RER1
Chr 1retention in endoplasmic reticulum sorting receptor 1
The protein localizes to the Golgi apparatus and retrieves endoplasmic reticulum membrane proteins from the early Golgi compartment, facilitating gamma-secretase complex assembly. Mutations cause autosomal recessive neurodevelopmental disorder with epilepsy and brain atrophy, typically presenting in infancy or early childhood. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.58), and the disorder primarily affects the central nervous system with seizures and developmental delays as prominent features.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Moderately missense-constrained (top ~2.5%)
The highest-scoring mechanism for this gene is dominant-negative.
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
188 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 | 123 | 0 | 123 |
Likely Pathogenic | 0 | 0 | 3 | 0 | 3 |
VUS | 0 | 9 | 36 | 0 | 45 |
Likely Benign | 0 | 0 | 2 | 0 | 2 |
Benign | 0 | 0 | 1 | 0 | 1 |
| Total | 0 | 9 | 165 | 0 | 174 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
RER1 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
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