RBBP8
Chr 18ARRB 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.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Tolerant to missense variation
Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.
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
498 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 3 | 0 | 35 | 0 | 38 |
Likely Pathogenic | 7 | 0 | 1 | 0 | 8 |
VUS | 11 | 186 | 13 | 0 | 210 |
Likely Benign | 1 | 12 | 74 | 79 | 166 |
Benign | 0 | 1 | 36 | 4 | 41 |
Conflicting | — | 14 | |||
| Total | 22 | 199 | 159 | 83 | 477 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View 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.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools