DNTT

Summary

DNTT (DNA nucleotidylexotransferase, HGNC:2983) is a protein-coding gene on chromosome 10q24.1, encoding DNA nucleotidylexotransferase (P04053). Template-independent DNA polymerase which catalyzes the random addition of deoxynucleoside 5’-triphosphate to the 3’-end of a DNA initiator.

This gene is a member of the DNA polymerase type-X family and encodes a template-independent DNA polymerase that catalyzes the addition of deoxynucleotides to the 3’-hydroxyl terminus of oligonucleotide primers. In vivo, the encoded protein is expressed in a restricted population of normal and malignant pre-B and pre-T lymphocytes during early differentiation, where it generates antigen receptor diversity by synthesizing non-germ line elements (N-regions) at the junctions of rearranged Ig heavy chain and T cell receptor gene segments. Alternatively spliced transcript variants encoding different isoforms of this gene have been described.

Source: NCBI Gene 1791 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 83 total
• Druggable target: yes
• MANE Select transcript: NM_004088

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2983
Approved symbol	DNTT
Name	DNA nucleotidylexotransferase
Location	10q24.1
Locus type	gene with protein product
Status	Approved
Aliases	TDT, TdT
Ensembl gene	ENSG00000107447
Ensembl biotype	protein_coding
OMIM	187410
Entrez	1791

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000371174, ENST00000630152

RefSeq mRNA: 2 — MANE Select: NM_004088 NM_001017520, NM_004088

CCDS: CCDS44465, CCDS7447

Canonical transcript exons

ENST00000371174 — 11 exons

Exon	Start	End
ENSE00000717360	96318352	96318526
ENSE00000717371	96319262	96319390
ENSE00000717393	96320618	96320788
ENSE00000717410	96322657	96322728
ENSE00000717425	96324266	96324389
ENSE00000717478	96327468	96327600
ENSE00000717489	96328725	96328830
ENSE00000717504	96332351	96332596
ENSE00000811044	96335891	96335974
ENSE00001826240	96304434	96304700
ENSE00001856643	96338138	96338564

Expression profiles

Bgee: expression breadth broad, 33 present calls, max score 93.04.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 2.1281 / max 789.7523, expressed in 24 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
106383	1.8055	24
106384	0.1640	15
106382	0.1587	15

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
thymus	UBERON:0002370	93.04	gold quality
bone marrow	UBERON:0002371	86.15	gold quality
trabecular bone tissue	UBERON:0002483	83.10	gold quality
bone marrow cell	CL:0002092	80.13	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	79.96	gold quality
endometrium epithelium	UBERON:0004811	74.39	gold quality
nipple	UBERON:0002030	72.65	silver quality
sperm	CL:0000019	71.99	gold quality
inferior vagus X ganglion	UBERON:0005363	70.98	gold quality
vena cava	UBERON:0004087	70.64	gold quality
subthalamic nucleus	UBERON:0001906	70.41	gold quality
ventral tegmental area	UBERON:0002691	70.41	gold quality
penis	UBERON:0000989	70.34	silver quality
male germ cell	CL:0000015	70.26	gold quality
superior surface of tongue	UBERON:0007371	70.25	gold quality
pericardium	UBERON:0002407	70.14	gold quality
pharyngeal mucosa	UBERON:0000355	70.13	gold quality
substantia nigra pars reticulata	UBERON:0001966	70.03	silver quality
renal medulla	UBERON:0000362	69.94	gold quality
lateral globus pallidus	UBERON:0002476	69.88	gold quality
pons	UBERON:0000988	69.86	gold quality
lateral nuclear group of thalamus	UBERON:0002736	69.86	gold quality
substantia nigra pars compacta	UBERON:0001965	69.83	silver quality
pylorus	UBERON:0001166	69.78	gold quality
body of tongue	UBERON:0011876	69.62	gold quality
synovial joint	UBERON:0002217	69.40	silver quality
tongue	UBERON:0001723	69.02	gold quality
superior vestibular nucleus	UBERON:0007227	68.44	gold quality
dorsal plus ventral thalamus	UBERON:0001897	68.41	gold quality
urethra	UBERON:0000057	68.35	gold quality

Single-cell (SCXA)

Detected in 11 experiment(s), a significant marker in 10.

Experiment	Marker?	Max mean expression
E-HCAD-6	yes	5649.59
E-CURD-6	yes	4222.73
E-HCAD-4	yes	3414.48
E-CURD-122	yes	3338.87
E-MTAB-10432	yes	3236.66
E-GEOD-76312	yes	2690.49
E-MTAB-9067	yes	2485.20
E-CURD-79	yes	2123.71
E-CURD-112	yes	998.35
E-CURD-77	yes	387.26
E-ANND-3	no	3.59

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ELF1, ETS1, IKZF1, TBPL1

miRNA regulators (miRDB)

17 targeting DNTT, 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-186-5P	99.99	70.83	3707
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-345-3P	99.89	70.23	1421
HSA-MIR-4496	99.88	68.89	2236
HSA-MIR-12124	99.68	69.17	2700
HSA-MIR-670-5P	99.67	69.94	1565
HSA-MIR-10393-5P	99.65	68.01	1368
HSA-MIR-5700	99.64	69.88	2280
HSA-MIR-7159-3P	99.51	70.17	1920
HSA-MIR-20A-3P	99.44	69.10	1575
HSA-MIR-5690	99.25	67.58	1012
HSA-MIR-6734-3P	99.15	66.27	1627
HSA-MIR-660-5P	98.16	68.27	680
HSA-MIR-660-3P	98.14	66.04	1434
HSA-MIR-3667-5P	97.16	64.87	591
HSA-MIR-548AO-3P	92.80	65.04	148

Literature-anchored findings (GeneRIF, showing 18)

• role in DNA repair (PMID:11974916)
• Overexpression of newly discovered alternatively spliced short or long human TdT isoforms greatly reduces the efficiency of recombination, which is reverted to normal levels by the simultaneous expression of both enzymes. (PMID:15356150)
• In spleen, appendix and branchial cleft cysts the range of TdT-positivity was 0-13, 0-96 and 0-6 TdT+ cells per high-power field. (PMID:16885057)
• The TdT binding, DNA binding and dimerization regions, and nuclear localization signal (NLS) in TdIF1, were identified. (PMID:17663723)
• Our study confirms that PAX5 and TdT expression can be expressed in a high percentage of Merkel cell carcinomas and so when positive are not diagnostic of lymphoblastic leukemia/lymphoma. (PMID:23329999)
• Absence of TdT expression identifies a subset of high-risk T-acute lymphoblastic leukemia/lymphoma that overlaps with, but is not identical to, the ETP leukemia, providing additional prognostic value. (PMID:23702731)
• Structural basis for a new templated activity by terminal deoxynucleotidyl transferase and implications for V(D)J recombination have been described. (PMID:27499438)
• TdT-positive cells may be part of the inflammatory milieu in infant kidneys. (PMID:28248816)
• TdT protein can be found in cells of epithelial origin and specifically sebaceous cells, both benign and malignant. (PMID:28677299)
• Data from one institution indicate that TdT-negative acute lymphoblastic leukemia (ALL) is not uncommon (14% of cases between 2005 and 2015) and that the lack of TdT and/or CD34 expression by flow cytometric analysis does not exclude the diagnosis of ALL. (PMID:29187045)
• Molecular roulette: nucleophosmin mutations in AML are orchestrated through N-nucleotide addition by TdT. (PMID:31650162)
• Terminal deoxynucleotidyl transferase promotes acute myeloid leukemia by priming FLT3-ITD replication slippage. (PMID:31650168)
• Prognostic implications of TdT expression in acute myeloid leukemia with an intermediate-risk karyotype. (PMID:32253665)
• Terminal deoxynucleotidyl transferase (TdT) expression is associated with FLT3-ITD mutations in Acute Myeloid Leukemia. (PMID:33091616)
• DNA strand displacement and TdT-Mediated DNA extension for swift, convenient, and quantitative evaluation of sperm DNA integrity and its clinical implications. (PMID:37858544)
• Terminal deoxynucleotidyl transferase expression in different subtypes of childhood B-cell acute lymphoblastic leukemia. (PMID:38579576)
• Terminal deoxynucleotidyl transferase and CD84 identify human multi-potent lymphoid progenitors. (PMID:39003273)
• Computational Modeling Study of the Molecular Basis of dNTP Selectivity in Human Terminal Deoxynucleotidyltransferase. (PMID:39199349)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	dntt	ENSDARG00000104792
mus_musculus	Dntt	ENSMUSG00000025014
rattus_norvegicus	Dntt	ENSRNOG00000013615

