TRMT44

Summary

TRMT44 (tRNA methyltransferase 44 homolog, HGNC:26653) is a protein-coding gene on chromosome 4p16.1, encoding Probable tRNA (uracil-O(2)-)-methyltransferase (Q8IYL2). Probable adenosyl-L-methionine (AdoMet)-dependent tRNA (uracil-O(2)-)-methyltransferase.

The protein encoded by this gene is a putative tRNA methyltransferase found in the cytoplasm. Defects in this gene may be a cause of partial epilepsy with pericentral spikes (PEPS), but that has not been proven definitively.

Source: NCBI Gene 152992 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 186 total
• MANE Select transcript: NM_152544

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26653
Approved symbol	TRMT44
Name	tRNA methyltransferase 44 homolog
Location	4p16.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ35725, TRM44
Ensembl gene	ENSG00000155275
Ensembl biotype	protein_coding
OMIM	614309
Entrez	152992

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 5 protein_coding, 4 protein_coding_CDS_not_defined, 2 retained_intron

ENST00000389737, ENST00000504134, ENST00000511149, ENST00000511366, ENST00000513449, ENST00000528167, ENST00000531038, ENST00000532477, ENST00000532937, ENST00000905716, ENST00000905717

RefSeq mRNA: 2 — MANE Select: NM_152544 NM_001350233, NM_152544

CCDS: CCDS3402

Canonical transcript exons

ENST00000389737 — 11 exons

Exon	Start	End
ENSE00001492302	8475772	8476555
ENSE00001624799	8451960	8452028
ENSE00001657077	8452882	8452989
ENSE00001722054	8449669	8449888
ENSE00002173758	8440777	8441441
ENSE00003461392	8471084	8471200
ENSE00003560601	8467914	8468346
ENSE00003599162	8454742	8454813
ENSE00003614957	8463985	8464091
ENSE00003628751	8465378	8465561
ENSE00003667962	8446476	8446590

Expression profiles

Bgee: expression breadth ubiquitous, 164 present calls, max score 89.39.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 13.8124 / max 265.8441, expressed in 1798 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
46888	13.6912	1797
46890	0.0979	42
46886	0.0232	7

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left ovary	UBERON:0002119	89.39	gold quality
lower esophagus mucosa	UBERON:0035834	89.15	gold quality
right ovary	UBERON:0002118	88.20	gold quality
right uterine tube	UBERON:0001302	88.18	gold quality
sural nerve	UBERON:0015488	87.06	gold quality
esophagus mucosa	UBERON:0002469	85.36	gold quality
skin of abdomen	UBERON:0001416	85.10	gold quality
skin of leg	UBERON:0001511	85.09	gold quality
right hemisphere of cerebellum	UBERON:0014890	84.73	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.30	gold quality
right lobe of thyroid gland	UBERON:0001119	84.09	gold quality
ovary	UBERON:0000992	84.01	gold quality
oocyte	CL:0000023	83.97	silver quality
left lobe of thyroid gland	UBERON:0001120	83.96	gold quality
endocervix	UBERON:0000458	83.92	gold quality
cerebellar hemisphere	UBERON:0002245	83.82	gold quality
cerebellar cortex	UBERON:0002129	83.60	gold quality
thyroid gland	UBERON:0002046	83.45	gold quality
body of uterus	UBERON:0009853	82.99	gold quality
ectocervix	UBERON:0012249	82.91	gold quality
esophagus	UBERON:0001043	82.90	gold quality
tibial nerve	UBERON:0001323	82.71	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	81.91	gold quality
left uterine tube	UBERON:0001303	81.84	gold quality
cerebellum	UBERON:0002037	81.73	gold quality
zone of skin	UBERON:0000014	81.70	gold quality
minor salivary gland	UBERON:0001830	81.58	gold quality
uterine cervix	UBERON:0000002	80.94	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	80.71	gold quality
gastrocnemius	UBERON:0001388	80.55	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	4.05

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

14 targeting TRMT44, 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-3925-3P	100.00	69.95	1237
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-3659	99.70	67.97	694
HSA-MIR-12124	99.68	69.17	2700
HSA-MIR-3191-5P	99.24	66.52	1722
HSA-MIR-6815-3P	99.13	68.98	1530
HSA-MIR-877-3P	99.09	68.10	1637
HSA-MIR-6846-5P	98.81	65.86	1121
HSA-MIR-6848-5P	98.81	65.49	1126
HSA-MIR-3138	98.41	67.53	744
HSA-MIR-618	97.62	67.46	861
HSA-MIR-4456	97.50	64.88	1678
HSA-MIR-2278	97.30	66.19	1130
HSA-MIR-4491	96.53	66.20	935

Literature-anchored findings (GeneRIF, showing 1)

• This study postulated that Q8IYL2 is a causative gene for PEPS , after exhaustive resequencing and bioinformatic analysis. (PMID:21658913)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	trmt44	ENSDARG00000033957
mus_musculus	Trmt44	ENSMUSG00000029097
rattus_norvegicus	Trmt44	ENSRNOG00000008898
drosophila_melanogaster	CG9386	FBGN0037708
caenorhabditis_elegans		WBGENE00016014

Protein

Protein identifiers

Probable tRNA (uracil-O(2)-)-methyltransferase — Q8IYL2 (reviewed: Q8IYL2)

Alternative names: Methyltransferase-like protein 19

All UniProt accessions (2): Q8IYL2, H0YDS2

UniProt curated annotations — full annotation on UniProt →

Function. Probable adenosyl-L-methionine (AdoMet)-dependent tRNA (uracil-O(2)-)-methyltransferase.

Subcellular location. Cytoplasm.

Similarity. Belongs to the TRM44 family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q8IYL2-1	1	yes
Q8IYL2-2	2
Q8IYL2-3	3

RefSeq proteins (2): NP_001337162, NP_689757* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000571	Znf_CCCH	Domain
IPR011671	tRNA_uracil_MeTrfase	Family
IPR029063	SAM-dependent_MTases_sf	Homologous_superfamily

Pfam: PF07757

Catalyzed reactions (Rhea), 1 shown:

• uridine(44) in tRNA(Ser) + S-adenosyl-L-methionine = 2’-O-methyluridine(44) in tRNA(Ser) + S-adenosyl-L-homocysteine + H(+) (RHEA:43100)

UniProt features (17 total): splice variant 5, sequence variant 4, region of interest 2, compositionally biased region 2, modified residue 2, chain 1, zinc finger region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IYL2-F1	75.75	0.39

Functional residue map

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

Post-translational modifications (2): 78, 533

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

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

MSigDB gene sets: 74 (showing top): GOBP_TRNA_METABOLIC_PROCESS, GOBP_RNA_METHYLATION, EVI1_05, GOBP_RNA_MODIFICATION, GOBP_TRNA_METHYLATION, chr4p16, GOBP_METHYLATION, GOBP_TRNA_PROCESSING, GATA_Q6, REACTOME_METABOLISM_OF_RNA, GOBP_TRNA_MODIFICATION, GOMF_RNA_METHYLTRANSFERASE_ACTIVITY, GOMF_TRANSFERASE_ACTIVITY_TRANSFERRING_ONE_CARBON_GROUPS, DODD_NASOPHARYNGEAL_CARCINOMA_DN, GOMF_TRNA_METHYLTRANSFERASE_ACTIVITY

GO Biological Process (3): tRNA methylation (GO:0030488), tRNA processing (GO:0008033), methylation (GO:0032259)

GO Molecular Function (6): zinc ion binding (GO:0008270), tRNA (uridine) methyltransferase activity (GO:0016300), tRNA(Ser) (uridine(44)-2’-O-ribose)-methyltransferase activity (GO:0141101), methyltransferase activity (GO:0008168), transferase activity (GO:0016740), metal ion binding (GO:0046872)

GO Cellular Component (1): 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
RNA methylation	1
tRNA modification	1
RNA processing	1
tRNA metabolic process	1
metabolic process	1
transition metal ion binding	1
tRNA methyltransferase activity	1
tRNA (uridine) methyltransferase activity	1
transferase activity, transferring one-carbon groups	1
catalytic activity	1
cation binding	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

686 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TRMT44	METTL1	Q9UBP6	689
TRMT44	FTSJ1	Q9UET6	666
TRMT44	TARBP1	Q13395	639
TRMT44	TRMT61A	Q96FX7	590
TRMT44	METTL13	Q8N6R0	586
TRMT44	TRUB1	Q8WWH5	579
TRMT44	TRMT6	Q9UJA5	573
TRMT44	WDR4	P57081	569
TRMT44	TRMT13	Q9NUP7	543
TRMT44	EEF1AKMT2	Q5JPI9	537
TRMT44	METTL5	Q9NRN9	534
TRMT44	NSUN2	Q08J23	530
TRMT44	WDR6	Q9NNW5	521
TRMT44	DUS2	Q9NX74	514
TRMT44	TRMT1	Q9NXH9	488

IntAct

41 interactions, top by confidence:

A	B	Type	Score
CDK13	CCNK	psi-mi:“MI:0914”(association)	0.830
PRKAB1	PRKAB2	psi-mi:“MI:0914”(association)	0.740
KLK5	DENND11	psi-mi:“MI:0914”(association)	0.640
CCNJL	PIK3C2A	psi-mi:“MI:0914”(association)	0.530
PLA2G10	CHEK1	psi-mi:“MI:0914”(association)	0.530
HLA-DQB2	POTEF	psi-mi:“MI:0914”(association)	0.530
ANTXR1	POTEF	psi-mi:“MI:0914”(association)	0.530
LRP1	NME4	psi-mi:“MI:0914”(association)	0.530
BCAT1	ARNT	psi-mi:“MI:0914”(association)	0.530
CCNJL	HSPA5	psi-mi:“MI:0914”(association)	0.530
TRMT44	PPCS	psi-mi:“MI:0915”(physical association)	0.400
P4HA2	CCDC85C	psi-mi:“MI:0914”(association)	0.350
F9	DDX11L8	psi-mi:“MI:0914”(association)	0.350
LYPD4	DPYSL4	psi-mi:“MI:0914”(association)	0.350
LOC554223	DCTN6	psi-mi:“MI:0914”(association)	0.350
MUC20	RAD51B	psi-mi:“MI:0914”(association)	0.350
IL12RB1	TUBB4A	psi-mi:“MI:0914”(association)	0.350
CDC16	IFT56	psi-mi:“MI:0914”(association)	0.350
TSHR	POTEF	psi-mi:“MI:0914”(association)	0.350
SKAP1	MYO9A	psi-mi:“MI:0914”(association)	0.350
F9	APBB1	psi-mi:“MI:0914”(association)	0.350
THBS3	APBB1	psi-mi:“MI:0914”(association)	0.350
LYPD4	PIK3C2A	psi-mi:“MI:0914”(association)	0.350
EDN3	ZNF195	psi-mi:“MI:0914”(association)	0.350
FEM1A	RNF113A	psi-mi:“MI:0914”(association)	0.350
SNX21	RBP4	psi-mi:“MI:0914”(association)	0.350

BioGRID (59): TRMT44 (Affinity Capture-MS), TRMT44 (Affinity Capture-MS), TRMT44 (Affinity Capture-MS), TRMT44 (Affinity Capture-MS), TRMT44 (Affinity Capture-MS), TRMT44 (Affinity Capture-MS), TRMT44 (Affinity Capture-MS), TRMT44 (Affinity Capture-MS), TRMT44 (Affinity Capture-MS), TRMT44 (Affinity Capture-MS), TRMT44 (Affinity Capture-MS), TRMT44 (Affinity Capture-MS), TRMT44 (Affinity Capture-MS), TRMT44 (Affinity Capture-MS), TRMT44 (Affinity Capture-MS)

ESM2 similar proteins: A1L3L1, A2RT67, A2RUS2, A3KPW7, A4IJ06, A6QNT4, D2HNY3, D3ZV31, E1BGQ2, E1C3P4, F1R7R1, O15040, O75031, P48553, P50747, Q0IHB3, Q2TBA3, Q3TLI0, Q3U0J8, Q3ZBA0, Q3ZBK7, Q496Y0, Q5F3F2, Q5M7Q1, Q5R5Y0, Q5ZJK1, Q66H91, Q69ZK0, Q69ZT1, Q6GR37, Q6NTL4, Q6VNB8, Q7TPQ3, Q7Z6L1, Q80VP0, Q8BKW4, Q8BXK4, Q8HXH0, Q8IWR0, Q8IYL2

Diamond homologs: O74516, Q02648, Q2U6Q1, Q45EK7, Q4I1M9, Q4KLT3, Q4WCV5, Q60K16, Q6BRY1, Q6C7U7, Q6CR42, Q6FKD6, Q751E7, Q7SE80, Q8IYL2, Q9D2Q2, Q9VHB9, Q5ASK9

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	150
Likely benign	13
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2550 predictions. Top by Δscore:

