RNFT1
Chr 17ring finger protein, transmembrane 1
Also known as: PTD016
The RNFT1 protein functions as an E3 ubiquitin-protein ligase in the endoplasmic reticulum-associated degradation (ERAD) pathway, targeting misfolded ER proteins for ubiquitination and proteasomal degradation while protecting cells from ER stress-induced apoptosis. Mutations in RNFT1 cause disease through a predicted gain-of-function mechanism. The gene shows tolerance to loss-of-function variants (pLI near zero, LOEUF 0.926), consistent with pathogenic variants likely acting through gain-of-function rather than haploinsufficiency.
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 (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
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
RNFT1 · 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 →No open access results found
External Resources
Links to major genomics databases and tools