DERL1
Chr 8derlin 1
Also known as: DER-1, DER1, derlin-1
The encoded protein forms channels in the endoplasmic reticulum membrane that retrotranslocate misfolded proteins from the ER lumen to the cytosol for proteasomal degradation, functioning as a key component of the ER-associated degradation (ERAD) pathway. Biallelic mutations cause infantile-onset epileptic encephalopathy with severe developmental delay, microcephaly, and visual impairment, following an autosomal recessive inheritance pattern. The gene shows low constraint against loss-of-function variants, consistent with the recessive disease mechanism.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
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.
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
100 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 | 48 | 0 | 48 |
Likely Pathogenic | 0 | 0 | 0 | 0 | 0 |
VUS | 0 | 31 | 1 | 0 | 32 |
Likely Benign | 0 | 0 | 0 | 0 | 0 |
Benign | 0 | 0 | 0 | 0 | 0 |
| Total | 0 | 31 | 49 | 0 | 80 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
DERL1 · 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