RBBP8

Summary

RBBP8 (RB binding protein 8, endonuclease, HGNC:9891) is a protein-coding gene on chromosome 18q11.2, encoding DNA endonuclease RBBP8 (Q99708). 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. It is a common-essential gene (DepMap: required in 95.0% of cancer cell lines).

The protein encoded by this gene is a ubiquitously expressed nuclear protein. It is found among several proteins that bind directly to retinoblastoma protein, which regulates cell proliferation. This protein complexes with transcriptional co-repressor CTBP. It is also associated with BRCA1 and is thought to modulate the functions of BRCA1 in transcriptional regulation, DNA repair, and/or cell cycle checkpoint control. It is suggested that this gene may itself be a tumor suppressor acting in the same pathway as BRCA1. Three transcript variants encoding two different isoforms have been found for this gene. More transcript variants exist, but their full-length natures have not been determined.

Source: NCBI Gene 5932 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Jawad syndrome (Definitive, GenCC) — +2 more curated relationships
• GWAS associations: 19
• Clinical variants (ClinVar): 457 total — 4 pathogenic, 6 likely-pathogenic
• Phenotypes (HPO): 56
• Cancer dependency (DepMap): dependent in 95.0% of screened cell lines (common-essential)
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity unscored
• MANE Select transcript: NM_002894

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9891
Approved symbol	RBBP8
Name	RB binding protein 8, endonuclease
Location	18q11.2
Locus type	gene with protein product
Status	Approved
Aliases	CtIP, RIM, COM1
Ensembl gene	ENSG00000101773
Ensembl biotype	protein_coding
OMIM	604124
Entrez	5932

Gene structure

Transcript identifiers

Ensembl transcripts: 23 — 20 protein_coding, 1 retained_intron, 1 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000327155, ENST00000360790, ENST00000399721, ENST00000399722, ENST00000399725, ENST00000577445, ENST00000577588, ENST00000579124, ENST00000580892, ENST00000581687, ENST00000581819, ENST00000582354, ENST00000583057, ENST00000583594, ENST00000583700, ENST00000585177, ENST00000873911, ENST00000873912, ENST00000873913, ENST00000873914, ENST00000873915, ENST00000921841, ENST00000921842

RefSeq mRNA: 3 — MANE Select: NM_002894 NM_002894, NM_203291, NM_203292

CCDS: CCDS11874, CCDS11875

Canonical transcript exons

ENST00000327155 — 19 exons

Exon	Start	End
ENSE00000666787	22992748	22993639
ENSE00000666788	22990937	22991049
ENSE00000915235	22975153	22975219
ENSE00001132909	22997620	22997734
ENSE00001132918	22996374	22996462
ENSE00001132929	22993721	22993847
ENSE00001179771	23006363	23006432
ENSE00001179824	22968806	22968918
ENSE00001179832	22949618	22949713
ENSE00001179835	22946444	22946486
ENSE00001289542	23001586	23001729
ENSE00001810750	22933328	22933564
ENSE00003491064	22982218	22982393
ENSE00003566090	23022129	23022270
ENSE00003594885	23026143	23026486
ENSE00003597336	22989221	22989318
ENSE00003600256	22984886	22984990
ENSE00003615227	23016828	23016924
ENSE00003774830	22936754	22936960

Expression profiles

Bgee: expression breadth ubiquitous, 273 present calls, max score 96.73.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 8.9835 / max 183.0428, expressed in 1654 samples.

FANTOM5 promoters (16 alternative TSS)

Promoter ID	TPM avg	Samples expressed
169652	8.9835	1654
169654	4.2401	1100
169651	2.6170	1323
169649	1.0770	177
169650	0.8432	144
169645	0.1257	45
169641	0.0522	31
169648	0.0435	23
169656	0.0311	10
169647	0.0308	20

Top tissues by expression

289 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
choroid plexus epithelium	UBERON:0003911	96.73	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	96.50	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	95.34	gold quality
cervix squamous epithelium	UBERON:0006922	94.77	gold quality
nephron tubule	UBERON:0001231	94.43	gold quality
cervix epithelium	UBERON:0004801	93.27	gold quality
oviduct epithelium	UBERON:0004804	93.20	gold quality
metanephros cortex	UBERON:0010533	92.78	gold quality
caput epididymis	UBERON:0004358	92.21	gold quality
epithelium of mammary gland	UBERON:0003244	92.18	gold quality
skin of hip	UBERON:0001554	92.12	gold quality
mammary duct	UBERON:0001765	92.07	gold quality
kidney epithelium	UBERON:0004819	92.03	gold quality
ventricular zone	UBERON:0003053	91.99	gold quality
islet of Langerhans	UBERON:0000006	91.97	gold quality
upper leg skin	UBERON:0004262	91.60	gold quality
fallopian tube	UBERON:0003889	91.18	gold quality
renal glomerulus	UBERON:0000074	91.08	gold quality
pancreatic ductal cell	CL:0002079	90.90	gold quality
adult mammalian kidney	UBERON:0000082	90.75	gold quality
metanephric glomerulus	UBERON:0004736	90.74	gold quality
endometrium	UBERON:0001295	90.68	gold quality
kidney	UBERON:0002113	90.67	gold quality
cortex of kidney	UBERON:0001225	90.63	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	90.47	gold quality
metanephros	UBERON:0000081	90.22	gold quality
right uterine tube	UBERON:0001302	90.18	gold quality
cauda epididymis	UBERON:0004360	89.58	gold quality
testis	UBERON:0000473	89.56	gold quality
hair follicle	UBERON:0002073	89.33	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	12.61
E-MTAB-6142	no	429.28
E-MTAB-10596	no	78.80

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
ATM	Activation

Upstream regulators (CollecTRI, top): E2F6, NRG1, YBX1, ZBTB17, ZNF350

miRNA regulators (miRDB)

70 targeting RBBP8, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502
HSA-MIR-548BB-5P	99.94	71.27	3509
HSA-MIR-548C-5P	99.94	71.24	3488

