PARP9

Summary

PARP9 (poly(ADP-ribose) polymerase family member 9, HGNC:24118) is a protein-coding gene on chromosome 3q21.1, encoding Protein mono-ADP-ribosyltransferase PARP9 (Q8IXQ6). ADP-ribosyltransferase which, in association with E3 ligase DTX3L, plays a role in DNA damage repair and in immune responses including interferon-mediated antiviral defenses.

Enables several functions, including ADP-D-ribose binding activity; STAT family protein binding activity; and pentosyltransferase activity. Involved in several processes, including DNA damage checkpoint signaling; regulation of defense response; and regulation of macromolecule metabolic process. Located in several cellular components, including mitochondrion; nucleoplasm; and site of DNA damage. Part of protein-containing complex.

Source: NCBI Gene 83666 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 131 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001146105

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24118
Approved symbol	PARP9
Name	poly(ADP-ribose) polymerase family member 9
Location	3q21.1
Locus type	gene with protein product
Status	Approved
Aliases	BAL, BAL1, ARTD9
Ensembl gene	ENSG00000138496
Ensembl biotype	protein_coding
OMIM	612065
Entrez	83666

Gene structure

Transcript identifiers

Ensembl transcripts: 42 — 41 protein_coding, 1 retained_intron

ENST00000360356, ENST00000462315, ENST00000466126, ENST00000471785, ENST00000477522, ENST00000489652, ENST00000492382, ENST00000682323, ENST00000893754, ENST00000893755, ENST00000893756, ENST00000893757, ENST00000893758, ENST00000893759, ENST00000893760, ENST00000893761, ENST00000893762, ENST00000893763, ENST00000893764, ENST00000893765, ENST00000893766, ENST00000893767, ENST00000893768, ENST00000893769, ENST00000893770, ENST00000893771, ENST00000945471, ENST00000945472, ENST00000945473, ENST00000945474, ENST00000945475, ENST00000945476, ENST00000945477, ENST00000945478, ENST00000945479, ENST00000945480, ENST00000945481, ENST00000945482, ENST00000945483, ENST00000945484, ENST00000945485, ENST00000945486

RefSeq mRNA: 23 — MANE Select: NM_001146105 NM_001146102, NM_001146103, NM_001146104, NM_001146105, NM_001146106, NM_001387871, NM_001387872, NM_001387873, NM_001387874, NM_001387875, NM_001387876, NM_001387877, NM_001387878, NM_001387879, NM_001387880, NM_001387881, NM_001387882, NM_001387883, NM_001387884, NM_001387885, NM_001387886, NM_001387887, NM_031458

CCDS: CCDS3014, CCDS54633, CCDS54634

Canonical transcript exons

ENST00000682323 — 11 exons

Exon	Start	End
ENSE00001049975	122552418	122552639
ENSE00001049979	122555286	122556121
ENSE00001049980	122545432	122545489
ENSE00001049981	122536168	122536342
ENSE00001049982	122550584	122550802
ENSE00001078782	122536934	122537073
ENSE00002344457	122558434	122558467
ENSE00002687963	122559606	122559709
ENSE00003314923	122527924	122528743
ENSE00003539357	122540472	122540852
ENSE00003920128	122564245	122564300

Expression profiles

Bgee: expression breadth ubiquitous, 232 present calls, max score 95.32.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 11.2097 / max 325.4795, expressed in 1576 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
44136	9.5891	1552
44135	1.2509	384
44138	0.3362	158
44134	0.0334	9

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	95.32	gold quality
leukocyte	CL:0000738	95.26	gold quality
right lobe of liver	UBERON:0001114	94.34	gold quality
granulocyte	CL:0000094	93.94	gold quality
vermiform appendix	UBERON:0001154	93.70	gold quality
spleen	UBERON:0002106	92.87	gold quality
epithelium of nasopharynx	UBERON:0001951	92.73	gold quality
blood	UBERON:0000178	92.50	gold quality
smooth muscle tissue	UBERON:0001135	92.37	gold quality
gall bladder	UBERON:0002110	92.37	gold quality
right adrenal gland	UBERON:0001233	92.01	gold quality
upper lobe of left lung	UBERON:0008952	91.66	gold quality
liver	UBERON:0002107	91.60	gold quality
upper lobe of lung	UBERON:0008948	91.50	gold quality
right adrenal gland cortex	UBERON:0035827	91.32	gold quality
palpebral conjunctiva	UBERON:0001812	91.24	gold quality
left adrenal gland	UBERON:0001234	91.23	gold quality
islet of Langerhans	UBERON:0000006	91.02	gold quality
nasal cavity epithelium	UBERON:0005384	91.02	gold quality
decidua	UBERON:0002450	90.91	gold quality
left adrenal gland cortex	UBERON:0035825	90.77	gold quality
ileal mucosa	UBERON:0000331	90.65	gold quality
apex of heart	UBERON:0002098	90.17	gold quality
right lung	UBERON:0002167	89.94	gold quality
lymph node	UBERON:0000029	89.87	gold quality
adrenal cortex	UBERON:0001235	89.76	gold quality
lung	UBERON:0002048	89.67	gold quality
adrenal gland	UBERON:0002369	89.40	gold quality
pancreatic ductal cell	CL:0002079	89.08	silver quality
lower lobe of lung	UBERON:0008949	89.08	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: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
PARP14	Repression

Upstream regulators (CollecTRI, top): PARP14

miRNA regulators (miRDB)

26 targeting PARP9, 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-190A-3P	100.00	80.35	5520
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-5002-5P	99.76	70.84	1763
HSA-MIR-4428	99.73	66.41	1733
HSA-MIR-875-3P	99.63	69.47	2548
HSA-MIR-1324	99.46	66.57	1302
HSA-MIR-3191-5P	99.24	66.52	1722
HSA-MIR-4279	99.19	66.70	2437
HSA-MIR-4528	99.18	69.77	1936
HSA-MIR-4426	99.17	66.74	1949
HSA-MIR-6768-3P	99.14	67.38	1319
HSA-MIR-628-3P	99.04	68.37	814
HSA-MIR-455-3P	98.94	67.68	878
HSA-MIR-3146	98.85	66.77	601
HSA-MIR-518C-5P	98.53	69.20	1640
HSA-MIR-449C-3P	97.75	67.86	462
HSA-MIR-4676-5P	97.54	65.29	715
HSA-MIR-8086	97.21	64.13	331

Literature-anchored findings (GeneRIF, showing 16)

• BAL1 and BBAP are located on chromosome 3q21 in a head-to-head orientation and are regulated by a IFN-gamma-responsive bidirectional promoter. (PMID:16809771)
• Determination of Poly (ADP-ribose) polymerase (PARP) homologues in human ejaculated sperm and its correlation with sperm maturation. (PMID:18339380)
• Data establish that BAL1 and BBAP are bona fide members of a DNA damage response pathway and are directly associated with PARP1 activation, BRCA1 recruitment, and double-strand break repair. (PMID:23230272)
• BAL1 represses the anti-proliferative and pro-apoptotic IFNgamma-STAT1-IRF1-p53 axis and mediates proliferation, survival and chemo-resistance in DLBCL. (PMID:23487038)
• The present study further suggests that the combined targeted inhibition of STAT1, ARTD8, ARTD9 and/or DTX3L could increase the efficacy of chemotherapy or radiation treatment in prostate and other high-risk tumor types with an increased STAT1 signaling. (PMID:24886089)
• PARP9 and PARP14 regulate macrophage activation in macrophage cell lines treated with either IFNgamma or IL-4; PARP14 silencing induces pro-inflammatory genes and STAT1 phosphorylation in M(IFNgamma) cells, whereas it suppresses anti-inflammatory gene expression and STAT6 phosphorylation in M(IL-4) cells (PMID:27796300)
• Dtx3L heterodimerization with Parp9 enables NAD(+) and poly(ADP-ribose) regulation of E3 activity. (PMID:28525742)
• This study summarizes specific molecular pathways, including those involving poly(ADP-ribose) polymerase family member 14 (PARP14) and poly(ADP-ribose) polymerase family member 9 (PARP9) at the intersection of interferon gamma (IFN-gamma) and ADP-ribosylation signaling pathways. (PMID:30848916)
• Decylubiquinone suppresses breast cancer growth and metastasis by inhibiting angiogenesis via the ROS/p53/ BAI1 signaling pathway. (PMID:32020421)
• Molecular and clinical characterization of PARP9 in gliomas: A potential immunotherapeutic target. (PMID:32678519)
• Engineering Af1521 improves ADP-ribose binding and identification of ADP-ribosylated proteins. (PMID:33060572)
• Androgen signaling uses a writer and a reader of ADP-ribosylation to regulate protein complex assembly. (PMID:33976187)
• Identification of poly(ADP-ribose) polymerase 9 (PARP9) as a noncanonical sensor for RNA virus in dendritic cells. (PMID:33976210)
• The SARS-CoV-2 Nsp3 macrodomain reverses PARP9/DTX3L-dependent ADP-ribosylation induced by interferon signaling. (PMID:34358560)
• Poly(ADP-ribose) polymerase 9 mediates early protection against Mycobacterium tuberculosis infection by regulating type I IFN production. (PMID:37200107)
• P. gingivalis-Induced TLR2 Interactome Analysis Reveals Association with PARP9. (PMID:38344758)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	parp9	ENSDARG00000006848
mus_musculus	Parp9	ENSMUSG00000022906
rattus_norvegicus	Parp9	ENSRNOG00000023463

Paralogs (8): PARP12 (ENSG00000059378), ZC3HAV1 (ENSG00000105939), PARP11 (ENSG00000111224), ZC3HAV1L (ENSG00000146858), TIPARP (ENSG00000163659), PARP14 (ENSG00000173193), PARP15 (ENSG00000173200), PARP10 (ENSG00000178685)

Protein

Protein identifiers

Protein mono-ADP-ribosyltransferase PARP9 — Q8IXQ6 (reviewed: Q8IXQ6)

Alternative names: ADP-ribosyltransferase diphtheria toxin-like 9, B aggressive lymphoma protein, Poly [ADP-ribose] polymerase 9

All UniProt accessions (3): Q8IXQ6, C9K0E5, G5E9U8

UniProt curated annotations — full annotation on UniProt →

Function. ADP-ribosyltransferase which, in association with E3 ligase DTX3L, plays a role in DNA damage repair and in immune responses including interferon-mediated antiviral defenses. Within the complex, enhances DTX3L E3 ligase activity which is further enhanced by PARP9 binding to poly(ADP-ribose). In association with DTX3L and in presence of E1 and E2 enzymes, mediates NAD(+)-dependent mono-ADP-ribosylation of ubiquitin which prevents ubiquitin conjugation to substrates such as histones. During DNA repair, PARP1 recruits PARP9/BAL1-DTX3L complex to DNA damage sites via PARP9 binding to ribosylated PARP1. Subsequent PARP1-dependent PARP9/BAL1-DTX3L-mediated ubiquitination promotes the rapid and specific recruitment of 53BP1/TP53BP1, UIMC1/RAP80, and BRCA1 to DNA damage sites. In response to DNA damage, PARP9-DTX3L complex is required for efficient non-homologous end joining (NHEJ); the complex function is negatively modulated by PARP9 activity. Dispensable for B-cell receptor (BCR) assembly through V(D)J recombination and class switch recombination (CSR). In macrophages, positively regulates pro-inflammatory cytokines production in response to IFNG stimulation by suppressing PARP14-mediated STAT1 ADP-ribosylation and thus promoting STAT1 phosphorylation. Also suppresses PARP14-mediated STAT6 ADP-ribosylation.

Subunit / interactions. Forms a stable complex with E3 ligase DTX3L; the interaction is required for PARP9 mediated ADP-ribosylation of ubiquitin. Interacts (via PARP catalytic domain) with DTX3L (via N-terminus). Forms a complex with STAT1 and DTX3L independently of IFNB1 or IFNG-mediated STAT1 ‘Tyr-701’ phosphorylation. Forms a complex with STAT1, DTX3L and histone H2B H2BC9/H2BJ; the interaction is likely to induce H2BC9/H2BJ ubiquitination. Interacts (via N-terminus) with STAT1. Interacts with PARP14 in IFNG-stimulated macrophages; the interaction prevents PARP14-mediated STAT1 and STAT6 ADP-riboslylation. Interacts with PARP1 (when poly-ADP-ribosylated).

Subcellular location. Cytoplasm. Cytosol. Nucleus.

Tissue specificity. Expressed in lymphocyte-rich tissues, spleen, lymph nodes, peripheral blood lymphocytes and colonic mucosa. Expressed in macrophages. Also expressed in nonhematopoietic tissues such as heart and skeletal muscle. Isoform 2 is the predominant form. Most abundantly expressed in lymphomas with a brisk host inflammatory response. In diffuse large B-cell lymphomas tumors, expressed specifically by malignant B-cells.

Post-translational modifications. ADP-ribosylated by PARP14.

Disease relevance. Overexpressed at significantly higher levels in fatal high-risk diffuse large B-cell lymphomas (DLB-CL) compared to cured low-risk tumors. Overexpression in B-cell lymphoma transfectants may promote malignant B-cell migration. May therefore be involved in promoting B-cell migration and dissemination of high-risk DLB-CL tumors.

Activity regulation. Binding to poly(ADP-ribose) does not affect its activity.

Domain organisation. Macro domains 1 and 2 may be involved in the binding to poly(ADP-ribose). Macro domain 2 is required for recruitment to DNA damage sites. Macro domains 1 and 2 are probably dispensable for the interaction with STAT1 and DTX3L and for STAT1 phosphorylation.

Induction. Up-regulated by IFNG in macrophages and in B-cell lymphoma cell lines. Up-regulated by IFNB1 or viral infection. Down-regulated by IL4 in macrophages.

Similarity. Belongs to the ARTD/PARP family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q8IXQ6-1	1, Long, L	yes
Q8IXQ6-2	2, Short, S
Q8IXQ6-3	3

RefSeq proteins (23): NP_001139574, NP_001139575, NP_001139576, NP_001139577, NP_001139578, NP_001374800, NP_001374801, NP_001374802, NP_001374803, NP_001374804, NP_001374805, NP_001374806, NP_001374807, NP_001374808, NP_001374809, NP_001374810, NP_001374811, NP_001374812, NP_001374813, NP_001374814, NP_001374815, NP_001374816, NP_113646 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002589	Macro_dom	Domain
IPR012317	Poly(ADP-ribose)pol_cat_dom	Domain
IPR043472	Macro_dom-like	Homologous_superfamily
IPR052056	Mono-ARTD/PARP	Family
IPR057049	PARP14_KH_8	Domain

Pfam: PF01661, PF23254

Catalyzed reactions (Rhea), 1 shown:

• [protein]-C-terminal glycine + NAD(+) = [protein]-C-terminal O-(ADP-D-ribosyl)-glycine + nicotinamide (RHEA:58268)

UniProt features (36 total): mutagenesis site 9, strand 8, helix 6, sequence variant 4, domain 3, splice variant 3, sequence conflict 2, chain 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
9QYF	X-RAY DIFFRACTION	1.3
9QYE	X-RAY DIFFRACTION	1.44
5AIL	X-RAY DIFFRACTION	1.55
9QYD	X-RAY DIFFRACTION	1.91
9QYH	X-RAY DIFFRACTION	2.5
9QYG	X-RAY DIFFRACTION	2.7

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IXQ6-F1	78.83	0.43

Functional residue map

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

Mutagenesis-validated functional residues (9):

Position	Phenotype
147	reduces the binding to poly(adp-ribose) by 50 percent and prevents increase in dtx3l-mediated histone ubiquitination wit
346	reduces the binding to poly(adp-ribose) by 50 percent and prevents increase in dtx3l-mediated histone ubiquitination wit
719–722	loss of adp ribosylation activity and interaction with dtx3l.
737	no defect in ubiquitin adp ribosylation and the interaction with dtx3l.
738	severe reduction in ubiquitin adp ribosylation. no effect on the interaction with dtx3l and on dtx3l e3 ligase activity.
766–769	loss of adp ribosylation activity and interaction with dtx3l.
780–784	reduces adp ribosylation activity and interaction with dtx3l.
802–803	no defect in adp ribosylation and interaction with dtx3l.
831–854	no defect in adp ribosylation and interaction with dtx3l.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-196807	Nicotinate metabolism
R-HSA-9683610	Maturation of nucleoprotein
R-HSA-9694631	Maturation of nucleoprotein

MSigDB gene sets: 362 (showing top): GOBP_REGULATION_OF_PHOSPHORYLATION, GOBP_REGULATION_OF_DEFENSE_RESPONSE_TO_VIRUS, GOBP_RESPONSE_TO_PEPTIDE, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GRAESSMANN_RESPONSE_TO_MC_AND_SERUM_DEPRIVATION_UP, GOBP_CELL_CYCLE_PHASE_TRANSITION, GOBP_POSITIVE_REGULATION_OF_PROTEIN_LOCALIZATION, GOBP_CELL_SURFACE_RECEPTOR_SIGNALING_PATHWAY_VIA_JAK_STAT, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_PEPTIDYL_TYROSINE_PHOSPHORYLATION, GOBP_POSITIVE_REGULATION_OF_BINDING, GOBP_POSITIVE_REGULATION_OF_RESPONSE_TO_EXTERNAL_STIMULUS, MARTORIATI_MDM4_TARGETS_NEUROEPITHELIUM_DN, GOBP_POST_TRANSCRIPTIONAL_REGULATION_OF_GENE_EXPRESSION, IRF7_01

GO Biological Process (24): DNA damage checkpoint signaling (GO:0000077), negative regulation of transcription by RNA polymerase II (GO:0000122), positive regulation of defense response to virus by host (GO:0002230), double-strand break repair (GO:0006302), post-transcriptional regulation of gene expression (GO:0010608), negative regulation of gene expression (GO:0010629), cell migration (GO:0016477), viral protein processing (GO:0019082), positive regulation of chromatin binding (GO:0035563), positive regulation of tyrosine phosphorylation of STAT protein (GO:0042531), negative regulation of catalytic activity (GO:0043086), innate immune response (GO:0045087), positive regulation of DNA-templated transcription (GO:0045893), defense response to virus (GO:0051607), regulation of response to type II interferon (GO:0060330), positive regulation of type II interferon-mediated signaling pathway (GO:0060335), positive regulation of protein localization to nucleus (GO:1900182), nicotinate metabolic process (GO:1901847), positive regulation of cytokine-mediated signaling pathway (GO:0001961), immune system process (GO:0002376), DNA repair (GO:0006281), DNA damage response (GO:0006974), NAD+ biosynthetic process via the salvage pathway (GO:0034355), regulation of type II interferon-mediated signaling pathway (GO:0060334)

GO Molecular Function (13): transcription corepressor activity (GO:0003714), NAD+ poly-ADP-ribosyltransferase activity (GO:0003950), enzyme inhibitor activity (GO:0004857), nucleotidyltransferase activity (GO:0016779), enzyme binding (GO:0019899), histone binding (GO:0042393), ubiquitin-like protein ligase binding (GO:0044389), ADP-D-ribose binding (GO:0072570), STAT family protein binding (GO:0097677), NAD+-protein-C-terminal glycine ADP-ribosyltransferase activity (GO:0140802), protein binding (GO:0005515), transferase activity (GO:0016740), glycosyltransferase activity (GO:0016757)

GO Cellular Component (8): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), mitochondrion (GO:0005739), cytosol (GO:0005829), membrane (GO:0016020), protein-containing complex (GO:0032991), site of DNA damage (GO:0090734)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Metabolism of water-soluble vitamins and cofactors	1
Translation of Structural Proteins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
catalytic activity	3
negative regulation of DNA-templated transcription	2
regulation of gene expression	2
protein binding	2
intracellular membrane-bounded organelle	2
cytoplasm	2
DNA integrity checkpoint signaling	1
signal transduction in response to DNA damage	1
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
regulation of defense response to virus by host	1
DNA repair	1
gene expression	1
negative regulation of macromolecule biosynthetic process	1
cell motility	1
viral process	1
viral gene expression	1
chromatin binding	1
positive regulation of binding	1
tyrosine phosphorylation of STAT protein	1
regulation of tyrosine phosphorylation of STAT protein	1
positive regulation of peptidyl-tyrosine phosphorylation	1
negative regulation of molecular function	1
regulation of catalytic activity	1
immune response	1
defense response to symbiont	1
DNA-templated transcription	1
regulation of DNA-templated transcription	1
positive regulation of RNA biosynthetic process	1
defense response	1
response to virus	1
response to type II interferon	1
regulation of innate immune response	1
regulation of response to cytokine stimulus	1
positive regulation of cytokine-mediated signaling pathway	1
positive regulation of response to type II interferon	1
type II interferon-mediated signaling pathway	1
regulation of type II interferon-mediated signaling pathway	1
protein localization to nucleus	1

Protein interactions and networks

STRING

1184 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PARP9	DTX3L	Q8TDB6	999
PARP9	DTX3	Q8N9I9	837
PARP9	PARP1	P09874	776
PARP9	IFI44L	Q53G44	723
PARP9	PARP4	Q9UKK3	719
PARP9	PARP3	Q9Y6F1	684
PARP9	PARP16	Q8N5Y8	675
PARP9	IFIT3	O14879	661
PARP9	IFI44	Q8TCB0	659
PARP9	PARP6	Q2NL67	637
PARP9	TNKS	O95271	616
PARP9	ISG15	P05161	611
PARP9	RSAD2	Q8WXG1	606
PARP9	PARP2	Q9UGN5	603
PARP9	IRF7	Q92985	598

IntAct

16 interactions, top by confidence:

A	B	Type	Score
DTX3L	PARP9	psi-mi:“MI:0915”(physical association)	0.560
PARP9	CLUH	psi-mi:“MI:0915”(physical association)	0.400
SORT1	SH3PXD2B	psi-mi:“MI:0914”(association)	0.350
TRAF3	POLA1	psi-mi:“MI:0914”(association)	0.350
DTX3L	LCN1	psi-mi:“MI:0914”(association)	0.350
RBM43	MAPKAPK2	psi-mi:“MI:0914”(association)	0.350
RNF166	SNX3	psi-mi:“MI:0914”(association)	0.350
CRYAB	HTRA2	psi-mi:“MI:0914”(association)	0.350
ERF	DVL2	psi-mi:“MI:0914”(association)	0.350
FTL		psi-mi:“MI:0914”(association)	0.350
MAGEA10	KANSL1L	psi-mi:“MI:0914”(association)	0.350
PARP12	CASC3	psi-mi:“MI:0914”(association)	0.350
SYNJ2BP	EEF1E1	psi-mi:“MI:0914”(association)	0.350
SLC35A5	CLGN	psi-mi:“MI:0914”(association)	0.350
SLC9A8	AP1G1	psi-mi:“MI:0914”(association)	0.350

BioGRID (51): PARP9 (Affinity Capture-MS), PARP9 (Affinity Capture-Western), STAT1 (Affinity Capture-Western), DTX3L (Affinity Capture-Western), PARP9 (Affinity Capture-Western), PARP9 (Affinity Capture-Western), PARP9 (Co-localization), PARP9 (Affinity Capture-MS), DTX3L (Affinity Capture-Western), DTX3L (Co-fractionation), DTX3L (Reconstituted Complex), HIST2H2BE (Biochemical Activity), PARP9 (Affinity Capture-MS), PARP9 (Affinity Capture-MS), STAT1 (Affinity Capture-Western)

ESM2 similar proteins: A0JPF9, A4D126, A4D7T3, A4QNL8, A5PKL6, B2GUS6, C0IN03, E1BCH6, E1BVR9, F1LW30, F1ND48, P19686, P19687, P33402, P48760, P57075, Q02108, Q07DZ7, Q08C84, Q09M05, Q108U1, Q1L5Z9, Q1LZ50, Q28CZ7, Q32PY6, Q3U3W5, Q3UY23, Q4R3W5, Q4ZHS0, Q5REW9, Q5RG49, Q5RJG7, Q5RL51, Q5S6T3, Q5T8I9, Q6GPJ4, Q6NXP6, Q6P2P2, Q7SXA9, Q8BTK5

Diamond homologs: A0A166ACJ5, A0A559KX76, A1Z1Q3, A4W960, A7MG20, A7T167, A8AI35, B4T2X8, B5F961, B5RBF3, B5XXK9, B7LT90, C9Y0V8, D2TT52, D3RKJ0, D5CE05, E1PL40, E1SDF1, O28751, O59182, O67112, O75367, O93327, P0A8D6, P0A8D7, P0A8D8, P0DC28, P0DC29, P0DN70, P67341, P67342, P67343, P67344, P9WK28, P9WK29, Q02874, Q0T5Z6, Q2EMV9, Q2KHU5, Q2KIX2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	90
Likely benign	11
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

2419 predictions. Top by Δscore:

Variant	Effect	Δscore
3:122528739:TGGAT:T	acceptor_gain	1.0000
3:122528740:GGAT:G	acceptor_gain	1.0000
3:122528741:GAT:G	acceptor_gain	1.0000
3:122528742:ATC:A	acceptor_loss	1.0000
3:122528743:TCT:T	acceptor_loss	1.0000
3:122528744:C:CC	acceptor_gain	1.0000
3:122528744:CTG:C	acceptor_loss	1.0000
3:122528747:A:AC	acceptor_gain	1.0000
3:122550579:CTTA:C	donor_loss	1.0000
3:122550580:TTAC:T	donor_loss	1.0000
3:122550581:TA:T	donor_loss	1.0000
3:122550582:A:AC	donor_gain	1.0000
3:122550583:C:CC	donor_gain	1.0000
3:122550800:TAT:T	acceptor_gain	1.0000
3:122550800:TATC:T	acceptor_loss	1.0000
3:122550801:ATCT:A	acceptor_loss	1.0000
3:122550802:TCTGC:T	acceptor_loss	1.0000
3:122550803:C:CA	acceptor_loss	1.0000
3:122550803:C:CC	acceptor_gain	1.0000
3:122552636:CTGC:C	acceptor_gain	1.0000
3:122552640:C:CC	acceptor_gain	1.0000
3:122564515:T:TA	donor_gain	1.0000
3:122528742:AT:A	acceptor_gain	0.9900
3:122528747:A:C	acceptor_gain	0.9900
3:122536163:CCTA:C	donor_loss	0.9900
3:122536166:A:AC	donor_gain	0.9900
3:122536166:ACCG:A	donor_loss	0.9900
3:122536167:C:CC	donor_gain	0.9900
3:122536167:C:CT	donor_loss	0.9900
3:122536340:CACCT:C	acceptor_loss	0.9900

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000243574 (3:122553978 G>A,T), RS1000276319 (3:122546731 A>T), RS1000333995 (3:122540166 A>G), RS1000449412 (3:122547203 T>G), RS1000565528 (3:122542157 T>C), RS1000660284 (3:122541835 C>A,T), RS1000819033 (3:122566193 A>G), RS1000957965 (3:122534990 T>C,G), RS1001090535 (3:122535638 T>C), RS1001135908 (3:122531708 T>C), RS1001157961 (3:122527731 G>A), RS1001167036 (3:122538890 A>C,T), RS1001384457 (3:122553091 A>G), RS1001450899 (3:122545203 T>C), RS1001450937 (3:122552237 G>A,T)

Disease associations

OMIM: gene MIM:612065 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST001469_2	Major depressive disorder	6.000000e-06
GCST006614_99	Total cholesterol levels	4.000000e-08
GCST010245_79	LDL cholesterol levels	1.000000e-10
GCST010991_33	Parkinson’s disease	3.000000e-07

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004574	total cholesterol measurement
EFO:0004611	low density lipoprotein cholesterol measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4295895 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 7,009 (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
CHEMBL1173055	RUCAPARIB	4	7,009

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

ChEMBL bioactivities

1 potent at pChembl≥5 of 3 total, top 1 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.51	Kd	3100	nM	RUCAPARIB

PubChem BioAssay actives

1 with measured affinity, of 15 total; 1 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
Rucaparib	1895785: Binding affinity to PARP9 (unknown origin) assessed as apparent dissociation constant	kd	3.1000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Acetaminophen	decreases expression	3
Benzo(a)pyrene	decreases expression, increases expression	3
(+)-JQ1 compound	decreases expression	2
Estradiol	decreases expression, increases expression	2
Nickel	decreases expression, increases expression	2
Tretinoin	increases expression	2
Valproic Acid	affects expression, decreases expression	2
aristolochic acid I	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	increases expression	1
arsenite	affects binding, decreases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	decreases expression	1
butyraldehyde	decreases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
hydroquinone	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
monomethylarsonous acid	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
belinostat	decreases expression	1
abrine	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
licochalcone B	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Temozolomide	increases expression	1
Air Pollutants	decreases expression	1

ChEMBL screening assays

5 unique, capped per target: 5 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4272754	Binding	Stabilization of human ARTD9 expressed in Escherichia coli assessed as change in melting temperature at 100 uM by SYPRO Orange-dye based differential scanning fluorimetric method	4-(Phenoxy) and 4-(benzyloxy)benzamides as potent and selective inhibitors of mono-ADP-ribosyltransferase PARP10/ARTD10. — Eur J Med Chem

Cellosaurus cell lines

4 cell lines: 4 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1GX	Abcam A-549 PARP9 KO 2	Cancer cell line	Male
CVCL_B2PF	Abcam A-549 PARP9 KO 1	Cancer cell line	Male
CVCL_TC24	HAP1 PARP9 (-) 1	Cancer cell line	Male
CVCL_TC25	HAP1 PARP9 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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