes for SOST Gene

    Size:
    213 amino acids
    Molecular mass:
    24031 Da
    Quaternary structure:
    • Interacts with LRP4 (via the extracellular domain); the interaction facilitates the inhibition of Wnt signaling. Interacts with LRP5 (via the first two YWTD-EGF repeat domains); the interaction inhibits Wnt-mediated signaling. Interacts with LRP6.

    Three dimensional structures from OCA and Proteopedia for SOST Gene

    Alternative splice isoforms for SOST Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for SOST Gene

Post-translational modifications for SOST Gene

  • Glycosylation at Asn53 and Asn175

Other Protein References for SOST Gene

ENSEMBL proteins:
REFSEQ proteins:

No data available for DME Specific Peptides for SOST Gene

Domains & Families for SOST Gene

Gene Families for SOST Gene

HGNC:
Human Protein Atlas (HPA):
  • Disease related genes
  • Predicted secreted proteins

Protein Domains for SOST Gene

InterPro:
Blocks:
  • Growth factor cystine knot superfamily signature
  • Cystine knot, C-terminal
  • Sclerostin

Suggested Antigen Peptide Sequences for SOST Gene

GenScript: Design optimal peptide antigens:
  • Sclerostin (SOST_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q9BQB4

UniProtKB/Swiss-Prot:

SOST_HUMAN :
  • Belongs to the sclerostin family.
Family:
  • Belongs to the sclerostin family.
genes like me logo Genes that share domains with SOST: view

Function for SOST Gene

Molecular function for SOST Gene

UniProtKB/Swiss-Prot Function:
Negative regulator of bone growth that acts through inhibition of Wnt signaling and bone formation.

Phenotypes From GWAS Catalog for SOST Gene

Gene Ontology (GO) - Molecular Function for SOST Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005515 protein binding IPI 15908424
GO:0008134 transcription factor binding IDA 17696759
GO:0008201 heparin binding IEA --
GO:0036122 BMP binding IBA 21873635
genes like me logo Genes that share ontologies with SOST: view
genes like me logo Genes that share phenotypes with SOST: view

Human Phenotype Ontology for SOST Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for SOST Gene

MGI Knock Outs for SOST:

Animal Models for research

  • Taconic Biosciences Mouse Models for SOST

miRNA for SOST Gene

miRTarBase miRNAs that target SOST

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for SOST

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targets and HOMER Transcription for SOST Gene

Localization for SOST Gene

Subcellular locations from UniProtKB/Swiss-Prot for SOST Gene

Secreted, extracellular space, extracellular matrix.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for SOST gene
Compartment Confidence
extracellular 5
nucleus 3
golgi apparatus 3
plasma membrane 2
cytoskeleton 2
mitochondrion 2
endoplasmic reticulum 2
cytosol 2
peroxisome 1
endosome 1
lysosome 1

Gene Ontology (GO) - Cellular Components for SOST Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005576 extracellular region TAS --
GO:0005615 extracellular space IBA 21873635
GO:0005794 Golgi apparatus IEA --
GO:0032991 protein-containing complex IEA --
GO:0062023 colocalizes_with collagen-containing extracellular matrix HDA 20551380
genes like me logo Genes that share ontologies with SOST: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for SOST Gene

Pathways & Interactions for SOST Gene

genes like me logo Genes that share pathways with SOST: view

SIGNOR curated interactions for SOST Gene

Inactivates:
Is activated by:

Gene Ontology (GO) - Biological Process for SOST Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001503 ossification IEA,IBA 21873635
GO:0009612 response to mechanical stimulus IEP 21723865
GO:0016055 Wnt signaling pathway IEA --
GO:0030178 negative regulation of Wnt signaling pathway IEA,IBA 21873635
GO:0030279 negative regulation of ossification NAS 11181578
genes like me logo Genes that share ontologies with SOST: view

Drugs & Compounds for SOST Gene

(7) Drugs for SOST Gene - From: DrugBank and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Romosozumab Approved, Investigational Pharma Target, inhibitor 0
genes like me logo Genes that share compounds with SOST: view

Transcripts for SOST Gene

mRNA/cDNA for SOST Gene

1 REFSEQ mRNAs :
10 NCBI additional mRNA sequence :
1 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for SOST

Alternative Splicing Database (ASD) splice patterns (SP) for SOST Gene

No ASD Table

Relevant External Links for SOST Gene

GeneLoc Exon Structure for
SOST

Expression for SOST Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for SOST Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for SOST Gene

This gene is overexpressed in Artery - Aorta (x27.8), Artery - Tibial (x14.3), and Kidney - Cortex (x5.6).

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for SOST

SOURCE GeneReport for Unigene cluster for SOST Gene:

Hs.349204

mRNA Expression by UniProt/SwissProt for SOST Gene:

Q9BQB4-SOST_HUMAN
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).

Evidence on tissue expression from TISSUES for SOST Gene

  • Bone(3.2)
  • Muscle(2.7)
  • Kidney(2.5)
  • Heart(2.5)
  • Bone marrow(2.3)
  • Blood(2.2)
  • Thyroid gland(2.2)

Phenotype-based relationships between genes and organs from Gene ORGANizer for SOST Gene

Germ Layers:
  • ectoderm
  • endoderm
  • mesoderm
Systems:
  • cardiovascular
  • digestive
  • endocrine
  • integumentary
  • nervous
  • respiratory
  • skeletal muscle
  • skeleton
Regions:
Head and neck:
  • brain
  • cerebrospinal fluid
  • cheek
  • cranial nerve
  • ear
  • eye
  • eyelid
  • face
  • forehead
  • head
  • inner ear
  • jaw
  • lip
  • mandible
  • maxilla
  • meninges
  • middle ear
  • mouth
  • neck
  • nose
  • outer ear
  • parathyroid
  • pharynx
  • skull
  • thyroid
  • tooth
Thorax:
  • chest wall
  • clavicle
  • rib
  • rib cage
  • scapula
  • sternum
Abdomen:
  • biliary tract
  • liver
Pelvis:
  • pelvis
Limb:
  • ankle
  • arm
  • digit
  • elbow
  • femur
  • fibula
  • finger
  • foot
  • forearm
  • hand
  • hip
  • humerus
  • knee
  • lower limb
  • nail
  • radius
  • shin
  • shoulder
  • thigh
  • tibia
  • toe
  • ulna
  • upper limb
  • wrist
General:
  • blood vessel
  • peripheral nervous system
  • skin
  • spinal column
  • spinal cord
  • vertebrae
genes like me logo Genes that share expression patterns with SOST: view

Primer products for research

No data available for Protein differential expression in normal tissues , Protein expression and Protein tissue co-expression partners for SOST Gene

Orthologs for SOST Gene

This gene was present in the common ancestor of chordates.

Orthologs for SOST Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia SOST 29 30
  • 99.84 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia SOST 29 30
  • 93.74 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia SOST 29 30
  • 93.24 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Sost 29
  • 89.11 (n)
Mouse
(Mus musculus)
Mammalia Sost 29 16 30
  • 88.83 (n)
OneToOne
Oppossum
(Monodelphis domestica)
Mammalia SOST 30
  • 66 (a)
OneToOne
Chicken
(Gallus gallus)
Aves SOST 29 30
  • 68.97 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia SOST 30
  • 52 (a)
OneToOne
Zebrafish
(Danio rerio)
Actinopterygii sost 29 30
  • 59.22 (n)
OneToOne
Species where no ortholog for SOST was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Fruit Fly (Drosophila melanogaster)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Platypus (Ornithorhynchus anatinus)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Squirt (Ciona savignyi)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Tropical Clawed Frog (Silurana tropicalis)
  • Wheat (Triticum aestivum)
  • Worm (Caenorhabditis elegans)

Evolution for SOST Gene

ENSEMBL:
Gene Tree for SOST (if available)
TreeFam:
Gene Tree for SOST (if available)
Aminode:
Evolutionary constrained regions (ECRs) for SOST: view image
Alliance of Genome Resources:
Additional Orthologs for SOST

Paralogs for SOST Gene

Paralogs for SOST Gene

(1) SIMAP similar genes for SOST Gene using alignment to 1 proteins:

  • SOST_HUMAN
genes like me logo Genes that share paralogs with SOST: view

Variants for SOST Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for SOST Gene

SNP ID Clinical significance and condition Chr 17 pos Variation AA Info Type
888823 Uncertain Significance: Sclerosteosis 1 43,753,844(-) C/T
NM_025237.3(SOST):c.*1498G>A
THREE_PRIME_UTR
888898 Uncertain Significance: Sclerosteosis 1 43,755,536(-) C/T
NM_025237.3(SOST):c.448G>A (p.Gly150Ser)
MISSENSE
888899 Uncertain Significance: Sclerosteosis 1 43,755,681(-) G/A
NM_025237.3(SOST):c.303C>T (p.Thr101=)
SYNONYMOUS
888900 Uncertain Significance: Sclerosteosis 1 43,758,599(-) G/A
NM_025237.3(SOST):c.143C>T (p.Pro48Leu)
MISSENSE
888901 Uncertain Significance: Sclerosteosis 1 43,758,628(-) G/A
NM_025237.3(SOST):c.114C>T (p.Pro38=)
SYNONYMOUS

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for SOST Gene

All consequence types are included: molecular consequences (e.g. missense, synonymous), and location-based (e.g. intron, upstream).

Structural Variations from Database of Genomic Variants (DGV) for SOST Gene

Variant ID Type Subtype PubMed ID
esv3640635 CNV gain 21293372
nsv1060861 CNV gain 25217958
nsv1146669 OTHER inversion 26484159
nsv2060 CNV insertion 18451855

Variation tolerance for SOST Gene

Residual Variation Intolerance Score: 39.1% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 0.39; 8.60% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for SOST Gene

Human Gene Mutation Database (HGMD)
SOST
SNPedia medical, phenotypic, and genealogical associations of SNPs for
SOST
Leiden Open Variation Database (LOVD)
SOST

SNP Genotyping and Copy Number Assays for research

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for SOST Gene

Disorders for SOST Gene

MalaCards: The human disease database

(41) MalaCards diseases for SOST Gene - From: OMI, CVR, GTR, ORP, SWI, COP, and GCD

- elite association - COSMIC cancer census association via MalaCards
Search SOST in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

SOST_HUMAN
  • 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:0000269 PubMed:11179006, ECO:0000269 PubMed:11181578, ECO:0000269 PubMed:20583295}. Note=The disease is caused by variants 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:0000269 PubMed:11836356}. Note=The disease is caused by variants 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:0000269 PubMed:21221996}. Note=The disease is caused by variants 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.

Additional Disease Information for SOST

Human Genome Epidemiology Navigator
(HuGE)
Atlas
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
Open Targets Platform
genes like me logo Genes that share disorders with SOST: view

No data available for Genatlas for SOST Gene

Publications for SOST Gene

  1. Bone dysplasia sclerosteosis results from loss of the SOST gene product, a novel cystine knot-containing protein. (PMID: 11179006) Brunkow ME … Mulligan J (American journal of human genetics 2001) 2 3 4 22 72
  2. Identification of a 52 kb deletion downstream of the SOST gene in patients with van Buchem disease. (PMID: 11836356) Balemans W … Van Hul W (Journal of medical genetics 2002) 3 4 22 72
  3. Increased bone density in sclerosteosis is due to the deficiency of a novel secreted protein (SOST). (PMID: 11181578) Balemans W … Van Hul W (Human molecular genetics 2001) 2 3 4 22
  4. Identification of signal peptide domain SOST mutations in autosomal dominant craniodiaphyseal dysplasia. (PMID: 21221996) Kim SJ … Jin DK (Human genetics 2011) 3 4 72
  5. Characterization of the structural features and interactions of sclerostin: molecular insight into a key regulator of Wnt-mediated bone formation. (PMID: 19208630) Veverka V … Carr MD (The Journal of biological chemistry 2009) 3 4 22

Products for SOST Gene

Sources for SOST Gene