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity Not yet evaluated (unscored). ClinGen Gene Dosage Map DepMap (CRISPR cell-line fitness): dependent in 95.0% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 40)

• These findings reveal a novel complex between BRCA1, LMO4, and CtIP and indicate a role for LMO4 as a repressor of BRCA1 activity in breast tissue. (PMID:11751867)
• a corepressor complex containing CtIP/CtBP facilitates RBP-Jkappa/SHARP-mediated repression of Notch target genes (PMID:16287852)
• CTIP activates its own and cyclin D promoters via the E2F/RB pathway during G1/S progression. (PMID:16581787)
• Since CtIP plays important roles in cell cycle checkpoint control and it has been implicated in tumorigenesis, our data suggest that TRB3 may be involved in these biological processes through interacting with CtIP. (PMID:17112672)
• Data show that CtIP expression is induced by AdE1A during viral infection and that reduction of CtIP expression with RNA interference can retard virus replication. (PMID:17546052)
• findings establish evolutionarily conserved roles for CtIP-like proteins in controlling DSB resection, checkpoint signalling and homologous recombination (PMID:17965729)
• Results idientify COM1, a novel plant gene essential for meiosis that is related to the human CtIP and the yeast COM1/SAE2 gene. (PMID:18007598)
• the BRCA1 interacting protein CTIP has a role in breast cancer (PMID:18095152)
• cell cycle-dependent complex formation of BRCA1, CtIP, and MRN contributes to the activation of HR-mediated DSB repair in the S and G(2) phases of the cell cycle. (PMID:18171670)
• CtIP silencing might be a novel mechanism for the development of tamoxifen resistance in breast cancer, suggesting that CtIP is likely associated with estrogen receptor function (PMID:18171986)
• Stresses and stimuli that reduce CtBP-mediated repression are associated with increased p16 expression; therefore, CtBP may provide a common final target for regulating the balance among tumor suppression, regenerative capacity, and senescence (PMID:18676825)
• unlike cells expressing wild-type CtIP, cells expressing the Thr-to-Glu mutant resect DSBs even after cyclin-dependent kinase inhibition (PMID:19202191)
• Single nucleotide polymorphisms in CASP5 and RBBP8 gene are associated with survival in ovarian cancer patients. (PMID:19270026)
• CtIP is recruited to S-phase DNA replication foci through a novel motif functioning as replication foci targeting sequence. (PMID:19342888)
• CtIP is required not only for repair of double strand breaks by homologous recombination in S/G2 phase but also for microhomology-mediated end-joining in G1 (PMID:19357644)
• Data show that silencing of Rad50 or CtIP decreases end-joining efficiency in the same pathway as Mre11. (PMID:19633668)
• Data found that HMGA2, along with a dozen of other genes, was co-repressed by ZBRK1, BRCA1, and CtIP. (PMID:20007691)
• CtIP facilitates the transition from DSB sensing to processing, by binding to the DNA at double-strand breaks (DSBs) after DSB sensing and ATM activation and then promoting DNA resection, leading to checkpoint activation and homologous recombination. (PMID:20064462)
• BCR-ABL promotes mutagenic DSB repair with the DSB end-processing protein CtIP acting as the key mediator downstream of BCR-ABL (PMID:20974687)
• Studies indicate that codon-based models of gene evolution yielded statistical support for the recurrent positive selection of five NHEJ genes during primate evolution: XRCC4, NBS1, Artemis, POLlambda, and CtIP. (PMID:20975951)
• This study identifies new functions of CtIP and EXO1 in DNA end resection and provides new information on the regulation of DNA double-strand breaks repair pathways, which is a key factor in the maintenance of genome integrity. (PMID:21052091)
• the SCKL2 mutation creates an alternative splicing site leading to both the normal and aberrant CtIP proteins coexisting in the cells of patients and carriers (PMID:21998596)
• The authors show that, in human and mouse, Mre11 controls these events through a direct interaction with CDK2 that is required for CtIP phosphorylation and BRCA1 interaction in normally dividing cells. (PMID:22231403)
• The severe repair defects of CtIP dimerization mutants are likely due to the failure in localization to chromosomal DSBs upon DNA damage. (PMID:22544744)
• show that CHK1 was rapidly and robustly activated before detectable end resection (PMID:22733999)
• CtIP binds to ATM protein proximal promoter, but after DNA damage Ctip is released. (PMID:22832221)
• RIF1 accumulation at DSB sites is strongly antagonized by BRCA1 and its interacting partner CtIP (PMID:23333306)
• Microsatellite instability dependent mutations were detected in CtIP in myeloid malignancies conferring hypersensitivity to PARP inhibitors. (PMID:23349304)
• Data suggest that overexpression of LMO4 may disrupt some of the normal tumour suppressor activities of CtIP, thereby contributing to breast cancer progression. (PMID:23353824)
• These studies reveal one important mechanism to regulate cell-cycle-dependent activation of HR upon DNA damage by coupling CDK- and ATM-mediated phosphorylation of CtIP through modulating the interaction of CtIP with Nbs1 (PMID:23468639)
• Taken together, these findings strongly suggest that an ATM-dependent CREB-miR-335-CtIP axis influences the selection of HRR for repair of certain DSB lesions (PMID:23696749)
• BRCA1/CtIP-mediated processing of the second end of the break controls the annealing step that normally terminates synthesis-dependent strand annealing, thereby suppressing the error-prone long-tract gene conversion outcome. (PMID:23994874)
• our data demonstrate that CtIP is required for DNA damage-induced P21 induction (PMID:24196441)
• Low or no expression of RBBP8 correlates with high-grade breast cancer, poor prognosis and with nodal metastasis. (PMID:24403251)
• study identified a homozygous mutation in RBBP8, which co-segregates with microcephaly-associated intellectual disability syndrome in a Pakistani family; also identified a heterozygous deletion encompassing the NRXN1 in this family, which is present in 2 affected sibs with complex phenotype and the mother with mild phenotype (PMID:24440292)
• Study identified CtIP as a novel interaction partner of FANCD2. CtIP binds and stabilizes FANCD2 in a DNA damage- and FA core complex-independent manner, suggesting that FANCD2 monoubiquitination is dispensable for its interaction with CtIP. (PMID:24556218)
• Data indicate that FANCD2 primes CtIP-dependent resection during HR after ICL induction but that CtIP helps prevent illegitimate recombination in FA cells. (PMID:24794434)
• These studies suggest that an end resection-independent CtIP function is important for processing double-strand break ends with secondary structures to promote homologous recombination. (PMID:24837675)
• human CtIP is a 5’ flap endonuclease and this activity is required in some contexts for the efficient function of CtIP. (PMID:24837676)
• Possible association of SOX-17 and RBBP8 with brain arteriovenous malformations, genes involved in cell cycle progression, deserves further investigation (PMID:25053769)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
mus_musculus	Rbbp8	ENSMUSG00000041238
rattus_norvegicus	Rbbp8	ENSRNOG00000012899
caenorhabditis_elegans		WBGENE00008082

Paralogs (1): RBBP8NL (ENSG00000130701)

Protein

Protein identifiers

DNA endonuclease RBBP8 — Q99708 (reviewed: Q99708)

Alternative names: CtBP-interacting protein, Retinoblastoma-binding protein 8, Retinoblastoma-interacting protein and myosin-like, Sporulation in the absence of SPO11 protein 2 homolog

All UniProt accessions (12): Q99708, A0A140TA82, F6Q6H0, I6L8A6, J3KSA4, J3QL00, J3QL93, J3QLH2, J3QLW6, J3QRM0, J3QSH7, V9GZ40

UniProt curated annotations — full annotation on UniProt →

Function. 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. HR is restricted to S and G2 phases of the cell cycle and preferentially repairs DSBs resulting from replication fork collapse. Key determinant of DSB repair pathway choice, as it commits cells to HR by preventing classical non-homologous end-joining (NHEJ). 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. 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. Component of the BRCA1-RBBP8 complex that regulates CHEK1 activation and controls cell cycle G2/M checkpoints on DNA damage. During immunoglobulin heavy chain class-switch recombination, promotes microhomology-mediated alternative end joining (A-NHEJ) and plays an essential role in chromosomal translocations. Binds preferentially to DNA Y-junctions and to DNA substrates with blocked ends and promotes intermolecular DNA bridging.

Subunit / interactions. Homotetramer; formed by antiparallel association of helical extensions protruding from the N-termini of two parallel coiled-coil dimers. Forms a dumbbell-shaped particle in which polar globular domains are held about 30 nm apart by a central rod. Homotetramerization is required for DNA-end resection and repair. Interacts (via the PXDLS motif) with CTBP1; the interaction is disrupted via binding of the adenovirus E1A to CTBP1. Component of the BRCA1-RBBP8 complex. Interacts (the Ser-327 phosphorylated form) with BRCA1 (via the C-terminal BRCT domains): the interaction occurs in the G2 phase, ubiquitinates RBBP8 and involves RBBP8 in BRCA1-dependent G2/M checkpoint control on DNA damage. Interacts with RB1. Interacts with the MRN complex; interacts directly with MRE11; the interaction is required for efficient homologous recombination (HR) and regulation of the MRN complex. Interacts directly with RAD50. Interacts (when phosphorylated by CDK1) with NBN; promoting association with the MRN complex. Interacts with LM04 (via the LIM zinc-binding 1 domain). Interacts with SIAH1. Interacts with RNF138. Interacts with EXD2. Interacts with CUL3 and KLHL15; this interaction leads to RBBP8 proteasomal degradation. Directly interacts with PIN1; this interaction depends upon RBBP8 phosphorylation, predominantly at Thr-315. Interacts with FZR1; this interaction leads to APC/C-mediated RBBP8 proteasomal degradation. Interacts with AUNIP; leading to recruitment of RBBP8 to sites of DNA damage. Interacts with SAMHD1. Interacts with HDGFL2. Interacts with HELLS; the interaction leads to recruitment of RBBP8/CtIP to sites of DNA breaks.

Subcellular location. Nucleus. Chromosome.

Tissue specificity. Expressed in ER-positive breast cancer lines, but tends to be down-regulated ER-negative cells (at protein level).

Post-translational modifications. Hyperphosphorylation upon ionizing radiation results in dissociation from BRCA1. Phosphorylation at Thr-847 by CDK1 is essential for the recruitment to DNA and the DNA repair function. Phosphorylation at Thr-847 and Thr-859 promote interaction with NBN and recruitment to double-strand breaks (DSBs). Phosphorylated on Ser-327 as cells enter G2 phase. This phosphorylation is required for binding BRCA1 and for the G2/M DNA damage transition checkpoint control. Phosphorylation at Thr-315, probably catalyzed by CDK2, is required for PIN1-binding, while phosphorylation at Ser-276 serves as a PIN1 isomerization site. Phosphorylation at Thr-315 is cell-cycle dependent. It steadily increases during S phase, peaks at late S/G2 phase, and drops at G1. Phosphorylation is not required for tetramerization. Binds to DNA more strongly when dephosphorylated. Ubiquitinated. Ubiquitination at multiple sites by BRCA1 (via its N-terminal RING domain) does not lead to its proteasomal degradation but instead the ubiquitinated RBBP8 binds to chromatin following DNA damage and may play a role in G2/M checkpoint control. Ubiquitinated by RNF138 at its N-terminus. Ubiquitinated through ‘Lys-48’ by the E3 CUL3-KLHL15 complex; this modification leads to proteasomal degradation. Ubiquitinated by the E3 FZR1/APC/C complex; this modification leads to proteasomal degradation.

Disease relevance. Seckel syndrome 2 (SCKL2) [MIM:606744] A rare autosomal recessive disorder characterized by proportionate dwarfism of prenatal onset associated with low birth weight, growth retardation, severe microcephaly with a bird-headed like appearance, and intellectual disability. The disease is caused by variants affecting the gene represented in this entry. Jawad syndrome (JWDS) [MIM:251255] A syndrome characterized by congenital microcephaly, moderately severe intellectual disability, and symmetrical digital anomalies. Digital malformations of variable degree include hallux valgus, syndactyly of toes 4 and 5, short fifth fingers, single flexion crease of fifth fingers, polydactyly and synpolydactyly. The disease is caused by variants affecting the gene represented in this entry. Genetic variability in RBBP8 is noted as a factor in BRCA1-associated breast cancer risk. Associated with sensitivity to tamoxifen in certain breast cancer cell lines.

Domain organisation. The PXDLS motif binds to a cleft in CtBP proteins. The damage-recruitment motif is required for DNA binding and translocation to sites of DNA damage.

Induction. Expression is cell-cycle regulated. Levels increase as dividing cells traverse the G1/S boundary. The protein is degraded by the proteasome pathway during mitotic exit. Also degraded in response to DNA damage in G2 cells; this degradation is mediated by the E3 FZR1/APC/C complex.

Miscellaneous. Binds one Zn(2+) atom per dimer. Zn(2+)-binding is not required for homotetramerization.

Similarity. Belongs to the COM1/SAE2/CtIP family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q99708-1	1	yes
Q99708-2	2
Q99708-3	3

RefSeq proteins (3): NP_002885, NP_976036, NP_976037 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013882	Ctp1_C	Domain
IPR019518	CtIP_N	Domain
IPR033316	RBBP8-like	Family

Pfam: PF08573, PF10482

UniProt features (102 total): mutagenesis site 36, cross-link 22, modified residue 13, sequence conflict 9, region of interest 8, splice variant 3, sequence variant 3, coiled-coil region 2, short sequence motif 2, compositionally biased region 2, chain 1, helix 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
4D2H	X-RAY DIFFRACTION	1.9
1Y98	X-RAY DIFFRACTION	2.5
7BGF	X-RAY DIFFRACTION	2.8
2L4Z	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q99708-F1	53.73	0.14

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (35): 233, 276, 315, 326, 327, 349, 379, 664, 679, 723, 745, 847, 859, 62, 115, 193, 360, 378, 396, 404 …

Mutagenesis-validated functional residues (36):

Position	Phenotype
27	can form homodimers but not homotetramers. abolishes ability to promote homologous recombination and dna resection. defe
31	no effect on rpa focus formation on dna damage.
35	no effect on rpa focus formation on dna damage.
41	no effect on rpa focus formation on dna damage.
45	no effect on rpa focus formation on dna damage.
62	in k12r; defects in ability to promoting dna resection and homologous recombination; when associated with r-78; r-115; r
78	in k12r; defects in ability to promoting dna resection and homologous recombination; when associated with r-62; r-115; r
89	reduces zn(2+) content; when associated with a-92.
92	reduces zn(2+) content; when associated with a-89.
115	in k12r; defects in ability to promoting dna resection and homologous recombination; when associated with r-62; r-78; r-
132	in k12r; defects in ability to promoting dna resection and homologous recombination; when associated with r-62; r-78; r-
133	in k12r; defects in ability to promoting dna resection and homologous recombination; when associated with r-62; r-78; r-
179	no effect on fzr1-binding.
276	no effect on pin1-binding. impaired pin1-binding, partially decreased cul3/klhl15-mediated proteasomal degradation, no e
315	decreased pin1-binding. impaired pin1-binding, partially decreased cul3/klhl15-mediated proteasomal degradation, no effe
327	abolishes brca1 interaction and ubiquitination. no activation of chek1 after dna damage.
404	in k12r; defects in ability to promoting dna resection and homologous recombination; when associated with r-62; r-78; r-
467	impaired fzr1-binding and apc/c-mediated polyubiquitination. increased stability. no effect on mre11-binding, nor on cul
513	abolishes damage recruitment capability.
515	abolishes damage recruitment capability.
572	in k12r; defects in ability to promoting dna resection and homologous recombination; when associated with r-62; r-78; r-
578	in k12r; defects in ability to promoting dna resection and homologous recombination; when associated with r-62; r-78; r-
640	in k12r; defects in ability to promoting dna resection and homologous recombination; when associated with r-62; r-78; r-
664	abrogates dissociation of brca1.
745	abrogates dissociation of brca1.

Function

Pathways and Gene Ontology

Reactome pathways

17 pathways

ID	Pathway
R-HSA-5685938	HDR through Single Strand Annealing (SSA)
R-HSA-5685939	HDR through MMEJ (alt-NHEJ)
R-HSA-5685942	HDR through Homologous Recombination (HRR)
R-HSA-5693554	Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA)
R-HSA-5693568	Resolution of D-loop Structures through Holliday Junction Intermediates
R-HSA-5693579	Homologous DNA Pairing and Strand Exchange
R-HSA-5693607	Processing of DNA double-strand break ends
R-HSA-5693616	Presynaptic phase of homologous DNA pairing and strand exchange
R-HSA-6804756	Regulation of TP53 Activity through Phosphorylation
R-HSA-69473	G2/M DNA damage checkpoint
R-HSA-8953750	Transcriptional Regulation by E2F6
R-HSA-912446	Meiotic recombination
R-HSA-9701192	Defective homologous recombination repair (HRR) due to BRCA1 loss of function
R-HSA-9704331	Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA1 binding function
R-HSA-9704646	Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA2/RAD51/RAD51C binding function
R-HSA-9709570	Impaired BRCA2 binding to RAD51
R-HSA-9709603	Impaired BRCA2 binding to PALB2

MSigDB gene sets: 532 (showing top): GOBP_DNA_TEMPLATED_DNA_REPLICATION_MAINTENANCE_OF_FIDELITY, MORF_RAGE, REACTOME_MEIOTIC_RECOMBINATION, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOMF_ENDONUCLEASE_ACTIVITY, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, BIOCARTA_ATM_PATHWAY, FISCHER_G1_S_CELL_CYCLE, GOMF_NUCLEASE_ACTIVITY, REACTOME_G2_M_DNA_DAMAGE_CHECKPOINT, MORF_ATRX, GOBP_CELL_CYCLE_PHASE_TRANSITION, CREBP1_Q2, MORF_ESR1

GO Biological Process (12): G1/S transition of mitotic cell cycle (GO:0000082), double-strand break repair via homologous recombination (GO:0000724), blastocyst hatching (GO:0001835), DNA double-strand break processing involved in repair via single-strand annealing (GO:0010792), homologous recombination (GO:0035825), mitotic G2/M transition checkpoint (GO:0044818), cell division (GO:0051301), meiotic cell cycle (GO:0051321), DNA strand resection involved in replication fork processing (GO:0110025), DNA repair (GO:0006281), DNA damage response (GO:0006974), negative regulation of DNA-templated transcription (GO:0045892)

GO Molecular Function (11): single-stranded DNA endonuclease activity (GO:0000014), damaged DNA binding (GO:0003684), transcription corepressor activity (GO:0003714), identical protein binding (GO:0042802), metal ion binding (GO:0046872), RNA polymerase II-specific DNA-binding transcription factor binding (GO:0061629), DNA binding (GO:0003677), nuclease activity (GO:0004518), endonuclease activity (GO:0004519), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (6): nucleus (GO:0005634), nucleoplasm (GO:0005654), transcription repressor complex (GO:0017053), site of double-strand break (GO:0035861), BRCA1-C complex (GO:0070533), chromosome (GO:0005694)

Reactome top-level categories

Rollup of top-12 pathways:

Category	Pathways
HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA)	3
Resolution of D-Loop Structures	2
Defective homologous recombination repair (HRR) due to PALB2 loss of function	2
Defective homologous recombination repair (HRR) due to BRCA2 loss of function	2
Homology Directed Repair	1
HDR through Homologous Recombination (HRR)	1
Homologous DNA Pairing and Strand Exchange	1
Regulation of TP53 Activity	1
G2/M Checkpoints	1
Generic Transcription Pathway	1
Meiosis	1
Diseases of DNA Double-Strand Break Repair	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
DNA metabolic process	2
mitotic cell cycle	1
mitotic cell cycle phase transition	1
cell cycle G1/S phase transition	1
recombinational repair	1
double-strand break repair	1
blastocyst development	1
hatching	1
DNA double-strand break processing	1
double-strand break repair via single-strand annealing	1
DNA recombination	1
mitotic cell cycle checkpoint signaling	1
negative regulation of G2/M transition of mitotic cell cycle	1
cellular process	1
cell cycle	1
sexual reproduction	1
reproductive process	1
meiotic nuclear division	1
replication fork processing	1
5’-3’ DNA exonuclease activity	1
DNA damage response	1
cellular response to stress	1
DNA-templated transcription	1
regulation of DNA-templated transcription	1
negative regulation of RNA biosynthetic process	1
DNA endonuclease activity	1
hydrolase activity, acting on ester bonds	1
DNA binding	1
transcription coregulator activity	1
negative regulation of DNA-templated transcription	1
protein binding	1
cation binding	1
DNA-binding transcription factor binding	1
nucleic acid binding	1
catalytic activity, acting on a nucleic acid	1
nuclease activity	1
binding	1
catalytic activity	1
intracellular membrane-bounded organelle	1
nuclear lumen	1

Protein interactions and networks

STRING

2815 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RBBP8	BRCA1	P38398	998
RBBP8	CTBP1	Q13363	994
RBBP8	CTBP2	P56545	994
RBBP8	ZNF350	Q9GZX5	987
RBBP8	NBN	O60934	979
RBBP8	EXO1	Q9UQ84	974
RBBP8	BRCA2	P51587	961
RBBP8	PSIP1	O75475	944
RBBP8	BARD1	Q99728	918
RBBP8	MDC1	Q14676	917
RBBP8	FANCD2	Q9BXW9	913
RBBP8	DNA2	P51530	912
RBBP8	RAD51	Q06609	901
RBBP8	USP4	Q13107	897
RBBP8	UIMC1	Q96RL1	881

IntAct

85 interactions, top by confidence:

A	B	Type	Score
BRCA1	RBBP8	psi-mi:“MI:0915”(physical association)	0.930
RBBP8	BRCA1	psi-mi:“MI:0915”(physical association)	0.930
RBBP8	BRCA1	psi-mi:“MI:0407”(direct interaction)	0.930
PALB2	BRCA1	psi-mi:“MI:0914”(association)	0.910
BRCA1	ABRAXAS1	psi-mi:“MI:0914”(association)	0.860
BRCA1	UIMC1	psi-mi:“MI:0914”(association)	0.780
UIMC1	BRCA1	psi-mi:“MI:0914”(association)	0.780
CTBP1	RBBP8	psi-mi:“MI:0915”(physical association)	0.690
RBBP8	CTBP1	psi-mi:“MI:0915”(physical association)	0.690
CTBP1	RBBP8	psi-mi:“MI:0407”(direct interaction)	0.690
RBBP8	MRE11	psi-mi:“MI:0914”(association)	0.670
RBBP8	MRE11	psi-mi:“MI:0915”(physical association)	0.670
PLK1	EVI5	psi-mi:“MI:0914”(association)	0.660
RBBP8	EXO1	psi-mi:“MI:0915”(physical association)	0.660
EXO1	RBBP8	psi-mi:“MI:0915”(physical association)	0.660
RBBP8	EXO1	psi-mi:“MI:0407”(direct interaction)	0.660
BRCA1	RPA1	psi-mi:“MI:0915”(physical association)	0.650
RBBP8	RBBP8	psi-mi:“MI:0407”(direct interaction)	0.650
RBBP8	RBBP8	psi-mi:“MI:0915”(physical association)	0.650
BRCA1	BRCA1	psi-mi:“MI:0914”(association)	0.650
PSIP1	RBBP8	psi-mi:“MI:0915”(physical association)	0.600

BioGRID (335): RBBP8 (Two-hybrid), RBBP8 (Two-hybrid), LMO4 (Two-hybrid), RBBP8 (Affinity Capture-Western), FZR1 (Reconstituted Complex), MRE11A (Reconstituted Complex), RBBP8 (Affinity Capture-MS), FANCD2 (Affinity Capture-Western), RBBP8 (Two-hybrid), HID1 (Two-hybrid), FXR2 (Two-hybrid), RBBP8 (Two-hybrid), WDYHV1 (Two-hybrid), RBL1 (Two-hybrid), RBBP8 (Affinity Capture-MS)

ESM2 similar proteins: A0A087WRU1, A0JNH1, A2RUB1, A6QNQ6, B0S6S9, B1WC58, D3Z987, D3ZJ47, E1BC15, O60673, P28358, P28359, P56716, P70347, Q0P5X5, Q0VAV2, Q0VBV7, Q15468, Q2M2Z5, Q3UXL4, Q3V089, Q49A88, Q569L8, Q5BQN8, Q5CZC0, Q5QGS0, Q5T1N1, Q5VWN6, Q60988, Q61493, Q62924, Q6ZP01, Q6ZU52, Q6ZVD7, Q80U59, Q80WQ8, Q86WS4, Q86YC2, Q8CB14, Q8IUR6

Diamond homologs: A6QNQ6, B1WC58, F1R983, F6SNN2, Q6GNV6, Q80YR6, Q8NC74, Q99708, Q9ZRT1

SIGNOR signaling

16 interactions.

A	Effect	B	Mechanism
RBBP8	down-regulates	SPEN	binding
BRCA1	up-regulates	RBBP8	ubiquitination
CDK2	up-regulates	RBBP8	phosphorylation
RBBP8	“up-regulates quantity by expression”	ATM	“transcriptional regulation”
ATR	up-regulates	RBBP8	phosphorylation
CyclinA2/CDK2	“up-regulates activity”	RBBP8	phosphorylation
KLHL15	“down-regulates quantity by destabilization”	RBBP8	binding
“Cullin 3-RBX1-Skp1”	“down-regulates quantity by destabilization”	RBBP8	polyubiquitination
PAN2	“up-regulates activity”	RBBP8	deubiquitination
PKM	“up-regulates activity”	RBBP8	phosphorylation
PLK1	“up-regulates activity”	RBBP8	phosphorylation
ATM	down-regulates	RBBP8	phosphorylation
RBBP8	“up-regulates activity”	“BRCC ubiquitin ligase complex”	relocalization
RBBP8	“up-regulates activity”	BRCA1	relocalization
RBBP8	“form complex”	“BRCA1-C complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 64 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Impaired BRCA2 binding to PALB2	5	54.4×	3e-06
Defective homologous recombination repair (HRR) due to BRCA1 loss of function	5	50.4×	3e-06
Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA1 binding function	5	50.4×	3e-06
Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA2/RAD51/RAD51C binding function	5	50.4×	3e-06
Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA)	5	46.9×	3e-06
Homologous DNA Pairing and Strand Exchange	5	45.3×	3e-06
Impaired BRCA2 binding to RAD51	5	36.7×	8e-06
Resolution of D-loop Structures through Holliday Junction Intermediates	5	35.8×	8e-06

GO biological processes:

GO term	Partners	Fold	FDR
mitotic G2/M transition checkpoint	5	75.7×	8e-07
mitotic G2 DNA damage checkpoint signaling	6	50.2×	5e-07
double-strand break repair	8	30.6×	1e-07
double-strand break repair via homologous recombination	6	17.7×	1e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

457 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	6
Uncertain significance	206
Likely benign	160
Benign	41

Top pathogenic / likely-pathogenic (10)

Variant ID	HGVS	Classification
1033553	NM_002894.3(RBBP8):c.317_318del (p.Glu105_Phe106insTer)	Pathogenic
2225501	NM_002894.3(RBBP8):c.2042C>G (p.Ser681Ter)	Pathogenic
30408	NM_002894.3(RBBP8):c.2287+53T>G	Pathogenic
30409	NM_002894.3(RBBP8):c.1808_1809del (p.Ile603fs)	Pathogenic
1324995	NM_002894.3(RBBP8):c.367G>T (p.Glu123Ter)	Likely pathogenic
1333383	NM_002894.3(RBBP8):c.2287+1G>A	Likely pathogenic
1683598	NM_002894.3(RBBP8):c.2048T>G (p.Leu683Ter)	Likely pathogenic
1723219	NM_002894.3(RBBP8):c.2474C>T (p.Ala825Val)	Likely pathogenic
3764625	NM_002894.3(RBBP8):c.1621_1625dup (p.Asn542fs)	Likely pathogenic
392730	NM_002894.3(RBBP8):c.139C>T (p.Gln47Ter)	Likely pathogenic

SpliceAI

3751 predictions. Top by Δscore:

Variant	Effect	Δscore
18:22933561:GGCG:G	donor_gain	1.0000
18:22933562:GCGG:G	donor_gain	1.0000
18:22936753:GGT:G	acceptor_gain	1.0000
18:22946438:TTTCA:T	acceptor_loss	1.0000
18:22946439:TTCA:T	acceptor_loss	1.0000
18:22946441:CA:C	acceptor_loss	1.0000
18:22946442:A:AG	acceptor_gain	1.0000
18:22946442:A:T	acceptor_loss	1.0000
18:22946443:G:GT	acceptor_gain	1.0000
18:22946482:ATCTT:A	donor_gain	1.0000
18:22946483:TCTT:T	donor_gain	1.0000
18:22946484:CTT:C	donor_gain	1.0000
18:22946485:TT:T	donor_gain	1.0000
18:22946487:G:GG	donor_gain	1.0000
18:22946488:TAA:T	donor_loss	1.0000
18:22946489:AAG:A	donor_loss	1.0000
18:22946497:G:GG	donor_gain	1.0000
18:22949616:A:AG	acceptor_gain	1.0000
18:22949617:G:GG	acceptor_gain	1.0000
18:22949617:GA:G	acceptor_gain	1.0000
18:22949709:GATCG:G	donor_gain	1.0000
18:22967542:A:G	donor_gain	1.0000
18:22968914:ACTTA:A	donor_gain	1.0000
18:22968915:CTTA:C	donor_gain	1.0000
18:22968916:TTA:T	donor_gain	1.0000
18:22968917:TA:T	donor_gain	1.0000
18:22968917:TAG:T	donor_loss	1.0000
18:22968918:AG:A	donor_loss	1.0000
18:22968919:G:GG	donor_gain	1.0000
18:22968919:GTG:G	donor_loss	1.0000

AlphaMissense

5977 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
18:22949662:T:C	L66P	0.999
18:22968831:T:C	C92R	0.999
18:22968898:T:C	L114P	0.999
18:22968904:T:C	L116P	0.999
18:22968916:T:C	L120P	0.999
18:23022228:T:A	W852R	0.999
18:23022228:T:C	W852R	0.999
18:23022230:G:C	W852C	0.999
18:23022230:G:T	W852C	0.999
18:22946468:T:C	L45P	0.998
18:22949683:T:C	L73P	0.998
18:22949713:G:C	R83P	0.998
18:22968808:T:C	L84S	0.998
18:22968822:T:C	C89R	0.998
18:22968823:G:A	C89Y	0.998
18:22968831:T:A	C92S	0.998
18:22968832:G:C	C92S	0.998
18:22968833:T:G	C92W	0.998
18:23016916:T:C	C816R	0.998
18:23022240:T:C	F856L	0.998
18:23022242:T:A	F856L	0.998
18:23022242:T:G	F856L	0.998
18:22936931:T:C	L27P	0.997
18:22946480:G:C	R49P	0.997
18:22949632:T:C	L56P	0.997
18:22949704:T:C	L80S	0.997
18:22968822:T:A	C89S	0.997
18:22968823:G:C	C89S	0.997
18:22968824:T:G	C89W	0.997
18:22968832:G:A	C92Y	0.997

dbSNP variants (sampled 300 via entrez): RS1000010761 (18:22986000 C>A,G,T), RS1000022563 (18:23008026 A>G), RS1000038774 (18:22986265 G>A), RS1000089092 (18:22935771 A>G), RS1000173382 (18:22969924 G>A), RS1000174475 (18:22927851 T>C), RS1000200925 (18:22969102 G>A), RS1000229679 (18:22934129 A>G), RS1000230001 (18:22916905 G>C), RS1000259914 (18:22914974 A>C), RS1000272713 (18:23004948 G>A), RS1000276423 (18:22960312 G>A), RS1000288562 (18:23008376 T>A), RS1000307642 (18:22960529 G>C), RS1000367847 (18:22930291 C>T)

Disease associations

OMIM: gene MIM:604124 | disease phenotypes: MIM:251255, MIM:606744

GenCC curated gene-disease

Disease	Classification	Inheritance
Jawad syndrome	Definitive	Autosomal recessive
Seckel syndrome 2	Strong	Autosomal recessive
Seckel syndrome	Supportive	Autosomal recessive

Mondo (5): Jawad syndrome (MONDO:0009622), Seckel syndrome 2 (MONDO:0011715), exocrine pancreatic carcinoma (MONDO:0005192), microcephaly (MONDO:0001149), Seckel syndrome (MONDO:0019342)

Orphanet (4): Jawad syndrome (Orphanet:313795), Seckel syndrome (Orphanet:808), Familial pancreatic carcinoma (Orphanet:1333), Rare carcinoma of pancreas (Orphanet:217074)

HPO phenotypes

56 total (30 of 56 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000047	Hypospadias
HP:0000086	Ectopic kidney
HP:0000171	Microglossia
HP:0000252	Microcephaly
HP:0000275	Narrow face
HP:0000278	Retrognathia
HP:0000340	Sloping forehead
HP:0000341	Narrow forehead
HP:0000347	Micrognathia
HP:0000363	Abnormal earlobe morphology
HP:0000387	Absent earlobe
HP:0000444	Convex nasal ridge
HP:0000448	Prominent nose
HP:0000494	Downslanted palpebral fissures
HP:0000501	Glaucoma
HP:0000568	Microphthalmia
HP:0000682	Abnormal dental enamel morphology
HP:0000691	Microdontia
HP:0000718	Aggressive behavior
HP:0001249	Intellectual disability
HP:0001263	Global developmental delay
HP:0001321	Cerebellar hypoplasia
HP:0001363	Craniosynostosis
HP:0001382	Joint hypermobility
HP:0001385	Hip dysplasia
HP:0001510	Growth delay
HP:0001511	Intrauterine growth retardation
HP:0001518	Small for gestational age
HP:0001620	Abnormally high-pitched voice

GWAS associations

19 associations (top):

Study	Trait	p-value
GCST000175_6	Height	4.000000e-09
GCST000646_1	Intracranial aneurysm	1.000000e-12
GCST000764_14	Tuberculosis	7.000000e-09
GCST002702_103	Height	7.000000e-23
GCST003251_13	Late-onset myasthenia gravis	4.000000e-07
GCST003474_9	Scalp hair shape	6.000000e-06
GCST003683_2	Intracranial, abdominal aortic or thoracic aortic aneurysm (pleiotropy)	2.000000e-09
GCST004600_148	Eosinophil percentage of white cells	8.000000e-09
GCST006481_23	Lung function (FEV1)	5.000000e-08
GCST006481_34	Lung function (FEV1)	4.000000e-07
GCST012226_815	Waist circumference adjusted for body mass index	5.000000e-08
GCST012226_816	Waist circumference adjusted for body mass index	2.000000e-10
GCST012226_817	Waist circumference adjusted for body mass index	2.000000e-09
GCST012227_705	Hip circumference adjusted for BMI	3.000000e-10
GCST012227_706	Hip circumference adjusted for BMI	2.000000e-08
GCST90002388_514	Lymphocyte count	3.000000e-09
GCST90020029_502	Waist circumference adjusted for body mass index	2.000000e-09
GCST90020029_503	Waist circumference adjusted for body mass index	8.000000e-09
GCST90020091_11	Estradiol levels	1.000000e-08

