RBBP6

Chr 16

RB binding protein 6, ubiquitin ligase

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

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.

OMIMResearchSummary from RefSeq, UniProt
LOFmechanismLOEUF 0.08
Clinical SummaryRBBP6
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.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.08LOEUF
pLI 1.000
Z-score 8.00
OE 0.03 (0.010.08)
Highly constrained

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

Missense Constraint
1.49Z-score
OE missense 0.86 (0.810.92)
809 obs / 937.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.03 (0.010.08)
00.351.4
Missense OE0.86 (0.810.92)
00.61.4
Synonymous OE1.11
01.21.6
LoF obs/exp: 2 / 78.4Missense obs/exp: 809 / 937.4Syn Z: -1.52
DN
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

0 submitted variants 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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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