SMOC2

Chr 6AR

SPARC related modular calcium binding 2

Also known as: DTDP1, DTDP1A, MST117, MSTP117, MSTP140, SMAP2, bA270C4A.1, bA37D8.1

NCBI Gene: 64094ENSG00000112562UniProt: Q9H3U7

This gene encodes a member of the SPARC family (secreted protein acidic and rich in cysteine/osteonectin/BM-40), which are highly expressed during embryogenesis and wound healing. The gene product is a matricellular protein which promotes matrix assembly and can stimulate endothelial cell proliferation and migration, as well as angiogenic activity. Associated with pulmonary function, this secretory gene product contains a Kazal domain, two thymoglobulin type-1 domains, and two EF-hand calcium-binding domains. The encoded protein may serve as a target for controlling angiogenesis in tumor growth and myocardial ischemia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2009]

Primary Disease Associations & Inheritance

Dentin dysplasia, type IAMIM #125400
AR
UniProtDentin dysplasia 1
260
ClinVar variants
73
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— SMOC2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
73 Pathogenic / Likely Pathogenic· 113 VUS of 260 total submissions

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.
0.62LOEUF
pLI 0.003
Z-score 3.00
OE 0.36 (0.21–0.62)
Tolerant

Typical tolerance to LoF variation

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.
0.64Z-score
OE missense 0.89 (0.81–0.99)
254 obs / 284.5 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.0.36 (0.21–0.62)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.89 (0.81–0.99)
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.1.00
0≤1.21.6
LoF obs/exp: 9 / 25.3Missense obs/exp: 254 / 284.5Syn Z: 0.03

ClinVar Variant Classifications

260 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic69
Likely Pathogenic4
VUS113
Likely Benign30
Benign43
Conflicting1
69
Pathogenic
4
Likely Pathogenic
113
VUS
30
Likely Benign
43
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
0
68
0
69
Likely Pathogenic
1
0
3
0
4
VUS
0
104
9
0
113
Likely Benign
0
3
11
16
30
Benign
0
1
30
12
43
Conflicting
—1
Total210812128260

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

View in ClinVar →

Protein Context — Lollipop Plot

SMOC2 · protein map & ClinVar variants

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

Gene2Phenotype Curations

SMOC2-related dentin dysplasia with microdontia and misshapen teeth

strong
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Dentin dysplasia, type IA

MIM #125400

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Comprehensive scRNA-seq analysis to identify new markers of M2 macrophages for predicting the prognosis of prostate cancer.
Ou Y et al.·Ann Med
2024
EGFR controls transcriptional and metabolic rewiring in KRAS(G12D) colorectal cancer.
Krauß D et al.·EMBO Mol Med
2025
Integrative analysis of gene expression and histone modifications for DES, DSP, GJA1 and SMOC2 in adipose tissue reveals potential relationship to cardiometabolic health.
Saeed S et al.·Mol Med
2025
SMOC2 promotes an epithelial-mesenchymal transition and a pro-metastatic phenotype in epithelial cells of renal cell carcinoma origin.
Feng D et al.·Cell Death Dis
2022
Role of SMOC2 in adenomyosis: implications for ECM remodeling and EMT pathogenesis.
Wang LN et al.·BMC Womens Health
2025Functional
Downregulation of SMOC2 expression in papillary thyroid carcinoma and its prognostic significance.
Kim HS et al.·Sci Rep
2020
SMOC2 gene variant and the risk of vitiligo in Jordanian Arabs.
Alkhateeb A et al.·Eur J Dermatol
2010
Dentin dysplasia type I-A dental disease with genetic heterogeneity.
Chen D et al.·Oral Dis
2019Review
SMOC2, an intestinal stem cell marker, is an independent prognostic marker associated with better survival in colorectal cancers.
Jang BG et al.·Sci Rep
2020
The Intestinal Stem Cell Marker SMOC2 Is an Independent Prognostic Marker Associated With Better Survival in Gastric Cancer.
Hyun CL et al.·Anticancer Res
2021
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