RBBP6

Chr 16

RB binding protein 6, ubiquitin ligase

Also known as: MY038, P2P-R, PACT, RBQ-1, SNAMA

NCBI Gene: 5930ENSG00000122257UniProt: Q7Z6E9

The retinoblastoma tumor suppressor (pRB) protein binds with many other proteins. In various human cancers, pRB suppresses cellular proliferation and is inactivated. Cell cycle-dependent phosphorylation regulates the activity of pRB. This gene encodes a protein which binds to underphosphorylated but not phosphorylated pRB. Multiple alternatively spliced transcript variants that encode different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

285
ClinVar variants
30
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— RBBP6
⚡
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
30 Pathogenic / Likely Pathogenic· 202 VUS of 285 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.
0.08LOEUF
pLI 1.000
Z-score 8.00
OE 0.03 (0.01–0.08)
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.
1.49Z-score
OE missense 0.86 (0.81–0.92)
809 obs / 937.4 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 (0.01–0.08)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.86 (0.81–0.92)
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.1.11
0≤1.21.6
LoF obs/exp: 2 / 78.4Missense obs/exp: 809 / 937.4Syn Z: -1.52

ClinVar Variant Classifications

285 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic27
Likely Pathogenic3
VUS202
Likely Benign24
Benign1
27
Pathogenic
3
Likely Pathogenic
202
VUS
24
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
27
0
27
Likely Pathogenic
0
0
3
0
3
VUS
0
194
8
0
202
Likely Benign
1
10
2
11
24
Benign
0
0
1
0
1
Total12044111257

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

View in ClinVar →

Protein Context — Lollipop Plot

RBBP6 · 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
TSPAN8(+) myofibroblastic cancer-associated fibroblasts promote chemoresistance in patients with breast cancer.
Fan G et al.·Sci Transl Med
2024Cohort
Germline genetic variants that predispose to myeloproliferative neoplasms and hereditary myeloproliferative phenotypes.
Lim J et al.·Leuk Res
2024Review
A Novel 167-Amino Acid Protein Encoded by CircPCSK6 Inhibits Intrahepatic Cholangiocarcinoma Progression via IKBα Ubiquitination.
Guan C et al.·Adv Sci (Weinh)
2025
Comparative proteomics analysis of gastric cancer stem cells.
Morisaki T et al.·PLoS One
2014
De-regulation of the RBBP6 isoform 3/DWNN in human cancers.
Mbita Z et al.·Mol Cell Biochem
2012
Abnormal expression of long non-coding RNA FGD5-AS1 affects the development of ovarian cancer through regulating miR-107/RBBP6 axis.
Zhang W et al.·Chin J Physiol
2023
Overexpression of RBBP6, alone or combined with mutant TP53, is predictive of poor prognosis in colon cancer.
Chen J et al.·PLoS One
2013
Advances in understanding the pathogenesis of familial myeloproliferative neoplasms.
Rumi E et al.·Br J Haematol
2017Review
Analysis of the expression and association of retinoblastoma binding protein 6 with the JNK signaling pathway in prostate cancers.
Guan WY et al.·Cell Biol Int
2020
The association of RBBP6 variant 3 expressions with apoptosis in human immunodeficiency virus-associated nephropathy (HIVAN).
Mbita Z et al.·Exp Mol Pathol
2015
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
RBBP6-induced destabilization of FOXP3 promotes glucose metabolism and malignant progression of HBV-related hepatocellular carcinoma.
Ge J et al.·Pathol Res Pract
2025
RBBP6 anchors pre-mRNA 3' end processing to nuclear speckles for efficient gene expression.
Yoon Y et al.·Mol Cell
2025
[The Impact of SRSF1 -Mediated Alternative Splicing of RBBP6 on the Proliferation of Multiple Myeloma Cells].
Zhang WM et al.·Zhongguo Shi Yan Xue Ye Xue Za Zhi
2024
Mbnl1-mediated alternative splicing of circMlxipl regulates Rbbp6-involved ChREBP turnover to inhibit lipotoxicity-induced β-cell damage.
Gong Y et al.·Mol Med
2024🔓 Open Access
Rbbp6-Mediated Bmal1 Ubiquitination Inhibits YAP1 Signaling Pathway to Promote Ferroptosis in Diabetes-Induced Testicular Damage.
Tian Y et al.·Diabetes Metab J
2025🔓 Open Access
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