TRDMT1

Summary

TRDMT1 (tRNA aspartic acid methyltransferase 1, HGNC:2977) is a protein-coding gene on chromosome 10p13, encoding tRNA (cytosine(38)-C(5))-methyltransferase (O14717). Specifically methylates cytosine 38 in the anticodon loop of tRNA(Asp).

This gene encodes a protein responsible for the methylation of aspartic acid transfer RNA, specifically at the cytosine-38 residue in the anticodon loop. This enzyme also possesses residual DNA-(cytosine-C5) methyltransferase activity. While similar in sequence and structure to DNA cytosine methyltransferases, this gene is distinct and highly conserved in its function among taxa.

Source: NCBI Gene 1787 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 80 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_004412

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2977
Approved symbol	TRDMT1
Name	tRNA aspartic acid methyltransferase 1
Location	10p13
Locus type	gene with protein product
Status	Approved
Aliases	RNMT1
Ensembl gene	ENSG00000107614
Ensembl biotype	protein_coding
OMIM	602478
Entrez	1787

Gene structure

Transcript identifiers

Ensembl transcripts: 24 — 17 protein_coding, 4 protein_coding_CDS_not_defined, 3 nonsense_mediated_decay

ENST00000313936, ENST00000354631, ENST00000377799, ENST00000424636, ENST00000436968, ENST00000451253, ENST00000452380, ENST00000479046, ENST00000486947, ENST00000488990, ENST00000495022, ENST00000525762, ENST00000852531, ENST00000852532, ENST00000852533, ENST00000929575, ENST00000929576, ENST00000929577, ENST00000929578, ENST00000929579, ENST00000949129, ENST00000949130, ENST00000949131, ENST00000949132

RefSeq mRNA: 8 — MANE Select: NM_004412 NM_001321006, NM_001321007, NM_001351219, NM_001351220, NM_001351221, NM_001351222, NM_001351223, NM_004412

CCDS: CCDS7114

Canonical transcript exons

ENST00000377799 — 11 exons

Exon	Start	End
ENSE00001908898	17201571	17201672
ENSE00001935652	17137336	17149140
ENSE00003468390	17153507	17153636
ENSE00003470449	17174551	17174660
ENSE00003541367	17162166	17162237
ENSE00003590387	17168841	17168917
ENSE00003604736	17161483	17161548
ENSE00003631784	17159146	17159229
ENSE00003656943	17160305	17160374
ENSE00003671036	17157441	17157784
ENSE00003687013	17154677	17154734

Expression profiles

Bgee: expression breadth ubiquitous, 205 present calls, max score 82.94.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 5.5156 / max 84.0652, expressed in 1582 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
108491	4.5105	1505
108490	0.7712	247
108489	0.1029	46
108488	0.0872	35
108487	0.0344	21
108486	0.0094	5

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ventricular zone	UBERON:0003053	82.94	gold quality
buccal mucosa cell	CL:0002336	81.88	gold quality
calcaneal tendon	UBERON:0003701	81.71	gold quality
cortical plate	UBERON:0005343	81.05	gold quality
ganglionic eminence	UBERON:0004023	80.82	gold quality
right uterine tube	UBERON:0001302	78.36	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	77.58	gold quality
colonic epithelium	UBERON:0000397	77.46	gold quality
monocyte	CL:0000576	77.16	gold quality
embryo	UBERON:0000922	76.80	gold quality
mononuclear cell	CL:0000842	76.65	gold quality
leukocyte	CL:0000738	76.44	gold quality
sural nerve	UBERON:0015488	76.22	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	76.03	gold quality
stromal cell of endometrium	CL:0002255	75.82	gold quality
corpus epididymis	UBERON:0004359	75.66	gold quality
popliteal artery	UBERON:0002250	75.61	gold quality
tibial artery	UBERON:0007610	75.58	gold quality
blood vessel layer	UBERON:0004797	75.49	gold quality
tendon	UBERON:0000043	75.42	gold quality
left ovary	UBERON:0002119	75.20	gold quality
adrenal tissue	UBERON:0018303	75.04	gold quality
aorta	UBERON:0000947	75.03	gold quality
tibial nerve	UBERON:0001323	75.02	gold quality
caput epididymis	UBERON:0004358	74.84	gold quality
thoracic aorta	UBERON:0001515	74.65	gold quality
ascending aorta	UBERON:0001496	74.53	gold quality
descending thoracic aorta	UBERON:0002345	74.50	gold quality
right ovary	UBERON:0002118	74.32	gold quality
islet of Langerhans	UBERON:0000006	74.14	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.50
E-MTAB-6142	no	76.83

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MAFB, TP53

miRNA regulators (miRDB)

352 targeting TRDMT1, 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-3163	100.00	77.23	8605
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-6748-5P	100.00	65.81	1057
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-520D-5P	99.98	73.34	4883

Literature-anchored findings (GeneRIF, showing 18)

• identification of residual DNA-(cytosine-C5) methyltransferase activity (PMID:12794065)
• cDNA microarray analysis identified several genes involved in DNA methylation, such as DNMT2 and DNMT3a that were more highly expressed in LNCaP-r (an androgen sensitive prostate cancer cell line). (PMID:16173030)
• genetic and biochemical approach revealed that DNMT2 did not methylate DNA but instead methylated aspartic acid transfer RNA (tRNA(Asp)) and that DNMT2 specifically methylated cytosine 38 in the anticodon loop (PMID:16424344)
• An association study of 45 folate-related genes in spina bifida: Involvement of tRNA aspartic acid methyltransferase 1 (TRDMT1) (PMID:19161160)
• The expression of DNMT1, DNMT2, DNMT3A and DNMT3B in pediatric acute lymphoblastic leukemia patients, was investigated. (PMID:19763880)
• Hepatitis B virus-induced overexpression of DNMTs leads to viral DNA methylation and decreased viral gene expression and also leads to methylation of host CpG islands. (PMID:20147412)
• the role of Dnmt2 in stress granules could represent a primitive cellular defense mechanism against viral infection. (PMID:20864816)
• Mapped is the tRNA binding site of DNMT2 by systematically mutating surface-exposed lysine and arginine residues to alanine and studying the tRNA methylation activity and binding of the corresponding variants. (PMID:22591353)
• DNMT1, DNMT2 and DNMT3A may play important roles in gastric cancer carcinogenesis. (PMID:22942708)
• The strong effect of some of the somatic cancer mutations on DNMT2 activity suggests that these mutations have a functional role in tumorigenesis. (PMID:25747896)
• Data suggest that, upon HIV-1 infection, DNMT2 is re-localized from the nucleus to cytoplasmic stress granules where DNMT2 methylates HIV-1 messenger RNA; this methylation increases the stability of the HIV-1 RNA genome and up-regulates virus replication; thus, DNMT2 appears to facilitate HIV-1 infection. (PMID:28476776)
• TRDMT1 has a role in 5-methylcytosine modification of mRNA and in HEK293 cell proliferation and migration (PMID:31570165)
• Trdmt1 3’-untranslated region functions as a competing endogenous RNA in leukemia HL-60 cell differentiation. (PMID:33331537)
• Decoding the Genetic Alterations in Genes of DNMT Family (DNA Methyl-Transferase) and their Association with Head and Neck Squamous Cell Carcinoma. (PMID:33369458)
• TRDMT1 participates in the DNA damage repair of granulosa cells in premature ovarian failure. (PMID:34100772)
• The lack of functional DNMT2/TRDMT1 gene modulates cancer cell responses during drug-induced senescence. (PMID:34139673)
• Position 34 of tRNA is a discriminative element for m5C38 modification by human DNMT2. (PMID:34871455)
• DNMT2/TRDMT1 gene knockout compromises doxorubicin-induced unfolded protein response and sensitizes cancer cells to ER stress-induced apoptosis. (PMID:36273376)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	trdmt1	ENSDARG00000034518
mus_musculus	Trdmt1	ENSMUSG00000026723
rattus_norvegicus	Trdmt1	ENSRNOG00000026132
drosophila_melanogaster	Mt2	FBGN0028707

Paralogs (1): DNMT1 (ENSG00000130816)

Protein

Protein identifiers

tRNA (cytosine(38)-C(5))-methyltransferase — O14717 (reviewed: O14717)

Alternative names: DNA (cytosine-5)-methyltransferase-like protein 2, DNA methyltransferase homolog HsaIIP, PuMet

All UniProt accessions (10): O14717, A0A0B4J214, A0A0C4DG18, A0A0U1SZ86, A0A0U1U562, B7Z8H2, H0Y2T8, H0Y4A2, Q6ICS7, Q7Z3E4

UniProt curated annotations — full annotation on UniProt →

Function. Specifically methylates cytosine 38 in the anticodon loop of tRNA(Asp). Has higher activity on tRNA(Asp) modified with queuosine at position 34.

Subcellular location. Cytoplasm.

Tissue specificity. Ubiquitous. Higher expression in testis, ovary and thymus and at much lower levels in spleen, prostate, colon, small intestine, and peripheral blood leukocytes.

Similarity. Belongs to the class I-like SAM-binding methyltransferase superfamily. C5-methyltransferase family.

Isoforms (6)

UniProt ID	Names	Canonical?
O14717-1	A	yes
O14717-2	B
O14717-3	C
O14717-4	D
O14717-5	E
O14717-6	F

RefSeq proteins (8): NP_001307935, NP_001307936, NP_001338148, NP_001338149, NP_001338150, NP_001338151, NP_001338152, NP_004403* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001525	C5_MeTfrase	Family
IPR029063	SAM-dependent_MTases_sf	Homologous_superfamily
IPR031303	C5_meth_CS	Conserved_site
IPR050750	C5-MTase	Family

Pfam: PF00145

Enzyme classification (BRENDA):

• EC 2.1.1.202 — multisite-specific tRNA:(cytosine-C5)-methyltransferase (BRENDA: 12 organisms, 133 substrates, 4 inhibitors, 1 Km, 0 kcat entries)
• EC 2.1.1.204 — tRNA (cytosine38-C5)-methyltransferase (BRENDA: 11 organisms, 56 substrates, 2 inhibitors, 5 Km, 1 kcat entries)

Substrate kinetics (BRENDA)

3 substrates with measured Km, best-characterized 3. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
CYTOSINE38 IN G34TRNAASP	0.0156	1
CYTOSINE38 IN Q34TRNAASP	0.0069	1
CYTOSINE38 IN TRNAGLY(GHCC)	0.0045	1

Catalyzed reactions (Rhea), 1 shown:

• cytidine(38) in tRNA + S-adenosyl-L-methionine = 5-methylcytidine(38) in tRNA + S-adenosyl-L-homocysteine + H(+) (RHEA:42956)

UniProt features (46 total): helix 18, splice variant 8, strand 8, binding site 5, turn 2, chain 1, domain 1, sequence variant 1, sequence conflict 1, active site 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
1G55	X-RAY DIFFRACTION	1.8
9HGM	X-RAY DIFFRACTION	2.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O14717-F1	87.28	0.76

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): 79

Ligand- & substrate-binding residues (5): 13–15; 34; 57–58; 76; 376

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-6782315	tRNA modification in the nucleus and cytosol

MSigDB gene sets: 204 (showing top): KEGG_CYSTEINE_AND_METHIONINE_METABOLISM, GOBP_TRNA_METABOLIC_PROCESS, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_RNA_METHYLATION, GOBP_POST_TRANSCRIPTIONAL_REGULATION_OF_GENE_EXPRESSION, chr10p13, GOBP_RNA_MODIFICATION, GOBP_REGULATION_OF_CATABOLIC_PROCESS, GOBP_TRNA_METHYLATION, ZHANG_BREAST_CANCER_PROGENITORS_UP, GOBP_METHYLATION, GOBP_TRNA_PROCESSING, GOBP_NEGATIVE_REGULATION_OF_CATABOLIC_PROCESS

GO Biological Process (5): tRNA modification (GO:0006400), tRNA methylation (GO:0030488), tRNA stabilization (GO:0036416), tRNA processing (GO:0008033), methylation (GO:0032259)

GO Molecular Function (5): RNA binding (GO:0003723), tRNA methyltransferase activity (GO:0008175), tRNA (cytidine-N5)-methyltransferase activity (GO:0016428), methyltransferase activity (GO:0008168), transferase activity (GO:0016740)

GO Cellular Component (3): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
tRNA processing	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
tRNA processing	1
RNA modification	1
RNA methylation	1
tRNA modification	1
regulation of tRNA stability	1
RNA stabilization	1
negative regulation of tRNA catabolic process	1
RNA processing	1
tRNA metabolic process	1
metabolic process	1
nucleic acid binding	1
RNA methyltransferase activity	1
catalytic activity, acting on a tRNA	1
tRNA (cytidine) methyltransferase activity	1
transferase activity, transferring one-carbon groups	1
catalytic activity	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1498 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TRDMT1	DNMT3B	Q9UBC3	933
TRDMT1	DNMT3A	Q9Y6K1	926
TRDMT1	DNMT3L	Q9UJW3	907
TRDMT1	NSUN3	Q9H649	879
TRDMT1	NSUN2	Q08J23	875
TRDMT1	HNRNPK	P61978	830
TRDMT1	NOP2	P46087	827
TRDMT1	NSUN5	Q96P11	807
TRDMT1	MBD4	O95243	806
TRDMT1	NSUN7	Q8NE18	806
TRDMT1	NSUN4	Q96CB9	795
TRDMT1	NSUN6	Q8TEA1	794
TRDMT1	ALYREF	Q86V81	695
TRDMT1	QTRT1	Q9BXR0	679
TRDMT1	QTRT2	Q9H974	642

IntAct

22 interactions, top by confidence:

A	B	Type	Score
GBE1	TRDMT1	psi-mi:“MI:0915”(physical association)	0.370
TRDMT1	NFRKB	psi-mi:“MI:0915”(physical association)	0.370
TRDMT1	SNRPD3	psi-mi:“MI:0915”(physical association)	0.370
TRDMT1	TBC1D2B	psi-mi:“MI:0915”(physical association)	0.370
PPP1R16B	MCRIP1	psi-mi:“MI:0914”(association)	0.350
PPP1R12A	TRDMT1	psi-mi:“MI:0914”(association)	0.350
TRDMT1	EPPK1	psi-mi:“MI:0915”(physical association)	0.000
TRDMT1	SNRPA1	psi-mi:“MI:0915”(physical association)	0.000
TRDMT1		psi-mi:“MI:0915”(physical association)	0.000
TRDMT1	IGKV2D-28	psi-mi:“MI:0915”(physical association)	0.000
UNC119	TRDMT1	psi-mi:“MI:0915”(physical association)	0.000
TRDMT1	EEF1A1	psi-mi:“MI:0915”(physical association)	0.000
TRDMT1	RIF1	psi-mi:“MI:0915”(physical association)	0.000
TRDMT1	SETDB1	psi-mi:“MI:0915”(physical association)	0.000
TRDMT1	COPS6	psi-mi:“MI:0915”(physical association)	0.000
TRDMT1	RBM48	psi-mi:“MI:0915”(physical association)	0.000
TRDMT1	UTP14A	psi-mi:“MI:0915”(physical association)	0.000
TRDMT1	STX1A	psi-mi:“MI:0915”(physical association)	0.000
DDX24	TRDMT1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (21): TRDMT1 (Affinity Capture-MS), TRDMT1 (Affinity Capture-MS), TRDMT1 (Proximity Label-MS), TRDMT1 (Proximity Label-MS), TMC6 (Affinity Capture-RNA), TRDMT1 (Two-hybrid), COPS6 (Two-hybrid), RBM48 (Two-hybrid), UTP14A (Two-hybrid), STX1A (Two-hybrid), EEF1A1 (Two-hybrid), LRIF1 (Two-hybrid), SETDB1 (Two-hybrid), UNC119 (Two-hybrid), TRDMT1 (Affinity Capture-RNA)

ESM2 similar proteins: A0JN95, A4IF87, A6NJ78, B5DEQ3, B7ZMP1, D3ZLY0, E9Q4Z2, F1QDI9, G1SPE9, O14717, O15228, O22268, O55055, O95453, O95671, P37287, P69341, P97770, Q05B63, Q08J23, Q0V8R7, Q0VGM9, Q10D00, Q1HFZ0, Q2T9W2, Q4G073, Q5R5T5, Q5R962, Q5R9W8, Q5RC51, Q5RJZ1, Q6GR37, Q6H1L8, Q6NYU2, Q6YJI5, Q7TNK6, Q7YS61, Q7Z4G4, Q8JZM0, Q8R2Y8

Diamond homologs: A0A2H1VE33, F4JWT7, O14717, O55055, P40999, Q4G073, Q54JH6, Q7YS61, Q59603, D4ZX35, P15446, P45000

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	53
Likely benign	3
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

2192 predictions. Top by Δscore:

Variant	Effect	Δscore
10:17157439:AC:A	donor_gain	1.0000
10:17157440:CC:C	donor_gain	1.0000
10:17157533:CTGGT:C	donor_gain	1.0000
10:17157534:TGGTT:T	donor_gain	1.0000
10:17157789:CAT:C	acceptor_gain	1.0000
10:17157791:T:TC	acceptor_gain	1.0000
10:17157795:A:C	acceptor_gain	1.0000
10:17159225:CCAAG:C	acceptor_gain	1.0000
10:17159226:CAAG:C	acceptor_gain	1.0000
10:17159226:CAAGC:C	acceptor_gain	1.0000
10:17160303:A:AC	donor_gain	1.0000
10:17160304:C:CC	donor_gain	1.0000
10:17160993:T:C	donor_gain	1.0000
10:17161022:CTG:C	donor_gain	1.0000
10:17161023:TGT:T	donor_gain	1.0000
10:17174549:A:AC	donor_gain	1.0000
10:17174550:C:CC	donor_gain	1.0000
10:17201565:TCTCA:T	donor_loss	1.0000
10:17201566:CTCA:C	donor_loss	1.0000
10:17201567:TCACC:T	donor_loss	1.0000
10:17201568:CA:C	donor_loss	1.0000
10:17201569:A:AC	donor_gain	1.0000
10:17201569:A:AT	donor_loss	1.0000
10:17201570:C:CC	donor_gain	1.0000
10:17201570:CCT:C	donor_gain	1.0000
10:17149072:C:CT	donor_gain	0.9900
10:17149073:T:TT	donor_gain	0.9900
10:17153506:CCGAA:C	donor_gain	0.9900
10:17154732:TAT:T	acceptor_gain	0.9900
10:17154734:TCT:T	acceptor_loss	0.9900

AlphaMissense

2566 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:17168864:G:C	S76R	0.996
10:17168864:G:T	S76R	0.996
10:17168866:T:G	S76R	0.996
10:17149088:A:C	S376R	0.995
10:17149088:A:T	S376R	0.995
10:17149090:T:G	S376R	0.995
10:17159210:C:A	R160M	0.995
10:17159210:C:G	R160T	0.995
10:17161512:A:C	N120K	0.994
10:17161512:A:T	N120K	0.994
10:17153560:C:G	R341P	0.992
10:17159209:C:A	R160S	0.992
10:17159209:C:G	R160S	0.992
10:17153554:A:G	F343S	0.991
10:17157449:A:C	F293L	0.991
10:17157449:A:T	F293L	0.991
10:17157450:A:G	F293S	0.991
10:17157451:A:G	F293L	0.991
10:17168846:G:C	F82L	0.991
10:17168846:G:T	F82L	0.991
10:17168848:A:G	F82L	0.991
10:17201594:C:T	G14D	0.991
10:17157480:A:T	V283D	0.990
10:17161516:T:A	E119V	0.990
10:17201579:G:T	A19E	0.990
10:17153530:A:G	L351P	0.989
10:17154702:A:T	V307E	0.989
10:17162195:G:C	S98R	0.989
10:17162195:G:T	S98R	0.989
10:17162197:T:G	S98R	0.989

dbSNP variants (sampled 300 via entrez): RS1000058417 (10:17195628 C>T), RS1000073296 (10:17169005 A>G), RS1000126837 (10:17189901 C>G), RS1000136523 (10:17150095 C>T), RS1000204890 (10:17184915 A>G), RS1000211015 (10:17184752 TCTC>T), RS1000276916 (10:17184718 A>C), RS1000281909 (10:17139370 A>C), RS1000308415 (10:17203084 A>G,T), RS1000368770 (10:17179267 A>G), RS1000440569 (10:17141894 A>C), RS1000461178 (10:17146272 G>A,C), RS1000490483 (10:17146025 T>C), RS1000606488 (10:17147392 G>A), RS1000700861 (10:17177964 A>C)

Disease associations

OMIM: gene MIM:602478 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST002336_8	Telomere length	4.000000e-06
GCST90002400_697	Plateletcrit	7.000000e-11
GCST90002401_205	Platelet distribution width	8.000000e-17
GCST90002402_110	Platelet count	2.000000e-09
GCST90011899_33	Aspartate aminotransferase levels	3.000000e-21

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0007985	platelet crit
EFO:0007984	platelet component distribution width
EFO:0004309	platelet count
EFO:0004736	aspartate aminotransferase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4523124 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 2,165 (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
CHEMBL1214186	SINEFUNGIN	2	2,165

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

ChEMBL bioactivities

16 potent at pChembl≥5 of 43 total, top 16 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.05	Kd	900	nM	CHEMBL5278294
5.96	IC50	1100	nM	CHEMBL5284517
5.92	IC50	1200	nM	CHEMBL5273612
5.72	Kd	1900	nM	CHEMBL5284517
5.64	IC50	2300	nM	CHEMBL5286276
5.64	Kd	2300	nM	CHEMBL5273612
5.60	IC50	2500	nM	CHEMBL5278294
5.60	Kd	2500	nM	CHEMBL5286276
5.58	Kd	2600	nM	CHEMBL5284517
5.38	Kd	4200	nM	CHEMBL5278294
5.37	Kd	4300	nM	CHEMBL5286276
5.31	Kd	4900	nM	CHEMBL5273612
5.22	Kd	6000	nM	CHEMBL5273501
5.12	Kd	7500	nM	SINEFUNGIN
5.09	Kd	8100	nM	CHEMBL5187166
5.07	IC50	8500	nM	CHEMBL5285928

PubChem BioAssay actives

16 with measured affinity, of 278 total; 8 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
(2S)-2-amino-4-[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl-[[4-nitro-3-(trifluoromethyl)phenyl]methyl]amino]butanoic acid	1948791: Binding affinity to full-length human DNMT2 expressed in bacteria assessed as apparent dissociation constant by ITC method	kd	0.9000	uM
(2S)-2-amino-4-[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl-(5-chloropyrazin-2-yl)sulfonylamino]butanoic acid	1948786: Inhibition of full-length human DNMT2 expressed in bacteria using tRNA-Asp as substrate and 3H-SAM as cosubstrate by tritium incorporation assay	ic50	1.1000	uM
(2S)-2-amino-4-[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl-(4-bromo-3-nitrophenyl)sulfonylamino]butanoic acid	1948786: Inhibition of full-length human DNMT2 expressed in bacteria using tRNA-Asp as substrate and 3H-SAM as cosubstrate by tritium incorporation assay	ic50	1.2000	uM
(2S)-2-amino-4-[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl-(4-chloro-3-nitrophenyl)sulfonylamino]butanoic acid	1948786: Inhibition of full-length human DNMT2 expressed in bacteria using tRNA-Asp as substrate and 3H-SAM as cosubstrate by tritium incorporation assay	ic50	2.3000	uM
(2S)-2-amino-4-[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl-[[4-chloro-3-(trifluoromethyl)phenyl]methyl]amino]butanoic acid	1948791: Binding affinity to full-length human DNMT2 expressed in bacteria assessed as apparent dissociation constant by ITC method	kd	6.0000	uM
(2S,5S)-2,5-diamino-6-[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]hexanoic acid	1881233: Binding affinity to full length human N-terminal his6-tagged DNMT2 expressed in Escherichia coli Rosetta2(DE3)pLysS assessed as dissociation constant at 100 uM by isothermal titration calorimetry assay	kd	7.5000	uM
(2S)-2-amino-4-[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl-but-3-yn-2-ylamino]butanoic acid	1881233: Binding affinity to full length human N-terminal his6-tagged DNMT2 expressed in Escherichia coli Rosetta2(DE3)pLysS assessed as dissociation constant at 100 uM by isothermal titration calorimetry assay	kd	8.1000	uM
(2S)-2-amino-4-[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl-(4-fluoro-3-nitrophenyl)sulfonylamino]butanoic acid	1948786: Inhibition of full-length human DNMT2 expressed in bacteria using tRNA-Asp as substrate and 3H-SAM as cosubstrate by tritium incorporation assay	ic50	8.5000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
trichostatin A	affects cotreatment, decreases expression	3
Valproic Acid	affects expression, increases expression	3
bisphenol A	decreases methylation, increases expression	2
Benzo(a)pyrene	decreases expression, increases mutagenesis	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
aristolochic acid I	decreases expression	1
GSK-J4	decreases expression	1
Batroxase, Bothrops atrox	increases expression	1
methylmercuric chloride	decreases expression	1
sodium arsenite	decreases expression	1
benzo(e)pyrene	decreases methylation	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
chromium hexavalent ion	decreases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Irinotecan	decreases expression	1
Decitabine	decreases expression	1
Vorinostat	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Curcumin	increases expression	1
Diethylhexyl Phthalate	decreases expression	1
Doxorubicin	decreases expression	1
Ethyl Methanesulfonate	decreases expression	1
Mercuric Chloride	decreases expression	1
Methapyrilene	decreases methylation	1
Methyl Methanesulfonate	decreases expression	1
Silicon Dioxide	increases expression	1

ChEMBL screening assays

23 unique, capped per target: 23 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4379082	Binding	Binding affinity to DNMT2 (unknown origin) at protein to compound concentration ratio of 1:20 by differential scanning fluorimetry	Discovery of 4H-Chromen-4-one Derivatives as a New Class of Selective Rho Kinase (ROCK) Inhibitors, which Showed Potent Activity in ex Vivo Diabetic Retinopathy Models. — J Med Chem

Cellosaurus cell lines

4 cell lines: 4 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D8D2	Ubigene A-549 TRDMT1 KO	Cancer cell line	Male
CVCL_TT68	HAP1 TRDMT1 (-) 1	Cancer cell line	Male
CVCL_TT69	HAP1 TRDMT1 (-) 2	Cancer cell line	Male
CVCL_TT70	HAP1 TRDMT1 (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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