PARP6

Summary

PARP6 (poly(ADP-ribose) polymerase family member 6, HGNC:26921) is a protein-coding gene on chromosome 15q23, encoding Protein mono-ADP-ribosyltransferase PARP6 (Q2NL67). Mono-ADP-ribosyltransferase that mediates mono-ADP-ribosylation of target proteins.

Enables NAD+-protein-aspartate ADP-ribosyltransferase activity and NAD+-protein-cysteine ADP-ribosyltransferase activity. Involved in protein auto-ADP-ribosylation. Predicted to be active in endoplasmic reticulum tubular network and nuclear envelope.

Source: NCBI Gene 56965 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neurodevelopmental disorder (Strong, GenCC)
• GWAS associations: 2
• Clinical variants (ClinVar): 72 total
• Druggable target: yes — 2 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001323532

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26921
Approved symbol	PARP6
Name	poly(ADP-ribose) polymerase family member 6
Location	15q23
Locus type	gene with protein product
Status	Approved
Aliases	pART17, ARTD17
Ensembl gene	ENSG00000137817
Ensembl biotype	protein_coding
OMIM	619439
Entrez	56965

Gene structure

Transcript identifiers

Ensembl transcripts: 39 — 25 protein_coding, 7 nonsense_mediated_decay, 4 retained_intron, 3 protein_coding_CDS_not_defined

ENST00000287196, ENST00000413097, ENST00000419739, ENST00000544520, ENST00000564610, ENST00000565443, ENST00000565999, ENST00000566831, ENST00000566844, ENST00000566991, ENST00000567042, ENST00000567263, ENST00000567440, ENST00000567633, ENST00000567974, ENST00000568213, ENST00000568360, ENST00000569173, ENST00000569795, ENST00000569890, ENST00000569972, ENST00000907967, ENST00000907968, ENST00000907969, ENST00000907970, ENST00000907971, ENST00000907972, ENST00000907973, ENST00000907974, ENST00000907975, ENST00000952256, ENST00000952257, ENST00000952258, ENST00000952259, ENST00000952260, ENST00000952261, ENST00000952262, ENST00000952263, ENST00000952264

RefSeq mRNA: 14 — MANE Select: NM_001323532 NM_001323515, NM_001323516, NM_001323519, NM_001323521, NM_001323522, NM_001323523, NM_001323524, NM_001323525, NM_001323526, NM_001323528, NM_001323530, NM_001323531, NM_001323532, NM_020214

CCDS: CCDS10241

Canonical transcript exons

ENST00000569795 — 24 exons

Exon	Start	End
ENSE00000931780	72260478	72260688
ENSE00001483033	72271023	72271287
ENSE00001623050	72241181	72241557
ENSE00001791848	72266745	72266822
ENSE00002611249	72272393	72272554
ENSE00003464576	72258037	72258132
ENSE00003470083	72256465	72256590
ENSE00003471061	72242620	72242699
ENSE00003471317	72250845	72250954
ENSE00003472650	72265413	72265473
ENSE00003482371	72253437	72253504
ENSE00003504865	72259608	72259661
ENSE00003535433	72267475	72267671
ENSE00003537723	72264555	72264621
ENSE00003546678	72265081	72265171
ENSE00003550643	72249245	72249314
ENSE00003561452	72254455	72254520
ENSE00003562293	72241901	72241985
ENSE00003575143	72257348	72257440
ENSE00003618353	72242157	72242220
ENSE00003633955	72250020	72250092
ENSE00003648979	72265897	72265991
ENSE00003682261	72251207	72251255
ENSE00003694609	72261558	72261707

Expression profiles

Bgee: expression breadth ubiquitous, 289 present calls, max score 98.89.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 26.0870 / max 283.1428, expressed in 1803 samples.

FANTOM5 promoters (12 alternative TSS)

Promoter ID	TPM avg	Samples expressed
150816	11.4025	1755
150820	6.2394	1490
150817	3.9999	1526
150824	1.6272	583
150819	0.8476	455
150823	0.8162	324
150821	0.4279	223
150818	0.3820	201
150814	0.1561	31
150815	0.1379	48

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	98.89	gold quality
left testis	UBERON:0004533	98.53	gold quality
right testis	UBERON:0004534	98.51	gold quality
right lobe of thyroid gland	UBERON:0001119	98.17	gold quality
left lobe of thyroid gland	UBERON:0001120	98.15	gold quality
right uterine tube	UBERON:0001302	97.99	gold quality
left ovary	UBERON:0002119	97.99	gold quality
ganglionic eminence	UBERON:0004023	97.98	gold quality
adenohypophysis	UBERON:0002196	97.94	gold quality
right ovary	UBERON:0002118	97.92	gold quality
right hemisphere of cerebellum	UBERON:0014890	97.72	gold quality
cerebellar hemisphere	UBERON:0002245	97.68	gold quality
cerebellar cortex	UBERON:0002129	97.64	gold quality
thyroid gland	UBERON:0002046	97.63	gold quality
pituitary gland	UBERON:0000007	97.46	gold quality
body of pancreas	UBERON:0001150	97.45	gold quality
body of uterus	UBERON:0009853	97.41	gold quality
metanephros cortex	UBERON:0010533	97.33	gold quality
muscle layer of sigmoid colon	UBERON:0035805	97.32	gold quality
endocervix	UBERON:0000458	97.16	gold quality
lower esophagus	UBERON:0013473	97.16	gold quality
lower esophagus muscularis layer	UBERON:0035833	97.16	gold quality
tibial nerve	UBERON:0001323	97.06	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	97.06	gold quality
cerebellum	UBERON:0002037	97.02	gold quality
right frontal lobe	UBERON:0002810	96.87	gold quality
right adrenal gland cortex	UBERON:0035827	96.86	gold quality
left uterine tube	UBERON:0001303	96.82	gold quality
skin of abdomen	UBERON:0001416	96.78	gold quality
testis	UBERON:0000473	96.63	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-6678	yes	10.47
E-ANND-3	yes	5.46
E-MTAB-6142	no	80.97

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

23 targeting PARP6, 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-3134	100.00	66.43	777
HSA-MIR-4493	99.90	66.48	977
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-3065-3P	99.87	70.25	1407
HSA-MIR-6852-5P	99.17	66.69	2073
HSA-MIR-4651	99.06	67.57	2002
HSA-MIR-939-3P	98.97	65.07	2347
HSA-MIR-5701	98.97	69.54	1502
HSA-MIR-608	98.93	67.83	2013
HSA-MIR-4436B-3P	98.25	65.26	1494
HSA-MIR-6735-5P	98.24	65.36	1488
HSA-MIR-6881-5P	98.16	67.38	665
HSA-MIR-7843-5P	98.12	65.26	1421
HSA-MIR-4483	98.09	64.12	1642
HSA-MIR-6742-3P	97.95	64.50	1490
HSA-MIR-4632-5P	97.82	65.38	1470
HSA-MIR-6879-5P	97.77	65.52	1521
HSA-MIR-1913	97.07	66.20	1417
HSA-MIR-3616-3P	96.96	65.45	983
HSA-MIR-7847-3P	96.63	64.58	952
HSA-MIR-1226-5P	96.50	65.28	643
HSA-MIR-1293	96.16	64.69	916

Literature-anchored findings (GeneRIF, showing 4)

• PARP6, a mono(ADP-ribosyl) transferase and a negative regulator of cell proliferation, is involved in colorectal cancer development, PARP6-positive colorectal cancer had a good prognosis. (PMID:23042038)
• PARP6 acts as a tumor suppressor via downregulating Survivin expression in CRC. PARP6 can be a novel diagnostic and therapeutic target together with Survivin for CRC. (PMID:26934315)
• Results showed that both PARP6 and survivin exhibited higher expression in colorectal adenocarcinoma tissues and cell lines. knockdown of either PARP6 or survivin promotes cell apoptosis and inhibits the cell invasion of colorectal adenocarcinoma cells suggesting a significant correlation between theses 2 proteins. (PMID:28260087)
• Characterization of PARP6 Function in Knockout Mice and Patients with Developmental Delay. (PMID:34067418)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	parp6a	ENSDARG00000042703
danio_rerio	parp6b	ENSDARG00000070473
danio_rerio		ENSDARG00000116666
mus_musculus	Parp6	ENSMUSG00000025237
rattus_norvegicus	Parp6	ENSRNOG00000011199

Paralogs (2): PARP16 (ENSG00000138617), PARP8 (ENSG00000151883)

Protein

Protein identifiers

Protein mono-ADP-ribosyltransferase PARP6 — Q2NL67 (reviewed: Q2NL67)

Alternative names: ADP-ribosyltransferase diphtheria toxin-like 17, Poly [ADP-ribose] polymerase 6

All UniProt accessions (13): Q2NL67, F5H3B4, H3BMA3, H3BQ70, H3BQK2, H3BQM7, H3BRR4, H3BRZ3, H3BSK7, H3BTE2, H3BTI3, H3BUQ6, H3BUY2

UniProt curated annotations — full annotation on UniProt →

Function. Mono-ADP-ribosyltransferase that mediates mono-ADP-ribosylation of target proteins.

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

Similarity. Belongs to the ARTD/PARP family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q2NL67-1	1, PARP6-FL	yes
Q2NL67-2	2, PARP6-S
Q2NL67-3	3

RefSeq proteins (14): NP_001310444, NP_001310445, NP_001310448, NP_001310450, NP_001310451, NP_001310452, NP_001310453, NP_001310454, NP_001310455, NP_001310457, NP_001310459, NP_001310460, NP_001310461, NP_064599 (=MANE)

Domains & families (InterPro)

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

Pfam: PF00644

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), 2 shown:

• L-aspartyl-[protein] + NAD(+) = 4-O-(ADP-D-ribosyl)-L-aspartyl-[protein] + nicotinamide (RHEA:54424)
• L-cysteinyl-[protein] + NAD(+) = S-(ADP-D-ribosyl)-L-cysteinyl-[protein] + nicotinamide + H(+) (RHEA:56612)

UniProt features (12 total): sequence conflict 4, splice variant 4, modified residue 2, chain 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q2NL67-F1	74.08	0.42

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 (2): 237, 600

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: 202 (showing top): GOBP_DENDRITE_DEVELOPMENT, GCACCTT_MIR18A_MIR18B, SHEPARD_BMYB_MORPHOLINO_UP, ACTACCT_MIR196A_MIR196B, GOBP_REGULATION_OF_CELL_MORPHOGENESIS, GOBP_RESPONSE_TO_ENDOPLASMIC_RETICULUM_STRESS, GOBP_REGULATION_OF_DENDRITE_MORPHOGENESIS, GCM_ZNF198, GCM_PPM1D, AP4_Q6, GOBP_NEUROGENESIS, GOBP_REGULATION_OF_NERVOUS_SYSTEM_DEVELOPMENT, ACTGCAG_MIR173P, GOBP_POSITIVE_REGULATION_OF_NERVOUS_SYSTEM_DEVELOPMENT, CAGCTG_AP4_Q5

GO Biological Process (3): endoplasmic reticulum unfolded protein response (GO:0030968), positive regulation of dendrite morphogenesis (GO:0050775), protein auto-ADP-ribosylation (GO:0070213)

GO Molecular Function (8): 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-cysteine ADP-ribosyltransferase activity (GO:0140803), NAD+-protein-aspartate ADP-ribosyltransferase activity (GO:0140806), transferase activity (GO:0016740), glycosyltransferase activity (GO:0016757)

GO Cellular Component (3): nuclear envelope (GO:0005635), 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	2
cellular response to unfolded protein	1
response to endoplasmic reticulum stress	1
intracellular signal transduction	1
positive regulation of cell morphogenesis	1
positive regulation of cell projection organization	1
dendrite morphogenesis	1
regulation of dendrite morphogenesis	1
positive regulation of neurogenesis	1
post-translational protein modification	1
pentosyltransferase activity	1
transferase activity, transferring phosphorus-containing groups	1
enzyme binding	1
protein serine/threonine kinase activity	1
protein kinase activator activity	1
catalytic activity	1
transferase activity	1
nucleus	1
endomembrane system	1
organelle envelope	1
cellular anatomical structure	1
endoplasmic reticulum subcompartment	1

Protein interactions and networks

STRING

2372 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PARP6	PARP3	Q9Y6F1	739
PARP6	PARP4	Q9UKK3	737
PARP6	PARP10	Q53GL7	716
PARP6	PARP15	Q460N3	705
PARP6	PARP11	Q9NR21	684
PARP6	PARP14	Q460N5	673
PARP6	PARP12	Q9H0J9	670
PARP6	PARP2	Q9UGN5	661
PARP6	PARP9	Q8IXQ6	637
PARP6	ZC3HAV1	Q7Z2W4	616
PARP6	TNKS2	Q9H2K2	610
PARP6	TNKS	O95271	607
PARP6	TIPARP	Q7Z3E1	580
PARP6	MACROD1	Q9BQ69	543
PARP6	PARP1	P09874	489

IntAct

0 interactions, top by confidence:

BioGRID (14): PARP6 (Protein-RNA), PARP6 (Affinity Capture-RNA), PARP6 (Cross-Linking-MS (XL-MS)), PARP6 (Affinity Capture-RNA), ANKMY2 (Co-fractionation), ARIH2 (Co-fractionation), NSFL1C (Co-fractionation), PARP6 (Co-fractionation), PARP6 (Co-fractionation), PARP6 (Co-fractionation), PARP6 (Co-fractionation), PLIN3 (Co-fractionation), RPRD1A (Co-fractionation), SURF2 (Co-fractionation)

ESM2 similar proteins: A2VEA3, B1H1E4, D3Z7P3, F1LSG8, O89050, O94925, P13264, P50876, P97834, Q07G17, Q08211, Q12800, Q13042, Q28141, Q28D01, Q2NL67, Q32NS4, Q3MHJ2, Q4R9A8, Q4VC33, Q5F398, Q5NVP9, Q5R532, Q5R874, Q5RB35, Q5RBB8, Q5RBN9, Q5RKJ1, Q6AYU1, Q6GR10, Q6NRT5, Q6NW85, Q6PFJ9, Q7L5Y9, Q7SXR3, Q7Z6J6, Q86TJ2, Q8C6G8, Q8CI71, Q8R349

Diamond homologs: Q2NL67, Q3UD82, Q5RDU4, Q6P6P7, Q8N3A8

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	48
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

3145 predictions. Top by Δscore:

Variant	Effect	Δscore
15:72241899:A:AC	donor_gain	1.0000
15:72241900:C:CC	donor_gain	1.0000
15:72241900:CA:C	donor_gain	1.0000
15:72241983:TCA:T	acceptor_gain	1.0000
15:72241984:CA:C	acceptor_gain	1.0000
15:72241984:CAC:C	acceptor_gain	1.0000
15:72241986:C:CC	acceptor_gain	1.0000
15:72242002:C:CT	acceptor_gain	1.0000
15:72249312:CAGCT:C	acceptor_gain	1.0000
15:72249316:T:C	acceptor_gain	1.0000
15:72249316:T:TC	acceptor_gain	1.0000
15:72250089:CCCA:C	acceptor_gain	1.0000
15:72250090:CCA:C	acceptor_gain	1.0000
15:72250090:CCAC:C	acceptor_gain	1.0000
15:72250091:CA:C	acceptor_gain	1.0000
15:72250091:CAC:C	acceptor_gain	1.0000
15:72250093:C:CC	acceptor_gain	1.0000
15:72250838:T:TA	donor_gain	1.0000
15:72250843:A:AC	donor_gain	1.0000
15:72250844:C:CC	donor_gain	1.0000
15:72250973:G:GC	acceptor_gain	1.0000
15:72250980:C:CT	acceptor_gain	1.0000
15:72250981:A:T	acceptor_gain	1.0000
15:72251202:CTTA:C	donor_loss	1.0000
15:72251203:TTACC:T	donor_loss	1.0000
15:72251204:TACCC:T	donor_loss	1.0000
15:72251205:AC:A	donor_gain	1.0000
15:72251206:CC:C	donor_gain	1.0000
15:72251206:CCCTG:C	donor_gain	1.0000
15:72251267:C:CT	acceptor_gain	1.0000

AlphaMissense

4163 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:72241537:C:T	G604D	1.000
15:72241538:C:G	G604R	1.000
15:72241904:A:G	F596S	1.000
15:72241910:A:G	F594S	1.000
15:72241912:T:A	R593S	1.000
15:72241912:T:G	R593S	1.000
15:72241913:C:A	R593I	1.000
15:72241913:C:G	R593T	1.000
15:72241914:T:C	R593G	1.000
15:72241918:G:C	C591W	1.000
15:72241922:A:T	V590D	1.000
15:72241939:G:C	C584W	1.000
15:72241940:C:T	C584Y	1.000
15:72241941:A:G	C584R	1.000
15:72241943:A:T	V583E	1.000
15:72241945:C:A	W582C	1.000
15:72241945:C:G	W582C	1.000
15:72241947:A:G	W582R	1.000
15:72241947:A:T	W582R	1.000
15:72241967:A:G	L575P	1.000
15:72241967:A:T	L575H	1.000
15:72241982:A:T	I570N	1.000
15:72242159:T:A	E568V	1.000
15:72242161:A:C	C567W	1.000
15:72242162:C:T	C567Y	1.000
15:72242163:A:G	C567R	1.000
15:72242165:A:G	L566P	1.000
15:72242165:A:T	L566H	1.000
15:72242168:G:T	A565E	1.000
15:72242169:C:G	A565P	1.000

dbSNP variants (sampled 300 via entrez): RS1000060414 (15:72271504 A>C), RS1000182470 (15:72244705 C>T), RS1000228961 (15:72258976 G>A), RS1000281 (15:72261081 T>C), RS1000486002 (15:72254087 T>C,G), RS1000524322 (15:72249125 G>A), RS1000749596 (15:72243197 A>G), RS1000948951 (15:72263036 T>C), RS1000999246 (15:72271250 GC>G), RS1001090467 (15:72255469 G>A,T), RS1001099065 (15:72265829 C>T), RS1001323647 (15:72271460 A>C), RS1001351621 (15:72261428 G>C,T), RS1001368326 (15:72270156 G>A,C), RS1001369327 (15:72274369 C>T)

Disease associations

OMIM: gene MIM:619439 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
neurodevelopmental disorder	Strong	Autosomal dominant

Mondo (1): neurodevelopmental disorder (MONDO:0700092)

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST004371_1	Rate of cognitive decline in mild cognitive impairment (time interaction)	1.000000e-15
GCST90011898_41	Alanine aminotransferase levels	5.000000e-08

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0007710	cognitive decline measurement
EFO:0008336	disease progression measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2380187 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

2 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 13,395 (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
CHEMBL521686	OLAPARIB	4	13,038
CHEMBL5095220	SARUPARIB	3	357

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

ChEMBL bioactivities

13 potent at pChembl≥5 of 33 total, top 12 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.02	IC50	9.5	nM	CHEMBL5402698
7.08	IC50	83	nM	CHEMBL3740897
6.92	IC50	120	nM	OLAPARIB
6.25	IC50	560.7	nM	OLAPARIB
6.19	IC50	640	nM	CHEMBL3740104
5.75	IC50	1800	nM	OLAPARIB
5.58	IC50	2600	nM	CHEMBL5199558
5.46	IC50	3480	nM	OLAPARIB
5.11	IC50	7700	nM	CHEMBL5404785
5.09	IC50	8200	nM	CHEMBL5968553
5.00	IC50	1e+04	nM	CHEMBL5841887
5.00	IC50	1e+04	nM	CHEMBL5750305

PubChem BioAssay actives

9 with measured affinity, of 33 total; 6 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-[[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	2012700: Inhibition of PARP6 (unknown origin) using biotinylated NAD+ as substrate by luminescence assay	ic50	0.0095	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	1265317: Inhibition of full length human PARP6 expressed in a Baculovirus infected Sf9 insect cells using activated DNA as substrate after 1 hr by streptavidin-horseradish peroxidase-based luminescence assay	ic50	0.0830	uM
Olaparib	2019986: Inhibition of human recombinant N-terminal GST-tagged PARP6 (1 to 630(end) residues) expressed in Sf9 cells	ic50	0.1200	uM
2-[4-[3-[(4-oxo-3H-phthalazin-1-yl)methyl]benzoyl]piperazin-1-yl]pyridine-3-carbonitrile	1265317: Inhibition of full length human PARP6 expressed in a Baculovirus infected Sf9 insect cells using activated DNA as substrate after 1 hr by streptavidin-horseradish peroxidase-based luminescence assay	ic50	0.6400	uM
3-[4-(2-hydroxypropan-2-yl)phenyl]-6-methyl-2H-pyrrolo[1,2-a]pyrazin-1-one	1925208: Inhibition of N-terminal GST-tagged human recombinant PARP6 (1 to 630 residues) expressed in Sf9 insect cells by chemiluminescence assay	ic50	2.6000	uM
5,8-dimethoxy-[1,2,4]triazolo[3,4-b][1,3]benzothiazol-1-amine	1965921: Inhibition of N-terminal 6 His-MBP tagged human PARP6 expressed in Sf21 cells incubated for 18 hrs in presence of NAD+	ic50	7.7000	uM

CTD chemical–gene interactions

24 total (human), top 24 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases abundance, decreases expression	2
Air Pollutants	increases expression, affects cotreatment, decreases expression, increases abundance	2
alpha-pinene	increases abundance, affects cotreatment, decreases expression	1
manganese chloride	decreases expression, increases abundance	1
potassium chromate(VI)	increases expression, affects cotreatment	1
methacrylaldehyde	affects cotreatment, decreases expression, increases abundance	1
epigallocatechin gallate	affects cotreatment, increases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
CGP 52608	affects binding, increases reaction	1
abrine	increases expression	1
Bortezomib	decreases expression	1
Sunitinib	increases expression	1
Acrolein	affects cotreatment, decreases expression, increases abundance	1
Arsenic	increases abundance, decreases expression	1
Benzo(a)pyrene	affects methylation	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Doxorubicin	decreases expression	1
Manganese	decreases expression, increases abundance	1
Methyl Methanesulfonate	increases expression	1
Ozone	affects cotreatment, decreases expression, increases abundance	1
Aflatoxin B1	increases methylation	1
Particulate Matter	increases expression, increases abundance	1
Volatile Organic Compounds	affects cotreatment, decreases expression	1

ChEMBL screening assays

21 unique, capped per target: 21 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2382484	Binding	Inhibition of PARP6 (unknown origin)	Fragment-based ligand design of novel potent inhibitors of tankyrases. — J Med Chem

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_TC21	HAP1 PARP6 (-) 1	Cancer cell line	Male
CVCL_TC22	HAP1 PARP6 (-) 2	Cancer cell line	Male
CVCL_TC23	HAP1 PARP6 (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT01783041	PHASE2/PHASE3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	PHASE2/PHASE3	RECRUITING	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	EARLY_PHASE1	NOT_YET_RECRUITING	Central Nervous System Stimulants and Physical Function in Children With Cerebral Palsy
NCT00783783	Not specified	COMPLETED	CYP2D6 Pharmacogenetics in Risperidone-Treated Children
NCT01778504	Not specified	RECRUITING	Studying Childhood-onset Behavioral, Psychiatric, and Developmental Disorders
NCT01850784	Not specified	UNKNOWN	High Energy Formula Feeding in Infants With Congenital Heart Disease
NCT01922791	Not specified	COMPLETED	Nutrition and Pregnancy Intervention Study
NCT01942525	Not specified	UNKNOWN	Influence of Intrauterine Growth Restriction on Amplitude-integrated EEG in Preterm Infants
NCT02003170	Not specified	COMPLETED	Etiology and Early Diagnosis of Neurodevelopmental Disorders
NCT02118649	Not specified	ACTIVE_NOT_RECRUITING	Enhancing Behavior and Brain Response to Visual Targets Using a Computer Game
NCT02557191	Not specified	TERMINATED	Biomarkers, Neurodevelopment and Preterm Infants
NCT02690675	Not specified	COMPLETED	Iron Supplement Effect on Child Development
NCT02694003	Not specified	COMPLETED	Better Nights, Better Days for Children With Neurodevelopment Disorders
NCT02792894	Not specified	COMPLETED	Family Networks (FaNs) for Children With Developmental Disorders and Delays
NCT02871674	Not specified	UNKNOWN	Good Night Project: Behavioural Sleep Interventions for Children With ADHD: A Randomised Controlled Trial
NCT02887157	Not specified	COMPLETED	Analyzing Retinal Microanatomy in ROP
NCT02898298	Not specified	COMPLETED	Positive Emotion Regulation Training in Children, Adolescents and Young Adults With and Without Developmental Disorder
NCT02912780	Not specified	UNKNOWN	Introduction of Microsystems in a Level 3 Neonatal Intensive Care Unit
NCT03023293	Not specified	COMPLETED	n-3 PUFAs, Irisin and Maternal Glucose Metabolism From Pregnancy to Postpartum
NCT03023644	Not specified	COMPLETED	Improving Neurodevelopmental Outcomes in Children With Congenital Heart Disease: An Intervention Study
NCT03032991	Not specified	UNKNOWN	Early Biomarkers of Neurodevelopment in Offspring of Diabetic Mothers
NCT03088189	Not specified	TERMINATED	Effect of Parental Peri-conceptional Vitamin B12 Supplementation on Infant Neurocognitive Development in Offspring
NCT03096028	Not specified	COMPLETED	Developmental Origins of Mental Health Disorders
NCT03148782	Not specified	COMPLETED	Brain Plasticity Underlying Acquisition of New Organizational Skills in Children-R61 Phase
NCT03172104	Not specified	COMPLETED	Neurobehavioural Development of Infants Born <30 Weeks Gestational Age Between Birth and Five Years of Age
NCT03222375	Not specified	RECRUITING	SQUED™ Series 28.1 Home-use and Treatment of Autowave Reverberator of Autism
NCT03229928	Not specified	COMPLETED	Clinical Testing of a Real-Time Behavior Measurement Tool: Measuring Outcomes for CHAnge
NCT03232489	Not specified	UNKNOWN	Study for the Evaluation of the Feasibility of Applying Advanced MRI Scanning in Pediatric Clinical Practice