SOSTDC1

Chr 7

sclerostin domain containing 1

Also known as: CDA019, DAND7, ECTODIN, USAG1

NCBI Gene: 25928ENSG00000171243UniProt: Q6X4U4

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]

69
ClinVar variants
39
Pathogenic / LP
0.16
pLI score
0
Active trials
Clinical Summary— SOSTDC1
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.32) despite low pLI — interpret in context.
📋
ClinVar Variants
39 Pathogenic / Likely Pathogenic· 23 VUS of 69 total submissions
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.01LOEUF
pLI 0.163
Z-score 1.56
OE 0.32 (0.13–1.01)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.66Z-score
OE missense 0.83 (0.70–0.98)
98 obs / 118.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.32 (0.13–1.01)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.83 (0.70–0.98)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.15
0≤1.21.6
LoF obs/exp: 2 / 6.2Missense obs/exp: 98 / 118.2Syn Z: -0.78

ClinVar Variant Classifications

69 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic36
Likely Pathogenic3
VUS23
Likely Benign3
Benign4
36
Pathogenic
3
Likely Pathogenic
23
VUS
3
Likely Benign
4
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
36
0
36
Likely Pathogenic
0
0
3
0
3
VUS
0
15
8
0
23
Likely Benign
1
1
1
0
3
Benign
0
2
0
2
4
Total11848269

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

SOSTDC1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Integrated Single-Cell Atlas of Endothelial Cells of the Human Lung.
Schupp JC et al.·Circulation
2021
Comprehensive proteogenomic characterization of rare kidney tumors.
Li GX et al.·Cell Rep Med
2024
USP15 negatively regulates lung cancer progression through the TRAF6-BECN1 signaling axis for autophagy induction.
Kim MJ et al.·Cell Death Dis
2022
MicroRNA-27a transfected dental pulp stem cells undergo odonto/osteogenic differentiation via targeting DKK3 and SOSTDC1 in Wnt/BMP signaling in vitro and enhance bone formation in vivo.
Yu Z et al.·J Transl Med
2025
SOSTDC1 differentially modulates Smad and beta-catenin activation and is down-regulated in breast cancer.
Clausen KA et al.·Breast Cancer Res Treat
2011
SOSTDC1 inhibits bone metastasis in non-small cell lung cancer and may serve as a clinical therapeutic target.
Chen G et al.·Int J Mol Med
2018
Two candidate tumor suppressor genes, MEOX2 and SOSTDC1, identified in a 7p21 homozygous deletion region in a Wilms tumor.
Ohshima J et al.·Genes Chromosomes Cancer
2009
Investigation of SOSTDC1 gene in non-syndromic patients with supernumerary teeth.
Arikan V et al.·Med Oral Patol Oral Cir Bucal
2018Cohort
Differential expression of secreted factors SOSTDC1 and ADAMTS8 cause profibrotic changes in linear morphoea fibroblasts.
Badshah II et al.·Br J Dermatol
2019
Identification of HOXA9 methylation as an epigenetic biomarker predicting prognosis and guiding treatment choice in acute myeloid leukemia.
Xie F et al.·BMC Cancer
2025
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools