STATH

Chr 4

statherin

Also known as: STR

NCBI Gene: 6779 ENSG00000126549 UniProt: P02808

The protein is a salivary component that stabilizes calcium salts in saliva and inhibits calcium phosphate precipitation, serving as a structural constituent of tooth enamel and modulating hydroxyapatite crystal formation on tooth surfaces. Based on current databases, no human diseases have been definitively associated with STATH mutations. The gene shows low constraint against loss-of-function variants, suggesting such variants may be well-tolerated.

ResearchSummary from RefSeq, UniProt

Predicted to enable extracellular matrix constituent, lubricant activity and hydroxyapatite binding activity. Predicted to be a structural constituent of tooth enamel. Predicted to be involved in negative regulation of bone mineralization; ossification; and saliva secretion. Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.81

Clinical Summary— STATH

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

10 VUS of 12 total submissions

Explore recent and relevant literature in Research Assistant →

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?

1.81LOEUF

pLI 0.000

Z-score -0.10

OE 1.04 (0.56–1.81)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.31Z-score

OE missense 1.15 (0.89–1.51)

38 obs / 33.1 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.04 (0.56–1.81)

0≤0.351.4

Missense OE?1.15 (0.89–1.51)

0≤0.61.4

Synonymous OE?1.63

0≤1.21.6

LoF obs/exp: 6 / 5.7Missense obs/exp: 38 / 33.1Syn Z: -1.65

This gene — mechanism propensity

0.87top 5%

GOF

0.6344th %ile

LOF

0.10100th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median

GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

12 submitted variants in ClinVar

ClinVar

Classification Summary

VUS10

Likely Benign1

Benign1

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	10	0	10
Likely Benign	1	0	1
Benign	0	1	1
Total	11	1	12

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

View in ClinVar →

22 pathogenic / likely-pathogenic (of 33) ClinVar copy-number / structural variants overlap STATH — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →