PARP16

Summary

PARP16 (poly(ADP-ribose) polymerase family member 16, HGNC:26040) is a protein-coding gene on chromosome 15q22.31, encoding Protein mono-ADP-ribosyltransferase PARP16 (Q8N5Y8). Intracellular mono-ADP-ribosyltransferase that plays a role in different processes, such as protein translation and unfolded protein response (UPR), through the mono-ADP-ribosylation of proteins involved in those processes.

Enables kinase binding activity; pentosyltransferase activity; and protein serine/threonine kinase activator activity. Involved in IRE1-mediated unfolded protein response; negative regulation of cytoplasmic translation; and protein auto-ADP-ribosylation. Located in endoplasmic reticulum tubular network and nuclear envelope.

Source: NCBI Gene 54956 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 61 total
• Druggable target: yes — 4 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001316943

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26040
Approved symbol	PARP16
Name	poly(ADP-ribose) polymerase family member 16
Location	15q22.31
Locus type	gene with protein product
Status	Approved
Aliases	FLJ20509, FLJ25281, pART15, ARTD15
Ensembl gene	ENSG00000138617
Ensembl biotype	protein_coding
OMIM	620391
Entrez	54956

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 12 protein_coding, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000261888, ENST00000444347, ENST00000558873, ENST00000559805, ENST00000560149, ENST00000649807, ENST00000906476, ENST00000906477, ENST00000906478, ENST00000906479, ENST00000906480, ENST00000906481, ENST00000906482, ENST00000906483, ENST00000966191

RefSeq mRNA: 3 — MANE Select: NM_001316943 NM_001316943, NM_001316944, NM_017851

CCDS: CCDS10204, CCDS81897, CCDS92018

Canonical transcript exons

ENST00000649807 — 6 exons

Exon	Start	End
ENSE00001287192	65266562	65266768
ENSE00003481379	65270935	65271072
ENSE00003531555	65260885	65261026
ENSE00003583632	65263149	65263320
ENSE00003838318	65286253	65286883
ENSE00003840599	65258099	65259542

Expression profiles

Bgee: expression breadth ubiquitous, 212 present calls, max score 96.97.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 10.4928 / max 106.5418, expressed in 1770 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
150539	9.0874	1742
150540	0.5463	189
150538	0.5270	304
150537	0.2120	94
207567	0.1201	35

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	96.97	gold quality
oocyte	CL:0000023	95.05	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.54	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.29	gold quality
calcaneal tendon	UBERON:0003701	86.19	gold quality
endocervix	UBERON:0000458	85.84	gold quality
cortical plate	UBERON:0005343	84.69	gold quality
ganglionic eminence	UBERON:0004023	84.25	gold quality
left ovary	UBERON:0002119	82.85	gold quality
right ovary	UBERON:0002118	82.84	gold quality
granulocyte	CL:0000094	82.81	gold quality
adrenal tissue	UBERON:0018303	82.79	gold quality
lower esophagus mucosa	UBERON:0035834	82.68	gold quality
right lobe of liver	UBERON:0001114	82.56	gold quality
ventricular zone	UBERON:0003053	82.53	gold quality
muscle layer of sigmoid colon	UBERON:0035805	82.47	gold quality
body of uterus	UBERON:0009853	82.46	gold quality
ectocervix	UBERON:0012249	82.30	gold quality
mucosa of stomach	UBERON:0001199	82.29	gold quality
ovary	UBERON:0000992	82.09	gold quality
right adrenal gland	UBERON:0001233	82.01	gold quality
right adrenal gland cortex	UBERON:0035827	81.90	gold quality
lower esophagus	UBERON:0013473	81.82	gold quality
lower esophagus muscularis layer	UBERON:0035833	81.81	gold quality
vagina	UBERON:0000996	81.78	gold quality
left adrenal gland	UBERON:0001234	81.57	gold quality
skin of leg	UBERON:0001511	81.51	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	81.44	gold quality
left adrenal gland cortex	UBERON:0035825	81.28	gold quality
popliteal artery	UBERON:0002250	81.27	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.70
E-MTAB-6142	no	138.76

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

73 targeting PARP16, 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-150-5P	99.99	66.69	1976
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-3617-3P	99.98	67.86	918
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-557	99.96	70.01	1640
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-548AE-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-548AQ-3P	99.93	72.66	4867
HSA-MIR-589-3P	99.91	69.62	2088
HSA-MIR-4493	99.90	66.48	977
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-8062	99.88	68.43	995
HSA-MIR-605-3P	99.88	69.22	1833
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-659-3P	99.85	70.69	1620
HSA-MIR-548AZ-3P	99.82	70.56	3549
HSA-MIR-548BC	99.82	70.61	3524
HSA-MIR-548E-3P	99.82	70.59	3514
HSA-MIR-548F-3P	99.82	70.59	3540

Literature-anchored findings (GeneRIF, showing 4)

• PARP16 is a tail-anchored endoplasmic reticulum protein required for the PERK- and IRE1alpha-mediated unfolded protein response. (PMID:23103912)
• ARTD15 plays role in nucleocytoplasmic shuttling, through karyopherin-beta1 mono-ADP-ribosylation. [review] (PMID:25037261)
• Regulation of poly ADP-ribosylation of VEGF by an interplay between PARP-16 and TNKS-2. (PMID:32472322)
• Poly (ADP-ribose) polymerases 16 triggers pathological cardiac hypertrophy via activating IRE1alpha-sXBP1-GATA4 pathway. (PMID:37219631)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	parp16	ENSDARG00000018593
mus_musculus	Parp16	ENSMUSG00000032392
rattus_norvegicus	Parp16	ENSRNOG00000029127

Paralogs (2): PARP6 (ENSG00000137817), PARP8 (ENSG00000151883)

Protein

Protein identifiers

Protein mono-ADP-ribosyltransferase PARP16 — Q8N5Y8 (reviewed: Q8N5Y8)

Alternative names: ADP-ribosyltransferase diphtheria toxin-like 15, Poly [ADP-ribose] polymerase 16

All UniProt accessions (2): Q8N5Y8, H3BV75

UniProt curated annotations — full annotation on UniProt →

Function. Intracellular mono-ADP-ribosyltransferase that plays a role in different processes, such as protein translation and unfolded protein response (UPR), through the mono-ADP-ribosylation of proteins involved in those processes. Acts as an inhibitor of protein translation by catalyzing mono-ADP-ribosylation of ribosomal subunits, such as RPL14 and RPS6, thereby inhibiting polysome assembly and mRNA loading. Mono-ADP-ribosylation of ribosomal subunits is promoted by NMNAT2. Involved in the unfolded protein response (UPR) by ADP-ribosylating and activating EIF2AK3 and ERN1, two important UPR effectors. May also mediate mono-ADP-ribosylation of karyopherin KPNB1 a nuclear import factor. May not modify proteins on arginine or cysteine residues compared to other mono-ADP-ribosyltransferases.

Subunit / interactions. Interacts with KPNB1.

Subcellular location. Endoplasmic reticulum membrane.

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

Activity regulation. In absence of activation signal, PARP16 is autoinhibited by the PARP alpha-helical domain (also named HD region), which prevents effective NAD(+)-binding. Activity is highly stimulated by signals, which unfold the PARP alpha-helical domain, relieving autoinhibition.

Domain organisation. The PARP alpha-helical domain (also named HD region) is regulatory, it packs against the catalytic domain.

Similarity. Belongs to the ARTD/PARP family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q8N5Y8-1	1	yes
Q8N5Y8-2	2
Q8N5Y8-3	3

RefSeq proteins (3): NP_001303872, NP_001303873, NP_060321 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR012317	Poly(ADP-ribose)pol_cat_dom	Domain
IPR041400	PARP16_N	Domain
IPR051838	ARTD_PARP	Family

Pfam: PF00644, PF18084

Enzyme classification (BRENDA):

• EC 2.4.2.30 — NAD+ ADP-ribosyltransferase (BRENDA: 32 organisms, 193 substrates, 306 inhibitors, 42 Km, 24 kcat entries)
• EC 2.4.2.31 — NAD+-protein-arginine ADP-ribosyltransferase (BRENDA: 29 organisms, 161 substrates, 61 inhibitors, 61 Km, 19 kcat entries)

Substrate kinetics (BRENDA)

17 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
NAD+	0.0007–8.67	44
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
AGMATINE	1–9.4	3
ARGININE METHYL ESTER	1.3–3	3
1-(4-AMINOBUTYL)GUANIDINE	0.26–15	2
(ADP-D-RIBOSYL)N-RHOA PROTEIN	0.017	1
N6-ETHENO-NAD+	0.0225	1
ALPHA-ACTIN-L-ARGININE	0.0025	1
BETA/GAMMA-ACTIN-L-ARGININE	0.015	1
GAMMA-ACTIN-L-ARGININE	0.01	1
NOMEGA-(ADP-D-RIBOSYL)-AGMATINE-L-ARGININE	0.272	1
PROTEIN L-ARGININE	4.1	1
PROTEIN L-ARGININE METHYL ESTER	1.3	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 (44 total): helix 14, strand 9, modified residue 4, mutagenesis site 4, binding site 3, topological domain 2, splice variant 2, domain 2, chain 1, sequence variant 1, transmembrane region 1, site 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
6HXS	X-RAY DIFFRACTION	2.05
6W65	X-RAY DIFFRACTION	2.13
4F0D	X-RAY DIFFRACTION	2.7
6HXR	X-RAY DIFFRACTION	2.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N5Y8-F1	87.96	0.65

Functional residue map

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

Catalytic / active sites (1): 193 (nicotinamide-stacking aromate)

Ligand- & substrate-binding residues (3): 152; 182; 254

Post-translational modifications (4): 37, 70, 110, 137

Mutagenesis-validated functional residues (4):

Position	Phenotype
152	loss of adp-ribosyltransferase activity; when associated with a-254.
152	adp-ribosyltransferase activity is only 6% of wild-type; when associated with a-182.
182	adp-ribosyltransferase activity is only 6% of wild-type; when associated with q-152.
254	loss of adp-ribosyltransferase activity; when associated with h-152.

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: 222 (showing top): GOBP_CYTOPLASMIC_TRANSLATION, MODULE_97, GOBP_IRE1_MEDIATED_UNFOLDED_PROTEIN_RESPONSE, GOBP_RESPONSE_TO_PEPTIDE, GOBP_RESPONSE_TO_ENDOPLASMIC_RETICULUM_STRESS, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, MODULE_182, MODULE_308, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, GOBP_NEGATIVE_REGULATION_OF_TRANSLATION, GOBP_CELLULAR_RESPONSE_TO_TOPOLOGICALLY_INCORRECT_PROTEIN, GOBP_TRANSLATION, GOMF_KINASE_ACTIVATOR_ACTIVITY, GTGCCTT_MIR506, GOBP_POST_TRANSCRIPTIONAL_REGULATION_OF_GENE_EXPRESSION

GO Biological Process (10): viral protein processing (GO:0019082), endoplasmic reticulum unfolded protein response (GO:0030968), IRE1-mediated unfolded protein response (GO:0036498), protein auto-ADP-ribosylation (GO:0070213), nicotinate metabolic process (GO:1901847), cellular response to leukemia inhibitory factor (GO:1990830), negative regulation of cytoplasmic translation (GO:2000766), cytoplasmic translation (GO:0002181), response to unfolded protein (GO:0006986), NAD+ biosynthetic process via the salvage pathway (GO:0034355)

GO Molecular Function (11): NAD+ poly-ADP-ribosyltransferase activity (GO:0003950), nucleotidyltransferase activity (GO:0016779), kinase binding (GO:0019900), protein serine/threonine kinase activator activity (GO:0043539), 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 (6): nuclear envelope (GO:0005635), endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), cytosol (GO:0005829), membrane (GO:0016020), endoplasmic reticulum tubular network (GO:0071782)

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
NAD+-protein mono-ADP-ribosyltransferase activity	3
pentosyltransferase activity	2
endomembrane system	2
cytoplasm	2
endoplasmic reticulum subcompartment	2
cellular anatomical structure	2
viral process	1
viral gene expression	1
cellular response to unfolded protein	1
response to endoplasmic reticulum stress	1
intracellular signal transduction	1
endoplasmic reticulum unfolded protein response	1
post-translational protein modification	1
alkaloid metabolic process	1
monocarboxylic acid metabolic process	1
pyridine-containing compound metabolic process	1
cellular response to cytokine stimulus	1
response to leukemia inhibitory factor	1
cytoplasmic translation	1
negative regulation of translation	1
regulation of cytoplasmic translation	1
translation	1
response to topologically incorrect protein	1
NAD+ biosynthetic process	1
pyridine nucleotide salvage	1
purine nucleotide salvage	1
transferase activity, transferring phosphorus-containing groups	1
enzyme binding	1
protein serine/threonine kinase activity	1
protein kinase activator activity	1
catalytic activity, acting on a protein	1
binding	1
catalytic activity	1
transferase activity	1
nucleus	1
organelle envelope	1
intracellular membrane-bounded organelle	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1

Protein interactions and networks

STRING

464 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PARP16	PARP15	Q460N3	806
PARP16	PARP4	Q9UKK3	780
PARP16	PARP10	Q53GL7	776
PARP16	PARP3	Q9Y6F1	774
PARP16	TIPARP	Q7Z3E1	736
PARP16	PARP12	Q9H0J9	731
PARP16	PARP14	Q460N5	720
PARP16	PARP11	Q9NR21	707
PARP16	PARP2	Q9UGN5	704
PARP16	PARP9	Q8IXQ6	675
PARP16	TNKS2	Q9H2K2	642
PARP16	TNKS	O95271	641
PARP16	ZC3HAV1	Q7Z2W4	628
PARP16	PARP1	P09874	587
PARP16	PARG	Q86W56	587

IntAct

36 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
NIPAL1	ESYT2	psi-mi:“MI:0914”(association)	0.640
PARP16	FLJ13057	psi-mi:“MI:0915”(physical association)	0.560
FLJ13057	PARP16	psi-mi:“MI:0915”(physical association)	0.560
GPC3	CLGN	psi-mi:“MI:0914”(association)	0.530
KLC4	PUF60	psi-mi:“MI:0914”(association)	0.350
DOT1L	IBTK	psi-mi:“MI:0914”(association)	0.350
Ccn1	SRGAP3	psi-mi:“MI:0914”(association)	0.350
PCIF1	POLR2A	psi-mi:“MI:0914”(association)	0.350
MLKL	CASP8	psi-mi:“MI:0914”(association)	0.350
Setd5	NCOR2	psi-mi:“MI:0914”(association)	0.350
ZNF644	ATP9A	psi-mi:“MI:0914”(association)	0.350
MRPL1	MRPL43	psi-mi:“MI:0914”(association)	0.350
PARP16	PGRMC1	psi-mi:“MI:0914”(association)	0.350
Npc1	ESYT2	psi-mi:“MI:0914”(association)	0.350
CCDC47	ESYT2	psi-mi:“MI:0914”(association)	0.350
TMED10	PGRMC1	psi-mi:“MI:0914”(association)	0.350
CHRNA4	TMEM223	psi-mi:“MI:0914”(association)	0.350
PARP16	VWA8	psi-mi:“MI:0914”(association)	0.350
SCN4A	C2CD4B	psi-mi:“MI:0914”(association)	0.350
NKAIN1	GPR89A	psi-mi:“MI:0914”(association)	0.350
H2AP	GNPAT	psi-mi:“MI:0914”(association)	0.350
MFSD14A	FAM171A2	psi-mi:“MI:0914”(association)	0.350
SLC1A2	UBXN8	psi-mi:“MI:0914”(association)	0.350
SLC22A9	ESYT2	psi-mi:“MI:0914”(association)	0.350
SLC39A14	ESYT2	psi-mi:“MI:0914”(association)	0.350

BioGRID (101): GMCL1 (Two-hybrid), MDN1 (Affinity Capture-MS), DDX20 (Affinity Capture-MS), RAI14 (Affinity Capture-MS), LRP6 (Affinity Capture-MS), LRP5 (Affinity Capture-MS), COG6 (Affinity Capture-MS), ECSIT (Affinity Capture-MS), VWA8 (Affinity Capture-MS), COG1 (Affinity Capture-MS), NEDD1 (Affinity Capture-MS), COG5 (Affinity Capture-MS), VAC14 (Affinity Capture-MS), B3GALNT2 (Affinity Capture-MS), LRBA (Affinity Capture-MS)

ESM2 similar proteins: A2VE39, B1H268, D2HRF1, E1BSI0, F1MX48, O00763, O14730, O54935, O88554, O95801, P26446, P42898, P47897, Q1RMT7, Q28DH9, Q2KIJ6, Q2YD98, Q3MHH4, Q3ULW8, Q4V7A9, Q5I598, Q5R981, Q5RHR0, Q5U2Q4, Q5U2Z5, Q60596, Q66H61, Q6DDX8, Q6MG55, Q6P9B6, Q7TMM8, Q810A5, Q8BML9, Q8K0P3, Q8N1G2, Q8N5Y8, Q8N6R0, Q91WR3, Q99PL6, Q9CZT4

Diamond homologs: Q5U2Q4, Q7TMM8, Q8N5Y8

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 48 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
R-HSA-425366	5	32.4×	1e-04
SLC-mediated transmembrane transport	5	10.6×	3e-03
Transport of small molecules	7	6.3×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	51
Likely benign	2
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

715 predictions. Top by Δscore:

Variant	Effect	Δscore
15:65260879:CCTTA:C	donor_loss	1.0000
15:65260880:CTTA:C	donor_loss	1.0000
15:65260881:TTAC:T	donor_loss	1.0000
15:65260882:TACCT:T	donor_loss	1.0000
15:65260883:A:AC	donor_gain	1.0000
15:65260884:C:CA	donor_loss	1.0000
15:65260884:C:CC	donor_gain	1.0000
15:65260884:CCT:C	donor_gain	1.0000
15:65261022:GGAAT:G	acceptor_gain	1.0000
15:65261023:GAAT:G	acceptor_gain	1.0000
15:65261024:AAT:A	acceptor_gain	1.0000
15:65261027:C:A	acceptor_loss	1.0000
15:65261027:C:CC	acceptor_gain	1.0000
15:65263147:AC:A	donor_gain	1.0000
15:65263148:CC:C	donor_gain	1.0000
15:65263148:CCCTT:C	donor_gain	1.0000
15:65263328:A:T	acceptor_gain	1.0000
15:65263331:A:T	acceptor_gain	1.0000
15:65263335:CCAA:C	acceptor_gain	1.0000
15:65263336:C:T	acceptor_gain	1.0000
15:65263336:CAA:C	acceptor_gain	1.0000
15:65263337:A:T	acceptor_gain	1.0000
15:65263338:A:AC	acceptor_gain	1.0000
15:65263338:A:C	acceptor_gain	1.0000
15:65266769:C:CC	acceptor_gain	1.0000
15:65266770:T:C	acceptor_gain	1.0000
15:65266770:T:TC	acceptor_gain	1.0000
15:65260922:T:TA	donor_gain	0.9900
15:65260922:TC:T	donor_gain	0.9900
15:65261025:AT:A	acceptor_gain	0.9900

AlphaMissense

2110 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:65260948:A:T	V257D	0.998
15:65263172:A:T	V223D	0.998
15:65263202:G:T	A213D	0.998
15:65263258:G:C	S194R	0.998
15:65263258:G:T	S194R	0.998
15:65263260:T:G	S194R	0.998
15:65263292:A:G	L183P	0.998
15:65263302:C:A	G180W	0.998
15:65263302:C:G	G180R	0.998
15:65263302:C:T	G180R	0.998
15:65266623:C:T	G153D	0.998
15:65266627:G:C	H152D	0.998
15:65260915:A:G	L268P	0.997
15:65263296:A:G	Y182H	0.997
15:65263301:C:T	G180E	0.997
15:65263309:G:C	F177L	0.997
15:65263309:G:T	F177L	0.997
15:65263311:A:G	F177L	0.997
15:65266619:G:C	S154R	0.997
15:65266619:G:T	S154R	0.997
15:65266621:T:G	S154R	0.997
15:65263203:C:G	A213P	0.996
15:65263271:G:T	A190D	0.996
15:65263296:A:C	Y182D	0.996
15:65263307:C:T	G178E	0.996
15:65266632:G:T	A150E	0.996
15:65286352:G:C	S25R	0.996
15:65286352:G:T	S25R	0.996
15:65286354:T:G	S25R	0.996
15:65260951:A:T	V256E	0.995

dbSNP variants (sampled 300 via entrez): RS1000003055 (15:65247994 T>C), RS1000056901 (15:65241644 T>C), RS1000136749 (15:65266273 T>C), RS1000136889 (15:65276798 T>C,G), RS1000145859 (15:65260839 A>G), RS1000170573 (15:65260621 G>A), RS1000175079 (15:65272070 G>C), RS1000187555 (15:65231723 C>T), RS1000204342 (15:65275354 CTG>C), RS1000289882 (15:65272362 G>A,C), RS1000319143 (15:65237284 T>C), RS1000328491 (15:65253456 A>G,T), RS1000330800 (15:65285553 G>A), RS1000376088 (15:65260363 C>A), RS1000466349 (15:65276557 G>A,T)

Disease associations

OMIM: gene MIM:620391 | 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 (1): CHEMBL4105981 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

4 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 25,827 (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
CHEMBL3137320	TALAZOPARIB	4	5,534
CHEMBL521686	OLAPARIB	4	13,038
CHEMBL5095043	ATAMPARIB	1	246

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

ChEMBL bioactivities

18 potent at pChembl≥5 of 20 total, top 17 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.80	Kd	1.6	nM	CHEMBL3752910
8.80	ED50	1.6	nM	CHEMBL3752910
6.44	IC50	362	nM	CHEMBL5189477
6.44	IC50	362	nM	CHEMBL5284069
6.37	IC50	427	nM	CHEMBL5172255
6.25	IC50	560	nM	CHEMBL4089522
6.00	Kd	1000	nM	TALAZOPARIB
5.73	IC50	1862	nM	CHEMBL3764816
5.72	IC50	1900	nM	CHEMBL3764816
5.54	Kd	2900	nM	RUCAPARIB
5.47	IC50	3400	nM	CHEMBL5404785
5.38	IC50	4200	nM	CHEMBL1438938
5.29	IC50	5100	nM	OLAPARIB
5.29	IC50	5129	nM	OLAPARIB
5.28	IC50	5200	nM	CHEMBL5431108
5.17	IC50	6700	nM	CHEMBL4545565
5.17	IC50	6761	nM	CHEMBL4545565

PubChem BioAssay actives

18 with measured affinity, of 54 total; 13 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
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148939: Binding affinity to human PARP16 incubated for 45 mins by Kinobead based pull down assay	kd	0.0016	uM
(4S,5R)-7,8-dichloro-5-hydroxy-4-pyridin-2-yl-2,3,4,5-tetrahydro-2-benzazepin-1-one	1869186: Inhibition of PARP16 (unknown origin) using IRE-1 as substrate incubated for 1 hr by chemiluminescence assay	ic50	0.3620	uM
(5R)-7,8-dichloro-5-hydroxy-4-pyridin-2-yl-2,3,4,5-tetrahydro-2-benzazepin-1-one	1936708: Inhibition of PARP16 (unknown origin)	ic50	0.3620	uM
12-amino-3,4-dibromo-5,8,11,13-tetrazatricyclo[8.4.0.02,6]tetradeca-1(14),2(6),3,10,12-pentaen-7-one	1869186: Inhibition of PARP16 (unknown origin) using IRE-1 as substrate incubated for 1 hr by chemiluminescence assay	ic50	0.4270	uM
3-[[(Z)-4-[4-(4-fluorophenyl)piperazin-1-yl]-4-oxobut-2-enoyl]amino]benzamide	1467144: Inhibition of His6-tagged PARP16 (unknown origin) preincubated for 15 mins followed by biotinylated NAD+ addition by chemiluminescence assay	ic50	0.5600	uM
Talazoparib	1895790: Binding affinity to PARP16 (unknown origin) assessed as apparent dissociation constant	kd	1.0000	uM
(11R,12S)-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	1428399: Inhibition of full length recombinant human His6-tagged PARP16 expressed in Escherichia coli BL21(DE3) preincubated for 15 mins followed by biotinylated NAD+ addition by chemiluminescence assay	ic50	1.8621	uM
Rucaparib	1895790: Binding affinity to PARP16 (unknown origin) assessed as apparent dissociation constant	kd	2.9000	uM
5,8-dimethoxy-[1,2,4]triazolo[3,4-b][1,3]benzothiazol-1-amine	1965933: Inhibition of N-terminal MBP tagged/C-terminal PARP16 (unknown origin) expressed in Escherichia coli in presence of NAD+ by proximity enhanced assay	ic50	3.4000	uM
4-(4-carbamoylphenoxy)benzamide	1802079: Enzymatic Activity Assay from Article 10.1016/j.chembiol.2016.08.012: “Small-Molecule Chemical Probe Rescues Cells from Mono-ADP-Ribosyltransferase ARTD10/PARP10-Induced Apoptosis and Sensitizes Cancer Cells to DNA Damage.”	ic50	4.1700	uM
Olaparib	1428399: Inhibition of full length recombinant human His6-tagged PARP16 expressed in Escherichia coli BL21(DE3) preincubated for 15 mins followed by biotinylated NAD+ addition by chemiluminescence assay	ic50	5.1000	uM
6-methyl-[1,2,4]triazolo[3,4-b][1,3]benzothiazol-1-amine	1965933: Inhibition of N-terminal MBP tagged/C-terminal PARP16 (unknown origin) expressed in Escherichia coli in presence of NAD+ by proximity enhanced assay	ic50	5.2000	uM
5-methyl-6-[2-(trifluoromethyl)-4-pyridinyl]-3,4-dihydro-2H-isoquinolin-1-one	1515561: Inhibition of human transmembrane domain deficient His-SUMO-tagged PARP16 expressed in Escherichia coli BL21 assessed as reduction in MARylation of His6-tagged SRPK2 substrate after 60 mins in presence of 6-a-NAD+ by chemifluorescence assay	ic50	6.7000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases abundance, increases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, decreases expression	2
bisphenol F	affects cotreatment, increases methylation	1
butyraldehyde	decreases expression	1
coumarin	decreases phosphorylation	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
N-(oxo-5,6-dihydrophenanthridin-2-yl)-N,N-dimethylacetamide hydrochloride	affects binding	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	increases expression	1
dorsomorphin	decreases expression, affects cotreatment	1
Resveratrol	affects cotreatment, decreases expression, increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Vorinostat	decreases expression	1
Arsenic	decreases expression, increases abundance	1
Benzo(a)pyrene	increases methylation	1
Cisplatin	increases expression	1
Diazinon	increases methylation	1
Estradiol	affects expression	1
Ethyl Methanesulfonate	increases expression	1
Methyl Methanesulfonate	increases expression	1
Plant Extracts	increases expression, affects cotreatment, decreases expression	1
Silicon Dioxide	decreases expression	1
Smoke	decreases expression	1
Thiram	increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Tretinoin	decreases expression	1
Valproic Acid	increases expression	1
Cyclosporine	increases expression	1

ChEMBL screening assays

15 unique, capped per target: 15 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3995372	Binding	Inhibition of full length recombinant human His6-tagged PARP16 expressed in Escherichia coli BL21(DE3) preincubated for 15 mins followed by biotinylated NAD+ addition by chemiluminescence assay	Structural Basis for Potency and Promiscuity in Poly(ADP-ribose) Polymerase (PARP) and Tankyrase Inhibitors. — J Med Chem

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_TC14	HAP1 PARP16 (-) 1	Cancer cell line	Male
CVCL_XR36	HAP1 PARP16 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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