EPSTI1
Chr 13epithelial stromal interaction 1
Also known as: BRESI1
The protein regulates macrophage polarization and is required for proper gene expression during M1 versus M2 macrophage differentiation, and may influence RELA/p65 and STAT1 phosphorylation and nuclear localization upon macrophage activation. The gene is extremely tolerant to loss-of-function variants (pLI near zero, LOEUF 1.719), and no Mendelian diseases have been established from mutations in this gene. Current evidence links the gene primarily to cancer biology and autoimmune conditions rather than pediatric neurogenetic disorders.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Tolerant to missense variation
This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
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
161 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 0 | 49 | 0 | 49 |
Likely Pathogenic | 0 | 0 | 0 | 0 | 0 |
VUS | 0 | 70 | 12 | 0 | 82 |
Likely Benign | 0 | 5 | 4 | 0 | 9 |
Benign | 0 | 1 | 1 | 0 | 2 |
| Total | 0 | 76 | 66 | 0 | 142 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
EPSTI1 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools