TP53BP1

Summary

TP53BP1 (tumor protein p53 binding protein 1, HGNC:11999) is a protein-coding gene on chromosome 15q15.3, encoding TP53-binding protein 1 (Q12888). Double-strand break (DSB) repair protein involved in response to DNA damage, telomere dynamics and class-switch recombination (CSR) during antibody genesis.

This gene encodes a protein that functions in the DNA double-strand break repair pathway choice, promoting non-homologous end joining (NHEJ) pathways, and limiting homologous recombination. This protein plays multiple roles in the DNA damage response, including promoting checkpoint signaling following DNA damage, acting as a scaffold for recruitment of DNA damage response proteins to damaged chromatin, and promoting NHEJ pathways by limiting end resection following a double-strand break. These roles are also important during V(D)J recombination, class switch recombination and at unprotected telomeres. Alternative splicing results in multiple transcript variants encoding different isoforms.

Source: NCBI Gene 7158 — RefSeq curated summary.

At a glance

• GWAS associations: 28
• Clinical variants (ClinVar): 266 total — 2 pathogenic
• Druggable target: yes
• MANE Select transcript: NM_001141980

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11999
Approved symbol	TP53BP1
Name	tumor protein p53 binding protein 1
Location	15q15.3
Locus type	gene with protein product
Status	Approved
Aliases	53BP1, p202, TDRD30
Ensembl gene	ENSG00000067369
Ensembl biotype	protein_coding
OMIM	605230
Entrez	7158

Gene structure

Transcript identifiers

Ensembl transcripts: 23 — 13 protein_coding, 4 protein_coding_CDS_not_defined, 3 nonsense_mediated_decay, 3 retained_intron

ENST00000263801, ENST00000382039, ENST00000382044, ENST00000411772, ENST00000413546, ENST00000414758, ENST00000417342, ENST00000434561, ENST00000434595, ENST00000450115, ENST00000467474, ENST00000476454, ENST00000477089, ENST00000480860, ENST00000571145, ENST00000572085, ENST00000605155, ENST00000858968, ENST00000931501, ENST00000931502, ENST00000931503, ENST00000966911, ENST00000966912

RefSeq mRNA: 5 — MANE Select: NM_001141980 NM_001141979, NM_001141980, NM_001355001, NM_001411050, NM_005657

CCDS: CCDS10096, CCDS45250, CCDS45251, CCDS91987

Canonical transcript exons

ENST00000382044 — 28 exons

Exon	Start	End
ENSE00001911653	43493037	43493156
ENSE00003460383	43416225	43416416
ENSE00003476899	43441526	43441583
ENSE00003504192	43420305	43420735
ENSE00003517900	43408897	43409096
ENSE00003518469	43421025	43421174
ENSE00003521208	43447366	43447485
ENSE00003527300	43479859	43480017
ENSE00003545052	43455892	43457218
ENSE00003547798	43438324	43438416
ENSE00003549471	43428016	43428168
ENSE00003565424	43432194	43432677
ENSE00003574753	43446387	43446590
ENSE00003575854	43480895	43481022
ENSE00003577045	43491669	43491753
ENSE00003582266	43475565	43475694
ENSE00003590260	43415594	43415809
ENSE00003602641	43492002	43492095
ENSE00003632459	43421855	43422126
ENSE00003634218	43469858	43470066
ENSE00003650329	43492284	43492468
ENSE00003663918	43409647	43409741
ENSE00003668684	43479397	43479526
ENSE00003672655	43477593	43477759
ENSE00003686245	43407943	43408088
ENSE00003686394	43413119	43413334
ENSE00003689220	43474673	43474767
ENSE00003719123	43403061	43407570

Expression profiles

Bgee: expression breadth ubiquitous, 285 present calls, max score 96.11.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 17.8047 / max 301.4259, expressed in 1777 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
149609	15.0118	1768
149610	0.7263	350
149612	0.5740	264
149611	0.5388	271
149607	0.5159	177
149608	0.4378	199

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
pituitary gland	UBERON:0000007	96.11	gold quality
adenohypophysis	UBERON:0002196	95.62	gold quality
adrenal tissue	UBERON:0018303	95.21	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	94.79	gold quality
ventricular zone	UBERON:0003053	94.39	gold quality
stromal cell of endometrium	CL:0002255	93.98	gold quality
calcaneal tendon	UBERON:0003701	93.89	gold quality
right uterine tube	UBERON:0001302	93.86	gold quality
cortical plate	UBERON:0005343	93.64	gold quality
ganglionic eminence	UBERON:0004023	93.19	gold quality
embryo	UBERON:0000922	92.63	gold quality
middle temporal gyrus	UBERON:0002771	92.54	gold quality
sural nerve	UBERON:0015488	92.40	gold quality
sperm	CL:0000019	92.39	gold quality
right lobe of thyroid gland	UBERON:0001119	92.07	gold quality
male germ cell	CL:0000015	92.06	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	92.00	gold quality
epithelium of bronchus	UBERON:0002031	92.00	gold quality
endocervix	UBERON:0000458	91.95	gold quality
bronchial epithelial cell	CL:0002328	91.90	gold quality
islet of Langerhans	UBERON:0000006	91.88	gold quality
left lobe of thyroid gland	UBERON:0001120	91.70	gold quality
right testis	UBERON:0004534	91.68	gold quality
bronchus	UBERON:0002185	91.63	gold quality
thyroid gland	UBERON:0002046	91.60	gold quality
colonic epithelium	UBERON:0000397	91.37	gold quality
left testis	UBERON:0004533	91.32	gold quality
lateral nuclear group of thalamus	UBERON:0002736	91.20	gold quality
testis	UBERON:0000473	90.92	gold quality
left ovary	UBERON:0002119	90.82	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-6819	yes	211.66
E-ANND-3	yes	5.53

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
BRCA1	Activation

Upstream regulators (CollecTRI, top): AP1, CTNNB1, FOS, JUN, JUND, MYC, MYOD1, MYOG, NFE2L2, NFKB, RELA, STAT1, TFAP2A, TFDP1, TP53

miRNA regulators (miRDB)

46 targeting TP53BP1, 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-8485	100.00	77.57	4731
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-145-5P	99.92	71.13	1836
HSA-MIR-5195-3P	99.92	70.92	1877
HSA-MIR-329-3P	99.91	66.56	1234
HSA-MIR-362-3P	99.91	66.38	1267
HSA-MIR-3941	99.86	70.54	2735
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-548AZ-5P	99.83	69.94	3230
HSA-MIR-548T-5P	99.83	69.91	3220
HSA-MIR-548AZ-3P	99.82	70.56	3549
HSA-MIR-548BC	99.82	70.61	3524
HSA-MIR-548E-3P	99.82	70.59	3514
HSA-MIR-548F-3P	99.82	70.59	3540
HSA-MIR-548A-3P	99.76	70.58	3524
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-466	99.67	70.85	2863
HSA-MIR-7159-5P	99.53	72.12	2472
HSA-MIR-4708-3P	99.51	67.99	870
HSA-MIR-4672	99.50	71.58	2893
HSA-MIR-154-3P	99.50	70.05	831
HSA-MIR-487A-3P	99.50	69.95	840
HSA-MIR-4311	99.31	70.47	3041

Literature-anchored findings (GeneRIF, showing 40)

• Structure of the human 53BP1 BRCT region bound to p53 and its comparison to the rat Brca1 BRCT structure is presented. (PMID:11877378)
• crystal structure of human 53BP1 BRCT domains bound to p53 tumour suppressor (PMID:12110597)
• Pts with p53 gene mutations were 3-times more likely to have an early onset breast cancer. Pts with both missense & silent mutations were 7-times & Pts with mutations in exon 8 of the p53 gene 6 times more likely to have early onset breast cancer. (PMID:12170762)
• Purification, crystallization and preliminary X-ray analysis of the BRCT domains of human 53BP1 bound to the p53 tumour suppressor (PMID:12351827)
• demonstrated that 53BP1 is a key transducer of the DNA damage checkpoint signal; required for p53 accumulation, G2-M checkpoint arrest, and the intra-S-phase checkpoint in response to ionizing radiation (PMID:12364621)
• Results suggest that 53BP1 and Snm1 may cooperate in the cellular response to genotoxic damage. (PMID:12446782)
• 53BP1 functions as a DNA damage checkpoint protein (PMID:12447382)
• 53BP1 is involved in a pathway with NFBD1, H2AX, and Chk2 in recruitment of repair and signaling proteins to sites of DNA damage (PMID:12551934)
• P202 inhibits E2F1-mediated apoptosis in prostate cancer cells (PMID:12646190)
• This protein interacts with HDAC4 protein to mediate DNA damage response. (PMID:12668657)
• 53BP1 has the potential to participate directly in the repair of DNA double-strand breaks (PMID:12824158)
• In cells with wild-type Nbs1, suppression of 53BP1 expression had no effect on ATM activation but was associated with increased recruitment of NFBD1/MDC1 and Nbs1 to sites of DNA breaks. (PMID:14695167)
• 53BP1 is an activator of ATM in response to DNA damage [review] (PMID:15279780)
• 53BP1 senses DNA double-stranded breaks indirectly through changes in higher-order chromatin structure that expose the 53BP1 binding site (PMID:15525939)
• Thus, optimal repair of damaged replication fork lesions likely requires both ATR and ATM. BLM recruits 53BP1 to these lesions independent of its helicase activity, and optimal activation of ATM requires both p53 and BLM helicase activities. (PMID:15539948)
• Snm1 and 53BP1 are components of a mitotic stress checkpoint that negatively targets the APC prior to chromosome condensation (PMID:15542852)
• LC8 binds to p53-binding protein 1 and mediates DNA damage-induced p53 nuclear accumulation (PMID:15611139)
• RNA has a role in the binding of 53BP1 to chromatin damaged by ionizing radiation (PMID:15840649)
• the BRCA1 promoter is positively regulated by 53BP1 (PMID:15970701)
• Jun activation domain-binding protein 1 (Jab1) was identified as a 53BP1-binding protein, and the interaction between them was confirmed to occur in mammalian cells. (PMID:16187115)
• GAR (Glycine Arginine rich) motif is a region required for 53BP1 DNA binding activity and as the site of methylation by PRMT1. (PMID:16294045)
• a glycine-arginine rich (GAR) stretch of 53BP1 lying upstream of the Tudor motifs is methylated by PRMT1 (PMID:16294047)
• 53BP1 only has limited checkpoint functions but rather acts as an adaptor in the repair of DNA double strand breaks (PMID:17043355)
• analysis of nonconserved residues that enforced p53 core domain binding with BRCA1-BRCT in a way similar to p53-53BP1 binding (PMID:17161371)
• Using X-ray crystallography and NMR spectroscopy, we show that, despite low amino acid sequence conservation, both 53BP1 and Crb2 contain tandem tudor domains that interact with histone H4 specifically dimethylated at Lys20 (H4-K20me2). (PMID:17190600)
• Contrary to carcinomas, almost no activation or loss of MDC1 or 53BP1 were found among testicular germ-cell tumours (TGCTs), a tumour type with unique biology and exceptionally low incidence of p53 mutations. (PMID:17546051)
• BLM helicase-dependent and -independent roles of TP53BP1 during replication stress-mediated homologous recombination were studied. (PMID:17591918)
• Genetic variation increases had and neck cancer risk. (PMID:17634560)
• These studies highlight the role of 53BP1 copy loss in primary human DLBCLs and the value of integrative analyses in detecting this genetic lesion in human tumors (PMID:17637749)
• 53BP1 oligomerization is not dependent on the presence of disulfide bridges (PMID:17695720)
• MDC1 and 53BP1 expressions were observed for the first time in human esophageal carcinoma cell lines TE-1,TE-13 and Eca109 cells, at both the mRNA and protein levels. (PMID:17884766)
• 53BP1 T885G mutation may not be correlated to the susceptibility to esophageal squamous cell carcinoma and gastric cardiac adenocarcinoma. (PMID:17927872)
• These data indicate the existence of a DNA double-strand break-repair protein that functions upstream of 53BP1 and contributes to the normal development of the human immune system. (PMID:17940005)
• the phosphorylation-mediated interactions between BLM, 53BP1 and RAD51 are required for their regulatory roles during homologous recombination (PMID:17984114)
• analysis of 53BP1 expression can be a useful tool to estimate the level of genomic instability and, simultaneously, the malignant potency of human thyroid tumors. (PMID:17985346)
• RNF8 ubiquitylation pathways are essential for 53BP1 regulation in response to ionizing radiation, whereas RNF8-independent pathways contribute to 53BP1 targeting and phosphorylation in response to UV light and other forms of DNA replication stress (PMID:18337245)
• a number of nuclear p53-binding protein 1 foci in human skin tumorigenesis (PMID:18380789)
• Nbs1 has a function in ATR signalling in a manner distinct to any role at stalled replication forks. Replication-independent ATR signalling also requires the mediator proteins, 53BP1 and MDC1, providing direct evidence for their role in ATR signalling. (PMID:18664457)
• The two major roles of 53BP1, the checkpoint signaling and repair for DNA damage, can be functionally separated. (PMID:18804090)
• analysis of the 53BP1 Tudor domain recognition of p53 dimethylated at lysine 382 in DNA damage signaling (PMID:18840612)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	tp53bp1	ENSDARG00000079000
mus_musculus	Trp53bp1	ENSMUSG00000043909
rattus_norvegicus	Tp53bp1	ENSRNOG00000013837
caenorhabditis_elegans	hsr-9	WBGENE00002027

Protein

Protein identifiers

TP53-binding protein 1 — Q12888 (reviewed: Q12888)

All UniProt accessions (8): Q12888, A6NNK5, C9JXV0, H7BZY0, H7C151, H7C3N7, H7C495, M0R142

UniProt curated annotations — full annotation on UniProt →

Function. Double-strand break (DSB) repair protein involved in response to DNA damage, telomere dynamics and class-switch recombination (CSR) during antibody genesis. Plays a key role in the repair of double-strand DNA breaks (DSBs) in response to DNA damage by promoting non-homologous end joining (NHEJ)-mediated repair of DSBs and specifically counteracting the function of the homologous recombination (HR) repair protein BRCA1. In response to DSBs, phosphorylation by ATM promotes interaction with RIF1 and dissociation from NUDT16L1/TIRR, leading to recruitment to DSBs sites. Recruited to DSBs sites by recognizing and binding histone H2A monoubiquitinated at ‘Lys-15’ (H2AK15Ub) and histone H4 dimethylated at ‘Lys-20’ (H4K20me2), two histone marks that are present at DSBs sites. Required for immunoglobulin class-switch recombination (CSR) during antibody genesis, a process that involves the generation of DNA DSBs. Participates in the repair and the orientation of the broken DNA ends during CSR. In contrast, it is not required for classic NHEJ and V(D)J recombination. Promotes NHEJ of dysfunctional telomeres via interaction with PAXIP1.

Subunit / interactions. Homoligomer. Interacts with p53/TP53 (via the central domain). Interacts with DCLRE1C. Interacts with histone H2AX and this requires phosphorylation of H2AX on ‘Ser-139’. Interacts with histone H4 that has been dimethylated at ‘Lys-20’ (H4K20me2). Has low affinity for histone H4 containing monomethylated ‘Lys-20’ (H4K20me1). Does not bind histone H4 containing unmethylated or trimethylated ‘Lys-20’ (H4K20me3). Has low affinity for histone H3 that has been dimethylated on ‘Lys-79’. Has very low affinity for histone H3 that has been monomethylated on ‘Lys-79’ (in vitro). Does not bind unmethylated histone H3. Interacts with histone H2A monoubiquitinated at ‘Lys-15’ (H2AK15Ub). Interacts with PWWP3A/EXPAND1. Interacts with CHEK2; modulates CHEK2 phosphorylation at ‘Thr-68’ in response to infrared. Interacts with MSL1; this interaction may be required for MSL1 DNA repair activity, but not for histone acetyltransferase activity. Interacts (when phosphorylated by ATM) with RIF1. Interacts (via the Tudor-like domain) with NUDT16L1/TIRR; interaction masks the Tudor-like domain and prevents recruitment to chromatin. Interacts with PAXIP1. Interacts with SHLD2. Interacts (when phosphorylated) with TOPBP1. Interacts with GFI1; promoting methylation by PRMT1. Interacts with (phosphorylated) DYNLL1; specifically binds DYNLL1 phosphorylated at ‘Ser-88’ and promotes its recruitment to double strand breaks (DSBs). (Microbial infection) Interacts (via C-terminus) with Epstein-Barr virus lytic switch protein BZLF1 (via C-terminus); this interaction is involved in the activation of the viral lytic cycle.

Subcellular location. Nucleus. Chromosome. Centromere. Kinetochore.

Post-translational modifications. Asymmetrically dimethylated on Arg residues by PRMT1. Methylation is required for DNA binding. Phosphorylated at basal level in the absence of DNA damage. Phosphorylated by ATM in response to DNA damage: phosphorylation at different sites promotes interaction with different set of proteins: phosphorylation at the N-terminus by ATM (residues from 6-178) promotes interaction with PAXIP1 and non-homologous end joining (NHEJ) of dysfunctional telomeres. Phosphorylation by ATM at residues that are located more C-terminus (residues 300-650) leads to promote interaction with RIF1. Interaction with RIF1 leads to disrupt interaction with NUDT16L1/TIRR. Phosphorylation at Thr-1609 and Ser-1618 in the UDR motif blocks interaction with H2AK15ub. Dephosphorylated by PPP4C. Hyperphosphorylation during mitosis correlates with its exclusion from chromatin and DNA lesions. Hyperphosphorylated in an ATR-dependent manner in response to DNA damage induced by UV irradiation. Dephosphorylated by PPP5C. Phosphorylation at Ser-366 and Thr-670 promotes interaction with TOPBP1. Phosphorylated by VRK1. Monoubiquitinated at Lys-1685 by MSL2 in response to DNA damage, leading to its stabilization.

Disease relevance. A chromosomal aberration involving TP53BP1 is found in a form of myeloproliferative disorder chronic with eosinophilia. Translocation t(5;15)(q33;q22) with PDGFRB creating a TP53BP1-PDGFRB fusion protein.

Domain organisation. The Tudor-like region mediates binding to histone H4 dimethylated at ‘Lys-20’ (H4K20me2). Interaction with NUDT16L1/TIRR masks the Tudor-like domain and prevents recruitment to chromatin. The UDR (ubiquitin-dependent recruitment) motif specifically recognizes and binds histone H2A monoubiquitinated at ‘Lys-15’ (H2AK15ub). Phosphorylation of the UDR blocks interaction with H2AK15ub.

Isoforms (3)

UniProt ID	Names	Canonical?
Q12888-1	1	yes
Q12888-2	2
Q12888-3	3

RefSeq proteins (5): NP_001135451, NP_001135452, NP_001341930, NP_001397979, NP_005648 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001357	BRCT_dom	Domain
IPR014722	Rib_uL2_dom2	Homologous_superfamily
IPR015125	53-BP1_Tudor	Domain
IPR036420	BRCT_dom_sf	Homologous_superfamily
IPR047249	BRCT_p53bp1-like_rpt1	Domain
IPR047250	BRCT_p53bp1-like_rpt2	Domain
IPR047252	TP53BP1-like	Family

Pfam: PF09038, PF18428

UniProt features (267 total): modified residue 79, mutagenesis site 67, compositionally biased region 26, strand 20, region of interest 16, helix 14, sequence variant 13, cross-link 12, turn 10, sequence conflict 3, domain 2, splice variant 2, short sequence motif 2, chain 1

Structure

Experimental structures (PDB)

45 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
8SVI	X-RAY DIFFRACTION	1.15
8SVH	X-RAY DIFFRACTION	1.16
8SVG	X-RAY DIFFRACTION	1.21
2G3R	X-RAY DIFFRACTION	1.25
6VA5	X-RAY DIFFRACTION	1.28
6VIP	X-RAY DIFFRACTION	1.36
7LIN	X-RAY DIFFRACTION	1.44
3LGF	X-RAY DIFFRACTION	1.5
4RG2	X-RAY DIFFRACTION	1.5
8SVJ	X-RAY DIFFRACTION	1.5
8F0W	X-RAY DIFFRACTION	1.52
3LGL	X-RAY DIFFRACTION	1.6
8SWJ	X-RAY DIFFRACTION	1.6
6MXY	X-RAY DIFFRACTION	1.62
2IG0	X-RAY DIFFRACTION	1.7
6IUA	X-RAY DIFFRACTION	1.7
8EOM	X-RAY DIFFRACTION	1.7
8T2D	X-RAY DIFFRACTION	1.75
5Z78	X-RAY DIFFRACTION	1.76
4X34	X-RAY DIFFRACTION	1.8
3LH0	X-RAY DIFFRACTION	1.9
6IU7	X-RAY DIFFRACTION	1.9
8HKW	X-RAY DIFFRACTION	1.9
6UPT	X-RAY DIFFRACTION	1.96
5ZCJ	X-RAY DIFFRACTION	2
6CO1	X-RAY DIFFRACTION	2.18
6MY0	X-RAY DIFFRACTION	2.2
6MXX	X-RAY DIFFRACTION	2.3
4CRI	X-RAY DIFFRACTION	2.35
6CO2	X-RAY DIFFRACTION	2.49

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q12888-F1	44.67	0.16

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 (91): 1214, 1216, 1219, 1317, 1342, 1355, 1362, 1368, 1372, 1426, 1430, 1460, 1462, 1474, 1609, 1618, 1631, 1635, 1638, 1648 …

Mutagenesis-validated functional residues (67):

