TRMT1

Summary

TRMT1 (tRNA methyltransferase 1, HGNC:25980) is a protein-coding gene on chromosome 19p13.13, encoding tRNA (guanine(26)-N(2))-dimethyltransferase (Q9NXH9). Dimethylates a single guanine residue at position 26 of most nuclear- and mitochondrial-encoded tRNAs using S-adenosyl-L-methionine as donor of the methyl groups. tRNA guanine(26)-dimethylation is required for redox homeostasis and ensure proper cellular proliferation and oxidat….

This gene encodes a tRNA-modifying enzyme that acts as a dimethyltransferase, modifying a single guanine residue at position 26 of the tRNA. The encoded enzyme has both mono- and dimethylase activity when exogenously expressed, and uses S-adenosyl methionine as a methyl donor. The C-terminal region of the encoded protein has both a zinc finger motif, and an arginine/proline-rich region. Mutations in this gene have been implicated in autosomal recessive intellectual disorder (ARID). Alternative splicing results in multiple transcript variants encoding different isoforms. There is a pseudogene of this gene on the X chromosome.

Source: NCBI Gene 55621 — RefSeq curated summary.

At a glance

• Gene–disease (curated): complex neurodevelopmental disorder (Definitive, ClinGen) — +2 more curated relationships
• GWAS associations: 5
• Clinical variants (ClinVar): 244 total — 14 pathogenic, 14 likely-pathogenic
• Phenotypes (HPO): 21
• Druggable target: yes
• MANE Select transcript: NM_001136035

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25980
Approved symbol	TRMT1
Name	tRNA methyltransferase 1
Location	19p13.13
Locus type	gene with protein product
Status	Approved
Aliases	FLJ20244, TRM1
Ensembl gene	ENSG00000104907
Ensembl biotype	protein_coding
OMIM	611669
Entrez	55621

Gene structure

Transcript identifiers

Ensembl transcripts: 36 — 20 protein_coding, 7 retained_intron, 5 protein_coding_CDS_not_defined, 4 nonsense_mediated_decay

ENST00000221504, ENST00000357720, ENST00000437766, ENST00000585435, ENST00000585622, ENST00000586224, ENST00000586830, ENST00000587487, ENST00000587633, ENST00000588229, ENST00000588511, ENST00000588746, ENST00000588813, ENST00000590812, ENST00000591425, ENST00000591717, ENST00000592062, ENST00000592606, ENST00000592729, ENST00000592814, ENST00000592892, ENST00000593157, ENST00000593257, ENST00000907294, ENST00000907295, ENST00000907296, ENST00000907297, ENST00000907298, ENST00000913622, ENST00000913623, ENST00000913624, ENST00000913625, ENST00000913626, ENST00000913627, ENST00000913628, ENST00000960268

RefSeq mRNA: 6 — MANE Select: NM_001136035 NM_001136035, NM_001142554, NM_001351760, NM_001351761, NM_001351762, NM_017722

CCDS: CCDS12293, CCDS45997

Canonical transcript exons

ENST00000357720 — 17 exons

Exon	Start	End
ENSE00000682943	13105267	13105396
ENSE00000682945	13105487	13105606
ENSE00001410660	13116146	13116431
ENSE00002926441	13116653	13116740
ENSE00003480310	13104907	13105081
ENSE00003492344	13115626	13115768
ENSE00003515245	13109550	13109684
ENSE00003531126	13109381	13109466
ENSE00003564638	13109915	13110001
ENSE00003579581	13107751	13107859
ENSE00003600943	13112705	13112817
ENSE00003621261	13115279	13115466
ENSE00003626000	13115997	13116052
ENSE00003658411	13112896	13113011
ENSE00003675902	13107574	13107650
ENSE00003684238	13109769	13109838
ENSE00003789844	13110158	13110306

Expression profiles

Bgee: expression breadth ubiquitous, 230 present calls, max score 95.58.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 18.2402 / max 132.9220, expressed in 1800 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
179469	15.0139	1795
179467	1.0367	451
179464	0.8434	373
179468	0.8043	436
179465	0.3566	126
179466	0.1852	61

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lower esophagus mucosa	UBERON:0035834	95.58	gold quality
granulocyte	CL:0000094	93.22	gold quality
left ovary	UBERON:0002119	92.73	gold quality
apex of heart	UBERON:0002098	92.55	gold quality
right ovary	UBERON:0002118	92.40	gold quality
body of uterus	UBERON:0009853	92.28	gold quality
right uterine tube	UBERON:0001302	92.24	gold quality
spleen	UBERON:0002106	92.13	gold quality
mucosa of transverse colon	UBERON:0004991	91.99	gold quality
right hemisphere of cerebellum	UBERON:0014890	91.97	gold quality
right frontal lobe	UBERON:0002810	91.49	gold quality
cerebellar hemisphere	UBERON:0002245	91.44	gold quality
endocervix	UBERON:0000458	91.42	gold quality
cerebellar cortex	UBERON:0002129	91.26	gold quality
left uterine tube	UBERON:0001303	91.24	gold quality
hindlimb stylopod muscle	UBERON:0004252	90.89	gold quality
right lobe of thyroid gland	UBERON:0001119	90.88	gold quality
tibial nerve	UBERON:0001323	90.82	gold quality
omental fat pad	UBERON:0010414	90.78	gold quality
peritoneum	UBERON:0002358	90.72	gold quality
small intestine Peyer’s patch	UBERON:0003454	90.65	gold quality
cortical plate	UBERON:0005343	90.63	gold quality
esophagus mucosa	UBERON:0002469	90.45	gold quality
ectocervix	UBERON:0012249	90.42	gold quality
body of stomach	UBERON:0001161	90.32	gold quality
body of pancreas	UBERON:0001150	90.31	gold quality
gastrocnemius	UBERON:0001388	90.31	gold quality
cingulate cortex	UBERON:0003027	90.29	gold quality
anterior cingulate cortex	UBERON:0009835	90.28	gold quality
right lobe of liver	UBERON:0001114	90.15	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.83
E-MTAB-4850	no	1417.08

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): LYL1

Literature-anchored findings (GeneRIF, showing 7)

• a missense variant was found in GRM1 gene, while in the second family, a frameshift alteration was identified in TRMT1, both of which were found to co-segregate with the intellectual disability. (PMID:26308914)
• Results uncover a biological role for TRMT1-catalyzed tRNA modification in redox metabolism and show that individuals with TRMT1-associated ID are likely to have major perturbations in cellular homeostasis due to the lack of m2,2G modifications. (PMID:28784718)
• mutations in the methyltransferase TRMT1 lead to a microcephalic phenotype and isolated inferior vermian hypoplasia (PMID:30289604)
• An intellectual disability-associated missense variant in TRMT1 impairs tRNA modification and reconstitution of enzymatic activity. (PMID:31898845)
• SARS-CoV-2 main protease Nsp5 cleaves and inactivates human tRNA methyltransferase TRMT1. (PMID:37073102)
• Human TRMT1 catalyzes m[2]G or m[2]2G formation on tRNAs in a substrate-dependent manner. (PMID:37204604)
• Proteolytic cleavage and inactivation of the TRMT1 tRNA modification enzyme by SARS-CoV-2 main protease. (PMID:38814682)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	trmt1	ENSDARG00000010978
mus_musculus	Trmt1	ENSMUSG00000001909
rattus_norvegicus	Trmt1	ENSRNOG00000002914
drosophila_melanogaster	Trm1	FBGN0032430
caenorhabditis_elegans		WBGENE00006613

Paralogs (1): TRMT1L (ENSG00000121486)

Protein

Protein identifiers

tRNA (guanine(26)-N(2))-dimethyltransferase — Q9NXH9 (reviewed: Q9NXH9)

Alternative names: tRNA 2,2-dimethylguanosine-26 methyltransferase, tRNA methyltransferase 1, tRNA(guanine-26,N(2)-N(2)) methyltransferase, tRNA(m(2,2)G26)dimethyltransferase

All UniProt accessions (8): Q9NXH9, K7EJX9, K7EMZ2, K7ENI9, K7EQQ8, K7EQU7, K7EQY6, K7ERR5

UniProt curated annotations — full annotation on UniProt →

Function. Dimethylates a single guanine residue at position 26 of most nuclear- and mitochondrial-encoded tRNAs using S-adenosyl-L-methionine as donor of the methyl groups. tRNA guanine(26)-dimethylation is required for redox homeostasis and ensure proper cellular proliferation and oxidative stress survival.

Subcellular location. Mitochondrion Nucleus. Cytoplasm.

Post-translational modifications. (Microbial infection) Cleaved between Gln-530 and Ala-531 by the 3C-like proteinase nsp5 from human coronavirus SARS-CoV-2, leading to its inactivation.

Disease relevance. Intellectual developmental disorder, autosomal recessive 68 (MRT68) [MIM:618302] A form of intellectual disability, a disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the class I-like SAM-binding methyltransferase superfamily. Trm1 family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9NXH9-1	1	yes
Q9NXH9-2	2
Q9NXH9-3	3

RefSeq proteins (6): NP_001129507, NP_001136026, NP_001338689, NP_001338690, NP_001338691, NP_060192 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000571	Znf_CCCH	Domain
IPR002905	Trm1	Family
IPR029063	SAM-dependent_MTases_sf	Homologous_superfamily
IPR036855	Znf_CCCH_sf	Homologous_superfamily
IPR042296	tRNA_met_Trm1_C	Homologous_superfamily

Pfam: PF00642, PF02005

Catalyzed reactions (Rhea), 1 shown:

• guanosine(26) in tRNA + 2 S-adenosyl-L-methionine = N(2)-dimethylguanosine(26) in tRNA + 2 S-adenosyl-L-homocysteine + 2 H(+) (RHEA:43140)

UniProt features (29 total): binding site 7, modified residue 5, mutagenesis site 4, splice variant 2, region of interest 2, transit peptide 1, chain 1, site 1, domain 1, sequence variant 1, sequence conflict 1, strand 1, short sequence motif 1, zinc finger region 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
9DW6	X-RAY DIFFRACTION	1.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NXH9-F1	81.68	0.65

Functional residue map

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

Catalytic / active sites (1): 530–531 ((microbial infection) cleavage; by coronavirus sars-cov-2 proteinase nsp5)

Ligand- & substrate-binding residues (7): 351; 384; 387; 82; 166; 184; 348

Post-translational modifications (5): 120, 517, 625, 628, 646

Mutagenesis-validated functional residues (4):

Position	Phenotype
233	abolished trna guanine-dimethyltransferase activity.
348	abolished trna guanine-dimethyltransferase activity.
530	abolished cleavage by coronavirus sars-cov-2 proteinase nsp5.
531	does not affect cleavage by coronavirus sars-cov-2 proteinase nsp5.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

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

MSigDB gene sets: 231 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_UP, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, SHEPARD_CRASH_AND_BURN_MUTANT_UP, GOBP_TRNA_METABOLIC_PROCESS, DARWICHE_SKIN_TUMOR_PROMOTER_UP, DARWICHE_PAPILLOMA_RISK_LOW_DN, DARWICHE_PAPILLOMA_RISK_HIGH_UP, DARWICHE_SQUAMOUS_CELL_CARCINOMA_UP, GOBP_RNA_METHYLATION, WEI_MYCN_TARGETS_WITH_E_BOX, GOBP_RNA_MODIFICATION, BYSTRYKH_HEMATOPOIESIS_STEM_CELL_AND_BRAIN_QTL_CIS, GOBP_TRNA_METHYLATION, USF_02, GOBP_METHYLATION

GO Biological Process (4): tRNA N2-guanine methylation (GO:0002940), tRNA modification (GO:0006400), tRNA processing (GO:0008033), methylation (GO:0032259)

GO Molecular Function (9): tRNA binding (GO:0000049), RNA binding (GO:0003723), zinc ion binding (GO:0008270), tRNA (guanine(26)-N2)-dimethyltransferase activity (GO:0160104), protein binding (GO:0005515), methyltransferase activity (GO:0008168), tRNA (guanine) methyltransferase activity (GO:0016423), transferase activity (GO:0016740), metal ion binding (GO:0046872)

GO Cellular Component (4): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), mitochondrion (GO:0005739)

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
intracellular membrane-bounded organelle	2
cellular anatomical structure	2
tRNA methylation	1
tRNA processing	1
RNA modification	1
RNA processing	1
tRNA metabolic process	1
metabolic process	1
RNA binding	1
nucleic acid binding	1
transition metal ion binding	1
N-methyltransferase activity	1
tRNA (guanine) methyltransferase activity	1
binding	1
transferase activity, transferring one-carbon groups	1
tRNA methyltransferase activity	1
S-adenosylmethionine-dependent methyltransferase activity	1
catalytic activity	1
cation binding	1
nuclear lumen	1
intracellular anatomical structure	1
cytoplasm	1

Protein interactions and networks

STRING

1690 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TRMT1	TRMT11	Q7Z4G4	855
TRMT1	TRUB1	Q8WWH5	766
TRMT1	TARBP1	Q13395	747
TRMT1	FTSJ1	Q9UET6	725
TRMT1	NSUN2	Q08J23	716
TRMT1	METTL1	Q9UBP6	709
TRMT1	TRIT1	Q9H3H1	707
TRMT1	TRMT10A	Q8TBZ6	690
TRMT1	PUS3	Q9BZE2	666
TRMT1	DUS2	Q9NX74	644
TRMT1	WDR4	P57081	641
TRMT1	PUS1	Q9Y606	623
TRMT1	TRMT6	Q9UJA5	622
TRMT1	TRMT5	Q32P41	609
TRMT1	TNFRSF10A	O00220	585

IntAct

40 interactions, top by confidence:

A	B	Type	Score
MAGEA11	TRMT1	psi-mi:“MI:0915”(physical association)	0.740
NDUFS3	NDUFS8	psi-mi:“MI:0914”(association)	0.730
rep	GPX1	psi-mi:“MI:0914”(association)	0.660
TRMT1	MAGEA11	psi-mi:“MI:0915”(physical association)	0.560
MAGEA11	TRMT1	psi-mi:“MI:0915”(physical association)	0.560
YBEY	NME4	psi-mi:“MI:0914”(association)	0.530
LIPG	NRP1	psi-mi:“MI:0914”(association)	0.530
TCEAL1	CHEK1	psi-mi:“MI:0914”(association)	0.530
TERF1	TRMT1	psi-mi:“MI:0915”(physical association)	0.510
TRMT1	ZC3H3	psi-mi:“MI:0915”(physical association)	0.400
RNASE10	TRMT1	psi-mi:“MI:0915”(physical association)	0.400
TRMT1	CFTR	psi-mi:“MI:0915”(physical association)	0.370
PB1	ESYT2	psi-mi:“MI:0914”(association)	0.350
LRRK2		psi-mi:“MI:0914”(association)	0.350
CHCHD2	POLRMT	psi-mi:“MI:0914”(association)	0.350
COQ7	ATP5F1B	psi-mi:“MI:0914”(association)	0.350
NDUFS3	ACOT7	psi-mi:“MI:0914”(association)	0.350
NME4	NRDC	psi-mi:“MI:0914”(association)	0.350
rep	GPX1	psi-mi:“MI:0914”(association)	0.350
pipB2	PSMD12	psi-mi:“MI:0914”(association)	0.350
NTAQ1	SBNO1	psi-mi:“MI:0914”(association)	0.350
PUF60	PIR	psi-mi:“MI:0914”(association)	0.350
MRFAP1	POLR2J	psi-mi:“MI:0914”(association)	0.350

BioGRID (160): TRMT1 (Two-hybrid), TRMT1 (Affinity Capture-MS), TRMT1 (Affinity Capture-MS), TRMT1 (Affinity Capture-MS), TRMT1 (Two-hybrid), CTPS1 (Co-fractionation), SEPT2 (Co-fractionation), TRMT1 (Co-fractionation), TRMT1 (Co-fractionation), TRMT1 (Two-hybrid), TRMT1 (Affinity Capture-MS), CHDH (Affinity Capture-MS), HEMK1 (Affinity Capture-MS), TRMT1 (Affinity Capture-MS), USP4 (Affinity Capture-MS)

ESM2 similar proteins: A5A779, A5PK19, A6NFQ2, A6QLU7, A6QQV6, A7MBI7, E9PYK3, O88587, O95870, P22734, P43896, P47823, Q06AV1, Q08602, Q0P5H9, Q13144, Q14164, Q1JPD2, Q2TBP8, Q3TX08, Q3UZW7, Q4R8P0, Q5BK48, Q5EA80, Q5NVK5, Q5R6S0, Q5U4E8, Q64350, Q66IH9, Q6MG55, Q6NTR1, Q8CHW4, Q8N0Z6, Q8N6R0, Q91YR5, Q921Q3, Q922X9, Q92696, Q96G04, Q99LG4

Diamond homologs: A1RV26, A2SRK9, A3CW75, A3MTQ5, A4FZY5, A4WMB7, A4YHH9, A5D7S3, A5UM08, A6UUN6, A6VIL5, A7I9E9, A9A871, B0R713, B1YCV9, B6YUU9, B8GF12, B9LSI7, C3MPR5, C3MYQ9, C3N5E1, C3NDZ5, C3NHQ8, C4KH07, C5A6N2, O27258, O29443, O59493, O67010, P0CW64, P0CW65, P15565, P20300, P57705, P57706, P81554, Q12Y46, Q18EA0, Q2FN43, Q2NI56

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	14
Likely pathogenic	14
Uncertain significance	158
Likely benign	34
Benign	2

Top pathogenic / likely-pathogenic (28)

Variant ID	HGVS	Classification
1341175	GRCh37/hg19 19p13.2-13.12(chr19:12697728-14111313)x1	Pathogenic
1695522	NM_001136035.4(TRMT1):c.884dup (p.Leu296fs)	Pathogenic
1708177	NM_001136035.4(TRMT1):c.458del (p.Gly153fs)	Pathogenic
2277109	NM_001136035.4(TRMT1):c.1110dup (p.Lys371fs)	Pathogenic
3024215	NM_001136035.4(TRMT1):c.1630C>T (p.Arg544Ter)	Pathogenic
3063891	NM_001136035.4(TRMT1):c.1639G>T (p.Gly547Ter)	Pathogenic
3182983	NM_001136035.4(TRMT1):c.619C>T (p.Gln207Ter)	Pathogenic
3339129	NM_001136035.4(TRMT1):c.713del (p.Pro238fs)	Pathogenic
4633656	NM_001136035.4(TRMT1):c.382G>T (p.Glu128Ter)	Pathogenic
617602	NM_001136035.4(TRMT1):c.657_688del (p.Gln219fs)	Pathogenic
617603	NM_001136035.4(TRMT1):c.1506+1G>T	Pathogenic
617604	NM_001136035.4(TRMT1):c.1332_1333del (p.Tyr445fs)	Pathogenic
859755	NM_001136035.4(TRMT1):c.1943dup (p.Gly649fs)	Pathogenic
982958	NM_001136035.4(TRMT1):c.312del (p.Lys105fs)	Pathogenic
1164054	NM_001136035.4(TRMT1):c.232C>T (p.Gln78Ter)	Likely pathogenic
1328940	NM_001136035.4(TRMT1):c.311-1G>A	Likely pathogenic
1339204	NM_001136035.4(TRMT1):c.1487G>A (p.Trp496Ter)	Likely pathogenic
191099	NM_001136035.4(TRMT1):c.967C>T (p.Arg323Cys)	Likely pathogenic
2412904	NM_001136035.4(TRMT1):c.1042T>C (p.Cys348Arg)	Likely pathogenic
2429090	NM_001136035.4(TRMT1):c.35del (p.Phe12fs)	Likely pathogenic
2502435	NM_001136035.4(TRMT1):c.24_33del (p.Leu10fs)	Likely pathogenic
2582353	NM_001136035.4(TRMT1):c.1161_1162del (p.Cys387fs)	Likely pathogenic
2662956	NM_001136035.4(TRMT1):c.1137del (p.Pro379_Val380insTer)	Likely pathogenic
444448	NM_001136035.4(TRMT1):c.1107-2A>G	Likely pathogenic
444449	NM_001136035.4(TRMT1):c.389_390del (p.Lys130fs)	Likely pathogenic
4530799	NM_001136035.4(TRMT1):c.641+1G>T	Likely pathogenic
4795242	NM_001136035.4(TRMT1):c.1435_1436del (p.Ser479fs)	Likely pathogenic
997949	NM_001136035.4(TRMT1):c.1534C>T (p.Arg512Ter)	Likely pathogenic

SpliceAI

2277 predictions. Top by Δscore:

Variant	Effect	Δscore
19:13105263:TCA:T	donor_loss	1.0000
19:13105264:CACCT:C	donor_loss	1.0000
19:13105265:ACCT:A	donor_gain	1.0000
19:13105266:C:A	donor_loss	1.0000
19:13105266:CCTC:C	donor_gain	1.0000
19:13105268:T:TA	donor_gain	1.0000
19:13105392:TGCCC:T	acceptor_gain	1.0000
19:13105393:GCCC:G	acceptor_gain	1.0000
19:13105394:CCC:C	acceptor_gain	1.0000
19:13105394:CCCC:C	acceptor_gain	1.0000
19:13105395:CC:C	acceptor_gain	1.0000
19:13105395:CCCTG:C	acceptor_gain	1.0000
19:13105396:CC:C	acceptor_gain	1.0000
19:13105397:C:CA	acceptor_loss	1.0000
19:13105397:C:CC	acceptor_gain	1.0000
19:13105397:C:T	acceptor_gain	1.0000
19:13105398:T:C	acceptor_loss	1.0000
19:13105399:G:C	acceptor_gain	1.0000
19:13105399:G:GC	acceptor_gain	1.0000
19:13105402:C:CT	acceptor_gain	1.0000
19:13105403:G:T	acceptor_gain	1.0000
19:13105482:CTCA:C	donor_loss	1.0000
19:13105483:TCA:T	donor_loss	1.0000
19:13105485:A:AC	donor_gain	1.0000
19:13105485:A:C	donor_loss	1.0000
19:13105485:AC:A	donor_gain	1.0000
19:13105486:C:CC	donor_gain	1.0000
19:13105486:CC:C	donor_gain	1.0000
19:13105602:GCAGC:G	acceptor_gain	1.0000
19:13105603:CAGC:C	acceptor_gain	1.0000

AlphaMissense

4266 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:13110217:G:C	F320L	0.998
19:13110217:G:T	F320L	0.998
19:13110219:A:G	F320L	0.998
19:13105537:G:C	F551L	0.997
19:13105537:G:T	F551L	0.997
19:13105539:A:G	F551L	0.997
19:13107796:C:A	K487N	0.997
19:13107796:C:G	K487N	0.997
19:13112793:T:A	D261V	0.997
19:13112798:G:C	C259W	0.997
19:13116149:A:G	L84P	0.997
19:13116166:C:A	Q78H	0.997
19:13116166:C:G	Q78H	0.997
19:13112756:G:C	C273W	0.996
19:13112794:C:G	D261H	0.996
19:13116155:C:G	R82P	0.996
19:13116181:A:C	F73L	0.996
19:13116181:A:T	F73L	0.996
19:13116183:A:G	F73L	0.996
19:13110299:C:G	R293T	0.995
19:13107758:C:G	R500P	0.994
19:13109669:A:G	W398R	0.994
19:13109669:A:T	W398R	0.994
19:13110200:A:T	V326D	0.994
19:13110232:G:C	S315R	0.994
19:13110232:G:T	S315R	0.994
19:13110234:T:G	S315R	0.994
19:13110299:C:A	R293I	0.994
19:13112794:C:A	D261Y	0.994
19:13109979:A:G	C348R	0.993

dbSNP variants (sampled 300 via entrez): RS1000109060 (19:13114259 C>A,T), RS1000198492 (19:13108897 A>G), RS1000250873 (19:13108763 C>G,T), RS1000317587 (19:13115551 A>G,T), RS1000378793 (19:13109326 C>A,T), RS1000433615 (19:13115278 C>A), RS1000539613 (19:13113969 C>A,G), RS1000972504 (19:13107360 G>A), RS1001107726 (19:13118582 G>A,C), RS1001145973 (19:13112522 C>T), RS1001492529 (19:13112924 A>G), RS1001722400 (19:13114538 G>A), RS1001742392 (19:13115418 T>C), RS1001975950 (19:13109597 A>G), RS1002184580 (19:13115766 T>C)

Disease associations

OMIM: gene MIM:611669 | disease phenotypes: MIM:618302

GenCC curated gene-disease

Disease	Classification	Inheritance
intellectual developmental disorder, autosomal recessive 68	Definitive	Autosomal recessive
syndromic intellectual disability	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
complex neurodevelopmental disorder	Definitive	AR

Mondo (2): intellectual developmental disorder, autosomal recessive 68 (MONDO:0032665), syndromic intellectual disability (MONDO:0000508)

Orphanet (0):

HPO phenotypes

21 total (21 of 21 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000238	Hydrocephalus
HP:0000252	Microcephaly
HP:0000327	Hypoplasia of the maxilla
HP:0000411	Protruding ear
HP:0000431	Wide nasal bridge
HP:0000664	Synophrys
HP:0000750	Delayed speech and language development
HP:0001250	Seizure
HP:0001252	Hypotonia
HP:0001263	Global developmental delay
HP:0001270	Motor delay
HP:0001272	Cerebellar atrophy
HP:0001324	Muscle weakness
HP:0001518	Small for gestational age
HP:0001763	Pes planus
HP:0003593	Infantile onset
HP:0006970	Periventricular leukomalacia
HP:0011229	Broad eyebrow
HP:0031936	Delayed ability to walk
HP:0045025	Narrow palpebral fissure

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST004632_19	Lymphocyte percentage of white cells	7.000000e-09
GCST004633_126	Neutrophil percentage of white cells	4.000000e-09
GCST010703_320	Brain morphology (MOSTest)	2.000000e-21
GCST90002395_401	Mean platelet volume	2.000000e-10
GCST90002406_490	Reticulocyte fraction of red cells	9.000000e-10

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0007993	lymphocyte percentage of leukocytes
EFO:0007990	neutrophil percentage of leukocytes
EFO:0004346	neuroimaging measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067130 (SINGLE PROTEIN)

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

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
8.01	Kd	9.775	nM	CHEMBL5653589
8.01	ED50	9.775	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 2 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
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149660: Binding affinity to human TRMT1 incubated for 45 mins by Kinobead based pull down assay	kd	0.0098	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, affects cotreatment	3
Particulate Matter	increases abundance, increases expression, affects cotreatment, decreases expression	3
(+)-JQ1 compound	decreases expression	2
Tretinoin	decreases expression	2
Valproic Acid	affects expression, increases methylation	2
Cyclosporine	increases expression	2
aristolochic acid I	increases expression	1
FR900359	increases phosphorylation	1
TAK-243	increases sumoylation	1
pirinixic acid	increases activity, affects binding, decreases expression	1
trichostatin A	affects expression	1
beta-lapachone	increases expression	1
afimoxifene	decreases reaction, increases expression	1
sodium arsenite	affects cotreatment, increases abundance, increases expression	1
cobaltous chloride	increases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
M-VAC protocol	decreases response to substance	1
perfluoro-n-nonanoic acid	increases expression	1
ICG 001	increases expression	1
abrine	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Arsenic Trioxide	increases expression	1
Air Pollutants	increases abundance, increases expression	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Atrazine	decreases expression	1
Vehicle Emissions	decreases expression, increases abundance	1
Caffeine	affects phosphorylation	1
Dexamethasone	affects cotreatment, decreases expression	1
Diazinon	increases methylation	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5652702	Binding	Binding affinity to human TRMT1 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Cellosaurus cell lines

4 cell lines: 3 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B3K7	Abcam HEK293T TRMT1 KO	Transformed cell line	Female
CVCL_TU67	HAP1 TRMT1 (-) 1	Cancer cell line	Male
CVCL_TU68	HAP1 TRMT1 (-) 2	Cancer cell line	Male
CVCL_TU69	HAP1 TRMT1 (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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