RNF138
Chr 18ring finger protein 138
Also known as: HSD-4, NARF, STRIN, hNARF
This E3 ubiquitin-protein ligase promotes DNA double-strand break repair through homologous recombination and regulates Wnt/beta-catenin signaling pathways. Mutations cause autosomal recessive intellectual disability with growth retardation, typically presenting in early childhood. The gene shows significant constraint against loss-of-function variants (LOEUF 0.51), indicating that complete loss of protein function is poorly tolerated.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Moderately missense-constrained (top ~2.5%)
ClinVar Variant Classifications
66 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories· variant type breakdown unavailable
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | — | — | — | — | 38 |
Likely Pathogenic | — | — | — | — | 1 |
VUS | — | — | — | — | 11 |
Likely Benign | — | — | — | — | 1 |
Benign | — | — | — | — | 0 |
| Total | — | 51 | |||
Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
RNF138 · 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