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0007991	eosinophil percentage of leukocytes
EFO:0004314	forced expiratory volume
EFO:0007789	BMI-adjusted waist circumference
EFO:0008039	BMI-adjusted hip circumference
EFO:0004587	lymphocyte count
EFO:0004697	estradiol measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D008831	Microcephaly	C05.660.207.620; C10.500.507.400.500; C16.131.621.207.620; C16.131.666.507.400.500
C537534	Seckel syndrome 2 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

74 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Estradiol	increases expression, affects cotreatment, decreases expression	11
bisphenol A	decreases methylation, increases expression	4
Tetrachlorodibenzodioxin	affects expression, affects cotreatment, decreases expression	4
Genistein	increases expression	4
Doxorubicin	affects binding, decreases reaction, increases expression, decreases expression, affects response to substance	3
Cyclosporine	increases expression	3
Cadmium Chloride	decreases expression, increases expression	3
sodium arsenite	decreases expression	2
Air Pollutants	decreases expression, increases abundance	2
Benzo(a)pyrene	increases expression, decreases expression	2
Smoke	decreases expression, increases abundance	2
Valproic Acid	decreases expression, increases expression	2
Particulate Matter	affects cotreatment, decreases expression, increases abundance, increases expression	2
aristolochic acid I	decreases expression	1
FR900359	decreases phosphorylation	1
TAK-243	affects sumoylation	1
pradimicin-IRD	decreases expression	1
dicrotophos	decreases expression	1
daidzein	increases expression	1
lasiocarpine	increases metabolic processing, decreases expression	1
oxybenzone	increases expression	1
2,2’-methylenebis(4-methyl-6-tert-butylphenol)	affects response to substance, affects expression	1
trichostatin A	decreases expression	1
riddelliine	decreases expression, increases metabolic processing	1
beta-lapachone	increases expression	1
shikonin	decreases reaction, increases expression	1
bromoacetate	increases expression	1
alkannin	decreases reaction, increases expression	1
quinoline yellow	increases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1

Clinical trials (associated diseases)

301 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00280709	PHASE4	COMPLETED	Biliary Metal Stent Study: Metal Stents for Management of Distal Malignant Biliary Obstruction
NCT00365508	PHASE4	COMPLETED	Counseling and Nicotine Replacement Therapy in Helping Adult Smokers Quit Smoking
NCT00558155	PHASE4	COMPLETED	The Impact of Immunostimulating Nutrition on the Outcome of Surgery
NCT00576940	PHASE4	COMPLETED	Standard and Immunostimulating Enteral Nutrition in Surgical Patients
NCT00578279	PHASE4	COMPLETED	Endoscopic Ultrasound-guided Celiac Plexus Neurolysis (EUS-CPN)With Alcohol in Unresectable Pancreatic Cancer: a Pilot Study
NCT00583479	PHASE4	COMPLETED	Prospective Study of Celiac Block Injection: 1 vs. 2
NCT00642733	PHASE4	TERMINATED	A Study of First Line Treatment With Tarceva (Erlotinib) in Combination With Gemcitabine in Patients With Locally Advanced Unresectable or Metastatic Pancreatic Cancer
NCT00666978	PHASE4	COMPLETED	Health Education Counseling With or Without Bupropion in Helping African Americans Stop Smoking
NCT00920023	PHASE4	COMPLETED	Pre-Operative Staging of Pancreatic Cancer Using Superparamagnetic Iron Oxide Magnetic Resonance Imaging (SPIO MRI)
NCT00966277	PHASE4	COMPLETED	Dalteparin for Primary Venous Thromboembolism (VTE) Prophylaxis in Pancreatic Cancer Patients
NCT01041612	PHASE4	COMPLETED	Comparing Covered Self-expandable Metallic Stent (SEMS) Above/Across the Sphincter of Oddi
NCT01111591	PHASE4	UNKNOWN	Cyclooxygenase-2 Inhibitor for Adjuvant Anticancer Effect in Patients With Biliary-pancreas Cancer
NCT01256034	PHASE4	COMPLETED	Effects of Preoperative Immunonutrition in Patients Undergoing Pancreaticoduodenectomy
NCT01642875	PHASE4	UNKNOWN	Early Oral Versus Enteral Nutrition After Pancreatoduodenectomy
NCT01768988	PHASE4	TERMINATED	Efficacy Of Pregabalin In The Treatment Of Pancreatic Cancer Pain. A Randomized Controlled Double-Blind, Parallel Group Study
NCT02027311	PHASE4	COMPLETED	Etomidate vs. Midazolam for Sedation During ERCP
NCT02044224	PHASE4	COMPLETED	Effects of Dexmedetomidine During IRE Procedures for Solid Tumours
NCT03642093	PHASE4	UNKNOWN	HOPE - A Study to Evaluate the Effect of a Prehabilitation Program on GI Cancer Patients Planning to Undergo Surgery
NCT03891979	PHASE4	WITHDRAWN	Gut Microbiome Modulation to Enable Efficacy of Checkpoint-based Immunotherapy in Pancreatic Adenocarcinoma
NCT04025840	PHASE4	ACTIVE_NOT_RECRUITING	Perioperative Epidural Block and Dexamethasone in Pancreatic Cancer Surgery
NCT04058236	PHASE4	UNKNOWN	Glycocalyx Levels in Patients Undergoing Pancreatectomy
NCT04155008	PHASE4	TERMINATED	Nutrition and Pharmacological Algorithm for Oncology Patients Study
NCT04217096	PHASE4	UNKNOWN	Efficacy and Safety of Paclitaxel Liposome and S-1 as First-line Therapy in \ Advanced Pancreatic Cancer Patients
NCT04269369	PHASE4	UNKNOWN	Implementation of Pre-emptive Geno- and Phenotyping in 5-Fluorouracil- or Capecitabine-treated Patients
NCT04809935	PHASE4	UNKNOWN	EUS-Coeliac Plexus Block Versus Radiofrequency Ablation in Pain Relief of Patients With Malignancy
NCT05035147	PHASE4	RECRUITING	Albumin-bound Paclitaxel Combined With Gemcitabine First-line Inoperable Pancreatic Cancer
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