TP53BP2

Summary

TP53BP2 (tumor protein p53 binding protein 2, HGNC:12000) is a protein-coding gene on chromosome 1q41, encoding Apoptosis-stimulating of p53 protein 2 (Q13625). Regulator that plays a central role in regulation of apoptosis and cell growth via its interactions with proteins such as TP53.

This gene encodes a member of the ASPP (apoptosis-stimulating protein of p53) family of p53 interacting proteins. The protein contains four ankyrin repeats and an SH3 domain involved in protein-protein interactions. It is localized to the perinuclear region of the cytoplasm, and regulates apoptosis and cell growth through interactions with other regulatory molecules including members of the p53 family. Multiple transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 7159 — RefSeq curated summary.

At a glance

• Gene–disease (curated): open-angle glaucoma (Disputed, ClinGen) — +1 more curated relationship
• GWAS associations: 2
• Clinical variants (ClinVar): 187 total
• Druggable target: yes
• MANE Select transcript: NM_001031685

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12000
Approved symbol	TP53BP2
Name	tumor protein p53 binding protein 2
Location	1q41
Locus type	gene with protein product
Status	Approved
Aliases	PPP1R13A, ASPP2, 53BP2
Ensembl gene	ENSG00000143514
Ensembl biotype	protein_coding
OMIM	602143
Entrez	7159

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 7 protein_coding_CDS_not_defined, 5 protein_coding, 2 retained_intron, 1 nonsense_mediated_decay

ENST00000343537, ENST00000391878, ENST00000464172, ENST00000465119, ENST00000472180, ENST00000473135, ENST00000481128, ENST00000483398, ENST00000489310, ENST00000490896, ENST00000494100, ENST00000496282, ENST00000498843, ENST00000863547, ENST00000863548

RefSeq mRNA: 2 — MANE Select: NM_001031685 NM_001031685, NM_005426

CCDS: CCDS1538, CCDS44319

Canonical transcript exons

ENST00000343537 — 18 exons

Exon	Start	End
ENSE00001069694	223803271	223803452
ENSE00001069702	223804174	223804348
ENSE00002238939	223845654	223845947
ENSE00003473562	223814240	223814353
ENSE00003477200	223792389	223792522
ENSE00003480334	223810431	223810513
ENSE00003485410	223821220	223821367
ENSE00003498984	223802731	223802895
ENSE00003510829	223802116	223802344
ENSE00003539869	223806846	223806947
ENSE00003553394	223800700	223800810
ENSE00003571068	223784115	223784314
ENSE00003575113	223799899	223800047
ENSE00003607869	223798215	223798677
ENSE00003619380	223789008	223789174
ENSE00003652660	223793303	223793440
ENSE00003686893	223795815	223796590
ENSE00003841781	223779893	223780894

Expression profiles

Bgee: expression breadth ubiquitous, 283 present calls, max score 94.59.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 21.1533 / max 235.2973, expressed in 1813 samples.

FANTOM5 promoters (14 alternative TSS)

Promoter ID	TPM avg	Samples expressed
17665	15.6972	1805
17664	1.2152	599
17650	1.1702	85
17663	0.9238	474
17651	0.7813	100
17662	0.5311	242
17660	0.2659	82
17653	0.1772	68
17646	0.1320	36
17652	0.0754	43

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ventricular zone	UBERON:0003053	94.59	gold quality
ganglionic eminence	UBERON:0004023	93.90	gold quality
caudate nucleus	UBERON:0001873	93.69	gold quality
putamen	UBERON:0001874	93.40	gold quality
lateral globus pallidus	UBERON:0002476	92.96	gold quality
nucleus accumbens	UBERON:0001882	92.90	gold quality
esophagus squamous epithelium	UBERON:0006920	92.75	gold quality
amygdala	UBERON:0001876	92.57	gold quality
pigmented layer of retina	UBERON:0001782	91.93	gold quality
blood vessel layer	UBERON:0004797	91.90	gold quality
embryo	UBERON:0000922	91.81	gold quality
substantia nigra pars reticulata	UBERON:0001966	91.58	gold quality
colonic epithelium	UBERON:0000397	91.50	gold quality
epithelium of esophagus	UBERON:0001976	91.43	gold quality
sural nerve	UBERON:0015488	91.37	gold quality
amniotic fluid	UBERON:0000173	90.99	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	90.93	gold quality
secondary oocyte	CL:0000655	90.73	gold quality
temporal lobe	UBERON:0001871	90.49	gold quality
bone marrow cell	CL:0002092	90.46	gold quality
trabecular bone tissue	UBERON:0002483	90.44	gold quality
right frontal lobe	UBERON:0002810	90.36	gold quality
CA1 field of hippocampus	UBERON:0003881	90.14	gold quality
cartilage tissue	UBERON:0002418	90.08	gold quality
corpus callosum	UBERON:0002336	89.87	gold quality
bone marrow	UBERON:0002371	89.87	gold quality
descending thoracic aorta	UBERON:0002345	89.83	gold quality
telencephalon	UBERON:0001893	89.52	gold quality
choroid plexus epithelium	UBERON:0003911	89.49	gold quality
right coronary artery	UBERON:0001625	89.33	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F1, E2F2, E2F3, NFKB, NFKBIA, RB1, RELA, TP53, TP63

miRNA regulators (miRDB)

76 targeting TP53BP2, 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-518D-5P	100.00	67.51	979
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954
HSA-MIR-526A-5P	100.00	67.51	979
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-3682-5P	99.93	67.97	1163
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-221-3P	99.86	71.56	1329
HSA-MIR-222-3P	99.86	71.35	1337
HSA-MIR-548BB-3P	99.86	70.58	4354

Literature-anchored findings (GeneRIF, showing 40)

• ASPP2 is a negative regulator of the neddylation pathway through specific interaction with APP-BP1 and suggest that dysfunction of the APP-BP1 interaction with APP may be one cause of Alzheimer’s disease (PMID:12694406)
• TP53BP2 encodes two mRNA species, either with (53BP2) or without exon 3 (ASPP2), by alternative splicing in various cell lines and tissues (PMID:14766226)
• downstream of E2F, suggesting that it functions as a common link between the p53/p73 and Rb/E2F apoptotic pathways (PMID:15592436)
• target of E2F transcription factor (PMID:15731768)
• ASPP2 CpG island aberrant methylation could be one molecular and genetic alteration in wild-type p53 tumours. (PMID:15757645)
• Mdm2 and mdmx prevent ASPP1 and ASPP2 from stimulating the apoptotic function of p53 by binding and inhibiting the transcriptional activity of p53. (PMID:15782125)
• results suggest that the tumor protein p53 binding protein(TP53BP2) locus is associated with susceptibility to gastric cancer in the Korean population (PMID:15986435)
• ASPP2/(53BP2L) expression regulation by proteasomal degradation modulates p53 apoptotic function (PMID:16091363)
• In this study we explored the effect of NF-kappaB activation elicited by a physiological NF-kappaB inducer, interleukin-1beta (IL-1beta), and anti-apoptotic Bcl-2 family proteins on the 53BP2S-mediated apoptosis (PMID:16098144)
• role of ASPP1, ASPP2, and iASPP as apoptotic specific regulators of p53 [review] (PMID:16139958)
• suggest a possible role for the N-termini of ASPP proteins in binding to other proteins in the apoptotic response network (PMID:17594908)
• 53BP2S interacts and modulates the insulin signals mediated by insulin receptor substrates. (PMID:17965023)
• identifies the interaction sites of Bcl-2 and its homologues with ASPP2 (PMID:18719108)
• Together these results identify ASPP2 as a bona fide DDA3 interacting protein, and suggest that the ASPP2/DDA3 interaction may inhibit ASPP2 in stimulating the apoptotic signaling of p53. (PMID:18793611)
• ASPP2 primarily binds to the core domain of p53, whereas iASPP predominantly interacts with a linker region adjacent to the core domain. (PMID:19246451)
• ASPP2(ANK-SH3) binds NFkappaB(p65) in a similar manner to its natural inhibitor IkappaB, suggesting a possible novel role for ASPP2 as an NFkappaB inhibitor (PMID:19507243)
• bcl2 -938C/C genotype has worse prognosis and lower survival in patients with renal cell carcinoma. In addition, the bcl2 -938C/A single nucleotide polymorphism was shown to be an independent adverse prognostic factor for renal cell carcinoma (PMID:19539330)
• ASPP1 and ASPP2 genes are frequently down-regulated by DNA methylation in HBV-positive hepatocellular carcinoma, which may play important roles in the development of HCC (PMID:20034025)
• study was to determine localization pattern of ASPP-2 in a variety of normal and malignant human tissues; study indicates that ASPP-2 has a specific distribution pattern within tissues and cells in a way that appears to be related to differentiation (PMID:21183427)
• PP1A and ASPP2 play a critical role in promoting TAZ function by antagonizing the LATS kinase through TAZ dephosphorylation. (PMID:21189257)
• Helicobacter pylori cytotoxin-associated gene A (CagA) subverts the apoptosis-stimulating protein of p53 (ASPP2) tumor suppressor pathway of the host (PMID:21562218)
• Methylation in the promoter region of ASPP2 gene was not detected in lung cancer or adjacent non-neoplastic lung tissue. (PMID:22169642)
• the mRNA expression of ASPP1 and ASPP2 was frequently dowregulated in tumor tissues, and this decreased significantly in samples expressing wild-type p53 (PMID:22552744)
• When the Px(T)PxR motif is deleted or mutated via insertion of a phosphorylation site mimic (T311D), PP-1c fails to bind to all three ASPP proteins, ASPP1, ASPP2 and iASPP. (PMID:23088536)
• ASPP2 binds to Ras-GTP at the plasma membrane and stimulates Ras-induced signaling and pERK1/2 levels via promoting Ras-GTP loading, B-Raf/C-Raf dimerization, and C-Raf phosphorylation. (PMID:23248303)
• ASPP1 and ASPP2 cooperate with RAS to enhance p53-induced apoptosis suggests that loss of ASPP1 or ASPP2 expression may be a frequent event in human cancers with mutant RAS. (PMID:23392125)
• the intramolecular interaction in ASPP2 regulates its binding to p53CD and ASPP2 Ank-SH3 binds Bcl-2 and NFkappaB via distinct sites (PMID:23472201)
• higher rate Helicobacter pylori infection, an increased expression of inhibitor of apoptosis stimulating protein of p53 (iASPP), and decreased expression of apoptosis-stimulating of p53 protein 2(ASPP2) was present in gastric cancer (PMID:23528480)
• FIH-1 depletion did lead to impaired binding of Par-3 to ASPP2. (PMID:23606740)
• our studies demonstrate the role of Siah2 in regulation of tight junction integrity and cell polarity under hypoxia, through its regulation of ASPP2 stability. (PMID:23644657)
• We also unveiled a possible mechanistic link between ASPP2 and Csk/Src signaling pathway, implicating the multiple cellular functions of ASPP2. (PMID:23671128)
• Attenuated expression of apoptosis stimulating protein of p53-2 (ASPP2) in human acute leukemia is associated with therapy failure. (PMID:24312201)
• phosphorylation of ASPP2 by RAS/MAPK pathway provides a novel link between RAS and p53 in regulating apoptosis (PMID:24312625)
• Disruption of CagA and ASPP2 binding alters the function of ASPP2 and leads to the decreased survival of H. pylori-infected cells (PMID:24474782)
• CHOP is critical for mediating ASPP2-induced autophagic apoptosis by decreasing Bcl-2 expression and maintaining nuclear ASPP2-Bcl-2 complexes. (PMID:25032846)
• ASPP2 may participate in the lipid metabolism of non-alcoholic steatohepatitis and attenuate liver failure. (PMID:25256142)
• ASPP2 prevents beta-catenin from transactivating ZEB1 directly by forming an ASPP2-beta-catenin-E-cadherin ternary complex (PMID:25344754)
• ASPP2 directly induces the dephosphorylation and activation of junctional YAP (PMID:25360797)
• these observations reveal that Itch and Yap1 have antagonistic roles in the regulation of ASPP2 protein stability through competing post-translational regulatory mechanism of ASPP2. (PMID:25436413)
• this study revealed a novel function of ASPP2 in modulating autophagy and apoptosis. (PMID:25534115)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	tp53bp2a	ENSDARG00000009136
danio_rerio	tp53bp2b	ENSDARG00000054858
mus_musculus	Trp53bp2	ENSMUSG00000026510
rattus_norvegicus	Tp53bp2	ENSRNOG00000003237
drosophila_melanogaster	ASPP	FBGN0034606
caenorhabditis_elegans		WBGENE00000146

Paralogs (1): PPP1R13B (ENSG00000088808)

Protein

Protein identifiers

Apoptosis-stimulating of p53 protein 2 — Q13625 (reviewed: Q13625)

Alternative names: Bcl2-binding protein, Renal carcinoma antigen NY-REN-51, Tumor suppressor p53-binding protein 2

All UniProt accessions (3): Q13625, H0Y847, H7C5L8

UniProt curated annotations — full annotation on UniProt →

Function. Regulator that plays a central role in regulation of apoptosis and cell growth via its interactions with proteins such as TP53. Regulates TP53 by enhancing the DNA binding and transactivation function of TP53 on the promoters of proapoptotic genes in vivo. Inhibits the ability of NAE1 to conjugate NEDD8 to CUL1, and thereby decreases NAE1 ability to induce apoptosis. Impedes cell cycle progression at G2/M. Its apoptosis-stimulating activity is inhibited by its interaction with DDX42.

Subunit / interactions. Interacts with P53/TP53; the interaction promotes pro-apoptotic activity. Interacts with BCL2. Interacts with protein phosphatase 1. Interacts with RELA NF-kappa-B subunit. This interaction probably prevents the activation of apoptosis, possibly by preventing its interaction with TP53. Interacts with APC2 and NAE1. Interacts with DDX42 (via the C-terminus); the interaction is not inhibited by TP53BP2 ubiquitination and is independent of p53/TP53.

Subcellular location. Cytoplasm. Perinuclear region. Nucleus.

Tissue specificity. Widely expressed. Expressed in spleen, thymus, prostate, testis, ovary, small intestine, colon and peripheral blood leukocyte. Reduced expression in breast carcinomas expressing a wild-type TP53 protein. Overexpressed in lung cancer cell lines.

Domain organisation. The ankyrin repeats and the SH3 domain are required for a specific interactions with TP53.

Induction. Following DNA damage induced by UV irradiation. Down-regulated by wild-type, but not mutant, p53/TP53.

Miscellaneous. Due to Alu sequence insertion that creates a shorter but existing form that may have an alternative function.

Similarity. Belongs to the ASPP family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q13625-1	1	yes
Q13625-2	2, Bbp
Q13625-3	3

RefSeq proteins (2): NP_001026855, NP_005417 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001452	SH3_domain	Domain
IPR002110	Ankyrin_rpt	Repeat
IPR029071	Ubiquitin-like_domsf	Homologous_superfamily
IPR036028	SH3-like_dom_sf	Homologous_superfamily
IPR036770	Ankyrin_rpt-contain_sf	Homologous_superfamily
IPR047163	ASPP1/2	Family
IPR047166	ASPP2_RA	Domain
IPR048942	ASPP2-like_RA	Domain

Pfam: PF00018, PF12796, PF21801

UniProt features (64 total): strand 13, helix 13, region of interest 8, modified residue 8, compositionally biased region 6, turn 6, repeat 4, splice variant 2, chain 1, short sequence motif 1, mutagenesis site 1, domain 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
6HKP	X-RAY DIFFRACTION	1.9
4IRV	X-RAY DIFFRACTION	2.04
6GHM	X-RAY DIFFRACTION	2.15
1YCS	X-RAY DIFFRACTION	2.2
4A63	X-RAY DIFFRACTION	2.27
2UWQ	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q13625-F1	59.81	0.18

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 (8): 480, 556, 569, 572, 576, 698, 714, 737

Mutagenesis-validated functional residues (1):

Position	Phenotype
1098	loss of interaction with apc2.

Function

Pathways and Gene Ontology

Reactome pathways

15 pathways

ID	Pathway
R-HSA-139915	Activation of PUMA and translocation to mitochondria
R-HSA-6803204	TP53 Regulates Transcription of Genes Involved in Cytochrome C Release
R-HSA-6803205	TP53 regulates transcription of several additional cell death genes whose specific roles in p53-dependent apoptosis remain uncertain
R-HSA-6803211	TP53 Regulates Transcription of Death Receptors and Ligands
R-HSA-6804759	Regulation of TP53 Activity through Association with Co-factors
R-HSA-109581	Apoptosis
R-HSA-109606	Intrinsic Pathway for Apoptosis
R-HSA-114452	Activation of BH3-only proteins
R-HSA-212436	Generic Transcription Pathway
R-HSA-3700989	Transcriptional Regulation by TP53
R-HSA-5357801	Programmed Cell Death
R-HSA-5633007	Regulation of TP53 Activity
R-HSA-5633008	TP53 Regulates Transcription of Cell Death Genes
R-HSA-73857	RNA Polymerase II Transcription
R-HSA-74160	Gene expression (Transcription)

MSigDB gene sets: 219 (showing top): PATIL_LIVER_CANCER, CHIBA_RESPONSE_TO_TSA_DN, GOBP_APOPTOTIC_SIGNALING_PATHWAY, GOBP_NEGATIVE_REGULATION_OF_CELL_CYCLE, LI_WILMS_TUMOR_VS_FETAL_KIDNEY_1_DN, GOBP_REGULATION_OF_CELL_CYCLE, DACOSTA_UV_RESPONSE_VIA_ERCC3_COMMON_DN, GOBP_INTRINSIC_APOPTOTIC_SIGNALING_PATHWAY, SCHLOSSER_SERUM_RESPONSE_DN, GOBP_SIGNAL_TRANSDUCTION_BY_P53_CLASS_MEDIATOR, LAU_APOPTOSIS_CDKN2A_UP, PID_P53_DOWNSTREAM_PATHWAY, GOBP_INTRINSIC_APOPTOTIC_SIGNALING_PATHWAY_BY_P53_CLASS_MEDIATOR, REACTOME_APOPTOSIS, OSAWA_TNF_TARGETS

GO Biological Process (6): signal transduction (GO:0007165), negative regulation of cell cycle (GO:0045786), intrinsic apoptotic signaling pathway by p53 class mediator (GO:0072332), positive regulation of execution phase of apoptosis (GO:1900119), apoptotic process (GO:0006915), regulation of apoptotic process (GO:0042981)

GO Molecular Function (6): p53 binding (GO:0002039), SH3 domain binding (GO:0017124), identical protein binding (GO:0042802), protein homodimerization activity (GO:0042803), NF-kappaB binding (GO:0051059), protein binding (GO:0005515)

GO Cellular Component (6): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), cell junction (GO:0030054), perinuclear region of cytoplasm (GO:0048471)

Reactome top-level categories

Rollup of top-10 pathways:

Category	Pathways
TP53 Regulates Transcription of Cell Death Genes	3
Transcriptional Regulation by TP53	2
Activation of BH3-only proteins	1
Regulation of TP53 Activity	1
Programmed Cell Death	1
Apoptosis	1
Intrinsic Pathway for Apoptosis	1
RNA Polymerase II Transcription	1
Generic Transcription Pathway	1
Gene expression (Transcription)	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
execution phase of apoptosis	2
protein binding	2
cytoplasm	2
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
cell cycle	1
negative regulation of cellular process	1
regulation of cell cycle	1
signal transduction by p53 class mediator	1
intrinsic apoptotic signaling pathway	1
positive regulation of apoptotic process	1
regulation of execution phase of apoptosis	1
programmed cell death	1
apoptotic signaling pathway	1
apoptotic process	1
regulation of programmed cell death	1
protein domain specific binding	1
identical protein binding	1
protein dimerization activity	1
RNA polymerase II-specific DNA-binding transcription factor binding	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

996 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TP53BP2	TP53	P04637	996
TP53BP2	BCL2	P10415	975
TP53BP2	DDX42	Q86XP3	897
TP53BP2	S100A8	P05109	835
TP53BP2	BAD	Q92934	774
TP53BP2	HERC1	Q15751	769
TP53BP2	TP53BP1	Q12888	756
TP53BP2	LGALS3	P17931	679
TP53BP2	BAG1	Q99933	630
TP53BP2	RASSF8	Q8NHQ8	623
TP53BP2	RASSF7	Q02833	611
TP53BP2	PPP1CB	P37140	578
TP53BP2	NEDD4	P46934	571
TP53BP2	CDH1	P12830	553
TP53BP2	AKT1	P31749	546

IntAct

251 interactions, top by confidence:

A	B	Type	Score
CEP97	CCP110	psi-mi:“MI:2364”(proximity)	0.950
PPP1CC	TP53BP2	psi-mi:“MI:0915”(physical association)	0.920
TP53	TP53BP2	psi-mi:“MI:0407”(direct interaction)	0.900
TP53	TP53BP2	psi-mi:“MI:0915”(physical association)	0.900
TP53BP2	TP53	psi-mi:“MI:0915”(physical association)	0.900
MED4	MED19	psi-mi:“MI:2364”(proximity)	0.900
TP53BP2	PPP1CA	psi-mi:“MI:0915”(physical association)	0.890
SGF29	NDC80	psi-mi:“MI:0914”(association)	0.840
YWHAH	ABLIM1	psi-mi:“MI:0914”(association)	0.800
PRPF19	AQR	psi-mi:“MI:0914”(association)	0.790
YAP1	MPDZ	psi-mi:“MI:0914”(association)	0.780
TP53BP2	YWHAZ	psi-mi:“MI:0915”(physical association)	0.760
PPP1CB	CCDC85C	psi-mi:“MI:0914”(association)	0.750
PPP1CB	CCDC85C	psi-mi:“MI:2364”(proximity)	0.750
BECN1	ZWINT	psi-mi:“MI:0914”(association)	0.750
PPP1CC	CCDC85C	psi-mi:“MI:0914”(association)	0.740
PPP1CC	CCDC85C	psi-mi:“MI:2364”(proximity)	0.740
HOMER1	TRAF5	psi-mi:“MI:0914”(association)	0.740
YWHAH	FAM83G	psi-mi:“MI:0914”(association)	0.710
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
TP53BP2	BCL2L2	psi-mi:“MI:0407”(direct interaction)	0.680

BioGRID (390): BCL2 (Reconstituted Complex), TP53BP2 (Protein-peptide), TP53BP2 (Protein-peptide), TP53BP2 (Co-crystal Structure), TP53BP2 (Two-hybrid), TP53BP2 (Two-hybrid), TP53BP2 (Two-hybrid), TP53BP2 (Two-hybrid), TP53BP2 (Two-hybrid), ZNF26 (Two-hybrid), TCL1A (Two-hybrid), HIST1H2BC (Two-hybrid), LMO4 (Two-hybrid), TRAF4 (Two-hybrid), TANK (Two-hybrid)

ESM2 similar proteins: A0A1L8GR68, A2CG63, E9Q9M8, F7AQ22, G3V8T1, O75152, O75376, P49140, P51826, P97432, Q13625, Q14596, Q17R98, Q1LY51, Q3TYA6, Q4KKX4, Q4LE39, Q4R6F6, Q501R9, Q505G8, Q5F3Z9, Q5HYC2, Q5RC94, Q5XJV7, Q60974, Q68FE8, Q69Z61, Q6A098, Q6NXK2, Q6NZF1, Q6PJT7, Q6ZNC4, Q86YI8, Q8BFU3, Q8BJ05, Q8CCH7, Q8CG79, Q8CHY6, Q8K2W6, Q8ND24

Diamond homologs: O35179, P19706, P29355, P42683, P62993, P62994, Q13625, Q5I1X5, Q5R4J7, Q60631, Q62415, Q66II3, Q6CHN0, Q6GPJ9, Q8AXU9, Q8AXV0, Q8AXV1, Q8CG79, Q8R550, Q8TC17, Q8WUF5, Q925Q9, Q96B97, Q96KQ4, Q9NR80, Q9XVN3, A0A8I3PDQ1, A0JNB0, A1Y2K1, A5GFW5, A6QLK6, O35177, O42287, O43281, P06241, P0C550, P10569, P14234, P27447, P34109

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
TP53BP2	up-regulates	TP53	binding
TP53BP2	down-regulates	PPP1R14A	binding
MAPK1	“up-regulates activity”	TP53BP2	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 147 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
Activation of BAD and translocation to mitochondria	8	59.7×	4e-11
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	7	46.1×	3e-09
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	7	46.1×	3e-09
Activation of BH3-only proteins	8	38.9×	1e-09
RHO GTPases activate PKNs	9	28.0×	1e-09
Intrinsic Pathway for Apoptosis	9	25.8×	3e-09
Anchoring of the basal body to the plasma membrane	18	19.9×	4e-16
Loss of Nlp from mitotic centrosomes	12	18.7×	2e-10

GO biological processes:

GO term	Partners	Fold	FDR
centriole replication	7	38.6×	2e-07
release of cytochrome c from mitochondria	7	37.0×	2e-07
centrosome cycle	8	20.3×	2e-06
protein targeting	7	19.3×	2e-05
regulation of cytokinesis	5	15.8×	2e-03
intracellular protein localization	17	13.4×	1e-11
non-motile cilium assembly	6	13.1×	1e-03
cellular response to glucose starvation	5	12.7×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	132
Likely benign	14
Benign	16

Top pathogenic / likely-pathogenic (0)

SpliceAI

2935 predictions. Top by Δscore:

Variant	Effect	Δscore
1:223784113:A:AC	donor_gain	1.0000
1:223784113:ACT:A	donor_gain	1.0000
1:223784113:ACTC:A	donor_gain	1.0000
1:223784114:C:CC	donor_gain	1.0000
1:223784114:CT:C	donor_gain	1.0000
1:223784114:CTC:C	donor_gain	1.0000
1:223784114:CTCC:C	donor_gain	1.0000
1:223784116:C:CA	donor_gain	1.0000
1:223784138:ATC:A	donor_gain	1.0000
1:223784143:T:TA	donor_gain	1.0000
1:223784149:T:C	donor_gain	1.0000
1:223784166:C:CT	donor_gain	1.0000
1:223784192:C:A	donor_gain	1.0000
1:223792382:ATCTT:A	donor_loss	1.0000
1:223792383:TCTTA:T	donor_loss	1.0000
1:223792385:TTA:T	donor_loss	1.0000
1:223792386:TAC:T	donor_loss	1.0000
1:223792387:A:C	donor_loss	1.0000
1:223792443:A:C	donor_gain	1.0000
1:223792520:AACCT:A	acceptor_loss	1.0000
1:223792521:ACC:A	acceptor_loss	1.0000
1:223792523:C:CA	acceptor_loss	1.0000
1:223792524:T:G	acceptor_loss	1.0000
1:223793297:TCATA:T	donor_loss	1.0000
1:223793298:CATAC:C	donor_loss	1.0000
1:223793299:ATAC:A	donor_loss	1.0000
1:223793300:TACCT:T	donor_loss	1.0000
1:223793301:A:AT	donor_loss	1.0000
1:223793302:CCT:C	donor_gain	1.0000
1:223793337:C:CA	donor_gain	1.0000

AlphaMissense

7459 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000024442 (1:223824259 C>T), RS1000160942 (1:223833395 A>C), RS1000204004 (1:223826870 T>C), RS1000204087 (1:223786807 C>G), RS1000291793 (1:223797589 T>C), RS1000372218 (1:223789773 G>A,C), RS1000425716 (1:223828270 A>G), RS1000447643 (1:223839489 T>C), RS1000451745 (1:223840981 G>A), RS1000457009 (1:223827802 A>T), RS1000546852 (1:223782703 T>C), RS1000571892 (1:223789821 A>C), RS1000669410 (1:223838307 A>T), RS1000677777 (1:223803842 G>A), RS1000680165 (1:223790013 G>A)

Disease associations

OMIM: gene MIM:602143 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
Tourette syndrome	No Known Disease Relationship	Unknown

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
open-angle glaucoma	Disputed	AD

Mondo (1): Tourette syndrome (MONDO:0007661)

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST003008_3	Triptolide cytotoxicity	9.000000e-06
GCST90013407_58	Liver enzyme levels (gamma-glutamyl transferase)	7.000000e-17

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0006952	cytotoxicity measurement
EFO:0004532	serum gamma-glutamyl transferase measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D005879	Tourette Syndrome	C10.228.140.079.898; C10.228.662.825.800; C10.574.500.850; C16.320.400.820; F03.625.992.850

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4742293 (PROTEIN-PROTEIN INTERACTION)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol S	decreases methylation, increases expression, affects cotreatment	3
bisphenol A	decreases expression, increases expression, affects cotreatment	2
sodium arsenite	increases expression, decreases expression	2
Resveratrol	increases expression, decreases expression, affects cotreatment	2
Benzo(a)pyrene	decreases expression, increases methylation	2
Paraquat	increases expression	2
Tunicamycin	decreases expression, increases expression	2
Cyclosporine	increases expression	2
Cadmium Chloride	decreases expression, increases abundance, increases expression	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
bisphenol F	increases expression	1
naringenin	affects cotreatment, increases expression	1
kojic acid	increases expression	1
arsenite	affects binding, decreases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
coumarin	increases phosphorylation	1
beta-methylcholine	affects expression	1
polyhexamethyleneguanidine	increases expression	1
di-n-butylphosphoric acid	affects expression	1
2,3,5-(triglutathion-S-yl)hydroquinone	increases ADP-ribosylation	1
CGP 52608	affects binding, increases reaction	1
oxidized-L-alpha-1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine	affects expression, increases reaction	1
abrine	increases expression	1
Acetaminophen	increases expression	1
Vehicle Emissions	affects expression, increases reaction	1
Cadmium	increases abundance, decreases expression	1
Caffeine	increases phosphorylation	1
Dexamethasone	affects cotreatment, increases expression	1
Drugs, Chinese Herbal	increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4713748	Binding	Protac activity at CRBN/TP53BP2 in human BxPC-3 cells assessed as TP53BP2 degradation incubated for 16 hrs by proteomic analysis	Discovery of a Napabucasin PROTAC as an Effective Degrader of the E3 Ligase ZFP91. — J Med Chem

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_TT43	HAP1 TP53BP2 (-) 1	Cancer cell line	Male
CVCL_TT44	HAP1 TP53BP2 (-) 2	Cancer cell line	Male
CVCL_TT45	HAP1 TP53BP2 (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00152750	PHASE4	UNKNOWN	Study of Clonidine on Sleep Architecture in Children With Tourette’s Syndrome (TS) and Comorbid ADHD
NCT00226824	PHASE4	TERMINATED	Safety Study of Galantamine in Tic Disorders
NCT00241176	PHASE4	COMPLETED	Open Label Trial of Aripiprazole in Children and Adolescents With Tourette’s Disorder
NCT00370838	PHASE4	COMPLETED	Comparison of Keppra and Clonidine in the Treatment of Tics
NCT01018056	PHASE4	COMPLETED	Developing New Treatments for Tourette Syndrome: Therapeutic Trials With Modulators of Glutamatergic Neurotransmission
NCT01547000	PHASE4	COMPLETED	Guanfacine in Children With Tic Disorders
NCT03239210	PHASE4	COMPLETED	Effects of Ondansetron in Obsessive-compulsive and Tic Disorders
NCT00004376	PHASE3	COMPLETED	Phase III Randomized, Double-Blind, Placebo-Controlled Study of Guanfacine for Tourette Syndrome and Attention Deficit Hyperactivity Disorder
NCT00206323	PHASE3	COMPLETED	A Randomized, Placebo-controlled, Tourette Syndrome Study.
NCT00206336	PHASE3	COMPLETED	An Open-label Study to Determine the Efficacy and Safety of Topiramate in the Treatment of Tourette Syndrome.
NCT00478842	PHASE3	COMPLETED	Pallidal Stimulation and Gilles de la Tourette Syndrome
NCT00681863	PHASE3	TERMINATED	Open-label Extension Study of Pramipexole in the Treatment of Children and Adolescents With Tourette Syndrome
NCT01501695	PHASE3	COMPLETED	Phase III Study of 5LGr to Treat Tic Disorder
NCT03087201	PHASE3	COMPLETED	CANNAbinoids in the Treatment of TICS (CANNA-TICS)
NCT03487783	PHASE3	COMPLETED	Aripiprazole Oral Solution in the Treatment of Children and Adolescents With Tourette’s Syndrome
NCT03567291	PHASE3	TERMINATED	Evaluation of Safety and Tolerability of Long-term TEV-50717 (Deutetrabenazine) for Treatment of Tourette Syndrome in Children and Adolescents
NCT03571256	PHASE3	COMPLETED	A Study to Test if TEV-50717 is Effective in Relieving Tics Associated With Tourette Syndrome (TS)
NCT06021522	PHASE3	ACTIVE_NOT_RECRUITING	A Study to Evaluate Long-term Safety of Ecopipam Tablets in Children, Adolescents and Adults With Tourette’s Disorder
NCT00004393	PHASE2	COMPLETED	Phase II Double Blind Placebo Controlled Trial of Risperidone in Tourette Syndrome
NCT00004652	PHASE2	COMPLETED	Phase II Pilot Controlled Study of Short Vs Longer Term Pimozide (Orap) Therapy in Tourette Syndrome
NCT00231985	PHASE2	COMPLETED	Effectiveness of Behavior Therapy and Psychosocial Therapy for the Treatment of Tourette Syndrome and Chronic Tic Disorder
NCT00311909	PHASE2	COMPLETED	Thalamic Deep Brain Stimulation for Tourette Syndrome
NCT00529308	PHASE2	COMPLETED	Transcranial Magnetic Stimulation (TMS) for Individuals With Tourette’s Syndrome
NCT00558467	PHASE2	COMPLETED	Pramipexole Pilot Phase II Study in Children and Adolescents With Tourette Disorder According to DSM-IV Criteria
NCT01043549	PHASE2	TERMINATED	Repetitive Transcranial Magnetic Stimulation of the Posterior Parietal Cortex in Patients Suffering From Gilles de la Tourette Syndrome
NCT01133353	PHASE2	WITHDRAWN	A Study of the Effectiveness and Safety of Tetrabenazine MR in Pediatric Subjects With Tourette’s Syndrome
NCT01475383	PHASE2	WITHDRAWN	Study Evaluating The Safety And Efficacy Of PF-03654746 In Adult Subjects With Tourette’s Syndrome
NCT01647269	PHASE2	COMPLETED	A Trial of Bilateral Deep Brain Stimulation to the Globus Pallidus Internum in Tourette Syndrome
NCT01904773	PHASE2	COMPLETED	Safety, Tolerability, Pharmacokinetic, and Efficacy Study of AZD5213 in Adolescents With Tourette’s Disorder
NCT02102698	PHASE2	COMPLETED	Ecopipam Treatment of Tourette’s Syndrome in Subjects 7-17 Years
NCT02217007	PHASE2	WITHDRAWN	A Trial Evaluating the Efficacy, Safety, and Pharmacokinetics of SNC-102 in Subjects With Tourette Syndrome
NCT02247206	PHASE2	COMPLETED	VoIP Delivered Behavior Therapy for Tourette Syndrome
NCT02581865	PHASE2	COMPLETED	Safety and Efficacy Study of NBI-98854 in Adults With Tourette Syndrome
NCT02619084	PHASE2	COMPLETED	Subthalamic Stimulation in Tourette’s Syndrome
NCT02679079	PHASE2	COMPLETED	Safety and Efficacy Study of NBI-98854 in Children and Adolescents With Tourette Syndrome
NCT02879578	PHASE2	COMPLETED	Safety and Tolerability Study of NBI-98854 for the Treatment of Subjects With Tourette Syndrome
NCT03066193	PHASE2	COMPLETED	Efficacy of a Therapeutic Combination of Dronabinol and PEA for Tourette Syndrome
NCT03247244	PHASE2	TERMINATED	Safety and Efficacy of Cannabis in Tourette Syndrome
NCT03325010	PHASE2	COMPLETED	Safety, Tolerability, and Efficacy of NBI-98854 for the Treatment of Pediatric Subjects With Tourette Syndrome
NCT03444038	PHASE2	COMPLETED	Open-Label Safety and Tolerability Study of NBI-98854 for the Treatment of Pediatric Subjects With Tourette Syndrome