ERLIN1
Chr 10ARER lipid raft associated 1
Also known as: C10orf69, Erlin-1, KE04, KEO4, SPFH1, SPG62
ERLIN1 encodes a protein that mediates endoplasmic reticulum-associated degradation of inositol 1,4,5-trisphosphate receptors and regulates cellular cholesterol homeostasis through the SREBP signaling pathway. Mutations cause spastic paraplegia 62, an autosomal recessive disorder affecting the pyramidal motor system. The gene shows moderate tolerance to loss-of-function variants (LOEUF 0.539).
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
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
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
ERLIN1 · 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