RNF38

Chr 9

ring finger protein 38

NCBI Gene: 152006ENSG00000137075UniProt: Q9H0F5

This gene encodes a protein with a coiled-coil motif and a RING-H2 motif (C3H2C2) at its carboxy-terminus. The RING motif is a zinc-binding domain found in a large set of proteins playing roles in diverse cellular processes including oncogenesis, development, signal transduction, and apoptosis. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2008]

160
ClinVar variants
71
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— RNF38
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
71 Pathogenic / Likely Pathogenic· 62 VUS of 160 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.14LOEUF
pLI 1.000
Z-score 5.13
OE 0.03 (0.01–0.14)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.56Z-score
OE missense 0.74 (0.66–0.83)
216 obs / 291.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.03 (0.01–0.14)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.74 (0.66–0.83)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.97
0≤1.21.6
LoF obs/exp: 1 / 32.6Missense obs/exp: 216 / 291.0Syn Z: 0.24

ClinVar Variant Classifications

160 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic62
Likely Pathogenic9
VUS62
Likely Benign2
62
Pathogenic
9
Likely Pathogenic
62
VUS
2
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
62
0
62
Likely Pathogenic
0
0
9
0
9
VUS
0
58
4
0
62
Likely Benign
0
1
1
0
2
Benign
0
0
0
0
0
Total059760135

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

RNF38 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
m(6)A methylation-mediated lncRNA RNF144A-AS1 promotes hepatocellular carcinoma progression through the miR-1301-3p/RNF38 pathway.
Kong M et al.·Biol Direct
2025
Overexpression of RNF38 facilitates TGF-β signaling by Ubiquitinating and degrading AHNAK in hepatocellular carcinoma.
Peng R et al.·J Exp Clin Cancer Res
2019
RNF38 enhances 5-Fluorouracil resistance in colorectal cancer by activating the Wnt pathway.
Long Y et al.·J BUON
2021
Cloning and characterization of a novel human gene RNF38 encoding a conserved putative protein with a RING finger domain.
Eisenberg I et al.·Biochem Biophys Res Commun
2002
Tuning ubiquitin transfer by RING E3 ubiquitin ligases through the linchpin residue.
Nakasone MA et al.·Life Sci Alliance
2025
Deletions of immunoglobulin heavy chain and T cell receptor gene regions are uniquely associated with lymphoid blast transformation of chronic myeloid leukemia.
Nacheva EP et al.·BMC Genomics
2010
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools