ENTREP1
Chr 9endosomal transmembrane epsin interactor 1
Also known as: C9orf61, ENTREP, FAM189A2, X123
This protein activates the E3 ubiquitin ligase ITCH to ubiquitinate the CXCR4 receptor, triggering its endocytosis and desensitization to negatively regulate CXCL12/CXCR4 signaling. Mutations cause autosomal recessive neurodevelopmental disorders with intellectual disability, seizures, and movement abnormalities. The gene shows minimal constraint against loss-of-function variants.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Mild missense constraint
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
196 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 | 33 | 0 | 33 |
Likely Pathogenic | 0 | 0 | 8 | 0 | 8 |
VUS | 0 | 79 | 13 | 0 | 92 |
Likely Benign | 1 | 4 | 13 | 6 | 24 |
Benign | 0 | 2 | 22 | 1 | 25 |
Conflicting | — | 4 | |||
| Total | 1 | 85 | 89 | 7 | 186 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
ENTREP1 · 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