Paralogs (3): POLB (ENSG00000070501), POLM (ENSG00000122678), POLL (ENSG00000166169)

Protein

Protein identifiers

DNA nucleotidylexotransferase — P04053 (reviewed: P04053)

Alternative names: Terminal addition enzyme, Terminal deoxynucleotidyltransferase

All UniProt accessions (1): P04053

UniProt curated annotations — full annotation on UniProt →

Function. Template-independent DNA polymerase which catalyzes the random addition of deoxynucleoside 5’-triphosphate to the 3’-end of a DNA initiator. One of the in vivo functions of this enzyme is the addition of nucleotides at the junction (N region) of rearranged Ig heavy chain and T-cell receptor gene segments during the maturation of B- and T-cells.

Subunit / interactions. Interacts with PRP19 and DNTTIP1. Forms a ternary complex with DNTTIP2 and core histone. Released from this complex by PCNA. Interacts with TRERF1.

Subcellular location. Nucleus.

Cofactor. Can also utilize other divalent cations, such as Mn(2+) and Co(2+) (in vitro).

Similarity. Belongs to the DNA polymerase type-X family.

Isoforms (2)

UniProt ID	Names	Canonical?
P04053-1	1	yes
P04053-2	2

RefSeq proteins (2): NP_001017520, NP_004079* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001357	BRCT_dom	Domain
IPR001726	TdT/Mu	Family
IPR002054	DNA-dir_DNA_pol_X	Domain
IPR002934	Polymerase_NTP_transf_dom	Domain
IPR010996	HHH_MUS81	Domain
IPR018944	DNA_pol_lambd_fingers_domain	Domain
IPR019843	DNA_pol-X_BS	Binding_site
IPR022312	DNA_pol_X	Family
IPR027292	TdT	Family
IPR027421	DNA_pol_lamdba_lyase_dom_sf	Homologous_superfamily
IPR029398	PolB_thumb	Domain
IPR036420	BRCT_dom_sf	Homologous_superfamily
IPR037160	DNA_Pol_thumb_sf	Homologous_superfamily
IPR043519	NT_sf	Homologous_superfamily

Pfam: PF00533, PF01909, PF10391, PF14716, PF14791

Enzyme classification (BRENDA):

• EC 2.7.7.31 — DNA nucleotidylexotransferase (BRENDA: 14 organisms, 99 substrates, 60 inhibitors, 30 Km, 4 kcat entries)

Substrate kinetics (BRENDA)

13 substrates with measured Km, best-characterized 13. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
DTTP	—	7
2BA FAM OLIGO	0.0065–0.0176	3
DGTP	0.083–0.114	3
DNA	0.0001–0.0002	3
DATP	0.004–0.01	2
POLY(DA)50	0.0003–0.0025	2
ALPHA-[2-N-(9-FLUORENYLMETHOXYCARBONYL)AMINOETHY	—	1
D-BETA-DEOXYTHYMIDINE-TRIPHOSPHATE	0.1	1
DCTP	0.071	1
HOMOPOLYMER PRIMERS	1	1
OLIGO(DA)12-18	0.02	1
OLIGONUCLEOTIDE PRIMERS	0.001	1

Catalyzed reactions (Rhea), 1 shown:

• DNA(n) + a 2’-deoxyribonucleoside 5’-triphosphate = DNA(n+1) + diphosphate (RHEA:22508)

UniProt features (31 total): binding site 6, sequence conflict 6, strand 5, region of interest 3, helix 3, chain 1, domain 1, modified residue 1, splice variant 1, sequence variant 1, mutagenesis site 1, turn 1, short sequence motif 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
5W4E	X-RAY DIFFRACTION	2.18
2COE	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P04053-F1	88.49	0.75

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 (6): 433; 448–449; 333–338; 342–345; 343; 345

Post-translational modifications (1): 134

Mutagenesis-validated functional residues (1):

