RNF138

Chr 18

ring 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.

OMIMResearchSummary from RefSeq, UniProt
LOEUF 0.51
Clinical SummaryRNF138
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.68) — some intolerance to loss-of-function variants.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.51LOEUF
pLI 0.675
Z-score 2.73
OE 0.16 (0.070.51)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
2.12Z-score
OE missense 0.47 (0.380.58)
60 obs / 127.2 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.16 (0.070.51)
00.351.4
Missense OE0.47 (0.380.58)
00.61.4
Synonymous OE0.83
01.21.6
LoF obs/exp: 2 / 12.3Missense obs/exp: 60 / 127.2Syn Z: 0.88

ClinVar Variant Classifications

0 submitted variants 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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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