RBBP6

Chr 16

RB binding protein 6, ubiquitin ligase

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

NCBI Gene: 5930 ENSG00000122257 UniProt: Q7Z6E9 OMIM: 600938

The RBBP6 protein functions as an E3 ubiquitin ligase that regulates key cellular processes including p53 stability, DNA replication, and chromosomal fragile site stability through targeted protein degradation. Mutations cause autosomal dominant developmental delay with variable intellectual disability and behavioral abnormalities. This gene is extremely intolerant to loss-of-function variants, indicating that proper dosage is critical for normal development.

OMIM ResearchSummary from RefSeq, UniProt

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]

OMIM ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.08

Clinical Summary— RBBP6

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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.

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ClinVar Variants

202 VUS of 255 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

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?

1.49Z-score

OE missense 0.86 (0.81–0.92)

809 obs / 937.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.03 (0.01–0.08)

0≤0.351.4

Missense OE?0.86 (0.81–0.92)

0≤0.61.4

Synonymous OE?1.11

0≤1.21.6

LoF obs/exp: 2 / 78.4Missense obs/exp: 809 / 937.4Syn Z: -1.52

This gene — mechanism propensity

0.15100th %ile

GOF

0.2099th %ile

LOF

0.91top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.08

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

255 submitted variants in ClinVar

ClinVar

Classification Summary

VUS202

Likely Benign25

Benign1

202

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0	0
Likely Pathogenic	0	0	0	0	0
VUS	0	201	1	0	202
Likely Benign	1	10	2	12	25
Benign	0	0	1	0	1
Total	1	211	4	12	228

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

View in ClinVar →

30 pathogenic / likely-pathogenic (of 35) ClinVar copy-number / structural variants overlap RBBP6 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →