SOSTDC1

protein-coding

sclerostin domain containing 1, the group of DAN family

Gene summary

This gene is a member of the sclerostin family and encodes an N-glycosylated, secreted protein with a C-terminal cystine knot-like domain. This protein functions as a bone morphogenetic protein (BMP) antagonist. Specifically, it directly associates with BMPs, prohibiting them from binding their receptors, thereby regulating BMP signaling during cellular proliferation, differentiation, and programmed cell death. [provided by RefSeq, Jul 2008]

MANE transcript

NM_015464.3

Inheritance

—

ClinVar variants

U:15B:6

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.32

Max pathogenic AF

—

Genomic locus

chr7:16,461,481-16,530,580

External References & Databases

Ensembl (ENSG00000171243)

Transcript & Mutation Effects

hg38 • Region Span ~69.1 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SOSTDC1 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 16

not providedTotal: 5

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_015464.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				1 clinvar	1 clinvar	2
missense			15 clinvar	1 clinvar	2 clinvar	18
nonsense						0
start loss						0
frameshift				1 clinvar		1
splice donor/acceptor (+/-2bp)						0
Total	0	0	15	3	3	21

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 5 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_015464.3	RefSeq	NP_056279.1	2	MANE Select
ENST00000307068.5	Ensembl	ENSP00000304930.4	2	MANE Select
ENST00000396652.1	Ensembl	ENSP00000379889.1	3	Standard
ENST00000396652.2	Ensembl	ENSP00000379889.1	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Vitamin D Receptor Pathway
EDA Signalling in Hair Follicle Development
BMP receptor signaling

Biological Process

pattern specification process
negative regulation of cell fate commitment
Wnt signaling pathway
negative regulation of Wnt signaling pathway
BMP signaling pathway

Molecular Function

BMP binding
BMP receptor activity

Cellular Component

extracellular space

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000307068
Coding exons: 2
Length: 69100
Individuals with no LoFs: 125739
Homozygous LoFs: 0
Heterozygous LoFs: 6
Defined: 125745
p: 0.0000239

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.661	98	118	0.829	0.00000670	1351
Missense (PolyPhen)		41	64.328	0.63736		691
Synonymous	-0.781	48	41.6	1.15	0.00000201	393
Loss of Function	1.56	2	6.19	0.323	2.64e-7	85

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000054	0.000054	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.0000088	0.0000088	rare
South Asian	0.000065	0.000065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May be involved in the onset of endometrial receptivity for implantation/sensitization for the decidual cell reaction Enhances Wnt signaling and inhibits TGF-beta signaling (By similarity). Directly antagonizes activity of BMP2, BMP4, BMP6 and BMP7 in a dose-dependent manner. {ECO:0000250, ECO:0000269|PubMed:15020244}.;

Recessive Scores

pRec: 0.158

Intolerance Scores

LoFtool: 0.289
RVIS EVS: 0.01
RVIS percentile EVS: 54.95

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.822

Gene Damage Prediction

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