PARP3

Summary

PARP3 (poly(ADP-ribose) polymerase family member 3, HGNC:273) is a protein-coding gene on chromosome 3p21.2, encoding Protein mono-ADP-ribosyltransferase PARP3 (Q9Y6F1). Mono-ADP-ribosyltransferase that mediates mono-ADP-ribosylation of target proteins and plays a key role in the response to DNA damage.

The protein encoded by this gene belongs to the PARP family. These enzymes modify nuclear proteins by poly-ADP-ribosylation, which is required for DNA repair, regulation of apoptosis, and maintenance of genomic stability. This gene encodes the poly(ADP-ribosyl)transferase 3, which is preferentially localized to the daughter centriole throughout the cell cycle. Alternatively spliced transcript variants encoding different isoforms have been identified.

Source: NCBI Gene 10039 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 113 total
• Druggable target: yes — 8 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001003931

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:273
Approved symbol	PARP3
Name	poly(ADP-ribose) polymerase family member 3
Location	3p21.2
Locus type	gene with protein product
Status	Approved
Aliases	ADPRT3, IRT1, hPARP-3, pADPRT-3, ARTD3
Ensembl gene	ENSG00000041880
Ensembl biotype	protein_coding
OMIM	607726
Entrez	10039

Gene structure

Transcript identifiers

Ensembl transcripts: 34 — 30 protein_coding, 3 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000398755, ENST00000417220, ENST00000431474, ENST00000470601, ENST00000470749, ENST00000471971, ENST00000475782, ENST00000486510, ENST00000498510, ENST00000910651, ENST00000910652, ENST00000910653, ENST00000910654, ENST00000910655, ENST00000910656, ENST00000910657, ENST00000910658, ENST00000910659, ENST00000910660, ENST00000910661, ENST00000910662, ENST00000919554, ENST00000949103, ENST00000949104, ENST00000949105, ENST00000949106, ENST00000949107, ENST00000949108, ENST00000949109, ENST00000949110, ENST00000949111, ENST00000949112, ENST00000949113, ENST00000949114

RefSeq mRNA: 4 — MANE Select: NM_001003931 NM_001003931, NM_001370239, NM_001370240, NM_005485

CCDS: CCDS43097

Canonical transcript exons

ENST00000398755 — 11 exons

Exon	Start	End
ENSE00001232749	51948311	51948867
ENSE00001850852	51942363	51942708
ENSE00002261288	51943354	51943538
ENSE00003475174	51944998	51945224
ENSE00003545084	51944778	51944910
ENSE00003551862	51946166	51946343
ENSE00003577798	51945495	51945644
ENSE00003608554	51944089	51944217
ENSE00003625548	51944390	51944578
ENSE00003632493	51947740	51947895
ENSE00003636597	51945853	51945939

Expression profiles

Bgee: expression breadth ubiquitous, 214 present calls, max score 94.59.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 7.3350 / max 54.2742, expressed in 1662 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
36786	5.1222	1558
36785	1.1617	753
36791	0.6672	355
36790	0.3838	220

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right adrenal gland cortex	UBERON:0035827	94.59	gold quality
right adrenal gland	UBERON:0001233	94.37	gold quality
left adrenal gland	UBERON:0001234	93.77	gold quality
left adrenal gland cortex	UBERON:0035825	93.66	gold quality
right lobe of liver	UBERON:0001114	93.10	gold quality
apex of heart	UBERON:0002098	91.70	gold quality
adrenal cortex	UBERON:0001235	91.58	gold quality
right lobe of thyroid gland	UBERON:0001119	91.29	gold quality
small intestine Peyer’s patch	UBERON:0003454	91.27	gold quality
metanephros cortex	UBERON:0010533	91.25	gold quality
left lobe of thyroid gland	UBERON:0001120	90.66	gold quality
adrenal gland	UBERON:0002369	90.30	gold quality
muscle layer of sigmoid colon	UBERON:0035805	89.69	gold quality
lower esophagus muscularis layer	UBERON:0035833	89.43	gold quality
lower esophagus	UBERON:0013473	89.42	gold quality
transverse colon	UBERON:0001157	89.32	gold quality
thyroid gland	UBERON:0002046	89.25	gold quality
small intestine	UBERON:0002108	89.24	gold quality
stromal cell of endometrium	CL:0002255	87.74	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	87.67	gold quality
body of stomach	UBERON:0001161	87.49	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	87.30	gold quality
minor salivary gland	UBERON:0001830	87.13	gold quality
mucosa of stomach	UBERON:0001199	87.11	gold quality
gall bladder	UBERON:0002110	86.92	gold quality
omental fat pad	UBERON:0010414	86.81	gold quality
peritoneum	UBERON:0002358	86.72	gold quality
left coronary artery	UBERON:0001626	86.49	gold quality
tibial nerve	UBERON:0001323	86.42	gold quality
spleen	UBERON:0002106	86.32	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.39

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 20)

• PARP-3 is a nuclear protein involved in transcriptional silencing and in the cellular response to DNA damage (PMID:16924674)
• the interaction between PARP-1 and PARP-3 is unrelated to DNA single-strand break repair (PMID:20064938)
• PARP-3 has a role in chromosomal DNA double-strand break repair. (PMID:21211721)
• PARP3 gene occupancy in the human neuroblastoma cell line SK-N-SH occurs preferentially with developmental genes regulating cell fate specification, tissue patterning, craniofacial development and neurogenesis. (PMID:21264220)
• PARP3 is a critical player in the stabilization of the mitotic spindle and in telomere integrity by associating and regulating the mitotic components NuMA and tankyrase 1. (PMID:21270334)
• In some cancer cells, repression of PARP3 could be responsible for an increased telomerase activity. (PMID:24528514)
• PARP3 likely facilitates the recruitment of Ku80 to double strand breaks to antagonize DNA end resection but facilitate Ku-mediated accurate classical non-homologous end-joining. (PMID:24598253)
• MiR-630 reduced apoptosis by downregulating several apoptotic modulators, PARP3, DDIT4, and EP300. (PMID:25255219)
• Identification of ADP-ribosylation sites in PARP3 and the determination of the extent ofpoly(ADP-ribosyl)ated residues in this protein was performed. (PMID:25800440)
• we found that PARP3 interacted with FoxM1 to enhance its transcriptional activity and conferred glioblastoma cell radioresistance. Thus, our data suggest that PARP3 could be a therapeutic target to overcome radioresistance in glioblastoma (PMID:26040766)
• These data identify PARP3 as a molecular sensor of nicked nucleosomes. (PMID:27530147)
• PARP3 controls of TGFbeta-induced epithelial mesenchymal transformation and acquisition of stem-like cell features by stimulation transglutaminase 2/SNAI1 signaling. (PMID:27579892)
• In a process of single-strand DNA repair, PARP3 mono-ADP-ribosylates nucleosomal histone H2B. (PMID:27716488)
• Data indicate that PARP3, a DNA damage-activated ADP-ribosyltransferase, can mono-ADP-ribosylate double-stranded DNA ends. (PMID:29054115)
• PARP3 can PARylate and mono(ADP-ribosyl)ate (MARylate), respectively, 5’- and 3’-terminal phosphate residues at double- and single-strand break termini of a DNA molecule containing multiple strand breaks. (PMID:29361132)
• gapped DNA that was ADP-ribosylated by PARP3 could be ligated to double-stranded DNA by DNA ligases. Moreover, this ADP-ribosylated DNA could serve as a primed DNA substrate for PAR chain elongation by the purified proteins PARP1 and PARP2 as well as by cell-free extracts. (PMID:29520010)
• The integral roles of PARP3 in DNA damage repair. (PMID:29676938)
• Our results indicated this approach with PARP3 inhibitors and vinorelbine is unique and promising for breast cancer patients with metastases. This combination could significantly increase the survival of breast cancer patients with metastases (PMID:30039287)
• Progress and outlook in studying the substrate specificities of PARPs and related enzymes. (PMID:32785980)
• PARP Power: A Structural Perspective on PARP1, PARP2, and PARP3 in DNA Damage Repair and Nucleosome Remodelling. (PMID:34066057)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	parp3	ENSDARG00000003961
mus_musculus	Parp3	ENSMUSG00000023249
rattus_norvegicus	Parp3	ENSRNOG00000012865
caenorhabditis_elegans		WBGENE00004053

Paralogs (2): PARP2 (ENSG00000129484), PARP1 (ENSG00000143799)

Protein

Protein identifiers

Protein mono-ADP-ribosyltransferase PARP3 — Q9Y6F1 (reviewed: Q9Y6F1)

Alternative names: ADP-ribosyltransferase diphtheria toxin-like 3, DNA ADP-ribosyltransferase PARP3, IRT1, NAD(+) ADP-ribosyltransferase 3, Poly [ADP-ribose] polymerase 3, Poly[ADP-ribose] synthase 3

All UniProt accessions (3): C9J9C7, Q9Y6F1, F8WAY7

UniProt curated annotations — full annotation on UniProt →

Function. Mono-ADP-ribosyltransferase that mediates mono-ADP-ribosylation of target proteins and plays a key role in the response to DNA damage. Mediates mono-ADP-ribosylation of glutamate, aspartate or lysine residues on target proteins. In contrast to PARP1 and PARP2, it is not able to mediate poly-ADP-ribosylation. Involved in DNA repair by mediating mono-ADP-ribosylation of a limited number of acceptor proteins involved in chromatin architecture and in DNA metabolism, such as histone H2B, XRCC5 and XRCC6. ADP-ribosylation follows DNA damage and appears as an obligatory step in a detection/signaling pathway leading to the reparation of DNA strand breaks. Involved in single-strand break repair by catalyzing mono-ADP-ribosylation of histone H2B on ‘Glu-2’ (H2BE2ADPr) of nucleosomes containing nicked DNA. Cooperates with the XRCC5-XRCC6 (Ku80-Ku70) heterodimer to limit end-resection thereby promoting accurate NHEJ. Suppresses G-quadruplex (G4) structures in response to DNA damage. Associates with a number of DNA repair factors and is involved in the response to exogenous and endogenous DNA strand breaks. Together with APLF, promotes the retention of the LIG4-XRCC4 complex on chromatin and accelerate DNA ligation during non-homologous end-joining (NHEJ). May link the DNA damage surveillance network to the mitotic fidelity checkpoint. Acts as a negative regulator of immunoglobulin class switch recombination, probably by controlling the level of AICDA /AID on the chromatin. In addition to proteins, also able to ADP-ribosylate DNA: mediates DNA mono-ADP-ribosylation of DNA strand break termini via covalent addition of a single ADP-ribose moiety to a 5’- or 3’-terminal phosphate residues in DNA containing multiple strand breaks.

Subunit / interactions. Interacts with PARP1; leading to activate PARP1 in absence of DNA. Interacts with PRKDC. Interacts with XRCC5/Ku80; the interaction is dependent on nucleic acids. Interacts with XRCC6/Ku70; the interaction is dependent on nucleic acids. Interacts with EZH2, HDAC1, HDAC2, SUZ12, YY1, LRIG3 and LIG4.

Subcellular location. Nucleus. Chromosome. Cytoplasm. Cytoskeleton. Microtubule organizing center. Centrosome. Centriole.

Tissue specificity. Widely expressed; the highest levels are in the kidney, skeletal muscle, liver, heart and spleen; also detected in pancreas, lung, placenta, brain, leukocytes, colon, small intestine, ovary, testis, prostate and thymus.

Post-translational modifications. Auto-mono-ADP-ribosylated.

Activity regulation. Mono-ADP-ribosyltransferase activity of PARP3 is selectively inhibited by ME0328 compound; ME0328 does not inhibit other ARTD/PARP enzymes, such as PARP1. Mono-ADP-ribosyltransferase is strongly inhibited by KU0058948 compound.

Miscellaneous. Most abundant isoform.

Similarity. Belongs to the ARTD/PARP family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9Y6F1-1	1, Short	yes
Q9Y6F1-2	2, Long

RefSeq proteins (4): NP_001003931, NP_001357168, NP_001357169, NP_005476 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004102	Poly(ADP-ribose)pol_reg_dom	Domain
IPR008893	WGR_domain	Domain
IPR012317	Poly(ADP-ribose)pol_cat_dom	Domain
IPR036616	Poly(ADP-ribose)pol_reg_dom_sf	Homologous_superfamily
IPR036930	WGR_dom_sf	Homologous_superfamily
IPR050800	ARTD/PARP	Family

Pfam: PF00644, PF02877, PF05406

Enzyme classification (BRENDA):

• EC 2.4.2.30 — NAD+ ADP-ribosyltransferase (BRENDA: 32 organisms, 193 substrates, 306 inhibitors, 42 Km, 24 kcat entries)

Substrate kinetics (BRENDA)

5 substrates with measured Km, best-characterized 5. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
NAD+	0.002–0.251	25
(ADP-D-RIBOSYL)N-ACTIN	0.011–0.037	7
(ADP-D-RIBOSYL)N-SOYBEAN-TRYPSIN-INHIBITOR	0.03–0.429	6
(ADP-D-RIBOSYL)N-RHOA PROTEIN	0.017	1
N6-ETHENO-NAD+	0.0225	1

Catalyzed reactions (Rhea), 3 shown:

• L-aspartyl-[protein] + NAD(+) = 4-O-(ADP-D-ribosyl)-L-aspartyl-[protein] + nicotinamide (RHEA:54424)
• L-lysyl-[protein] + NAD(+) = N(6)-(ADP-D-ribosyl)-L-lysyl-[protein] + nicotinamide + H(+) (RHEA:58220)
• L-glutamyl-[protein] + NAD(+) = 5-O-(ADP-D-ribosyl)-L-glutamyl-[protein] + nicotinamide (RHEA:58224)

UniProt features (80 total): strand 26, helix 17, modified residue 14, turn 6, domain 3, sequence variant 3, mutagenesis site 3, sequence conflict 3, region of interest 2, chain 1, splice variant 1, short sequence motif 1

Structure

Experimental structures (PDB)

16 structures.

PDB	Method	Resolution (Å)
4GV2	X-RAY DIFFRACTION	1.8
4GV4	X-RAY DIFFRACTION	1.8
4L7N	X-RAY DIFFRACTION	1.8
4GV0	X-RAY DIFFRACTION	1.9
4L6Z	X-RAY DIFFRACTION	2
4L70	X-RAY DIFFRACTION	2
4L7O	X-RAY DIFFRACTION	2
3C4H	X-RAY DIFFRACTION	2.1
4L7L	X-RAY DIFFRACTION	2.1
4L7R	X-RAY DIFFRACTION	2.2
3FHB	X-RAY DIFFRACTION	2.3
4L7P	X-RAY DIFFRACTION	2.3
3C49	X-RAY DIFFRACTION	2.8
3CE0	X-RAY DIFFRACTION	2.8
4L7U	X-RAY DIFFRACTION	2.8
2EOC	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y6F1-F1	85.68	0.66

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 (14): 26, 34, 37, 141, 163, 210, 231, 309, 310, 344, 449, 6, 12, 15

Mutagenesis-validated functional residues (3):

Position	Phenotype
83	does not affect activation by nicked dna, while it prevents activation by a 3’-overhang substrate.
101	reduced activity on nicked dna.
103	abolished activation by nicked dna.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 296 (showing top): GOBP_REGULATION_OF_DOUBLE_STRAND_BREAK_REPAIR, GOBP_RNA_TEMPLATED_DNA_BIOSYNTHETIC_PROCESS, GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_CHROMOSOME_ORGANIZATION, SHEPARD_BMYB_MORPHOLINO_UP, GOBP_REGULATION_OF_DNA_RECOMBINATION, GOBP_NEGATIVE_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, GOBP_NEGATIVE_REGULATION_OF_TELOMERE_MAINTENANCE_VIA_TELOMERASE, GOBP_REGULATION_OF_MICROTUBULE_BASED_PROCESS, GOBP_B_CELL_ACTIVATION, GOBP_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, SHEPARD_CRASH_AND_BURN_MUTANT_UP, GOBP_NEGATIVE_REGULATION_OF_PRODUCTION_OF_MOLECULAR_MEDIATOR_OF_IMMUNE_RESPONSE, GOBP_NEGATIVE_REGULATION_OF_LEUKOCYTE_MEDIATED_IMMUNITY, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP

GO Biological Process (14): telomere maintenance (GO:0000723), double-strand break repair (GO:0006302), double-strand break repair via nonhomologous end joining (GO:0006303), DNA ADP-ribosylation (GO:0030592), negative regulation of telomere maintenance via telomerase (GO:0032211), negative regulation of isotype switching (GO:0045829), regulation of mitotic spindle organization (GO:0060236), protein auto-ADP-ribosylation (GO:0070213), protein localization to site of double-strand break (GO:1990166), positive regulation of double-strand break repair via nonhomologous end joining (GO:2001034), DNA repair (GO:0006281), DNA damage response (GO:0006974), negative regulation of macromolecule biosynthetic process (GO:0010558), negative regulation of DNA metabolic process (GO:0051053)

GO Molecular Function (11): catalytic activity (GO:0003824), NAD+ poly-ADP-ribosyltransferase activity (GO:0003950), nucleotidyltransferase activity (GO:0016779), NAD DNA ADP-ribosyltransferase activity (GO:0140294), NAD+-protein-lysine ADP-ribosyltransferase activity (GO:0140804), NAD+-protein-aspartate ADP-ribosyltransferase activity (GO:0140806), NAD+-protein-glutamate ADP-ribosyltransferase activity (GO:0140807), NAD+-protein mono-ADP-ribosyltransferase activity (GO:1990404), protein binding (GO:0005515), transferase activity (GO:0016740), glycosyltransferase activity (GO:0016757)

GO Cellular Component (11): nucleoplasm (GO:0005654), nucleolus (GO:0005730), centrosome (GO:0005813), centriole (GO:0005814), nuclear body (GO:0016604), site of double-strand break (GO:0035861), intercellular bridge (GO:0045171), nucleus (GO:0005634), chromosome (GO:0005694), cytoplasm (GO:0005737), cytoskeleton (GO:0005856)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular membraneless organelle	5
DNA metabolic process	3
pentosyltransferase activity	3
NAD+-protein mono-ADP-ribosyltransferase activity	3
cellular anatomical structure	3
negative regulation of macromolecule metabolic process	2
nuclear lumen	2
microtubule organizing center	2
telomere organization	1
DNA repair	1
double-strand break repair	1
DNA modification	1
telomere maintenance via telomerase	1
regulation of telomere maintenance via telomerase	1
negative regulation of telomere maintenance via telomere lengthening	1
negative regulation of DNA biosynthetic process	1
negative regulation of immunoglobulin production	1
negative regulation of immunoglobulin mediated immune response	1
isotype switching	1
regulation of isotype switching	1
negative regulation of DNA recombination	1
negative regulation of B cell activation	1
negative regulation of developmental process	1
mitotic spindle organization	1
regulation of spindle organization	1
post-translational protein modification	1
protein localization to chromosome	1
double-strand break repair via nonhomologous end joining	1
positive regulation of double-strand break repair	1
regulation of double-strand break repair via nonhomologous end joining	1
DNA damage response	1
cellular response to stress	1
macromolecule biosynthetic process	1
negative regulation of biosynthetic process	1
regulation of macromolecule biosynthetic process	1
negative regulation of nucleobase-containing compound metabolic process	1
regulation of DNA metabolic process	1
molecular_function	1
transferase activity, transferring phosphorus-containing groups	1
catalytic activity, acting on a protein	1

Protein interactions and networks

STRING

1022 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PARP3	APLF	Q8IW19	880
PARP3	PARP16	Q8N5Y8	774
PARP3	PARG	Q86W56	756
PARP3	PARP10	Q53GL7	753
PARP3	PARP15	Q460N3	749
PARP3	XRCC6	P12956	744
PARP3	PARP6	Q2NL67	739
PARP3	TNKS	O95271	713
PARP3	BRCA1	P38398	705
PARP3	TNKS2	Q9H2K2	695
PARP3	PARP14	Q460N5	686
PARP3	PARP9	Q8IXQ6	684
PARP3	PARP12	Q9H0J9	683
PARP3	PRKDC	P78527	679
PARP3	ZC3HAV1	Q7Z2W4	660

IntAct

6 interactions, top by confidence:

A	B	Type	Score
PARP3	H3C13	psi-mi:“MI:0915”(physical association)	0.590
PARP3	DMWD	psi-mi:“MI:0914”(association)	0.350
RPA3	PARP3	psi-mi:“MI:0915”(physical association)	0.000
PARP3	H3C13	psi-mi:“MI:0915”(physical association)	0.000
PARP3	MTHFD2	psi-mi:“MI:0915”(physical association)	0.000
PARP3	H2BC21	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (27): RPA3 (Affinity Capture-MS), MTHFD2 (Affinity Capture-MS), HIST2H2BE (Affinity Capture-MS), HIST2H3C (Affinity Capture-MS), PARP1 (Affinity Capture-Western), GSK3B (Affinity Capture-Western), MEOX2 (Two-hybrid), DMWD (Affinity Capture-MS), RALGAPB (Affinity Capture-MS), PAK1 (Affinity Capture-MS), PARP3 (Positive Genetic), FOXM1 (Affinity Capture-Western), PARP3 (Reconstituted Complex), PARP3 (Co-localization), ATM (Co-localization)

ESM2 similar proteins: A5PJN5, A6H603, A6NFQ2, A6QLU7, D3ZKX9, D3ZQF9, F1LQ70, O00411, O15296, O35936, O70582, O75342, O95932, P09917, P0C869, P12527, P12530, P16050, P16469, P18054, P27479, P39654, P39655, P48999, P51399, P55249, P56201, Q02759, Q08DJ7, Q149M9, Q2KMM4, Q4R7D0, Q5R5N9, Q5R8R3, Q5RBE8, Q643R3, Q6NVG1, Q8BKF1, Q8K4F2, Q8R5K4

Diamond homologs: E1BSI0, O50017, O88554, P09874, P11103, P18493, P26446, P27008, P31669, P35875, Q08824, Q0JMY1, Q11207, Q11208, Q3ULW8, Q5RHR0, Q5Z8Q9, Q7EYV7, Q9R152, Q9UGN5, Q9Y6F1, Q9ZP54, Q9ZSV1, Q9N4H4, P49916, P97386, Q84JE8, Q0E0Q3, Q1SGF1, Q9FK91, Q9SWB4, Q9VBP3

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
olaparib	“down-regulates activity”	PARP3	“chemical inhibition”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	82
Likely benign	13
Benign	5

Top pathogenic / likely-pathogenic (0)

SpliceAI

1645 predictions. Top by Δscore:

Variant	Effect	Δscore
3:51943348:GGACA:G	acceptor_gain	1.0000
3:51944081:T:A	acceptor_gain	1.0000
3:51944088:GGT:G	acceptor_gain	1.0000
3:51944213:GTGTG:G	donor_gain	1.0000
3:51944214:TGTGG:T	donor_loss	1.0000
3:51944215:GTG:G	donor_gain	1.0000
3:51944218:G:GG	donor_gain	1.0000
3:51944218:G:T	donor_loss	1.0000
3:51944219:T:G	donor_loss	1.0000
3:51944564:G:GT	donor_gain	1.0000
3:51944576:AAGGT:A	donor_loss	1.0000
3:51944578:GGTGA:G	donor_loss	1.0000
3:51944580:T:A	donor_loss	1.0000
3:51944776:AGGT:A	acceptor_gain	1.0000
3:51944776:AGGTG:A	acceptor_gain	1.0000
3:51944777:GGTG:G	acceptor_gain	1.0000
3:51944777:GGTGG:G	acceptor_gain	1.0000
3:51944874:G:GT	donor_gain	1.0000
3:51944880:TTC:T	donor_gain	1.0000
3:51944904:GACC:G	donor_gain	1.0000
3:51944915:GGG:G	donor_gain	1.0000
3:51944916:GGG:G	donor_gain	1.0000
3:51944987:T:TA	acceptor_gain	1.0000
3:51944994:CTAG:C	acceptor_loss	1.0000
3:51944996:A:AG	acceptor_gain	1.0000
3:51944996:AG:A	acceptor_loss	1.0000
3:51944996:AGAT:A	acceptor_gain	1.0000
3:51944997:G:GT	acceptor_gain	1.0000
3:51944997:GA:G	acceptor_gain	1.0000
3:51944997:GAT:G	acceptor_gain	1.0000

AlphaMissense

3575 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:51944450:T:C	F125L	0.959
3:51944452:T:A	F125L	0.959
3:51944452:T:G	F125L	0.959
3:51944462:T:C	F129L	0.959
3:51944464:T:A	F129L	0.959
3:51944464:T:G	F129L	0.959
3:51944149:T:C	F82L	0.951
3:51944151:C:A	F82L	0.951
3:51944151:C:G	F82L	0.951
3:51944504:T:C	F143L	0.934
3:51944506:T:A	F143L	0.934
3:51944506:T:G	F143L	0.934
3:51945132:T:C	F257L	0.924
3:51945134:T:A	F257L	0.924
3:51945134:T:G	F257L	0.924
3:51948406:T:C	F510L	0.923
3:51948408:C:A	F510L	0.923
3:51948408:C:G	F510L	0.923
3:51944463:T:C	F129S	0.903
3:51944488:G:C	W137C	0.897
3:51944488:G:T	W137C	0.897
3:51944865:T:C	F197L	0.875
3:51944867:C:A	F197L	0.875
3:51944867:C:G	F197L	0.875
3:51944486:T:A	W137R	0.871
3:51944486:T:C	W137R	0.871
3:51948391:T:C	F505L	0.871
3:51948393:C:A	F505L	0.871
3:51948393:C:G	F505L	0.871
3:51945156:T:C	F265L	0.860

dbSNP variants (sampled 300 via entrez): RS1000590171 (3:51948607 A>C), RS1001031386 (3:51940491 C>T), RS1001420596 (3:51945679 G>A), RS1001556641 (3:51943264 C>T), RS1001632740 (3:51948810 T>C,G), RS1002292665 (3:51942946 G>A,C,T), RS1002671818 (3:51940682 C>CA), RS1002823611 (3:51946143 T>C), RS1002975399 (3:51945280 C>A,G,T), RS1003061603 (3:51940926 C>G), RS1004396042 (3:51941749 C>T), RS1004527470 (3:51946351 G>A), RS1004900993 (3:51941197 A>G), RS1005267048 (3:51948137 G>A), RS1005791052 (3:51947995 G>A)

Disease associations

OMIM: gene MIM:607726 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL3390820 (PROTEIN FAMILY), CHEMBL5083 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

8 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 40,152 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1094636	NIRAPARIB	4	6,433
CHEMBL1173055	RUCAPARIB	4	7,009
CHEMBL3137320	TALAZOPARIB	4	5,534
CHEMBL521686	OLAPARIB	4	13,038
CHEMBL506871	VELIPARIB	3	5,421
CHEMBL4112930	PAMIPARIB	3	2,114
CHEMBL5095220	SARUPARIB	3	357
CHEMBL5095043	ATAMPARIB	1	246

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

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — Mono-ADP-ribosylating PARPs

Most potent curated ligand interactions (3 total), top 3:

Ligand	Action	Affinity	Parameter
olaparib	Inhibition	8.24	pKd
KU0058948	Inhibition	7.15	pKd
ME0328	Inhibition	6.05	pIC50

Binding affinities (BindingDB)