Position	Phenotype
6	in 28a: defects in recruitment to double strand breaks (dsbs), abolished interaction with rif1 and abolished ability to
13	in 28a: defects in recruitment to double strand breaks (dsbs), abolished interaction with rif1 and abolished ability to
25	in 28a: defects in recruitment to double strand breaks (dsbs), abolished interaction with rif1 and abolished ability to
29	in 28a: defects in recruitment to double strand breaks (dsbs), abolished interaction with rif1 and abolished ability to
105	in 28a: defects in recruitment to double strand breaks (dsbs), abolished interaction with rif1 and abolished ability to
166	in 28a: defects in recruitment to double strand breaks (dsbs), abolished interaction with rif1 and abolished ability to
176–178	loss of phosphorylation site.
176	in 28a: defects in recruitment to double strand breaks (dsbs), abolished interaction with rif1 and abolished ability to
178	in 28a: defects in recruitment to double strand breaks (dsbs), abolished interaction with rif1 and abolished ability to
302	in 28a: defects in recruitment to double strand breaks (dsbs), abolished interaction with rif1 and abolished ability to
366	decreased interaction with topbp1.
437	in 28a: defects in recruitment to double strand breaks (dsbs), abolished interaction with rif1 and abolished ability to
452	in 28a: defects in recruitment to double strand breaks (dsbs), abolished interaction with rif1 and abolished ability to
523	in 28a: defects in recruitment to double strand breaks (dsbs), abolished interaction with rif1 and abolished ability to
543	in 28a: defects in recruitment to double strand breaks (dsbs), abolished interaction with rif1 and abolished ability to
580	in 28a: defects in recruitment to double strand breaks (dsbs), abolished interaction with rif1 and abolished ability to
625	in 28a: defects in recruitment to double strand breaks (dsbs), abolished interaction with rif1 and abolished ability to
670	decreased interaction with topbp1.
674	in 28a: defects in recruitment to double strand breaks (dsbs), abolished interaction with rif1 and abolished ability to
696	in 28a: defects in recruitment to double strand breaks (dsbs), abolished interaction with rif1 and abolished ability to
698	in 28a: defects in recruitment to double strand breaks (dsbs), abolished interaction with rif1 and abolished ability to
784	in 28a: defects in recruitment to double strand breaks (dsbs), abolished interaction with rif1 and abolished ability to
831	in 28a: defects in recruitment to double strand breaks (dsbs), abolished interaction with rif1 and abolished ability to
855	in 28a: defects in recruitment to double strand breaks (dsbs), abolished interaction with rif1 and abolished ability to
892	in 28a: defects in recruitment to double strand breaks (dsbs), abolished interaction with rif1 and abolished ability to

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-3232118	SUMOylation of transcription factors
R-HSA-5693565	Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks
R-HSA-5693571	Nonhomologous End-Joining (NHEJ)
R-HSA-5693607	Processing of DNA double-strand break ends
R-HSA-69473	G2/M DNA damage checkpoint

MSigDB gene sets: 0 (showing top):

GO Biological Process (19): DNA damage checkpoint signaling (GO:0000077), double-strand break repair via nonhomologous end joining (GO:0006303), DNA damage response (GO:0006974), positive regulation of isotype switching (GO:0045830), positive regulation of DNA-templated transcription (GO:0045893), positive regulation of transcription by RNA polymerase II (GO:0045944), protein homooligomerization (GO:0051260), cellular response to X-ray (GO:0071481), double-strand break repair via classical nonhomologous end joining (GO:0097680), positive regulation of intrinsic apoptotic signaling pathway by p53 class mediator (GO:1902255), protein localization to site of double-strand break (GO:1990166), negative regulation of double-strand break repair via homologous recombination (GO:2000042), DNA repair (GO:0006281), double-strand break repair (GO:0006302), chromatin organization (GO:0006325), chromatin remodeling (GO:0006338), regulation of DNA-templated transcription (GO:0006355), DNA strand resection involved in replication fork processing (GO:0110025), negative regulation of DNA strand resection involved in replication fork processing (GO:0110027)

GO Molecular Function (14): p53 binding (GO:0002039), damaged DNA binding (GO:0003684), transcription coregulator activity (GO:0003712), transcription coactivator activity (GO:0003713), telomeric repeat DNA binding (GO:0042162), histone binding (GO:0042393), RNA polymerase II-specific DNA-binding transcription factor binding (GO:0061629), ubiquitin-modified histone reader activity (GO:0061649), histone H4K20me2 reader activity (GO:0140005), histone reader activity (GO:0140566), histone H4K20me methyltransferase activity (GO:0140941), DNA binding (GO:0003677), protein binding (GO:0005515), sequence-specific DNA binding (GO:0043565)

GO Cellular Component (11): kinetochore (GO:0000776), chromosome, telomeric region (GO:0000781), nucleus (GO:0005634), nucleoplasm (GO:0005654), replication fork (GO:0005657), cytoplasm (GO:0005737), nuclear body (GO:0016604), site of double-strand break (GO:0035861), DNA repair complex (GO:1990391), chromosome, centromeric region (GO:0000775), chromosome (GO:0005694)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
SUMO E3 ligases SUMOylate target proteins	1
DNA Double Strand Break Response	1
DNA Double-Strand Break Repair	1
HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA)	1
G2/M Checkpoints	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular membraneless organelle	3
cellular anatomical structure	3
DNA-templated transcription	2
positive regulation of DNA-templated transcription	2
DNA metabolic process	2
protein binding	2
DNA binding	2
chromosomal region	2
DNA integrity checkpoint signaling	1
signal transduction in response to DNA damage	1
double-strand break repair	1
cellular response to stress	1
positive regulation of immunoglobulin production	1
positive regulation of immunoglobulin mediated immune response	1
isotype switching	1
regulation of isotype switching	1
positive regulation of DNA recombination	1
positive regulation of B cell activation	1
positive regulation of developmental process	1
regulation of DNA-templated transcription	1
positive regulation of RNA biosynthetic process	1
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
protein complex oligomerization	1
response to X-ray	1
cellular response to ionizing radiation	1
double-strand break repair via nonhomologous end joining	1
intrinsic apoptotic signaling pathway by p53 class mediator	1
positive regulation of signal transduction by p53 class mediator	1
regulation of intrinsic apoptotic signaling pathway by p53 class mediator	1
positive regulation of intrinsic apoptotic signaling pathway	1
protein localization to chromosome	1
double-strand break repair via homologous recombination	1
regulation of double-strand break repair via homologous recombination	1
negative regulation of DNA recombination	1
negative regulation of double-strand break repair	1
DNA damage response	1
DNA repair	1
cellular component organization	1
chromatin organization	1

Protein interactions and networks

STRING

3345 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TP53BP1	MDC1	Q14676	999
TP53BP1	BRCA1	P38398	999
TP53BP1	TP53	P04637	997
TP53BP1	H2AX	P16104	997
TP53BP1	ATM	Q13315	996
TP53BP1	PAXIP1	Q6ZW49	994
TP53BP1	USP28	Q96RU2	993
TP53BP1	H2AC20	Q16777	991
TP53BP1	H2AC19	P20670	991
TP53BP1	RNF8	O76064	984
TP53BP1	H4C7	Q99525	979
TP53BP1	H4C16	P02304	978
TP53BP1	RNF168	Q8IYW5	973
TP53BP1	H3-3A	P06351	963
TP53BP1	H3C1	P02295	963

IntAct

309 interactions, top by confidence:

