RBBP8

Chr 18q11.2

RB binding protein 8, endonuclease

Aliases:: CtIP, RIM, COM1
MANE:: ENST00000327155.10

OMIM: 604124 ↗NCBI: 5932 ↗Ensembl ↗

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Predicted protein structure

AlphaFold predicted structure

RBBP8 · Q99708

v62025-08-01

Predicted Aligned Error matrix for RBBP8 — diagonal shows residue index, colour shows pairwise prediction confidence (lower is better) — Predicted Aligned Error

Mean pLDDT

53.0/ 100

Low

897 residues

Confidence breakdown

Very high(≥ 90)13%
Confident(70–90)10%
Low(50–70)13%
Very low(< 50)64%

Open interactive 3D viewer

AlphaFold (Jumper et al., 2021) · CC BY 4.0

Clinical relevance (Genomics England PanelApp)

Diagnostic Grade (Green)

DDG2P
BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies
BIALLELIC, autosomal or pseudoautosomal
Intellectual disability
BIALLELIC, autosomal or pseudoautosomal
IUGR and IGF abnormalities
BIALLELIC, autosomal or pseudoautosomal
Severe microcephaly
BIALLELIC, autosomal or pseudoautosomal
Cerebral vascular malformations
BIALLELIC, autosomal or pseudoautosomal
Monogenic short stature
BIALLELIC, autosomal or pseudoautosomal

Disease associations (Open Targets)

Jawad syndrome
0.75
Seckel syndrome 2
0.69
Seckel syndrome
0.56
cancer
0.55
hereditary disease
0.47
Inguinal hernia
0.40
microcephalic primordial dwarfism
0.37
Primary microcephaly
0.37
autosomal recessive primary microcephaly
0.37
microcephaly with intellectual disability
0.37

Score is the Open Targets composite evidence score (0-1). Higher = stronger gene-disease association.

Protein function (UniProt)

DNA endonuclease RBBP8

Endonuclease that cooperates with the MRE11-RAD50-NBN (MRN) complex in DNA-end resection, the first step of double-strand break (DSB) repair through the homologous recombination (HR) pathway (PubMed:17965729, PubMed:19202191, PubMed:19759395, PubMed:20064462, PubMed:23273981, PubMed:26721387, PubMed:27814491, PubMed:27889449, PubMed:30787182, PubMed:31802118). HR is restricted to S and G2 phases of the cell cycle and preferentially repairs DSBs resulting from replication fork collapse (PubMed:17965729, PubMed:19202191, PubMed:23273981, PubMed:27814491, PubMed:27889449, PubMed:30787182). Key determinant of DSB repair pathway choice, as it commits cells to HR by preventing classical non-homologous end-joining (NHEJ) (PubMed:19202191). Specifically promotes the endonuclease activity of the MRN complex to clear DNA ends containing protein adducts: recruited to DSBs by NBN following phosphorylation by CDK1, and promotes the endonuclease activity of MRE11 to clear protein-DNA adducts and generate clean double-strand break ends (PubMed:27814491, PubMed:27889449, PubMed:30787182, PubMed:33836577). Functions downstream of the MRN complex and ATM, promotes ATR activation and its recruitment to DSBs in the S/G2 phase facilitating the generation of ssDNA (PubMed:16581787, PubMed:17965729, PubMed:19759395, PubMed:20064462). Component of the BRCA1-RBBP8 complex that regulates CHEK1 activation and controls cell cycle G2/M checkpoints on DNA damage (PubMed:15485915, PubMed:16818604). During immunoglobulin heavy chain class-switch recombination, promotes microhomology-mediated alternative end joining (A-NHEJ) and plays an essential role in chromosomal translocations (By similarity). Binds preferentially to DNA Y-junctions and to DNA substrates with blocked ends and promotes intermolecular DNA bridging (PubMed:30601117)