24 measured of 34 human assays (34 total across all organisms); most potent 24 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
4-(2-aminoethoxy)-3-(4-chloro-3-methylphenyl)-7-fluoro-3,4,4a,5,6,7,8,8a-octahydro-2H-isoquinolin-1-one	IC50	0.2 nM	US-9422243: 3-phenyl-isoquinolin-1(2H)-one derivatives as PARP-1 inhibitors
4-({3-[(4-cyclopropanecarbonylpiperazin-1-yl)carbonyl]-4-fluorophenyl}methyl)-1,2-dihydrophthalazin-1-one	IC50	0.9 nM	US-9255106: Substituted [1,2,4]triazolo[4,3-a]pyrazines as PARP-1 inhibitors
4-(2-aminoethoxy)-3-(3,4-dichlorophenyl)-7-fluoro-3,4,4a,5,6,7,8,8a-octahydro-2H-isoquinolin-1-one	IC50	1 nM	US-9422243: 3-phenyl-isoquinolin-1(2H)-one derivatives as PARP-1 inhibitors
4-(2-aminoethoxy)-7-fluoro-3-(3-fluoro-4-methoxyphenyl)-3,4,4a,5,6,7,8,8a-octahydro-2H-isoquinolin-1-one	IC50	6 nM	US-9422243: 3-phenyl-isoquinolin-1(2H)-one derivatives as PARP-1 inhibitors
4-(2-aminoethoxy)-3-(4-bromophenyl)-7-fluoro-3,4,4a,5,6,7,8,8a-octahydro-2H-isoquinolin-1-one	IC50	10 nM	US-9422243: 3-phenyl-isoquinolin-1(2H)-one derivatives as PARP-1 inhibitors
4-(2-aminoethoxy)-3-(4-chlorophenyl)-7-fluoro-3,4,4a,5,6,7,8,8a-octahydro-2H-isoquinolin-1-one	IC50	10 nM	US-9422243: 3-phenyl-isoquinolin-1(2H)-one derivatives as PARP-1 inhibitors
3-[4-(2-aminoethoxy)-7-fluoro-1-oxo-4H-isoquinolin-3-yl]benzonitrile	IC50	10 nM	US-9422243: 3-phenyl-isoquinolin-1(2H)-one derivatives as PARP-1 inhibitors
2-(1-cyclohexylpiperidin-4-yl)-6-fluoro-1-methyl-3-oxoindazole-4-carboxamide	IC50	15 nM	US-9073893: 3-Oxo-2,3-dihydro-1H-indazole-4-carboxamide derivatives as PARP-1 inhibitors
US9260440, 62	IC50	18 nM	US-9260440: Fused tetra or penta-cyclic dihydrodiazepinocarbazolones as PARP inhibitors
4-(2-aminoethoxy)-3-(3-bromo-4-morpholin-4-ylphenyl)-7-fluoro-3,4,4a,5,6,7,8,8a-octahydro-2H-isoquinolin-1-one	IC50	20 nM	US-9422243: 3-phenyl-isoquinolin-1(2H)-one derivatives as PARP-1 inhibitors
4-(2-aminoethoxy)-3-(4-bromophenyl)-7,8-difluoro-3,4,4a,5,6,7,8,8a-octahydro-2H-isoquinolin-1-one	IC50	20 nM	US-9422243: 3-phenyl-isoquinolin-1(2H)-one derivatives as PARP-1 inhibitors
4-(2-aminoethoxy)-7-fluoro-3-(4-fluorophenyl)-3,4,4a,5,6,7,8,8a-octahydro-2H-isoquinolin-1-one	IC50	60 nM	US-9422243: 3-phenyl-isoquinolin-1(2H)-one derivatives as PARP-1 inhibitors
4-(2-aminoethoxy)-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-7-fluoro-3,4,4a,5,6,7,8,8a-octahydro-2H-isoquinolin-1-one	IC50	70 nM	US-9422243: 3-phenyl-isoquinolin-1(2H)-one derivatives as PARP-1 inhibitors
4-(2-aminoethoxy)-3-(1,3-benzodioxol-5-yl)-7-fluoro-3,4,4a,5,6,7,8,8a-octahydro-2H-isoquinolin-1-one	IC50	80 nM	US-9422243: 3-phenyl-isoquinolin-1(2H)-one derivatives as PARP-1 inhibitors
4-(2-aminoethoxy)-3-(3,4-difluorophenyl)-7-fluoro-3,4,4a,5,6,7,8,8a-octahydro-2H-isoquinolin-1-one	IC50	130 nM	US-9422243: 3-phenyl-isoquinolin-1(2H)-one derivatives as PARP-1 inhibitors
4-(2-aminoethoxy)-3-(3-bromo-4-pyrrolidin-1-ylphenyl)-7-fluoro-3,4,4a,5,6,7,8,8a-octahydro-2H-isoquinolin-1-one	IC50	130 nM	US-9422243: 3-phenyl-isoquinolin-1(2H)-one derivatives as PARP-1 inhibitors
US10501467, Example 9	IC50	136 nM	US-9260440: Fused tetra or penta-cyclic dihydrodiazepinocarbazolones as PARP inhibitors
US10501467, Example 47	IC50	180 nM	US-9260440: Fused tetra or penta-cyclic dihydrodiazepinocarbazolones as PARP inhibitors
US10501467, Example 69	IC50	185 nM	US-9260440: Fused tetra or penta-cyclic dihydrodiazepinocarbazolones as PARP inhibitors
US10501467, Example 2	IC50	199 nM	US-9260440: Fused tetra or penta-cyclic dihydrodiazepinocarbazolones as PARP inhibitors
US10501467, Example 51	IC50	660 nM	US-9260440: Fused tetra or penta-cyclic dihydrodiazepinocarbazolones as PARP inhibitors
US10501467, Example 45	IC50	760 nM	US-9260440: Fused tetra or penta-cyclic dihydrodiazepinocarbazolones as PARP inhibitors
3,3-dimethyl-16-(oxiran-2-ylmethyl)-6,7,16-triazatetracyclo[11.2.1.05,15.09,14]hexadeca-1(15),6,10,12-tetraen-8-one	IC50	1000 nM	US-9260440: Fused tetra or penta-cyclic dihydrodiazepinocarbazolones as PARP inhibitors
16-[2-(diethylamino)ethyl]-3,3-dimethyl-6,7,16-triazatetracyclo[11.2.1.05,15.09,14]hexadeca-1(15),6,10,12-tetraen-8-one	IC50	11000 nM	US-9260440: Fused tetra or penta-cyclic dihydrodiazepinocarbazolones as PARP inhibitors

ChEMBL bioactivities

190 potent at pChembl≥5 of 222 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.31	IC50	0.49	nM	CHEMBL2323226
8.96	IC50	1.1	nM	CHEMBL5402698
8.60	EC50	2.5	nM	TALAZOPARIB
8.60	EC50	2.51	nM	TALAZOPARIB
8.52	EC50	3	nM	CHEMBL3740104
8.46	IC50	3.5	nM	NIRAPARIB
8.45	EC50	3.57	nM	OLAPARIB
8.42	EC50	3.81	nM	CHEMBL3763674
8.40	EC50	4	nM	NIRAPARIB
8.40	IC50	4	nM	NIRAPARIB
8.36	IC50	4.4	nM	OLAPARIB
8.33	EC50	4.69	nM	RUCAPARIB
8.29	EC50	5.1	nM	CHEMBL3763446
8.26	EC50	5.48	nM	CHEMBL3765528
8.24	Kd	5.8	nM	OLAPARIB
8.23	EC50	5.94	nM	VELIPARIB
8.22	EC50	6	nM	CHEMBL3764052
8.21	EC50	6.1	nM	CHEMBL3765611
8.20	EC50	6.3	nM	CHEMBL3764920
8.17	EC50	6.7	nM	CHEMBL3763661
8.16	EC50	6.94	nM	CHEMBL3765056
8.16	EC50	6.9	nM	CHEMBL3763822
8.07	EC50	8.48	nM	CHEMBL3764670
8.07	IC50	8.6	nM	OLAPARIB
8.03	EC50	9.33	nM	CHEMBL3764188
8.02	EC50	9.47	nM	CHEMBL3763844
8.01	EC50	9.7	nM	CHEMBL3763243
8.00	Kd	10	nM	CHEMBL3901209
7.97	EC50	10.8	nM	CHEMBL3763531
7.93	EC50	11.8	nM	CHEMBL3765670
7.89	EC50	13	nM	CHEMBL1098296
7.82	EC50	15.2	nM	CHEMBL3763164
7.77	EC50	16.9	nM	CHEMBL3765291
7.77	EC50	17	nM	CHEMBL3764085
7.75	EC50	17.9	nM	CHEMBL3764202
7.75	IC50	18	nM	CHEMBL3970252
7.74	EC50	18.1	nM	CHEMBL3763188
7.73	EC50	18.6	nM	CHEMBL3764811
7.73	EC50	18.5	nM	CHEMBL3764422
7.71	EC50	19.7	nM	CHEMBL3765434
7.70	Kd	20	nM	CHEMBL3952782
7.70	Kd	20	nM	CHEMBL3911149
7.70	Kd	20	nM	CHEMBL3905973
7.70	Kd	20	nM	CHEMBL3975515
7.70	Kd	20	nM	CHEMBL3969175
7.70	Kd	20	nM	CHEMBL3939639
7.68	IC50	20.9	nM	OLAPARIB
7.64	EC50	23	nM	CHEMBL3765318
7.62	EC50	24	nM	CHEMBL1098298
7.62	Kd	24	nM	TALAZOPARIB

PubChem BioAssay actives

155 with measured affinity, of 350 total; 50 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
5-[2-fluoro-5-[(4-oxo-3H-phthalazin-1-yl)methyl]benzoyl]-5-azatricyclo[6.3.1.04,12]dodeca-1(11),8(12),9-trien-2-one	728422: Inhibition of PARP1/PARP2 in human SKOV3 cells assessed as reduction in H2O2-induced PARylation incubated for 4 hrs prior to H2O2 treatment	ic50	0.0005	uM
4-[[3-[3-(5-bromofuran-2-yl)-6,8-dihydro-5H-[1,2,4]triazolo[4,3-a]pyrazine-7-carbonyl]-4-fluorophenyl]methyl]-2H-phthalazin-1-one	2012696: Inhibition of PARP3 (unknown origin) using biotinylated NAD+ as substrate by luminescence assay	ic50	0.0011	uM
Talazoparib	1205328: Inhibition of PARP in human LoVo cells assessed as inhibition of hydrogen peroxide-induced PARylation treated for 30 mins prior to incubation with H2O2 for 5 mins by fluorescence analysis	ec50	0.0025	uM
2-[4-[3-[(4-oxo-3H-phthalazin-1-yl)methyl]benzoyl]piperazin-1-yl]pyridine-3-carbonitrile	1265323: Inhibition of PARP in human MDA-MB-468 cells assessed as induction of centrosome declustering after 48 hrs by DAPI-staining based image analysis	ec50	0.0030	uM
Niraparib	1205301: Inhibition of PARP in BRCA2-deficient human CAPAN-1 cells assessed as inhibition of hydrogen peroxide-induced PARylation by cell-based assay	ic50	0.0035	uM
Olaparib	1276416: Inhibition of PARP in human LoVo cells assessed as inhibition of poly(ADP)-ribose polymerization for 30 mins by fluorescence assay	ec50	0.0036	uM
11-[4-(azetidin-1-ylmethyl)phenyl]-12-(4-fluorophenyl)-2,3,10-triazatricyclo[7.3.1.05,13]trideca-1,5(13),6,8-tetraen-4-one	1276416: Inhibition of PARP in human LoVo cells assessed as inhibition of poly(ADP)-ribose polymerization for 30 mins by fluorescence assay	ec50	0.0038	uM
Rucaparib	1276416: Inhibition of PARP in human LoVo cells assessed as inhibition of poly(ADP)-ribose polymerization for 30 mins by fluorescence assay	ec50	0.0047	uM
(11S,12R)-11-(4-fluorophenyl)-12-(2-methyl-1,2,4-triazol-3-yl)-2,3,10-triazatricyclo[7.3.1.05,13]trideca-1,5(13),6,8-tetraen-4-one	1276416: Inhibition of PARP in human LoVo cells assessed as inhibition of poly(ADP)-ribose polymerization for 30 mins by fluorescence assay	ec50	0.0051	uM
7-fluoro-11-(4-fluorophenyl)-12-(2-methyl-1,2,4-triazol-3-yl)-2,3,10-triazatricyclo[7.3.1.05,13]trideca-1,5(13),6,8-tetraen-4-one	1276416: Inhibition of PARP in human LoVo cells assessed as inhibition of poly(ADP)-ribose polymerization for 30 mins by fluorescence assay	ec50	0.0055	uM
2-[(2R)-2-methylpyrrolidin-2-yl]-1H-benzimidazole-4-carboxamide	1276416: Inhibition of PARP in human LoVo cells assessed as inhibition of poly(ADP)-ribose polymerization for 30 mins by fluorescence assay	ec50	0.0059	uM
11-[4-[(dimethylamino)methyl]phenyl]-12-phenyl-2,3,10-triazatricyclo[7.3.1.05,13]trideca-1,5(13),6,8-tetraen-4-one	1276416: Inhibition of PARP in human LoVo cells assessed as inhibition of poly(ADP)-ribose polymerization for 30 mins by fluorescence assay	ec50	0.0060	uM
11-[4-[(dimethylamino)methyl]phenyl]-7-fluoro-12-(4-fluorophenyl)-2,3,10-triazatricyclo[7.3.1.05,13]trideca-1,5(13),6,8-tetraen-4-one	1276416: Inhibition of PARP in human LoVo cells assessed as inhibition of poly(ADP)-ribose polymerization for 30 mins by fluorescence assay	ec50	0.0061	uM
(11S,12R)-11-[4-(azetidin-1-ylmethyl)phenyl]-12-(4-fluorophenyl)-2,3,10-triazatricyclo[7.3.1.05,13]trideca-1,5(13),6,8-tetraen-4-one	1276416: Inhibition of PARP in human LoVo cells assessed as inhibition of poly(ADP)-ribose polymerization for 30 mins by fluorescence assay	ec50	0.0063	uM
11-[4-[(dimethylamino)methyl]phenyl]-12-[4-(trifluoromethyl)phenyl]-2,3,10-triazatricyclo[7.3.1.05,13]trideca-1,5(13),6,8-tetraen-4-one	1276416: Inhibition of PARP in human LoVo cells assessed as inhibition of poly(ADP)-ribose polymerization for 30 mins by fluorescence assay	ec50	0.0067	uM
11-(4-fluorophenyl)-12-(2-methyl-1,2,4-triazol-3-yl)-2,3,10-triazatricyclo[7.3.1.05,13]trideca-1,5(13),6,8-tetraen-4-one	1276416: Inhibition of PARP in human LoVo cells assessed as inhibition of poly(ADP)-ribose polymerization for 30 mins by fluorescence assay	ec50	0.0069	uM
(11S,12R)-11-(4-fluorophenyl)-12-(1-methylimidazol-2-yl)-2,3,10-triazatricyclo[7.3.1.05,13]trideca-1,5(13),6,8-tetraen-4-one	1276416: Inhibition of PARP in human LoVo cells assessed as inhibition of poly(ADP)-ribose polymerization for 30 mins by fluorescence assay	ec50	0.0069	uM
11-[4-[(dimethylamino)methyl]phenyl]-7-fluoro-12-phenyl-2,3,10-triazatricyclo[7.3.1.05,13]trideca-1,5(13),6,8-tetraen-4-one	1276416: Inhibition of PARP in human LoVo cells assessed as inhibition of poly(ADP)-ribose polymerization for 30 mins by fluorescence assay	ec50	0.0085	uM
7-fluoro-11-(4-fluorophenyl)-12-(2-methylpyrazol-3-yl)-2,3,10-triazatricyclo[7.3.1.05,13]trideca-1,5(13),6,8-tetraen-4-one	1276416: Inhibition of PARP in human LoVo cells assessed as inhibition of poly(ADP)-ribose polymerization for 30 mins by fluorescence assay	ec50	0.0093	uM
12-phenyl-11-[4-(pyrrolidin-1-ylmethyl)phenyl]-2,3,10-triazatricyclo[7.3.1.05,13]trideca-1,5(13),6,8-tetraen-4-one	1276416: Inhibition of PARP in human LoVo cells assessed as inhibition of poly(ADP)-ribose polymerization for 30 mins by fluorescence assay	ec50	0.0095	uM
11-[4-(azetidin-1-ylmethyl)phenyl]-12-phenyl-2,3,10-triazatricyclo[7.3.1.05,13]trideca-1,5(13),6,8-tetraen-4-one	1276416: Inhibition of PARP in human LoVo cells assessed as inhibition of poly(ADP)-ribose polymerization for 30 mins by fluorescence assay	ec50	0.0097	uM
11-[4-[(dimethylamino)methyl]phenyl]-12-(4-methylphenyl)-2,3,10-triazatricyclo[7.3.1.05,13]trideca-1,5(13),6,8-tetraen-4-one	1276416: Inhibition of PARP in human LoVo cells assessed as inhibition of poly(ADP)-ribose polymerization for 30 mins by fluorescence assay	ec50	0.0108	uM
(11R,12S)-11-[4-(azetidin-1-ylmethyl)phenyl]-12-(4-fluorophenyl)-2,3,10-triazatricyclo[7.3.1.05,13]trideca-1,5(13),6,8-tetraen-4-one	1276416: Inhibition of PARP in human LoVo cells assessed as inhibition of poly(ADP)-ribose polymerization for 30 mins by fluorescence assay	ec50	0.0118	uM
2-(1,2,3,4-tetrahydroisoquinolin-6-yl)indazole-7-carboxamide	1205270: Inhibition of PARP in human HeLa cells assessed as inhibition of hydrogen peroxide-induced PARylation by cell-based assay	ec50	0.0130	uM
4-[[3-[(6S)-6-methyl-3-(trifluoromethyl)-6,8-dihydro-5H-[1,2,4]triazolo[4,3-a]pyrazine-7-carbonyl]phenyl]methyl]-2H-phthalazin-1-one	1265280: Inhibition of PARP in human HeLa cells assessed as induction of centrosome declustering after 48 hrs by DAPI-staining based image analysis	ec50	0.0150	uM
11-[4-[(dimethylamino)methyl]phenyl]-12-(4-propan-2-ylphenyl)-2,3,10-triazatricyclo[7.3.1.05,13]trideca-1,5(13),6,8-tetraen-4-one	1276416: Inhibition of PARP in human LoVo cells assessed as inhibition of poly(ADP)-ribose polymerization for 30 mins by fluorescence assay	ec50	0.0152	uM
12-(1-methylimidazol-2-yl)-11-phenyl-2,3,10-triazatricyclo[7.3.1.05,13]trideca-1,5(13),6,8-tetraen-4-one	1276416: Inhibition of PARP in human LoVo cells assessed as inhibition of poly(ADP)-ribose polymerization for 30 mins by fluorescence assay	ec50	0.0169	uM
7-fluoro-11-(4-fluorophenyl)-12-(1-methylimidazol-2-yl)-2,3,10-triazatricyclo[7.3.1.05,13]trideca-1,5(13),6,8-tetraen-4-one	1276416: Inhibition of PARP in human LoVo cells assessed as inhibition of poly(ADP)-ribose polymerization for 30 mins by fluorescence assay	ec50	0.0170	uM
(11S,12R)-7-fluoro-11-(4-fluorophenyl)-12-(1-methylimidazol-2-yl)-2,3,10-triazatricyclo[7.3.1.05,13]trideca-1,5(13),6,8-tetraen-4-one	1276416: Inhibition of PARP in human LoVo cells assessed as inhibition of poly(ADP)-ribose polymerization for 30 mins by fluorescence assay	ec50	0.0179	uM
7-fluoro-12-(1-methylimidazol-2-yl)-11-phenyl-2,3,10-triazatricyclo[7.3.1.05,13]trideca-1,5(13),6,8-tetraen-4-one	1276416: Inhibition of PARP in human LoVo cells assessed as inhibition of poly(ADP)-ribose polymerization for 30 mins by fluorescence assay	ec50	0.0181	uM
11-[4-[(dimethylamino)methyl]phenyl]-12-(4-fluorophenyl)-2,3,10-triazatricyclo[7.3.1.05,13]trideca-1,5(13),6,8-tetraen-4-one	1276416: Inhibition of PARP in human LoVo cells assessed as inhibition of poly(ADP)-ribose polymerization for 30 mins by fluorescence assay	ec50	0.0185	uM
11,12-bis[4-[(dimethylamino)methyl]phenyl]-2,3,10-triazatricyclo[7.3.1.05,13]trideca-1,5(13),6,8-tetraen-4-one	1276416: Inhibition of PARP in human LoVo cells assessed as inhibition of poly(ADP)-ribose polymerization for 30 mins by fluorescence assay	ec50	0.0186	uM
11-(4-fluorophenyl)-12-(1-methylimidazol-2-yl)-2,3,10-triazatricyclo[7.3.1.05,13]trideca-1,5(13),6,8-tetraen-4-one	1276416: Inhibition of PARP in human LoVo cells assessed as inhibition of poly(ADP)-ribose polymerization for 30 mins by fluorescence assay	ec50	0.0197	uM
12-(4-fluorophenyl)-11-[4-(pyrrolidin-1-ylmethyl)phenyl]-2,3,10-triazatricyclo[7.3.1.05,13]trideca-1,5(13),6,8-tetraen-4-one	1276416: Inhibition of PARP in human LoVo cells assessed as inhibition of poly(ADP)-ribose polymerization for 30 mins by fluorescence assay	ec50	0.0230	uM
2-(4-piperidin-3-ylphenyl)indazole-7-carboxamide	1205270: Inhibition of PARP in human HeLa cells assessed as inhibition of hydrogen peroxide-induced PARylation by cell-based assay	ec50	0.0240	uM
11-(4-fluorophenyl)-12-(1,3-thiazol-2-yl)-2,3,10-triazatricyclo[7.3.1.05,13]trideca-1,5(13),6,8-tetraen-4-one	1276416: Inhibition of PARP in human LoVo cells assessed as inhibition of poly(ADP)-ribose polymerization for 30 mins by fluorescence assay	ec50	0.0244	uM
2-[4-[3-[1-(4-oxo-3H-phthalazin-1-yl)ethyl]benzoyl]piperazin-1-yl]pyridine-3-carbonitrile	1265280: Inhibition of PARP in human HeLa cells assessed as induction of centrosome declustering after 48 hrs by DAPI-staining based image analysis	ec50	0.0270	uM
12-(1-methylimidazol-2-yl)-11-[4-(trifluoromethyl)phenyl]-2,3,10-triazatricyclo[7.3.1.05,13]trideca-1,5(13),6,8-tetraen-4-one	1276416: Inhibition of PARP in human LoVo cells assessed as inhibition of poly(ADP)-ribose polymerization for 30 mins by fluorescence assay	ec50	0.0272	uM
4-[[3-[(6S)-3-(1,1-difluoroethyl)-6-methyl-6,8-dihydro-5H-[1,2,4]triazolo[4,3-a]pyrazine-7-carbonyl]phenyl]-difluoromethyl]-2H-phthalazin-1-one	1265324: Inhibition of PARP in human HCC1806 cells assessed as induction of centrosome declustering after 48 hrs by DAPI-staining based image analysis	ec50	0.0300	uM
2-[4-[(3R)-piperidin-3-yl]phenyl]indazole-7-carboxamide	1205270: Inhibition of PARP in human HeLa cells assessed as inhibition of hydrogen peroxide-induced PARylation by cell-based assay	ec50	0.0300	uM
2-(4-pyrrolidin-2-ylphenyl)indazole-7-carboxamide	1205270: Inhibition of PARP in human HeLa cells assessed as inhibition of hydrogen peroxide-induced PARylation by cell-based assay	ec50	0.0310	uM
11-[4-[(4-methylpiperazin-1-yl)methyl]phenyl]-12-phenyl-2,3,10-triazatricyclo[7.3.1.05,13]trideca-1,5(13),6,8-tetraen-4-one	1276416: Inhibition of PARP in human LoVo cells assessed as inhibition of poly(ADP)-ribose polymerization for 30 mins by fluorescence assay	ec50	0.0406	uM
4-[difluoro-[3-[(6S)-3-(2-fluoropropan-2-yl)-6-methyl-6,8-dihydro-5H-[1,2,4]triazolo[4,3-a]pyrazine-7-carbonyl]phenyl]methyl]-2H-phthalazin-1-one	1265280: Inhibition of PARP in human HeLa cells assessed as induction of centrosome declustering after 48 hrs by DAPI-staining based image analysis	ec50	0.0430	uM
2-(1,2,3,4-tetrahydroisoquinolin-7-yl)indazole-7-carboxamide	477515: Inhibition of PARP in hydrogen peroxide-induced human HeLa cells assessed as inhibition DNA-damage-induced PARylation	ec50	0.0460	uM
4-[[3-[(6S)-3-cyclobutyl-6-methyl-6,8-dihydro-5H-[1,2,4]triazolo[4,3-a]pyrazine-7-carbonyl]phenyl]-difluoromethyl]-2H-phthalazin-1-one	1265280: Inhibition of PARP in human HeLa cells assessed as induction of centrosome declustering after 48 hrs by DAPI-staining based image analysis	ec50	0.0490	uM
2-(2-pyridin-3-ylacetyl)-2,11-diazatricyclo[7.3.1.05,13]trideca-5(13),6,8-trien-10-one	455969: Inhibition of PARP3	ic50	0.0500	uM
sodium 1-[[4-fluoro-3-(3-oxo-4-pentan-3-ylpiperazine-1-carbonyl)phenyl]methyl]quinazolin-3-ide-2,4-dione	2019983: Inhibition of human recombinant N-terminal GST-tagged PARP3 (2 to 540(end) residues) expressed in Sf9 cells	ic50	0.0510	uM
4-[[3-[3-(trifluoromethyl)-6,8-dihydro-5H-[1,2,4]triazolo[4,3-a]pyrazine-7-carbonyl]phenyl]methyl]-2H-phthalazin-1-one	1265280: Inhibition of PARP in human HeLa cells assessed as induction of centrosome declustering after 48 hrs by DAPI-staining based image analysis	ec50	0.0510	uM
4-(5-chloro-2-methoxyphenyl)-N-[5-[[1-[2-fluoro-5-[(4-oxo-3H-phthalazin-1-yl)methyl]benzoyl]piperidin-4-yl]methoxy]-1,3,4-thiadiazol-2-yl]-6-methylpyridine-3-carboxamide	2080537: Inhibition of PARP3 (unknown origin)	ic50	0.0512	uM
2-[4-[3-[amino-(4-oxo-3H-phthalazin-1-yl)methyl]benzoyl]piperazin-1-yl]pyridine-3-carbonitrile	1265280: Inhibition of PARP in human HeLa cells assessed as induction of centrosome declustering after 48 hrs by DAPI-staining based image analysis	ec50	0.0570	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
N-(oxo-5,6-dihydrophenanthridin-2-yl)-N,N-dimethylacetamide hydrochloride	affects cotreatment, increases expression, affects binding	3
Cisplatin	affects cotreatment, increases expression, increases response to substance	3
bisphenol A	decreases expression, affects cotreatment, increases expression	2
(+)-JQ1 compound	decreases expression	2
pirinixic acid	affects binding, decreases expression, increases activity	1
beta-lapachone	increases expression	1
sodium arsenite	increases expression	1
perfluorooctane sulfonic acid	increases expression	1
CGP 52608	affects binding, increases reaction	1
nutlin 3	affects cotreatment, increases expression	1
ICG 001	increases expression	1
jinfukang	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1
Benzo(a)pyrene	increases methylation	1
Chelating Agents	affects binding, decreases expression	1
Copper	affects binding, decreases expression	1
Dactinomycin	increases expression, affects cotreatment	1
Dexamethasone	affects cotreatment, increases expression	1
Doxorubicin	increases response to substance	1
Estradiol	affects expression	1
Indomethacin	affects cotreatment, increases expression	1
Silicon Dioxide	decreases methylation	1
Smoke	decreases expression	1
Thiram	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Tretinoin	decreases expression	1
Valproic Acid	decreases expression	1
Vanadates	increases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1
Carboplatin	increases response to substance	1