A	B	Type	Score
TP53	TP53BP1	psi-mi:“MI:0407”(direct interaction)	0.870
TP53BP1	TP53	psi-mi:“MI:0915”(physical association)	0.870
TP53BP1	H4C16	psi-mi:“MI:0407”(direct interaction)	0.870
TP53	TP53BP1	psi-mi:“MI:0915”(physical association)	0.870
CDK8	MED19	psi-mi:“MI:2364”(proximity)	0.850
TP53BP1	H2AX	psi-mi:“MI:0403”(colocalization)	0.790
DYNLL1	BLTP3B	psi-mi:“MI:0914”(association)	0.730
VAC14	TP53BP1	psi-mi:“MI:0915”(physical association)	0.720
TP53BP1	PLK1	psi-mi:“MI:0915”(physical association)	0.720
TP53BP1	PLK1	psi-mi:“MI:0217”(phosphorylation reaction)	0.720
TP53BP1	BRCA1	psi-mi:“MI:0915”(physical association)	0.700
TP53BP1	BRCA1	psi-mi:“MI:0403”(colocalization)	0.700
TP53	WDR5	psi-mi:“MI:0914”(association)	0.690
TP53BP1	H2AC11	psi-mi:“MI:0915”(physical association)	0.670

BioGRID (757): TP53BP1 (Two-hybrid), VAC14 (Two-hybrid), UBE2L3 (Affinity Capture-Western), TP53BP1 (Affinity Capture-RNA), TP53BP1 (Affinity Capture-RNA), TP53BP1 (Affinity Capture-RNA), TP53BP1 (Affinity Capture-RNA), TP53BP1 (Two-hybrid), TP53BP1 (Affinity Capture-Western), MSL1 (Affinity Capture-Western), TP53BP1 (Affinity Capture-MS), TP53BP1 (Reconstituted Complex), TP53BP1 (Reconstituted Complex), RNF168 (Affinity Capture-Western), TP53BP1 (Affinity Capture-MS)

ESM2 similar proteins: A0JM08, A0MS83, A2AEY4, A7MC64, E9PVX6, E9Q0C6, O54963, O75952, O95197, P10637, P11137, P15146, P19332, P20357, P34627, P50534, P51954, P70399, P86839, Q12888, Q13127, Q498L0, Q4R3X7, Q5H9B9, Q5R782, Q5S6V2, Q5SW79, Q66H17, Q6A065, Q6NWJ0, Q6RJR6, Q710D7, Q80XP9, Q8C4A5, Q8C5V0, Q8C5W0, Q8IWC1, Q8VIG1, Q95J40, Q96JQ2

Diamond homologs: P70399, Q12888

SIGNOR signaling

33 interactions.

A	Effect	B	Mechanism
ATM	unknown	TP53BP1	phosphorylation
TP53BP1	unknown	H4C1	binding
PIAS1	up-regulates	TP53BP1	sumoylation
PIAS4	up-regulates	TP53BP1	sumoylation
ATM	up-regulates	TP53BP1	phosphorylation
VRK1	up-regulates	TP53BP1	phosphorylation
BRD2	“up-regulates activity”	TP53BP1	relocalization
L3MBTL1	“down-regulates activity”	TP53BP1	binding
AURKB	“up-regulates activity”	TP53BP1	phosphorylation
ZNF420	“down-regulates activity”	TP53BP1	binding
H1-2	“down-regulates activity”	TP53BP1	binding
PPM1D	“down-regulates activity”	TP53BP1	dephosphorylation
GSK3B	“up-regulates activity”	TP53BP1	phosphorylation
RAD18	“up-regulates activity”	TP53BP1	ubiquitination
RNF168	“up-regulates quantity”	TP53BP1	ubiquitination
TP53BP1	“up-regulates activity”	RIF1	binding
“BRCA1-C complex”	“up-regulates activity”	TP53BP1	relocalization
CDK1	“down-regulates activity”	TP53BP1	phosphorylation
PLK1	“down-regulates activity”	TP53BP1	phosphorylation
CyclinB/CDK1	“down-regulates activity”	TP53BP1	phosphorylation
p38	“down-regulates activity”	TP53BP1	phosphorylation
MAPK14	“down-regulates activity”	TP53BP1	phosphorylation
MAPK11	“down-regulates activity”	TP53BP1	phosphorylation
MAPK12	“down-regulates activity”	TP53BP1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 97 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
DNA Double Strand Break Response	5	34.5×	2e-05
Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks	12	25.5×	2e-11
Formation of WDR5-containing histone-modifying complexes	6	23.1×	2e-05
Nonhomologous End-Joining (NHEJ)	9	21.9×	5e-08
DNA Double-Strand Break Repair	5	18.0×	3e-04
G2/M DNA damage checkpoint	10	17.4×	5e-08
Deactivation of the beta-catenin transactivating complex	5	16.9×	4e-04
Formation of the beta-catenin:TCF transactivating complex	9	15.7×	8e-07

GO biological processes:

GO term	Partners	Fold	FDR
double-strand break repair	8	18.5×	5e-06
double-strand break repair via homologous recombination	6	10.6×	3e-03
DNA damage response	14	8.5×	7e-07
regulation of cell cycle	7	5.9×	9e-03

Disease & clinical

Cancer significance

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	160
Likely benign	57
Benign	8

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
1454253	NM_014444.5(TUBGCP4):c.1784dup (p.Val596fs)	Pathogenic
1513915	NM_014444.5(TUBGCP4):c.1848+5G>A	Pathogenic

SpliceAI

5520 predictions. Top by Δscore:

Variant	Effect	Δscore
15:43407568:TAT:T	acceptor_gain	1.0000
15:43407582:A:T	acceptor_gain	1.0000
15:43407942:C:CA	donor_loss	1.0000
15:43407987:C:CT	donor_gain	1.0000
15:43407988:C:CT	donor_gain	1.0000
15:43408084:GTTGC:G	acceptor_gain	1.0000
15:43408085:TTGC:T	acceptor_gain	1.0000
15:43408086:TGC:T	acceptor_gain	1.0000
15:43408087:GC:G	acceptor_gain	1.0000
15:43408088:CC:C	acceptor_gain	1.0000
15:43408089:C:CC	acceptor_gain	1.0000
15:43408091:A:C	acceptor_gain	1.0000
15:43408891:ACTT:A	donor_loss	1.0000
15:43408892:CTTA:C	donor_loss	1.0000
15:43408893:TTACC:T	donor_loss	1.0000
15:43408894:TACCA:T	donor_loss	1.0000
15:43408895:A:AC	donor_gain	1.0000
15:43408895:A:AT	donor_loss	1.0000
15:43408896:C:CG	donor_gain	1.0000
15:43408896:CCA:C	donor_gain	1.0000
15:43408896:CCAG:C	donor_gain	1.0000
15:43409042:T:TA	donor_gain	1.0000
15:43409064:C:CT	acceptor_gain	1.0000
15:43409064:C:T	acceptor_gain	1.0000
15:43409092:TTACA:T	acceptor_gain	1.0000
15:43409093:TACA:T	acceptor_gain	1.0000
15:43409094:ACA:A	acceptor_gain	1.0000
15:43409095:CA:C	acceptor_gain	1.0000
15:43409095:CAC:C	acceptor_gain	1.0000
15:43409096:AC:A	acceptor_loss	1.0000

AlphaMissense

12983 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:43407450:A:G	L1951P	1.000
15:43407464:C:A	W1946C	1.000
15:43407464:C:G	W1946C	1.000
15:43407466:A:G	W1946R	1.000
15:43407466:A:T	W1946R	1.000
15:43407486:A:G	L1939P	1.000
15:43407501:G:T	A1934D	1.000
15:43407540:A:T	V1921E	1.000
15:43407999:A:G	L1892P	1.000
15:43407999:A:T	L1892H	1.000
15:43408012:A:G	W1888R	1.000
15:43408012:A:T	W1888R	1.000
15:43408050:A:G	L1875P	1.000
15:43408930:C:T	G1851E	1.000
15:43408931:C:A	G1851W	1.000
15:43408990:A:T	V1831D	1.000
15:43408992:C:A	W1830C	1.000
15:43408992:C:G	W1830C	1.000
15:43408994:A:G	W1830R	1.000
15:43408994:A:T	W1830R	1.000
15:43409005:A:T	V1826E	1.000
15:43409026:A:G	L1819P	1.000
15:43409028:G:C	C1818W	1.000
15:43409030:A:G	C1818R	1.000
15:43409032:A:G	L1817P	1.000
15:43409068:A:T	I1805N	1.000
15:43409071:A:G	L1804P	1.000
15:43409669:A:G	L1788P	1.000
15:43409678:C:T	G1785D	1.000
15:43409679:C:G	G1785R	1.000

dbSNP variants (sampled 300 via entrez): RS1000039569 (15:43480839 A>G), RS1000051278 (15:43474336 C>T), RS1000079745 (15:43473029 A>G), RS1000086293 (15:43489899 T>C), RS1000108974 (15:43433853 A>T), RS1000141565 (15:43447000 AGACT>A), RS1000147731 (15:43404608 T>C,G), RS1000213708 (15:43434996 C>T), RS1000217660 (15:43486644 G>A), RS1000233528 (15:43468660 A>G,T), RS1000265193 (15:43440243 A>G), RS1000311514 (15:43452363 C>A,T), RS1000313557 (15:43482024 G>A), RS1000317937 (15:43439849 C>A), RS1000323460 (15:43410908 A>C)

Disease associations

OMIM: gene MIM:605230 | disease phenotypes: MIM:616335

GenCC curated gene-disease

Mondo (1): microcephaly and chorioretinopathy 3 (MONDO:0014592)

Orphanet (1): Autosomal recessive chorioretinopathy-microcephaly syndrome (Orphanet:2518)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

28 associations (top):

Study	Trait	p-value
GCST002804_4	Antibody level in response to infection	5.000000e-07
GCST003661_3	Triglycerides	1.000000e-15
GCST004749_36	Lung cancer in ever smokers	4.000000e-06
GCST004963_9	Lipoprotein phospholipase A2 activity in cardiovascular disease	3.000000e-08
GCST006101_8	Cardiometabolic and hematological traits	7.000000e-17
GCST008070_20	HDL cholesterol levels	1.000000e-11
GCST008070_77	HDL cholesterol levels	4.000000e-11
GCST008074_36	Triglyceride levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	3.000000e-33
GCST008074_99	Triglyceride levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	1.000000e-31
GCST008075_155	HDL cholesterol levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	3.000000e-33
GCST008075_16	HDL cholesterol levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	7.000000e-33
GCST008076_26	Triglyceride levels	8.000000e-17
GCST008076_60	Triglyceride levels	4.000000e-16
GCST008083_144	Triglyceride levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	5.000000e-30
GCST008083_77	Triglyceride levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	2.000000e-31
GCST008084_236	HDL cholesterol levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	3.000000e-35
GCST008084_33	HDL cholesterol levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	8.000000e-33
GCST008085_130	HDL cholesterol levels in current drinkers	7.000000e-19
GCST008085_58	HDL cholesterol levels in current drinkers	2.000000e-20
GCST008087_71	Triglyceride levels in current drinkers	8.000000e-29
GCST008087_95	Triglyceride levels in current drinkers	3.000000e-27
GCST010241_121	Apolipoprotein A1 levels	3.000000e-34
GCST010242_527	HDL cholesterol levels	2.000000e-51
GCST90002381_615	Eosinophil count	2.000000e-16
GCST90002383_267	Hematocrit	6.000000e-34
GCST90002384_378	Hemoglobin	2.000000e-35
GCST90002392_425	Mean corpuscular volume	6.000000e-15
GCST90016666_7	Liver volume	8.000000e-34

EFO canonical traits (11, from GWAS)

EFO ID	Trait name
EFO:0007034	seropositivity measurement
EFO:0007038	Influenza A seropositivity
EFO:0004530	triglyceride measurement
EFO:0004746	lipoprotein-associated phospholipase A(2) measurement
EFO:0004309	platelet count
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004329	alcohol drinking
EFO:0004614	apolipoprotein A 1 measurement
EFO:0004842	eosinophil count
EFO:0004348	hematocrit
EFO:0004509	hemoglobin measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2424509 (SINGLE PROTEIN)

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

ChEMBL bioactivities

37 potent at pChembl≥5 of 65 total, top 37 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.77	Kd	170	nM	CHEMBL5439383
6.39	Kd	410	nM	CHEMBL5439383
6.34	IC50	460	nM	CHEMBL5439383
6.33	IC50	470	nM	CHEMBL5403027
6.10	Kd	790	nM	CHEMBL5403027
6.07	IC50	860	nM	CHEMBL5402301
6.07	Kd	850	nM	CHEMBL5403027
5.89	IC50	1300	nM	CHEMBL5431269
5.85	IC50	1400	nM	CHEMBL5433157
5.77	IC50	1690	nM	CHEMBL4746871
5.72	IC50	1900	nM	CHEMBL5415556
5.66	IC50	2200	nM	CHEMBL5423332
5.57	Kd	2690	nM	CHEMBL4746871
5.57	Kd	2700	nM	CHEMBL4746871
5.47	IC50	3400	nM	CHEMBL5440895
5.46	IC50	3500	nM	CHEMBL2426376
5.42	IC50	3800	nM	CHEMBL5421180
5.40	IC50	4000	nM	CHEMBL2426364
5.39	IC50	4100	nM	CHEMBL5430714
5.38	IC50	4200	nM	CHEMBL4740162
5.33	IC50	4700	nM	CHEMBL2426479
5.30	IC50	5000	nM	CHEMBL5440393
5.25	IC50	5600	nM	CHEMBL5397384
5.24	IC50	5700	nM	CHEMBL5400477
5.23	IC50	5900	nM	CHEMBL5397306
5.18	IC50	6600	nM	CHEMBL5395836
5.17	IC50	6800	nM	CHEMBL5428966
5.16	IC50	6900	nM	CHEMBL5439383
5.13	IC50	7400	nM	CHEMBL2426482
5.13	IC50	7400	nM	CHEMBL5429915
5.11	IC50	7800	nM	CHEMBL5412662
5.10	IC50	7900	nM	CHEMBL2426480
5.09	IC50	8100	nM	CHEMBL5418978
5.07	IC50	8500	nM	CHEMBL5403027
5.06	IC50	8700	nM	CHEMBL2426365
5.00	IC50	1e+04	nM	CHEMBL5398002
5.00	IC50	1e+04	nM	CHEMBL5438168

PubChem BioAssay actives

37 with measured affinity, of 183 total; 29 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
(3S)-1-[4-(4-methylpiperazin-1-yl)pyridine-2-carbonyl]-N-[3-(3-oxo-1,2-dihydroisoindol-5-yl)phenyl]piperidine-3-carboxamide	2019093: Binding affinity to N-terminal his6-tagged 53BP1 (1484 to 1603 residues) (unknown origin) expressed in Rosetta2 BL21 (DE3) pLysS competent cells assessed as dissociation constant by SPR analysis	kd	0.1700	uM
(3S)-N-[3-(4-carbamoylphenyl)phenyl]-1-[4-(4-methylpiperazin-1-yl)pyridine-2-carbonyl]piperidine-3-carboxamide	2019092: Displacement of Biotin-p53K381acK382me2 from N-terminal his6-tagged 53BP1 (1484 to 1603 residues) (unknown origin) expressed in Rosetta2 BL21 (DE3) pLysS competent cells by TR-FRET assay	ic50	0.4700	uM
(3S)-1-[4-(4-ethylpiperazin-1-yl)pyridine-2-carbonyl]-N-[3-(3-oxo-1,2-dihydroisoindol-5-yl)phenyl]piperidine-3-carboxamide;dihydrochloride	2019092: Displacement of Biotin-p53K381acK382me2 from N-terminal his6-tagged 53BP1 (1484 to 1603 residues) (unknown origin) expressed in Rosetta2 BL21 (DE3) pLysS competent cells by TR-FRET assay	ic50	0.8600	uM
(3S)-N-[3-(4-carbamoylphenyl)phenyl]-1-[3-(4-methylpiperazin-1-yl)benzoyl]piperidine-3-carboxamide	2019092: Displacement of Biotin-p53K381acK382me2 from N-terminal his6-tagged 53BP1 (1484 to 1603 residues) (unknown origin) expressed in Rosetta2 BL21 (DE3) pLysS competent cells by TR-FRET assay	ic50	1.3000	uM
(3S)-N-[3-(4-carbamoylphenyl)phenyl]-1-[4-(4-ethylpiperazin-1-yl)pyridine-2-carbonyl]piperidine-3-carboxamide;dihydrochloride	2019092: Displacement of Biotin-p53K381acK382me2 from N-terminal his6-tagged 53BP1 (1484 to 1603 residues) (unknown origin) expressed in Rosetta2 BL21 (DE3) pLysS competent cells by TR-FRET assay	ic50	1.4000	uM
(E)-N-[2-(diethylamino)-4-methylquinolin-6-yl]-3-(furan-2-yl)prop-2-enamide	1694458: Inhibition of recombinant human N-terminal His6-tagged 53BP1 TTD (1484 to1603 residues) expressed in Escherichia coli BL21 (DE3) cells using Biotin-H4K2Ome2 as substrate preincubated for 30 mins followed by substrate addition and measured after 30 mins by AlphaScreen assay	ic50	1.6900	uM
(3S)-N-[3-(3-carbamoylphenyl)phenyl]-1-[4-(4-methylpiperazin-1-yl)pyridine-2-carbonyl]piperidine-3-carboxamide	2019092: Displacement of Biotin-p53K381acK382me2 from N-terminal his6-tagged 53BP1 (1484 to 1603 residues) (unknown origin) expressed in Rosetta2 BL21 (DE3) pLysS competent cells by TR-FRET assay	ic50	1.9000	uM
(3S)-N-[3-(4-carbamoylphenyl)phenyl]-1-[4-(4-methylpiperazin-1-yl)pyridine-2-carbonyl]pyrrolidine-3-carboxamide	2019092: Displacement of Biotin-p53K381acK382me2 from N-terminal his6-tagged 53BP1 (1484 to 1603 residues) (unknown origin) expressed in Rosetta2 BL21 (DE3) pLysS competent cells by TR-FRET assay	ic50	2.2000	uM
(3S)-1-[4-(4-methylpiperazin-1-yl)pyridine-2-carbonyl]-N-[3-(1-oxo-2,3-dihydroisoindol-5-yl)phenyl]piperidine-3-carboxamide	2019092: Displacement of Biotin-p53K381acK382me2 from N-terminal his6-tagged 53BP1 (1484 to 1603 residues) (unknown origin) expressed in Rosetta2 BL21 (DE3) pLysS competent cells by TR-FRET assay	ic50	3.4000	uM
2-anilino-N-(2-ethyl-1,3-dihydroisoindol-5-yl)-4-(4-pyrrolidin-2-ylpiperidine-1-carbonyl)benzamide	771613: Inhibition of 53BP1 (unknown origin) after 30 mins by AlphaScreen assay	ic50	3.5000	uM
(3S)-1-[4-(4-methylpiperazin-1-yl)pyridine-2-carbonyl]-N-(3-phenylphenyl)piperidine-3-carboxamide	2019092: Displacement of Biotin-p53K381acK382me2 from N-terminal his6-tagged 53BP1 (1484 to 1603 residues) (unknown origin) expressed in Rosetta2 BL21 (DE3) pLysS competent cells by TR-FRET assay	ic50	3.8000	uM
[3-anilino-4-(4-pyrrolidin-1-ylpiperidine-1-carbonyl)phenyl]-(4-pyrrolidin-1-ylpiperidin-1-yl)methanone	2189755: Inhibition of tudor domain containing 53BP1 (unknown origin) using H4K20me2 peptide by Alpha-Screen methylated histone peptide competition assay	ic50	4.0000	uM
(3S)-N-[3-(4-carbamoylphenyl)phenyl]-1-[4-(4-propan-2-ylpiperazin-1-yl)pyridine-2-carbonyl]piperidine-3-carboxamide;dihydrochloride	2019092: Displacement of Biotin-p53K381acK382me2 from N-terminal his6-tagged 53BP1 (1484 to 1603 residues) (unknown origin) expressed in Rosetta2 BL21 (DE3) pLysS competent cells by TR-FRET assay	ic50	4.1000	uM
(E)-N-[2-(dimethylamino)-4-methylquinolin-6-yl]-3-(furan-2-yl)prop-2-enamide	1694458: Inhibition of recombinant human N-terminal His6-tagged 53BP1 TTD (1484 to1603 residues) expressed in Escherichia coli BL21 (DE3) cells using Biotin-H4K2Ome2 as substrate preincubated for 30 mins followed by substrate addition and measured after 30 mins by AlphaScreen assay	ic50	4.2000	uM
[2-(4-pyrrolidin-1-ylpiperidine-1-carbonyl)phenyl]-(4-pyrrolidin-1-ylpiperidin-1-yl)methanone	771613: Inhibition of 53BP1 (unknown origin) after 30 mins by AlphaScreen assay	ic50	4.7000	uM
(2R)-N-[3-(4-carbamoylphenyl)phenyl]-1-[4-(4-methylpiperazin-1-yl)pyridine-2-carbonyl]pyrrolidine-2-carboxamide	2019092: Displacement of Biotin-p53K381acK382me2 from N-terminal his6-tagged 53BP1 (1484 to 1603 residues) (unknown origin) expressed in Rosetta2 BL21 (DE3) pLysS competent cells by TR-FRET assay	ic50	5.0000	uM
(3S)-N-[3-[4-(methylcarbamoyl)phenyl]phenyl]-1-[4-(4-methylpiperazin-1-yl)pyridine-2-carbonyl]piperidine-3-carboxamide;dihydrochloride	2019092: Displacement of Biotin-p53K381acK382me2 from N-terminal his6-tagged 53BP1 (1484 to 1603 residues) (unknown origin) expressed in Rosetta2 BL21 (DE3) pLysS competent cells by TR-FRET assay	ic50	5.6000	uM
(2S)-N-[3-(4-carbamoylphenyl)phenyl]-1-[4-(4-methylpiperazin-1-yl)pyridine-2-carbonyl]azetidine-2-carboxamide	2019092: Displacement of Biotin-p53K381acK382me2 from N-terminal his6-tagged 53BP1 (1484 to 1603 residues) (unknown origin) expressed in Rosetta2 BL21 (DE3) pLysS competent cells by TR-FRET assay	ic50	5.7000	uM
(3S)-1-[4-(4-methylpiperazin-1-yl)pyridine-2-carbonyl]-N-(5-phenyl-3-pyridinyl)piperidine-3-carboxamide	2019092: Displacement of Biotin-p53K381acK382me2 from N-terminal his6-tagged 53BP1 (1484 to 1603 residues) (unknown origin) expressed in Rosetta2 BL21 (DE3) pLysS competent cells by TR-FRET assay	ic50	5.9000	uM
(3S)-1-[4-(4-methylpiperazin-1-yl)pyridine-2-carbonyl]-N-(3-pyridin-4-ylphenyl)piperidine-3-carboxamide	2019092: Displacement of Biotin-p53K381acK382me2 from N-terminal his6-tagged 53BP1 (1484 to 1603 residues) (unknown origin) expressed in Rosetta2 BL21 (DE3) pLysS competent cells by TR-FRET assay	ic50	6.6000	uM
(3S)-N-[3-(3-oxo-1,2-dihydroisoindol-5-yl)phenyl]-1-[4-(4-propylpiperazin-1-yl)pyridine-2-carbonyl]piperidine-3-carboxamide;dihydrochloride	2019092: Displacement of Biotin-p53K381acK382me2 from N-terminal his6-tagged 53BP1 (1484 to 1603 residues) (unknown origin) expressed in Rosetta2 BL21 (DE3) pLysS competent cells by TR-FRET assay	ic50	6.8000	uM
(3S)-1-[4-(4-methylpiperazin-1-yl)pyridine-2-carbonyl]-N-(6-phenyl-2-pyridinyl)piperidine-3-carboxamide	2019092: Displacement of Biotin-p53K381acK382me2 from N-terminal his6-tagged 53BP1 (1484 to 1603 residues) (unknown origin) expressed in Rosetta2 BL21 (DE3) pLysS competent cells by TR-FRET assay	ic50	7.4000	uM
(4-pyrrolidin-1-ylpiperidin-1-yl)-[4-(4-pyrrolidin-1-ylpiperidin-1-yl)phenyl]methanone	771613: Inhibition of 53BP1 (unknown origin) after 30 mins by AlphaScreen assay	ic50	7.4000	uM
(3S)-N-[3-(2,3-dihydro-1H-indol-5-yl)phenyl]-1-[4-(4-methylpiperazin-1-yl)pyridine-2-carbonyl]piperidine-3-carboxamide;trihydrochloride	2019092: Displacement of Biotin-p53K381acK382me2 from N-terminal his6-tagged 53BP1 (1484 to 1603 residues) (unknown origin) expressed in Rosetta2 BL21 (DE3) pLysS competent cells by TR-FRET assay	ic50	7.8000	uM
[3,4-bis(4-pyrrolidin-1-ylpiperidine-1-carbonyl)phenyl]-(4-pyrrolidin-1-ylpiperidin-1-yl)methanone	771613: Inhibition of 53BP1 (unknown origin) after 30 mins by AlphaScreen assay	ic50	7.9000	uM
4-[3-[[(3S)-1-[4-(4-methylpiperazin-1-yl)pyridine-2-carbonyl]piperidine-3-carbonyl]amino]phenyl]benzoic acid;dihydrochloride	2019092: Displacement of Biotin-p53K381acK382me2 from N-terminal his6-tagged 53BP1 (1484 to 1603 residues) (unknown origin) expressed in Rosetta2 BL21 (DE3) pLysS competent cells by TR-FRET assay	ic50	8.1000	uM
[3-(benzylamino)-4-(4-pyrrolidin-1-ylpiperidine-1-carbonyl)phenyl]-(4-pyrrolidin-1-ylpiperidin-1-yl)methanone	771613: Inhibition of 53BP1 (unknown origin) after 30 mins by AlphaScreen assay	ic50	8.7000	uM
methyl 4-[3-[[(3S)-1-[4-(4-methylpiperazin-1-yl)pyridine-2-carbonyl]piperidine-3-carbonyl]amino]phenyl]benzoate;dihydrochloride	2019092: Displacement of Biotin-p53K381acK382me2 from N-terminal his6-tagged 53BP1 (1484 to 1603 residues) (unknown origin) expressed in Rosetta2 BL21 (DE3) pLysS competent cells by TR-FRET assay	ic50	10.0000	uM
methyl 3-[3-[[(3S)-1-[4-(4-methylpiperazin-1-yl)pyridine-2-carbonyl]piperidine-3-carbonyl]amino]phenyl]benzoate	2019092: Displacement of Biotin-p53K381acK382me2 from N-terminal his6-tagged 53BP1 (1484 to 1603 residues) (unknown origin) expressed in Rosetta2 BL21 (DE3) pLysS competent cells by TR-FRET assay	ic50	10.0000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, increases expression, increases methylation	5
Benzo(a)pyrene	affects methylation, decreases expression, increases expression, increases methylation, decreases reaction	5
sodium arsenite	increases reaction, decreases expression, increases abundance, increases activity, affects binding	3
Doxorubicin	affects response to substance, decreases expression, increases phosphorylation, affects reaction, affects phosphorylation	3
Arsenic	decreases expression, increases abundance	2
Etoposide	decreases reaction, increases expression, affects localization	2
aristolochic acid I	decreases expression	1
AZ10606120	affects localization, decreases reaction, increases expression, increases reaction	1
FR900359	affects phosphorylation	1
bisphenol F	affects cotreatment, decreases expression	1
Cesium-137	affects localization, increases expression, increases reaction, decreases reaction	1
TAK-243	decreases sumoylation	1
geldanamycin	increases expression	1
2,4,6-tribromophenol	decreases expression	1
propylene dichloride	affects localization	1
methylmercuric chloride	increases expression	1
oxybenzone	increases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, decreases expression, increases abundance	1
propylparaben	increases expression	1
4-biphenylamine	decreases reaction, increases expression	1
decabromobiphenyl ether	increases expression	1
trichostatin A	decreases expression	1
beta-lapachone	increases expression	1
pinocembrin	decreases reaction, increases expression	1
4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone	increases expression	1
manganese chloride	decreases expression, increases abundance	1
ochratoxin A	increases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
4-hydroxy-2-nonenal	affects cotreatment, affects expression	1

