TENT4A

Summary

TENT4A (terminal nucleotidyltransferase 4A, HGNC:16705) is a protein-coding gene on chromosome 5p15.31, encoding Terminal nucleotidyltransferase 4A (Q5XG87). Terminal nucleotidyltransferase that catalyzes preferentially the transfer of ATP and GTP on RNA 3’ poly(A) tail creating a heterogeneous 3’ poly(A) tail leading to mRNAs stabilization by protecting mRNAs from active deadenylation.

The protein encoded by this gene is a DNA polymerase that is likely involved in DNA repair. In addition, the encoded protein may be required for sister chromatid adhesion. Alternatively spliced transcript variants that encode different isoforms have been described.

Source: NCBI Gene 11044 — RefSeq curated summary.

At a glance

• GWAS associations: 9
• Clinical variants (ClinVar): 89 total — 1 pathogenic
• Druggable target: yes
• MANE Select transcript: NM_006999

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16705
Approved symbol	TENT4A
Name	terminal nucleotidyltransferase 4A
Location	5p15.31
Locus type	gene with protein product
Status	Approved
Aliases	POLK, TRF4, LAK-1, TRF4-1
Ensembl gene	ENSG00000112941
Ensembl biotype	protein_coding
OMIM	605198
Entrez	11044

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 7 protein_coding, 4 retained_intron

ENST00000230859, ENST00000505457, ENST00000511764, ENST00000514410, ENST00000514697, ENST00000515721, ENST00000631941, ENST00000932304, ENST00000932305, ENST00000955123, ENST00000955124

RefSeq mRNA: 2 — MANE Select: NM_006999 NM_001171805, NM_006999

CCDS: CCDS3871

Canonical transcript exons

ENST00000230859 — 13 exons

Exon	Start	End
ENSE00001216238	6754751	6757044
ENSE00001306157	6737510	6737633
ENSE00001416802	6713432	6714699
ENSE00003784399	6738683	6738729
ENSE00003784457	6752873	6753037
ENSE00003785525	6751039	6751197
ENSE00003785649	6739732	6739852
ENSE00003786885	6742490	6742597
ENSE00003787825	6746214	6746427
ENSE00003788425	6748464	6748590
ENSE00003789074	6750331	6750503
ENSE00003790522	6743712	6743840
ENSE00003791144	6749557	6749657

Expression profiles

Bgee: expression breadth ubiquitous, 293 present calls, max score 99.98.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 11.7904 / max 148.7481, expressed in 1795 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
55638	6.5379	1724
55639	3.3975	1293
55640	1.4710	1020
55641	0.3840	197

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	99.98	gold quality
oocyte	CL:0000023	99.62	gold quality
tibia	UBERON:0000979	94.74	gold quality
cartilage tissue	UBERON:0002418	94.63	gold quality
upper leg skin	UBERON:0004262	94.31	gold quality
middle temporal gyrus	UBERON:0002771	94.27	gold quality
skin of hip	UBERON:0001554	92.42	gold quality
cervix squamous epithelium	UBERON:0006922	92.12	silver quality
Brodmann (1909) area 23	UBERON:0013554	91.97	gold quality
hair follicle	UBERON:0002073	91.86	gold quality
gingival epithelium	UBERON:0001949	91.18	gold quality
tongue squamous epithelium	UBERON:0006919	91.18	gold quality
squamous epithelium	UBERON:0006914	90.95	gold quality
skin of abdomen	UBERON:0001416	90.32	gold quality
parietal pleura	UBERON:0002400	90.29	gold quality
mammalian vulva	UBERON:0000997	90.22	gold quality
pleura	UBERON:0000977	90.00	gold quality
right hemisphere of cerebellum	UBERON:0014890	89.91	gold quality
left ovary	UBERON:0002119	89.85	gold quality
esophagus squamous epithelium	UBERON:0006920	89.85	gold quality
zone of skin	UBERON:0000014	89.65	gold quality
skin of leg	UBERON:0001511	89.54	gold quality
cerebellar hemisphere	UBERON:0002245	89.49	gold quality
cerebellum	UBERON:0002037	89.43	gold quality
body of uterus	UBERON:0009853	89.42	gold quality
right ovary	UBERON:0002118	89.40	gold quality
cerebellar cortex	UBERON:0002129	89.36	gold quality
gingiva	UBERON:0001828	89.35	gold quality
sural nerve	UBERON:0015488	89.30	gold quality
epithelium of nasopharynx	UBERON:0001951	89.20	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.28

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ARID3B, TBP

miRNA regulators (miRDB)

88 targeting TENT4A, 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-3613-3P	100.00	76.36	7965
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-6793-5P	99.97	65.95	758
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-6845-3P	99.94	66.88	1439
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-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-3663-3P	99.84	70.39	798
HSA-MIR-548AZ-3P	99.82	70.56	3549
HSA-MIR-548BC	99.82	70.61	3524

Literature-anchored findings (GeneRIF, showing 6)

• These results suggest that PAPD7 l is the major and active isoform of PAPD7 expressed in cells. (PMID:23376078)
• TENT4A and TENT4B produce a mixed tail that shields mRNA from rapid deadenylation. (PMID:30026317)
• Viral hijacking of the TENT4-ZCCHC14 complex protects viral RNAs via mixed tailing. (PMID:32451488)
• Chemical inhibition of PAPD5/7 rescues telomerase function and hematopoiesis in dyskeratosis congenita. (PMID:32559291)
• TENT4A Non-Canonical Poly(A) Polymerase Regulates DNA-Damage Tolerance via Multiple Pathways That Are Mutated in Endometrial Cancer. (PMID:34203408)
• The ZCCHC14/TENT4 complex is required for hepatitis A virus RNA synthesis. (PMID:35867748)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	tent4a	ENSDARG00000062114
mus_musculus	Tent4a	ENSMUSG00000034575
rattus_norvegicus	Tent4a	ENSRNOG00000017613
drosophila_melanogaster	Trf4-1	FBGN0030049
drosophila_melanogaster	Trf4-2	FBGN0039251
caenorhabditis_elegans	gld-4	WBGENE00014115

Paralogs (1): TENT4B (ENSG00000121274)

Protein

Protein identifiers

Terminal nucleotidyltransferase 4A — Q5XG87 (reviewed: Q5XG87)

Alternative names: DNA polymerase sigma, LAK-1, Non-canonical poly(A) RNA polymerase PAPD7, PAP-associated domain-containing protein 7, TRAMP-like complex polyadenylate polymerase, Terminal guanylyltransferase, Terminal uridylyltransferase 5, Topoisomerase-related function protein 4-1

All UniProt accessions (3): A0A9H4DBI9, D6RJD0, Q5XG87

UniProt curated annotations — full annotation on UniProt →

Function. Terminal nucleotidyltransferase that catalyzes preferentially the transfer of ATP and GTP on RNA 3’ poly(A) tail creating a heterogeneous 3’ poly(A) tail leading to mRNAs stabilization by protecting mRNAs from active deadenylation. Also functions as a catalytic subunit of a TRAMP-like complex which has a poly(A) RNA polymerase activity and is involved in a post-transcriptional quality control mechanism. Polyadenylation with short oligo(A) tails is required for the degradative activity of the exosome on several of its nuclear RNA substrates. Has no terminal uridylyltransferase activity, and does not play a role in replication-dependent histone mRNA degradation via uridylation.

Subunit / interactions. Component of a nuclear TRAMP-like complex, an ATP-dependent exosome regulatory complex consisting of a helicase (MTREX), an oligadenylate polymerase (TENT4B or TENT4A), and a substrate specific RNA-binding factor (ZCCHC7 or ZCCHC8). Several TRAMP-like complexes exist with specific compositions and are associated with nuclear, or nucleolar RNA exosomes.

Subcellular location. Cytoplasm. Nucleus. Nucleoplasm.

Miscellaneous. Exhibits poor nucleotidyl transferase activity.

Similarity. Belongs to the DNA polymerase type-B-like family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q5XG87-1	1, l	yes
Q5XG87-2	2, s

RefSeq proteins (2): NP_001165276, NP_008930* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002058	PAP_assoc	Domain
IPR043519	NT_sf	Homologous_superfamily
IPR045862	Trf4-like	Family
IPR054708	MTPAP-like_central	Domain

Pfam: PF03828, PF22600

Enzyme classification (BRENDA):

• EC 2.7.7.19 — polynucleotide adenylyltransferase (BRENDA: 35 organisms, 181 substrates, 125 inhibitors, 114 Km, 53 kcat entries)

Substrate kinetics (BRENDA)

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

Substrate	Km (mM)	Measurements
ATP	0.028–2.191	54
RNA (A)15	0.51–24.99	23
CTP	0.1036–4.7	7
(A)N	0.0468–0.711	5
OLIGO(A)14	0.0005–0.037	5
(A)15	0.0009–0.0053	3
GTP	0.055–0.062	2
OLIGO(A)18	0.0468–0.0642	2
OLIGO(A)N	0.01–0.3	2
2-AMINOPURINE RIBOSIDE TRIPHOSPHATE	0.0197	1
DATP	0.06	1
OLIGO(A)12	0.0004	1
OLIGO(A)17C	0.0263	1
OLIGOADENYLATE	0.2	1
POLY(A)N	0.0036	1

Catalyzed reactions (Rhea), 1 shown:

• RNA(n) + ATP = RNA(n)-3’-adenine ribonucleotide + diphosphate (RHEA:11332)

UniProt features (22 total): binding site 8, compositionally biased region 5, region of interest 3, sequence variant 2, chain 1, domain 1, splice variant 1, mutagenesis site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5XG87-F1	62.58	0.37

Functional residue map

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

Ligand- & substrate-binding residues (8): 297; 299; 360; 385; 403; 404; 488; 492

Mutagenesis-validated functional residues (1):

Position	Phenotype
187–250	localizes to cytoplasm.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-6802952	Signaling by BRAF and RAF1 fusions
R-HSA-9930044	Nuclear RNA decay

MSigDB gene sets: 450 (showing top): RNGTGGGC_UNKNOWN, GOBP_CHROMOSOME_ORGANIZATION, RRAGTTGT_UNKNOWN, GOBP_REGULATION_OF_MRNA_CATABOLIC_PROCESS, GOBP_CELLULAR_RESPONSE_TO_UV, GOBP_CELLULAR_RESPONSE_TO_LIGHT_STIMULUS, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GEORGES_CELL_CYCLE_MIR192_TARGETS, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, GOBP_3_UTR_MEDIATED_MRNA_STABILIZATION, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_DNA_DAMAGE_TOLERANCE, RIZKI_TUMOR_INVASIVENESS_3D_DN, KAUFFMANN_DNA_REPAIR_GENES, CTATGCA_MIR153

GO Biological Process (10): double-strand break repair (GO:0006302), mRNA processing (GO:0006397), RNA catabolic process (GO:0006401), sister chromatid cohesion (GO:0007062), mitotic chromosome condensation (GO:0007076), response to xenobiotic stimulus (GO:0009410), RNA 3’-end processing (GO:0031123), polyadenylation-dependent ncRNA catabolic process (GO:0043634), negative regulation of nuclear-transcribed mRNA poly(A) tail shortening (GO:0060212), positive regulation of 3’-UTR-mediated mRNA stabilization (GO:1905870)

GO Molecular Function (10): ATP binding (GO:0005524), SMC family protein binding (GO:0043221), metal ion binding (GO:0046872), adenylyltransferase activity (GO:0070566), guanylyltransferase activity (GO:0070568), poly(A) RNA polymerase activity (GO:1990817), nucleotide binding (GO:0000166), protein binding (GO:0005515), transferase activity (GO:0016740), nucleotidyltransferase activity (GO:0016779)

GO Cellular Component (7): nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730), Golgi apparatus (GO:0005794), TRAMP complex (GO:0031499), nuclear membrane (GO:0031965), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Oncogenic MAPK signaling	1
Metabolism of RNA	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA processing	2
nucleotidyltransferase activity	2
intracellular membrane-bounded organelle	2
nuclear lumen	2
cellular anatomical structure	2
DNA repair	1
mRNA metabolic process	1
RNA metabolic process	1
nucleic acid catabolic process	1
cell cycle process	1
chromosome organization	1
mitotic sister chromatid segregation	1
mitotic cell cycle	1
chromosome condensation	1
mitotic cell cycle process	1
response to chemical	1
polyadenylation-dependent RNA catabolic process	1
nuclear-transcribed mRNA poly(A) tail shortening	1
regulation of nuclear-transcribed mRNA poly(A) tail shortening	1
negative regulation of nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay	1
positive regulation of gene expression	1
3’-UTR-mediated mRNA stabilization	1
regulation of 3’-UTR-mediated mRNA stabilization	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
protein binding	1
cation binding	1
adenylyltransferase activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
catalytic activity	1
transferase activity, transferring phosphorus-containing groups	1
intracellular membraneless organelle	1
cytoplasm	1
endomembrane system	1
nuclear protein-containing complex	1
nucleus	1
nuclear envelope	1
organelle membrane	1

Protein interactions and networks

STRING

1274 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TENT4A	MTREX	P42285	997
TENT4A	ZCCHC7	Q8N3Z6	997
TENT4A	POLL	Q9UGP5	957
TENT4A	POLM	Q9NP87	947
TENT4A	URI1	O94763	822
TENT4A	PAPOLB	Q9NRJ5	817
TENT4A	PAPOLA	P51003	815
TENT4A	PAPOLG	Q9BWT3	815
TENT4A	PFDN2	Q9UHV9	776
TENT4A	EXOSC10	Q01780	760
TENT4A	REV1	Q9UBZ9	730
TENT4A	POLR2E	P19388	726
TENT4A	RAD18	Q9NS91	713
TENT4A	AARS2	Q5JTZ9	711
TENT4A	POLI	Q9UNA4	686

IntAct

11 interactions, top by confidence:

A	B	Type	Score
ARMC8	HTRA2	psi-mi:“MI:0914”(association)	0.750
GID8	HTRA2	psi-mi:“MI:0914”(association)	0.610
TENT4A	LRP6	psi-mi:“MI:0915”(physical association)	0.590
RMND5A	HTRA2	psi-mi:“MI:0914”(association)	0.350
TXNIP	ZSWIM8	psi-mi:“MI:0914”(association)	0.350
PTBP3		psi-mi:“MI:0914”(association)	0.350
SQSTM1	VWA8	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (20): PAPD7 (Affinity Capture-MS), PAPD7 (Affinity Capture-MS), LRP6 (Affinity Capture-MS), PAPD7 (Affinity Capture-RNA), PAPD7 (Proximity Label-MS), LRP6 (Affinity Capture-MS), PAPD7 (Affinity Capture-MS), PAPD7 (Affinity Capture-MS), PAPD7 (Affinity Capture-MS), PAPD7 (Affinity Capture-MS), PAPD7 (Negative Genetic), PAPD7 (Affinity Capture-MS), PAPD7 (Reconstituted Complex), PAPD7 (Protein-RNA), PAPD7 (Affinity Capture-RNA)

ESM2 similar proteins: A2A699, A5PKW4, A8MVW0, D3ZG83, E9PZZ1, F1MUS9, O14512, O14559, O15534, O35973, O95180, P09084, P22460, P22462, P50638, P79197, Q01956, Q02779, Q03721, Q09019, Q12852, Q14003, Q14B80, Q15569, Q29RK8, Q4ZHA6, Q5DTT2, Q5RBI7, Q5XG87, Q5XJV6, Q60700, Q61762, Q63572, Q63734, Q63796, Q63959, Q63HR2, Q66L42, Q80XF7, Q8BQU6

Diamond homologs: G5EFL0, P48561, P53632, Q5XG87, Q68ED3, Q6PB75, Q7KVS9, Q8NDF8, Q9HFW3, Q9UTN3, Q9VC07, Q5K9E2, O74518, Q9VD44, Q503I9

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
TENT4A	“form complex”	“NEXT complex, TENT4A-ZCCHC7 variant”	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	72
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
3062868	GRCh37/hg19 5p15.33-15.31(chr5:113576-7436985)x1	Pathogenic

SpliceAI

5809 predictions. Top by Δscore:

Variant	Effect	Δscore
5:6714697:GGG:G	donor_gain	1.0000
5:6714698:GGG:G	donor_gain	1.0000
5:6737504:CATTA:C	acceptor_loss	1.0000
5:6737505:ATTAG:A	acceptor_loss	1.0000
5:6737506:TTAGA:T	acceptor_loss	1.0000
5:6737508:A:AG	acceptor_gain	1.0000
5:6737508:AG:A	acceptor_loss	1.0000
5:6737509:G:GG	acceptor_gain	1.0000
5:6737553:T:TA	acceptor_gain	1.0000
5:6737638:G:GG	donor_gain	1.0000
5:6739726:T:TA	acceptor_gain	1.0000
5:6739730:A:AG	acceptor_gain	1.0000
5:6739730:AGC:A	acceptor_gain	1.0000
5:6739731:G:GA	acceptor_gain	1.0000
5:6739731:GC:G	acceptor_gain	1.0000
5:6739731:GCG:G	acceptor_gain	1.0000
5:6739731:GCGA:G	acceptor_gain	1.0000
5:6739731:GCGAC:G	acceptor_gain	1.0000
5:6739732:C:CA	acceptor_gain	1.0000
5:6739847:GC:G	donor_gain	1.0000
5:6739853:G:A	donor_loss	1.0000
5:6739853:G:GG	donor_gain	1.0000
5:6739854:TGAG:T	donor_loss	1.0000
5:6739855:GAGT:G	donor_loss	1.0000
5:6742486:ACAG:A	acceptor_loss	1.0000
5:6742487:CAGG:C	acceptor_loss	1.0000
5:6747709:T:G	donor_gain	1.0000
5:6748458:CTGCA:C	acceptor_loss	1.0000
5:6748459:TGCAG:T	acceptor_loss	1.0000
5:6748460:GCA:G	acceptor_loss	1.0000

AlphaMissense

5108 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000009135 (5:6727108 C>T), RS1000124072 (5:6731025 C>T), RS1000134809 (5:6727302 C>T), RS1000138173 (5:6718306 G>A), RS1000199581 (5:6747153 C>T), RS1000225301 (5:6755038 G>A), RS1000313828 (5:6713226 C>A,T), RS1000322313 (5:6717117 T>C), RS1000345524 (5:6728436 C>G,T), RS1000374275 (5:6722555 T>G), RS1000436846 (5:6717416 G>T), RS1000477727 (5:6732761 T>C), RS1000560685 (5:6754178 GT>G,GTT), RS1000584749 (5:6739245 C>T), RS1000660095 (5:6718477 A>C)

Disease associations

OMIM: gene MIM:605198 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST001413_1	Sphingolipid levels	1.000000e-08
GCST001929_2	Eye color	9.000000e-07
GCST002074_3	Paclitaxel-induced neuropathy	3.000000e-06
GCST004867_28	Systemic lupus erythematosus	5.000000e-06
GCST005196_80	Coronary artery disease	1.000000e-06
GCST005312_12	Menopause (age at onset)	4.000000e-09
GCST007231_9	Tuberculosis	5.000000e-06
GCST007559_19	Sleep duration (short sleep)	9.000000e-09
GCST009153_9	Adverse response to chemotherapy (amenorrhea) in breast cancer	1.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0003949	eye color
EFO:0004704	age at menopause

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4680033 (SINGLE PROTEIN)

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

PharmGKB clinical annotations

2 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs274713	Efficacy	3	gemcitabine	Pancreatic Neoplasms
rs274717	Efficacy	3	gemcitabine	Pancreatic Neoplasms

PharmGKB variants

2 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs274713	TENT4A	3	1.75	1	gemcitabine
rs274717	TENT4A	3	0.00	1	gemcitabine

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.30	IC50	498	nM	CHEMBL5573474
5.96	IC50	1100	nM	CHEMBL6143667

PubChem BioAssay actives

1 with measured affinity, of 4 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
(6S)-2-methoxy-3-(3-methoxypropoxy)-10-oxo-6-propan-2-yl-5,6-dihydropyrido[1,2-h][1,7]naphthyridine-9-carboxylic acid	2098384: Inhibition of recombinant human PAPD7 expressed in Escherichia coli BL21 (DE3) using 5’-GCCUUUCAUCUC UAACUGCGAAAAAAAAAA-3’ as RNA substrate incubated for 3 hrs in presence of ATP by ATP depletion based kinase-glo luminescent assay	ic50	0.4980	uM

CTD chemical–gene interactions

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	decreases expression	1
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
dicrotophos	increases expression	1
bisphenol A	decreases methylation	1
2-butenal	decreases expression	1
diethyl maleate	increases expression	1
cobaltous chloride	increases expression	1
di-n-butylphosphoric acid	affects expression	1
2-palmitoylglycerol	increases expression	1
Sunitinib	increases expression	1
Acetaminophen	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Atrazine	decreases expression	1
Benzo(a)pyrene	increases methylation	1
Cadmium	decreases expression, increases abundance	1
Cisplatin	decreases expression	1
Coumestrol	increases expression	1
Doxorubicin	decreases expression	1
Nickel	increases expression	1
Nicotine	increases splicing	1
Smoke	decreases expression, increases abundance	1
Thiram	increases expression	1
Valproic Acid	decreases methylation	1
Vitamin E	decreases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	1
Cyclosporine	increases expression	1
Aflatoxin B1	decreases methylation	1
Cadmium Chloride	decreases expression, increases abundance	1
Okadaic Acid	increases expression	1

ChEMBL screening assays

4 unique, capped per target: 4 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4672540	Binding	Binding affinity to PAPD7 in human HePAD38 cells infected with HBV assessed as protein labelling at 20 uM after 1 hr by photoaffinity labelling in-situ fluorescence gel-based LC-MS/MS analysis	Development of DHQ-based chemical biology probe to profile cellular targets for HBV. — Bioorg Med Chem Lett

Clinical trials (associated diseases)

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