ChEMBL screening assays

71 unique, capped per target: 69 binding, 2 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1115416	Binding	Inhibition of PARP in hydrogen peroxide-induced human HeLa cells assessed as inhibition DNA-damage-induced PARylation	Discovery of 2-{4-[(3S)-piperidin-3-yl]phenyl}-2H-indazole-7-carboxamide (MK-4827): a novel oral poly(ADP-ribose)polymerase (PARP) inhibitor efficacious in BRCA-1 and -2 mutant tumors. — J Med Chem
CHEMBL3429724	Functional	Inhibition of PARP activity in tumor of immunocompromised mouse xenografted with human MDA-MB-436 cells harboring BRCA1 mutant assessed as incorporation of [3H]NAD in PAR chains in response to nicked DNA at 50 to 100 mg/kg, po measured afte	Niraparib: A Poly(ADP-ribose) Polymerase (PARP) Inhibitor for the Treatment of Tumors with Defective Homologous Recombination. — J Med Chem

Cellosaurus cell lines

6 cell lines: 6 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2A0	Abcam HeLa PARP3 KO	Cancer cell line	Female
CVCL_B8M0	Abcam HCT 116 PARP3 KO	Cancer cell line	Male
CVCL_B8ZX	Abcam MCF-7 PARP3 KO	Cancer cell line	Female
CVCL_B9P7	Abcam A-549 PARP3 KO	Cancer cell line	Male
CVCL_TC17	HAP1 PARP3 (-) 1	Cancer cell line	Male
CVCL_TC18	HAP1 PARP3 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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