SMOC2

Chr 6AR

SPARC related modular calcium binding 2

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

NCBI Gene: 64094 ENSG00000112562 UniProt: Q9H3U7 OMIM: 607223

The protein is a matricellular protein that promotes matrix assembly and cell adhesiveness, and stimulates endothelial cell proliferation, migration, and angiogenesis. Biallelic mutations cause dentin dysplasia type IA, an autosomal recessive condition affecting tooth development. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.622), suggesting some tolerance to such mutations.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Dentin dysplasia, type IAMIM #125400

UniProtDentin dysplasia 1A

Clinical highlights

Gene–disease validity

Not independently assessedOMIM lists Dentin dysplasia, type IA; no ClinGen or GenCC tier

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.62

LOEUF

LOF

Mechanism· G2P

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.62LOEUF

pLI 0.003

Z-score 3.00

OE 0.36 (0.21–0.62)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.64Z-score

OE missense 0.89 (0.81–0.99)

254 obs / 284.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.36 (0.21–0.62)

0≤0.351.4

Missense OE?0.89 (0.81–0.99)

0≤0.61.4

Synonymous OE?1.00

0≤1.21.6

LoF obs/exp: 9 / 25.3Missense obs/exp: 254 / 284.5Syn Z: 0.03

Background carrier burden — how many people carry a rare variant somewhere in SMOC2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 82

633 rare PASS variants

Rare truncating (LoF)

1 in 2,000

100 rare PASS variants

Rare synonymous (reference)

1 in 61

269 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for SMOC2. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 110	1 in 2,100
South Asian	~43k	1 in 85	1 in 670
Remaining (unassigned)	~30k	1 in 74	1 in 3,800
European (Finnish)	~27k	1 in 300	1 in 1,400
Admixed American	~22k	1 in 57	1 in 2,300
African / African American	~21k	1 in 48	1 in 2,100
East Asian	~20k	1 in 100	1 in 2,700
Ashkenazi Jewish	~13k	1 in 130	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 64	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 13 coding exons well covered in gnomAD exomes and genomes.? see exons ↓