RNF114
Chr 20ring finger protein 114
Also known as: PSORS12, ZNF313
The protein functions as an E3 ubiquitin ligase that regulates multiple cellular processes including cell cycle progression, immune responses, and NF-kappa-B signaling by promoting ubiquitination and degradation of various target proteins. Pathogenic variants in RNF114 cause autosomal recessive intellectual disability with microcephaly, seizures, and spasticity, typically presenting in infancy with developmental delays and neurological symptoms. The gene shows relatively low constraint to loss-of-function variants, consistent with its recessive inheritance pattern.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
The highest-scoring mechanism for this gene is gain-of-function.
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
54 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 | 8 | 0 | 8 |
Likely Pathogenic | 0 | 0 | 2 | 0 | 2 |
VUS | 0 | 32 | 3 | 0 | 35 |
Likely Benign | 0 | 3 | 0 | 0 | 3 |
Benign | 0 | 0 | 0 | 0 | 0 |
| Total | 0 | 35 | 13 | 0 | 48 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
RNF114 · 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