RBBP8

Chr 18AR

RB binding protein 8, endonuclease

Also known as: COM1, CTIP, JAWAD, JWDS, RIM, SAE2, SCKL2

The RBBP8 protein is an endonuclease that cooperates with the MRE11-RAD50-NBN complex in DNA double-strand break repair through homologous recombination and regulates cell cycle checkpoints. Biallelic mutations cause autosomal recessive Seckel syndrome 2 and Jawad syndrome, both presenting with severe growth restriction and microcephaly from birth. The gene is highly constrained against loss-of-function variants (pLI near 0, LOEUF 0.749), reflecting its essential role in DNA repair.

Summary from RefSeq, OMIM, UniProt
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Primary Disease Associations & Inheritance

Jawad syndromeMIM #251255
AR
Pancreatic carcinoma, somatic
Seckel syndrome 2MIM #606744
AR
0
Active trials
4
Pubs (1 yr)
0
P/LP submissions
P/LP missense
0.75
LOEUF
DN
Mechanism· predicted
Clinical SummaryRBBP8
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.75LOEUF
pLI 0.000
Z-score 2.99
OE 0.54 (0.400.75)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
-0.02Z-score
OE missense 1.00 (0.931.08)
466 obs / 464.8 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.54 (0.400.75)
00.351.4
Missense OE1.00 (0.931.08)
00.61.4
Synonymous OE0.99
01.21.6
LoF obs/exp: 27 / 49.7Missense obs/exp: 466 / 464.8Syn Z: 0.09
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveRBBP8-related microcephaly and intellectual disabilityOTHERAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.6550th %ile
GOF
0.3094th %ile
LOF
0.4332th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

RBBP8 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

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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