ChEMBL screening assays

24 unique, capped per target: 24 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2429072	Binding	Inhibition of 53BP1 (unknown origin) after 30 mins by AlphaScreen assay	Small-molecule ligands of methyl-lysine binding proteins: optimization of selectivity for L3MBTL3. — J Med Chem

Cellosaurus cell lines

11 cell lines: 11 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_1R00	HCT116-53BPI(+/-)	Cancer cell line	Male
CVCL_B8R9	Abcam HCT 116 TP53BP1 KO	Cancer cell line	Male
CVCL_B9TN	Abcam A-549 TP53BP1 KO	Cancer cell line	Male
CVCL_D8CS	Ubigene A-549 TP53BP1 KO	Cancer cell line	Male
CVCL_D8XG	Ubigene HCT 116 TP53BP1 KO	Cancer cell line	Male
CVCL_KU12	HeLa SilenciX TP53BP1	Cancer cell line	Female
CVCL_TT38	HAP1 TP53BP1 (-) 1	Cancer cell line	Male
CVCL_TT39	HAP1 TP53BP1 (-) 2	Cancer cell line	Male
CVCL_TT40	HAP1 TP53BP1 (-) 3	Cancer cell line	Male
CVCL_TT41	HAP1 TP53BP1 (-) 4	Cancer cell line	Male

Clinical trials (associated diseases)

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