TYW3

Summary

TYW3 (tRNA-yW synthesizing protein 3 homolog, HGNC:24757) is a protein-coding gene on chromosome 1p31.1, encoding tRNA wybutosine-synthesizing protein 3 homolog (Q6IPR3). Probable S-adenosyl-L-methionine-dependent methyltransferase that acts as a component of the wybutosine biosynthesis pathway.

Wybutosine (yW) is a hypermodified guanosine at the 3-prime position adjacent to the anticodon of phenylalanine tRNA that stabilizes codon-anticodon interactions during decoding on the ribosome. TYW3 is the human homolog of a yeast gene essential for yW synthesis (Noma and Suzuki, 2006).

Source: NCBI Gene 127253 — RefSeq curated summary.

At a glance

• GWAS associations: 9
• Clinical variants (ClinVar): 45 total
• MANE Select transcript: NM_138467

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24757
Approved symbol	TYW3
Name	tRNA-yW synthesizing protein 3 homolog
Location	1p31.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ40918
Ensembl gene	ENSG00000162623
Ensembl biotype	protein_coding
OMIM	611245
Entrez	127253

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 10 protein_coding, 4 protein_coding_CDS_not_defined

ENST00000370867, ENST00000449696, ENST00000457880, ENST00000467646, ENST00000479111, ENST00000483990, ENST00000485401, ENST00000486467, ENST00000905124, ENST00000905125, ENST00000905126, ENST00000922905, ENST00000922906, ENST00000922907

RefSeq mRNA: 2 — MANE Select: NM_138467 NM_001162916, NM_138467

CCDS: CCDS53334, CCDS666

Canonical transcript exons

ENST00000370867 — 6 exons

Exon	Start	End
ENSE00002212439	74733152	74733418
ENSE00003514580	74736542	74736622
ENSE00003609110	74738690	74738788
ENSE00003637838	74748751	74748822
ENSE00003710038	74752292	74752425
ENSE00003846826	74763894	74766677

Expression profiles

Bgee: expression breadth ubiquitous, 241 present calls, max score 92.96.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 20.1648 / max 465.3557, expressed in 1731 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
3515	13.6059	1716
3516	6.2614	1569
3514	0.2975	150

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
epithelial cell of pancreas	CL:0000083	92.96	gold quality
left ventricle myocardium	UBERON:0006566	92.93	silver quality
calcaneal tendon	UBERON:0003701	92.67	gold quality
tendon of biceps brachii	UBERON:0008188	92.57	gold quality
tendon	UBERON:0000043	91.83	gold quality
sperm	CL:0000019	91.27	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	91.05	gold quality
tibialis anterior	UBERON:0001385	89.81	gold quality
cardiac muscle of right atrium	UBERON:0003379	89.53	silver quality
myocardium	UBERON:0002349	89.48	gold quality
islet of Langerhans	UBERON:0000006	89.41	gold quality
secondary oocyte	CL:0000655	89.05	gold quality
smooth muscle tissue	UBERON:0001135	88.96	gold quality
left ovary	UBERON:0002119	88.73	gold quality
mucosa of stomach	UBERON:0001199	88.54	gold quality
tibia	UBERON:0000979	88.19	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	88.11	gold quality
pancreatic ductal cell	CL:0002079	87.73	gold quality
ovary	UBERON:0000992	87.50	gold quality
right ovary	UBERON:0002118	87.18	gold quality
popliteal artery	UBERON:0002250	86.98	gold quality
tibial artery	UBERON:0007610	86.98	gold quality
body of uterus	UBERON:0009853	86.89	gold quality
descending thoracic aorta	UBERON:0002345	86.81	gold quality
right adrenal gland	UBERON:0001233	86.75	gold quality
lower esophagus muscularis layer	UBERON:0035833	86.75	gold quality
lower esophagus	UBERON:0013473	86.73	gold quality
left adrenal gland	UBERON:0001234	86.68	gold quality
aorta	UBERON:0000947	86.63	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	86.56	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.09

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

98 targeting TYW3, 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-9-5P	100.00	72.28	2361
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-23B-5P	99.98	66.07	587
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-613	99.91	71.50	1710
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-LET-7A-2-3P	99.87	70.53	1921
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-LET-7G-3P	99.85	70.43	1929
HSA-MIR-548AZ-5P	99.83	69.94	3230
HSA-MIR-548T-5P	99.83	69.91	3220
HSA-MIR-1255A	99.74	68.09	744
HSA-MIR-1255B-5P	99.74	68.16	741
HSA-MIR-5003-5P	99.61	69.13	1624
HSA-MIR-6758-3P	99.57	67.55	1078
HSA-MIR-3616-5P	99.55	67.02	989
HSA-MIR-573	99.55	67.44	955
HSA-MIR-6832-3P	99.52	70.44	1726
HSA-MIR-5571-5P	99.49	66.99	1764

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	tyw3	ENSDARG00000038222
mus_musculus	Tyw3	ENSMUSG00000047583
rattus_norvegicus	Tyw3	ENSRNOG00000028328

Paralogs (2): TRMT5 (ENSG00000126814), TRMT12 (ENSG00000183665)

Protein

Protein identifiers

tRNA wybutosine-synthesizing protein 3 homolog — Q6IPR3 (reviewed: Q6IPR3)

Alternative names: tRNA(Phe) 7-((3-amino-3-carboxypropyl)-4-demethylwyosine(37)-N(4))-methyltransferase

All UniProt accessions (4): Q6IPR3, B4DFU6, V9GY40, V9GZ67

UniProt curated annotations — full annotation on UniProt →

Function. Probable S-adenosyl-L-methionine-dependent methyltransferase that acts as a component of the wybutosine biosynthesis pathway. Wybutosine is a hyper modified guanosine with a tricyclic base found at the 3’-position adjacent to the anticodon of eukaryotic phenylalanine tRNA.

Pathway. tRNA modification; wybutosine-tRNA(Phe) biosynthesis.

Similarity. Belongs to the TYW3 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q6IPR3-1	1	yes
Q6IPR3-2	2

RefSeq proteins (2): NP_001156388, NP_612476* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003827	tRNA_yW-synthesising	Domain
IPR036602	tRNA_yW-synthesising-like_sf	Homologous_superfamily

Pfam: PF02676

Catalyzed reactions (Rhea), 1 shown:

• 4-demethyl-7-[(3S)-3-amino-3-carboxypropyl]wyosine(37) in tRNA(Phe) + S-adenosyl-L-methionine = 7-[(3S)-3-amino-3-carboxypropyl]wyosine(37) in tRNA(Phe) + S-adenosyl-L-homocysteine + H(+) (RHEA:36635)

UniProt features (6 total): sequence variant 2, chain 1, modified residue 1, splice variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6IPR3-F1	80.08	0.63

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 (1): 25

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-6782861	Synthesis of wybutosine at G37 of tRNA(Phe)

MSigDB gene sets: 86 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_DN, SHEPARD_BMYB_MORPHOLINO_UP, GOBP_TRNA_METABOLIC_PROCESS, GOBP_RNA_METHYLATION, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, YORDY_RECIPROCAL_REGULATION_BY_ETS1_AND_SP100_DN, GOBP_RNA_MODIFICATION, GOBP_CARBOHYDRATE_DERIVATIVE_BIOSYNTHETIC_PROCESS, GOBP_TRNA_METHYLATION, GOBP_METHYLATION, ACEVEDO_METHYLATED_IN_LIVER_CANCER_DN, GOBP_GLYCOSYL_COMPOUND_BIOSYNTHETIC_PROCESS, GOBP_TRNA_PROCESSING, REACTOME_METABOLISM_OF_RNA, GOBP_TRNA_MODIFICATION

GO Biological Process (4): tRNA methylation (GO:0030488), wybutosine biosynthetic process (GO:0031591), tRNA processing (GO:0008033), methylation (GO:0032259)

GO Molecular Function (4): tRNA methyltransferase activity (GO:0008175), protein binding (GO:0005515), methyltransferase activity (GO:0008168), transferase activity (GO:0016740)

GO Cellular Component (1): cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
tRNA modification in the nucleus and cytosol	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
tRNA modification	2
RNA methylation	1
glycosyl compound biosynthetic process	1
RNA processing	1
tRNA metabolic process	1
metabolic process	1
RNA methyltransferase activity	1
catalytic activity, acting on a tRNA	1
binding	1
transferase activity, transferring one-carbon groups	1
catalytic activity	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

830 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TYW3	TYW2	Q53H54	916
TYW3	LCMT2	O60294	901
TYW3	TYW1	Q9NV66	873
TYW3	TRMT5	Q32P41	839
TYW3	TYW5	A2RUC4	743
TYW3	FTSJ1	Q9UET6	601
TYW3	CIMIP7	H3BNL1	570
TYW3	CRYZ	Q08257	491
TYW3	TRMT2A	Q8IZ69	487
TYW3	PUS7	Q96PZ0	479
TYW3	LGSN	Q5TDP6	460
TYW3	LCMT1	Q9UIC8	459
TYW3	BEGAIN	Q9BUH8	458
TYW3	TRMT1	Q9NXH9	433
TYW3	SON	P18583	430

IntAct

41 interactions, top by confidence:

A	B	Type	Score
TYW3	PICK1	psi-mi:“MI:0915”(physical association)	0.560
TYW3	DDIT4L	psi-mi:“MI:0915”(physical association)	0.560
ZKSCAN4	ZNF213	psi-mi:“MI:0914”(association)	0.530
Mis12		psi-mi:“MI:0914”(association)	0.350
ZWINT	ARHGAP32	psi-mi:“MI:0914”(association)	0.350
Smchd1	SRRM1	psi-mi:“MI:0914”(association)	0.350
KCTD17	CBX4	psi-mi:“MI:0914”(association)	0.350
TYW3	KIF2A	psi-mi:“MI:0914”(association)	0.350
PROZ	ARVCF	psi-mi:“MI:0914”(association)	0.350
NELL1	MATN2	psi-mi:“MI:0914”(association)	0.350
NELL2	MATN2	psi-mi:“MI:0914”(association)	0.350
SYDE1	POLR2D	psi-mi:“MI:0914”(association)	0.350
TINAG	VPS26A	psi-mi:“MI:0914”(association)	0.350
CDKAL1	CIAO1	psi-mi:“MI:0914”(association)	0.350
NAGPA	TYW3	psi-mi:“MI:0914”(association)	0.350
RIN3		psi-mi:“MI:0914”(association)	0.350
LDLRAD1	GXYLT2	psi-mi:“MI:0914”(association)	0.350
SCFD2	NBAS	psi-mi:“MI:0914”(association)	0.350
FAXC	METTL15	psi-mi:“MI:0914”(association)	0.350
ALPK2	C2CD4B	psi-mi:“MI:0914”(association)	0.350
MTRF1	MEIS1	psi-mi:“MI:0914”(association)	0.350
DDHD1	USP9Y	psi-mi:“MI:0914”(association)	0.350
VWC2L	CHEK1	psi-mi:“MI:0914”(association)	0.350
LYZL6	PLXNA2	psi-mi:“MI:0914”(association)	0.350

BioGRID (76): TYW3 (Affinity Capture-MS), TYW3 (Affinity Capture-MS), TYW3 (Affinity Capture-MS), TYW3 (Affinity Capture-MS), KIF3A (Affinity Capture-MS), KIF2A (Affinity Capture-MS), TYW3 (Affinity Capture-MS), GCLC (Affinity Capture-MS), SORL1 (Affinity Capture-MS), ZKSCAN3 (Affinity Capture-MS), PCBP3 (Affinity Capture-MS), TYW3 (Affinity Capture-MS), TYW3 (Affinity Capture-MS), KIF2C (Affinity Capture-MS), TYW3 (Affinity Capture-MS)

