RBX1

Chr 22

ring-box 1

Also known as: BA554C12.1, RNF75, ROC1

NCBI Gene: 9978ENSG00000100387UniProt: P62877

This locus encodes a RING finger-like domain-containing protein. The encoded protein interacts with cullin proteins and likely plays a role in ubiquitination processes necessary for cell cycle progression. This protein may also affect protein turnover. Related pseudogenes exist on chromosomes 2 and 5.[provided by RefSeq, Sep 2010]

34
ClinVar variants
20
Pathogenic / LP
0.95
pLI score· haploinsufficient
1
Active trials
Clinical Summary— RBX1
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.95). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
20 Pathogenic / Likely Pathogenic· 10 VUS of 34 total submissions
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

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.
0.32LOEUF
pLI 0.947
Z-score 2.82
OE 0.00 (0.00–0.32)
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.
2.38Z-score
OE missense 0.17 (0.10–0.28)
11 obs / 65.1 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.0.00 (0.00–0.32)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.17 (0.10–0.28)
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.1.07
0≤1.21.6
LoF obs/exp: 0 / 9.3Missense obs/exp: 11 / 65.1Syn Z: -0.27

ClinVar Variant Classifications

34 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic19
Likely Pathogenic1
VUS10
19
Pathogenic
1
Likely Pathogenic
10
VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories· variant type breakdown unavailable

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
————19
Likely Pathogenic
————1
VUS
————10
Likely Benign
————0
Benign
————0
Total—30

Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

RBX1 · 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
RING-BOX 1; RBX1
MIM #603814 · *
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
CC-90009, a novel cereblon E3 ligase modulator, targets acute myeloid leukemia blasts and leukemia stem cells.
Surka C et al.·Blood
2021
Lenalidomide induces ubiquitination and degradation of CK1α in del(5q) MDS.
Krönke J et al.·Nature
2015
Structural basis of lenalidomide-induced CK1α degradation by the CRL4(CRBN) ubiquitin ligase.
Petzold G et al.·Nature
2016
RBX1 mitigates ferroptosis by inhibiting NCOA4-mediated ferritinophagy and contributes to the attenuation of intervertebral disc degeneration.
Zhou LP et al.·J Transl Med
2025
METTL3 inhibits liver fibrosis via RBX1 stability and TXNIP-mediated ferroptosis.
Liao X et al.·Hepatol Commun
2025
E3 ubiquitin ligase RBX1 drives the metastasis of triple negative breast cancer through a FBXO45-TWIST1-dependent degradation mechanism.
Shao J et al.·Aging (Albany NY)
2022Functional
Neddylation-CRLs regulate the functions of Treg immune cells.
Wu D et al.·Bioessays
2023
Multifactor assessment of ovarian cancer reveals immunologically interpretable molecular subtypes with distinct prognoses.
Guo Y et al.·Front Immunol
2023
pVHL regulates protein stability of the TCF/LEF transcription factor family via ubiquitin-independent proteasomal degradation.
Wang C et al.·Cell Mol Life Sci
2025
Reduced RBX1 expression induces chromosome instability and promotes cellular transformation in high-grade serous ovarian cancer precursor cells.
Bungsy M et al.·Cancer Lett
2021
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
Digestive Disease

A Population-based, Multicenter Cohort Study of Combined Screening for Gastrointestinal Tumors

RECRUITING
NCT05996458Xijing HospitalStarted 2023-08-01
Gastroenteroscopy；Risk factor investigation; FIT-HP;RNF180 and SEPTIN9 gene methylation testRisk factor investigation;Gastroenteroscopy；Risk factor investigation; FIT-HP;RNF180 and SEPTIN9 gene methylation test

External Resources

Links to major genomics databases and tools