SOST

sclerostin, the group of DAN family

Basic information

Region (hg38): 17:43753738-43758791

Links

ENSG00000167941 ∙ NCBI:50964 ∙ OMIM:605740 ∙ HGNC:13771 ∙ Uniprot:Q9BQB4 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• sclerosteosis 1 (Strong), mode of inheritance: AR
• craniodiaphyseal dysplasia (Supportive), mode of inheritance: AD
• sclerosteosis (Supportive), mode of inheritance: AR
• hyperostosis corticalis generalisata (Supportive), mode of inheritance: AD
• craniodiaphyseal dysplasia, autosomal dominant (Limited), mode of inheritance: Unknown
• sclerosteosis 1 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Craniodiaphyseal dysplasia, autosomal dominant; Sclerosteosis 1; van Buchem disease	AD/AR	Musculoskeletal	Starting in infancy, regular surveillance for sequelae related to overgrowth, including hearing evaluation, assessment of signs of increased intracranial pressure and cranial nerve entrapment, can allow early surgical management	Audiologic/Otolaryngologic; Craniofacial; Musculoskeletal	13924477; 3276528; 6323069; 8433139; 9712543; 9463328; 11179006; 11836356; 12116252; 12694228; 14671168; 17245025; 17853455; 20301406; 20583295; 21221996

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SOST gene.

• Sclerosteosis 1 (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SOST gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			2	8		10
missense		1	21	2	1	25
nonsense	1	1				2
start loss						0
frameshift	1					1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding			17	5	9	31
Total	2	2	40	15	10

Variants in SOST

This is a list of pathogenic ClinVar variants found in the SOST region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
17-43753813-A-G		Sclerosteosis 1	Uncertain significance (Jan 13, 2018)
17-43753844-C-T		Sclerosteosis 1	Uncertain significance (Jan 13, 2018)
17-43753917-A-C		Primary bone dysplasia with increased bone density	Uncertain significance (Jun 14, 2016)
17-43753937-GC-G		Primary bone dysplasia with increased bone density	Benign (Jun 14, 2016)
17-43753940-A-C		Sclerosteosis 1	Uncertain significance (Jan 13, 2018)
17-43753948-G-C		Sclerosteosis 1	Benign (Jan 12, 2018)
17-43753951-C-G		Sclerosteosis 1	Likely benign (Jan 12, 2018)
17-43753979-G-A		Sclerosteosis 1	Uncertain significance (Jan 13, 2018)
17-43753993-CT-C		Primary bone dysplasia with increased bone density	Benign (Jun 14, 2016)
17-43754075-G-C		Sclerosteosis 1	Uncertain significance (Jan 12, 2018)
17-43754075-G-GC		Primary bone dysplasia with increased bone density	Benign (Jun 14, 2016)
17-43754166-T-C		Sclerosteosis 1	Uncertain significance (Jan 13, 2018)
17-43754279-G-A		Sclerosteosis 1	Uncertain significance (Jan 13, 2018)
17-43754338-C-T		Sclerosteosis 1	Benign (Jan 13, 2018)
17-43754440-A-G		Sclerosteosis 1	Uncertain significance (Jan 12, 2018)
17-43754459-T-A		Sclerosteosis 1	Uncertain significance (Jan 12, 2018)
17-43754476-G-A		Sclerosteosis 1	Benign (Aug 23, 2019)
17-43754653-A-G		Sclerosteosis 1	Uncertain significance (Jan 13, 2018)
17-43754676-A-G		Sclerosteosis 1	Uncertain significance (Jan 13, 2018)
17-43754773-C-A		Sclerosteosis 1	Uncertain significance (Jan 13, 2018)
17-43754780-C-T		Sclerosteosis 1	Benign (Jan 13, 2018)
17-43755022-G-A		Sclerosteosis 1	Benign (Jan 13, 2018)
17-43755028-G-C		Sclerosteosis 1	Uncertain significance (Jan 12, 2018)
17-43755120-T-C		Sclerosteosis 1	Likely benign (Jan 13, 2018)
17-43755123-A-G		Sclerosteosis 1	Uncertain significance (Jan 13, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SOST	protein_coding	protein_coding	ENST00000301691	2	5058

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.867	0.131	125744	0	3	125747	0.0000119

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.835	106	133	0.796	0.00000745	1331
Missense in Polyphen		34	44.002	0.77269		426
Synonymous	0.0468	62	62.5	0.992	0.00000378	453
Loss of Function	2.38	0	6.60	0.00	2.84e-7	71

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000187	0.0000176
Middle Eastern	0.00	0.00
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Negative regulator of bone growth that acts through inhibition of Wnt signaling and bone formation. {ECO:0000269|PubMed:15908424}.
• Disease: DISEASE: 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 mutations affecting the gene represented in this entry. A 52 kb deletion downstream of SOST results in SOST transcription suppression causing van Buchem disease.; 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 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.
• Pathway: Wnt signaling pathway - Homo sapiens (human);Role of Osx and miRNAs in tooth development;Wnt Signaling Pathway;Signaling by WNT;Signal Transduction;Negative regulation of TCF-dependent signaling by WNT ligand antagonists;TCF dependent signaling in response to WNT (Consensus)

Recessive Scores

• pRec: 0.405

Haploinsufficiency Scores

• pHI: 0.477
• hipred: Y
• hipred_score: 0.831
• ghis: 0.453

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.283

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Sost
• Phenotype: normal phenotype; skeleton phenotype; limbs/digits/tail phenotype; growth/size/body region phenotype; homeostasis/metabolism phenotype; cellular phenotype

Gene ontology

• Biological process: ossification;response to mechanical stimulus;Wnt signaling pathway;negative regulation of ossification;negative regulation of BMP signaling pathway;negative regulation of protein complex assembly;positive regulation of transcription, DNA-templated;cellular response to parathyroid hormone stimulus;negative regulation of canonical Wnt signaling pathway
• Cellular component: extracellular region;extracellular space;Golgi apparatus;protein-containing complex;collagen-containing extracellular matrix
• Molecular function: protein binding;transcription factor binding;heparin binding