RNF8

Chr 6

ring finger protein 8

Also known as: hRNF8

NCBI Gene: 9025ENSG00000112130UniProt: O76064

The protein encoded by this gene contains a RING finger motif and an FHA domain. This protein has been shown to interact with several class II ubiquitin-conjugating enzymes (E2), including UBE2E1/UBCH6, UBE2E2, and UBE2E3, and may act as an ubiquitin ligase (E3) in the ubiquitination of certain nuclear proteins. This protein is also known to play a role in the DNA damage response and depletion of this protein causes cell growth inhibition and cell cycle arrest. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2012]

46
ClinVar variants
6
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— RNF8
⚡
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
6 Pathogenic / Likely Pathogenic· 37 VUS of 46 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.
0.18LOEUF
pLI 0.999
Z-score 4.54
OE 0.04 (0.01–0.18)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

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.
2.16Z-score
OE missense 0.62 (0.54–0.71)
156 obs / 252.5 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

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.0.04 (0.01–0.18)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.62 (0.54–0.71)
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.0.73
0≤1.21.6
LoF obs/exp: 1 / 25.9Missense obs/exp: 156 / 252.5Syn Z: 2.05

ClinVar Variant Classifications

46 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic6
VUS37
Likely Benign2
Benign1
6
Pathogenic
37
VUS
2
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
6
0
6
Likely Pathogenic
0
0
0
0
0
VUS
0
36
1
0
37
Likely Benign
0
0
0
2
2
Benign
0
0
1
0
1
Total0368246

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

View in ClinVar →

Protein Context — Lollipop Plot

RNF8 · 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
UBE2T-regulated H2AX monoubiquitination induces hepatocellular carcinoma radioresistance by facilitating CHK1 activation.
Sun J et al.·J Exp Clin Cancer Res
2020
Synergistic interaction of Rnf8 and p53 in the protection against genomic instability and tumorigenesis.
Halaby MJ et al.·PLoS Genet
2013
RAP80 and RNF8, key players in the recruitment of repair proteins to DNA damage sites.
Yan J et al.·Cancer Lett
2008Review
RNF8 depletion attenuates hepatocellular carcinoma progression by inhibiting epithelial-mesenchymal transition and enhancing drug sensitivity.
Kuang J et al.·Acta Biochim Biophys Sin (Shanghai)
2023
RNF8-mediated regulation of Akt promotes lung cancer cell survival and resistance to DNA damage.
Xu Y et al.·Cell Rep
2021
RNF8 up-regulates AR/ARV7 action to contribute to advanced prostate cancer progression.
Zhou T et al.·Cell Death Dis
2022
RNF8 identified as a co-activator of estrogen receptor α promotes cell growth in breast cancer.
Wang S et al.·Biochim Biophys Acta Mol Basis Dis
2017
Resistance to Intervention: Paclitaxel in Breast Cancer.
Dan VM et al.·Mini Rev Med Chem
2021Review
RNF8 regulates active epigenetic modifications and escape gene activation from inactive sex chromosomes in post-meiotic spermatids.
Sin HS et al.·Genes Dev
2012
Early lipid genetics: identification of common and rare genetic variants for lipid traits in Indian adolescents.
Nair JM et al.·J Hum Genet
2025
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