Variant	Effect	Δscore
4:8446470:TTCCA:T	acceptor_loss	1.0000
4:8446471:TCCA:T	acceptor_loss	1.0000
4:8446472:CCAGA:C	acceptor_loss	1.0000
4:8446473:CAGAT:C	acceptor_loss	1.0000
4:8446474:A:AG	acceptor_gain	1.0000
4:8446474:AGATG:A	acceptor_loss	1.0000
4:8446475:G:GG	acceptor_gain	1.0000
4:8446475:GAT:G	acceptor_gain	1.0000
4:8446544:A:G	donor_gain	1.0000
4:8446586:GAATG:G	donor_gain	1.0000
4:8446589:TGG:T	donor_loss	1.0000
4:8446591:G:GA	donor_loss	1.0000
4:8446591:G:GG	donor_gain	1.0000
4:8446592:T:A	donor_loss	1.0000
4:8449691:T:A	acceptor_gain	1.0000
4:8449696:A:AG	acceptor_gain	1.0000
4:8449697:G:GG	acceptor_gain	1.0000
4:8449697:GAA:G	acceptor_gain	1.0000
4:8449697:GAAA:G	acceptor_gain	1.0000
4:8449834:G:GT	donor_gain	1.0000
4:8449856:G:GT	donor_gain	1.0000
4:8449867:G:GT	donor_gain	1.0000
4:8449877:G:GT	donor_gain	1.0000
4:8449878:A:T	donor_gain	1.0000
4:8449884:TTA:T	donor_gain	1.0000
4:8449885:TAAG:T	donor_loss	1.0000
4:8449886:AAG:A	donor_gain	1.0000
4:8449889:G:GA	donor_loss	1.0000
4:8451949:AACT:A	acceptor_gain	1.0000
4:8451952:T:A	acceptor_gain	1.0000

AlphaMissense

4922 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:8451963:T:A	W320R	0.999
4:8451963:T:C	W320R	0.999
4:8451990:T:C	F329L	0.999
4:8451992:C:A	F329L	0.999
4:8451992:C:G	F329L	0.999
4:8452000:A:T	E332V	0.998
4:8452001:A:C	E332D	0.998
4:8452001:A:T	E332D	0.998
4:8451965:G:C	W320C	0.997
4:8451965:G:T	W320C	0.997
4:8452003:A:C	D333A	0.997
4:8452888:T:A	W344R	0.997
4:8452888:T:C	W344R	0.997
4:8454781:T:A	W391R	0.997
4:8454781:T:C	W391R	0.997
4:8464033:T:A	W418R	0.997
4:8464033:T:C	W418R	0.997
4:8464069:T:A	W430R	0.997
4:8464069:T:C	W430R	0.997
4:8452002:G:C	D333H	0.996
4:8452956:T:A	N366K	0.996
4:8452956:T:G	N366K	0.996
4:8449864:A:C	K310N	0.995
4:8449864:A:T	K310N	0.995
4:8451994:T:A	V330E	0.995
4:8452003:A:T	D333V	0.995
4:8452933:T:C	F359L	0.995
4:8452935:T:A	F359L	0.995
4:8452935:T:G	F359L	0.995
4:8454773:G:C	R388T	0.995

dbSNP variants (sampled 300 via entrez): RS1000046229 (4:8475483 G>A,C), RS1000050789 (4:8477773 C>G,T), RS1000056880 (4:8510788 C>A,T), RS1000120918 (4:8477062 T>G), RS10001657 (4:8496729 A>G), RS1000194100 (4:8470210 T>G), RS1000226358 (4:8491398 G>A,T), RS1000263241 (4:8512796 G>A), RS1000285497 (4:8464925 G>A), RS1000294974 (4:8459995 G>A), RS1000307495 (4:8454632 T>C), RS1000337605 (4:8498739 C>G), RS1000345523 (4:8459839 G>A,T), RS1000345859 (4:8466094 C>T), RS1000389066 (4:8452827 T>C)

Disease associations

OMIM: gene MIM:614309 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST001095_5	Response to antineoplastic agents	8.000000e-07
GCST008466_19	Alanine aminotransferase levels in non-alcoholic fatty liver disease	9.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

19 total (human), top 19 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	increases expression	1
triphenyl phosphate	affects expression	1
terbufos	decreases methylation	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
cylindrospermopsin	increases expression	1
clothianidin	increases expression	1
abrine	increases expression	1
Sunitinib	increases expression	1
Leflunomide	increases expression	1
Benzo(a)pyrene	increases methylation	1
Cisplatin	increases expression	1
Fonofos	decreases methylation	1
Parathion	decreases methylation	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Valproic Acid	decreases methylation	1
Zidovudine	affects cotreatment, increases expression	1
Aflatoxin B1	increases methylation	1
Copper Sulfate	increases expression	1

Clinical trials (associated diseases)

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