SMOC1

Chr 14AR

SPARC related modular calcium binding 1

Also known as: OAS

NCBI Gene: 64093 ENSG00000198732 UniProt: Q9H4F8 OMIM: 608488

This gene encodes a multi-domain secreted protein that regulates osteoblast differentiation and plays essential roles in eye and limb development. Mutations cause microphthalmia with limb anomalies, inherited in an autosomal recessive pattern. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.59).

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a multi-domain secreted protein that may have a critical role in ocular and limb development. Mutations in this gene are associated with microphthalmia and limb anomalies. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2011]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Microphthalmia with limb anomaliesMIM #206920

UniProtOphthalmoacromelic syndrome

Clinical highlights

Gene–disease validity

Not independently assessedOMIM lists Microphthalmia with limb anomalies; no ClinGen or GenCC tier

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.59

LOEUF

LOF

Mechanism· G2P

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.59LOEUF

pLI 0.009

Z-score 3.08

OE 0.33 (0.19–0.59)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

0.74Z-score

OE missense 0.87 (0.78–0.97)

214 obs / 246.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.33 (0.19–0.59)

0≤0.351.4

Missense OE?0.87 (0.78–0.97)

0≤0.61.4

Synonymous OE?0.80

0≤1.21.6

LoF obs/exp: 8 / 24.4Missense obs/exp: 214 / 246.8Syn Z: 1.55

Background carrier burden — how many people carry a rare variant somewhere in SMOC1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 110

543 rare PASS variants

Rare truncating (LoF)

1 in 2,900

49 rare PASS variants

Rare synonymous (reference)

1 in 210

206 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for SMOC1. 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 160	1 in 2,600
South Asian	~43k	1 in 110	1 in 6,100
Remaining (unassigned)	~30k	1 in 110	1 in 2,500
European (Finnish)	~27k	1 in 580	≈ 1 in 10,000
Admixed American	~22k	1 in 150	1 in 1,100
African / African American	~21k	1 in 110	≈ 1 in 8,800
East Asian	~20k	1 in 110	≈ 1 in 4,900
Ashkenazi Jewish	~13k	1 in 120	≈ 1 in 5,700
Middle Eastern	~2,884	1 in 110	≈ 1 in 2,300

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): 12 of 12 coding exons well covered in gnomAD exomes. Genomes: 11 of 12 (exon 12 below).? see exons ↓