Position	Phenotype
343	nearly abolishes enzyme activity.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 166 (showing top): VERHAAK_AML_WITH_NPM1_MUTATED_DN, CHIARETTI_T_ALL_REFRACTORY_TO_THERAPY, WEI_MYCN_TARGETS_WITH_E_BOX, GOBP_DNA_MODIFICATION, GOMF_DNA_POLYMERASE_ACTIVITY, MODULE_213, GOBP_DNA_DAMAGE_RESPONSE, GOBP_DNA_BIOSYNTHETIC_PROCESS, MORI_PRE_BI_LYMPHOCYTE_UP, MODULE_165, IVANOVA_HEMATOPOIESIS_STEM_CELL_SHORT_TERM, KAMMINGA_EZH2_TARGETS, DANG_BOUND_BY_MYC, MORI_MATURE_B_LYMPHOCYTE_DN, TGGAAA_NFAT_Q4_01

GO Biological Process (6): DNA metabolic process (GO:0006259), double-strand break repair via nonhomologous end joining (GO:0006303), DNA modification (GO:0006304), response to ATP (GO:0033198), DNA repair (GO:0006281), DNA biosynthetic process (GO:0071897)

GO Molecular Function (8): DNA binding (GO:0003677), DNA-directed DNA polymerase activity (GO:0003887), DNA nucleotidylexotransferase activity (GO:0003912), metal ion binding (GO:0046872), protein binding (GO:0005515), transferase activity (GO:0016740), nucleotidyltransferase activity (GO:0016779), DNA polymerase activity (GO:0034061)

GO Cellular Component (6): euchromatin (GO:0000791), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytosol (GO:0005829), nuclear matrix (GO:0016363), chromatin (GO:0000785)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
DNA metabolic process	3
DNA polymerase activity	2
nuclear lumen	2
nucleic acid metabolic process	1
double-strand break repair	1
macromolecule modification	1
response to purine-containing compound	1
response to organophosphorus	1
response to oxygen-containing compound	1
DNA damage response	1
nucleic acid biosynthetic process	1
nucleic acid binding	1
cation binding	1
binding	1
catalytic activity	1
transferase activity, transferring phosphorus-containing groups	1
nucleotidyltransferase activity	1
DNA biosynthetic process	1
catalytic activity, acting on DNA	1
chromatin	1
intracellular membrane-bounded organelle	1
cytoplasm	1
chromosome	1

Protein interactions and networks

STRING

2720 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DNTT	DNTTIP1	Q9H147	951
DNTT	CASP3	P42574	883
DNTT	BCL2	P10415	827
DNTT	CD79A	P11912	807
DNTT	PXDN	Q92626	786
DNTT	ANXA5	P08758	786
DNTT	PXDNL	A1KZ92	786
DNTT	ANPEP	P15144	779
DNTT	MME	P08473	773
DNTT	CD22	P20273	771
DNTT	CD19	P15391	768
DNTT	DNTTIP2	Q5QJE6	767
DNTT	CD7	P09564	761
DNTT	CD4	P01730	727
DNTT	CD5	P06127	722

IntAct

13 interactions, top by confidence:

A	B	Type	Score
REL	DNTT	psi-mi:“MI:0915”(physical association)	0.560
DNTT	REL	psi-mi:“MI:0915”(physical association)	0.560
DNTT	TCF4	psi-mi:“MI:0915”(physical association)	0.560
MEI4	DNTT	psi-mi:“MI:0915”(physical association)	0.560
DNTT	PTBP1	psi-mi:“MI:0915”(physical association)	0.400
APOA1	CNMD	psi-mi:“MI:0914”(association)	0.350
P		psi-mi:“MI:0914”(association)	0.350
DNTT	TCF4	psi-mi:“MI:0915”(physical association)	0.000
DNTT	MEI4	psi-mi:“MI:0915”(physical association)	0.000
MEI4	DNTT	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (28): REL (Two-hybrid), PRPF19 (Affinity Capture-MS), DNTT (Affinity Capture-Western), DNTTIP2 (Reconstituted Complex), DNTT (Two-hybrid), TCF4 (Two-hybrid), MEI4 (Two-hybrid), DNTT (Affinity Capture-Western), PTBP1 (Proximity Label-MS), DNTT (Affinity Capture-MS), PCNA (Two-hybrid), PCNA (Reconstituted Complex), PCNA (Co-purification), ABTB2 (Reconstituted Complex), DNTT (Reconstituted Complex)

ESM2 similar proteins: A2ADA5, A4PCD4, A6H611, D3ZDM7, F6PHZ6, O75344, P04053, P09838, P17256, P36195, P47823, P55345, Q01992, Q03426, Q08602, Q0V8R7, Q13144, Q1L8I0, Q3MIT2, Q4KM92, Q4QQT0, Q5CZL1, Q5E9Z1, Q5I0L3, Q5M7T9, Q5M934, Q5RFE6, Q5XGM5, Q64350, Q6GQ53, Q7L3T8, Q80W22, Q86YJ6, Q8BYL4, Q8C0D0, Q8CHW4, Q8N0Z8, Q8WWH5, Q91XW8, Q92089

Diamond homologs: A4PCD4, O02789, O57486, P04053, P06526, P09838, P36195, P42118, Q92089, Q9JIW4, Q9NP87, Q4R380, Q09693, Q9UGP5

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	72
Likely benign	6
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

1383 predictions. Top by Δscore:

Variant	Effect	Δscore
10:96304671:G:GT	donor_gain	1.0000
10:96304672:A:T	donor_gain	1.0000
10:96318348:GCA:G	acceptor_loss	1.0000
10:96318349:CA:C	acceptor_loss	1.0000
10:96318350:A:AG	acceptor_gain	1.0000
10:96318350:AGT:A	acceptor_gain	1.0000
10:96318350:AGTG:A	acceptor_loss	1.0000
10:96318351:G:A	acceptor_loss	1.0000
10:96318351:G:GG	acceptor_gain	1.0000
10:96318351:GT:G	acceptor_gain	1.0000
10:96318351:GTG:G	acceptor_gain	1.0000
10:96318351:GTGA:G	acceptor_gain	1.0000
10:96318351:GTGAT:G	acceptor_gain	1.0000
10:96318510:G:GT	donor_gain	1.0000
10:96318511:A:T	donor_gain	1.0000
10:96318522:TTGTT:T	donor_gain	1.0000
10:96318524:GTT:G	donor_gain	1.0000
10:96318525:TT:T	donor_gain	1.0000
10:96318527:G:GG	donor_gain	1.0000
10:96318527:GTA:G	donor_loss	1.0000
10:96320789:G:T	donor_loss	1.0000
10:96322645:A:G	acceptor_gain	1.0000
10:96322647:T:TA	acceptor_gain	1.0000
10:96322655:A:G	acceptor_loss	1.0000
10:96322656:GGA:G	acceptor_gain	1.0000
10:96322725:CAAA:C	donor_gain	1.0000
10:96322725:CAAAG:C	donor_loss	1.0000
10:96322727:AA:A	donor_gain	1.0000
10:96322728:AGTAA:A	donor_loss	1.0000
10:96322729:G:GG	donor_gain	1.0000

AlphaMissense

3363 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:96338215:A:C	R507S	0.997
10:96338215:A:T	R507S	0.997
10:96332582:T:A	W449R	0.995
10:96332582:T:C	W449R	0.995
10:96338214:G:C	R507T	0.995
10:96324311:T:A	W266R	0.994
10:96324311:T:C	W266R	0.994
10:96328752:T:A	D345E	0.993
10:96328752:T:G	D345E	0.993
10:96324281:T:C	F256L	0.991
10:96324283:T:A	F256L	0.991
10:96324283:T:G	F256L	0.991
10:96328725:G:C	R336S	0.991
10:96328725:G:T	R336S	0.991
10:96332536:T:A	D433E	0.991
10:96332536:T:G	D433E	0.991
10:96332584:G:C	W449C	0.991
10:96332584:G:T	W449C	0.991
10:96335907:T:C	L459P	0.991
10:96335910:G:C	R460P	0.990
10:96327600:G:C	R336T	0.989
10:96335919:C:A	A463D	0.989
10:96327593:T:C	F334L	0.988
10:96327595:C:A	F334L	0.988
10:96327595:C:G	F334L	0.988
10:96328746:T:A	D343E	0.988
10:96328746:T:G	D343E	0.988
10:96328751:A:C	D345A	0.988
10:96328751:A:T	D345V	0.988
10:96332535:A:C	D433A	0.988

dbSNP variants (sampled 300 via entrez): RS1000005301 (10:96304598 A>G), RS1000073333 (10:96319003 G>A), RS1000114593 (10:96310366 A>C), RS1000225770 (10:96328519 C>T), RS1000260902 (10:96322523 A>G), RS1000391487 (10:96316148 C>T), RS1000566751 (10:96322297 T>C), RS1000694889 (10:96322167 A>G), RS1000743563 (10:96315834 A>G), RS1000779699 (10:96316343 T>C), RS1000808720 (10:96334153 A>G), RS1000959470 (10:96310213 C>A,G), RS1000982541 (10:96329186 G>A), RS1001047247 (10:96304444 C>T), RS1001061654 (10:96305867 A>G)

Disease associations

OMIM: gene MIM:187410 | 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): CHEMBL4810 (SINGLE PROTEIN)

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

ChEMBL bioactivities

9 potent at pChembl≥5 of 15 total, top 9 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.40	Ki	400	nM	CHEMBL2441983
6.35	Ki	450	nM	CHEMBL2441974
6.30	Ki	500	nM	CHEMBL2441974
6.30	Ki	500	nM	CHEMBL2441983
5.82	Ki	1500	nM	CHEMBL2441980
5.77	Ki	1700	nM	CHEMBL2441980
5.60	IC50	2500	nM	CHEMBL380892
5.60	IC50	2500	nM	CHEMBL368976
5.07	IC50	8600	nM	CHEMBL210047

PubChem BioAssay actives

9 with measured affinity, of 76 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
(E)-6-[4-(2-fluorobenzoyl)-1H-pyrrol-2-yl]-2,4-dioxohex-5-enoic acid	778707: Non-competitive inhibition of human TdT using 3’-OH as substrate	ki	0.4000	uM
(E)-6-[1-[(4-hydroxyphenyl)methyl]indol-3-yl]-2,4-dioxohex-5-enoic acid	778708: Competitive inhibition of human TdT using TTP as substrate	ki	0.4500	uM
ethyl (E)-6-[4-(4-cyanobenzoyl)-1H-pyrrol-2-yl]-2,4-dioxohex-5-enoate	778708: Competitive inhibition of human TdT using TTP as substrate	ki	1.5000	uM
(3aS,4S,7R,7aR)-1,6-dihexadecyl-2,7-bis(methoxycarbonyl)-3-oxo-3a,4,7,7a-tetrahydroindene-4-carboxylic acid	265078: Inhibition of human TdT	ic50	2.5000	uM
(3aS,4R,7R,7aR)-1,6-dihexadecyl-7-methoxycarbonyl-3a,4,7,7a-tetrahydro-3H-indene-2,4-dicarboxylic acid	212913: Inhibitory activity against human terminal deoxynucleotidyltransferase	ic50	2.5000	uM
(3aS,4S,7R,7aR)-1,6-didodecyl-2,7-bis(methoxycarbonyl)-3-oxo-3a,4,7,7a-tetrahydroindene-4-carboxylic acid	265078: Inhibition of human TdT	ic50	8.6000	uM

CTD chemical–gene interactions

5 total (human), top 5 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
gardenoside	affects binding, decreases reaction, decreases expression	1
CGP 52608	affects binding, increases reaction	1
bisphenol S	affects cotreatment, decreases methylation	1
Fulvestrant	affects cotreatment, decreases methylation	1
Benzo(a)pyrene	increases methylation	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
CHEMBL2445052	Binding	Non-competitive inhibition of human TdT using 3’-OH as substrate	New nucleotide-competitive non-nucleoside inhibitors of terminal deoxynucleotidyl transferase: discovery, characterization, and crystal structure in complex with the target. — 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_D1MB	Abcam K-562 DNTT KO	Cancer cell line	Female
CVCL_D2IW	Abcam Raji DNTT KO	Cancer cell line	Male
CVCL_UQ43	Abcam Jurkat DNTT KO	Cancer cell line	Male

Clinical trials (associated diseases)

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