ESM2 similar proteins: A0JMU5, A3KN24, A9ULH0, B2RXC1, B6DMK2, B6NXD5, O60678, O70467, P0C7N0, P81128, P83509, P97393, Q13017, Q19QT9, Q28YQ7, Q3EBC8, Q3SYG4, Q4PJX1, Q4R6F3, Q4R6P2, Q501D5, Q5E9U4, Q5R5S9, Q5R629, Q5R6E9, Q5RDC7, Q5SWX8, Q5ZJM3, Q641F8, Q68F70, Q6DHJ1, Q6GL75, Q6GMB0, Q6IPR3, Q6NU25, Q6PBV4, Q7EYV7, Q7KRR5, Q7Z392, Q811G0

Diamond homologs: C6A5A3, O28220, O58796, O59533, Q19QT9, Q58905, Q5E9U4, Q5JES6, Q5JFK6, Q5R5S9, Q641F8, Q6DHJ1, Q6IPR3, Q8BSA9, Q8H4D4, Q8TZG0, Q8U1V7, Q8W4K1, Q9UTA5, Q9UX16, Q9V074, Q9V1Y5, Q9YDV3, P53177, A8N339, D3ZN95, E3KWE1, O58523, P51610, P51611, P60882, P80197, Q04235, Q09832, Q0P466, Q10AZ7, Q19981, Q2R2W1, Q4R3U8, Q4V8B8

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	35
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1142 predictions. Top by Δscore:

Variant	Effect	Δscore
1:74736540:AG:A	acceptor_gain	1.0000
1:74736541:GG:G	acceptor_gain	1.0000
1:74738774:G:GT	donor_gain	1.0000
1:74748749:A:AG	acceptor_gain	1.0000
1:74748750:G:GG	acceptor_gain	1.0000
1:74752286:TTGTA:T	acceptor_loss	1.0000
1:74752287:TGTAG:T	acceptor_loss	1.0000
1:74752288:GTAGG:G	acceptor_loss	1.0000
1:74752290:A:AC	acceptor_loss	1.0000
1:74752290:A:AG	acceptor_gain	1.0000
1:74752290:AG:A	acceptor_gain	1.0000
1:74752290:AGGCT:A	acceptor_gain	1.0000
1:74752291:G:GC	acceptor_gain	1.0000
1:74752291:GG:G	acceptor_gain	1.0000
1:74752291:GGC:G	acceptor_gain	1.0000
1:74752291:GGCT:G	acceptor_gain	1.0000
1:74752291:GGCTG:G	acceptor_gain	1.0000
1:74752423:GAG:G	donor_gain	1.0000
1:74752423:GAGG:G	donor_loss	1.0000
1:74752424:AG:A	donor_loss	1.0000
1:74752425:GG:G	donor_loss	1.0000
1:74733329:G:GT	donor_gain	0.9900
1:74733417:GG:G	donor_gain	0.9900
1:74733417:GGGT:G	donor_loss	0.9900
1:74733418:GG:G	donor_gain	0.9900
1:74733418:GGTGA:G	donor_loss	0.9900
1:74733419:G:T	donor_loss	0.9900
1:74733420:T:G	donor_loss	0.9900
1:74736620:GTG:G	donor_gain	0.9900
1:74738686:TTAGA:T	acceptor_gain	0.9900

AlphaMissense

1743 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:74752301:A:C	S146R	0.993
1:74752303:T:A	S146R	0.993
1:74752303:T:G	S146R	0.993
1:74752296:T:A	V144D	0.992
1:74733383:A:C	S47R	0.986
1:74733385:C:A	S47R	0.986
1:74733385:C:G	S47R	0.986
1:74733399:G:C	R52P	0.986
1:74752299:G:C	R145P	0.986
1:74752408:C:A	N181K	0.984
1:74752408:C:G	N181K	0.984
1:74752320:T:A	V152D	0.982
1:74738748:T:C	L105P	0.980
1:74748776:T:C	F127S	0.980
1:74738761:T:G	C109W	0.979
1:74738732:T:C	F100L	0.977
1:74738734:T:A	F100L	0.977
1:74738734:T:G	F100L	0.977
1:74738759:T:C	C109R	0.977
1:74733398:C:A	R52S	0.975
1:74733263:T:C	F7L	0.974
1:74733265:C:A	F7L	0.974
1:74733265:C:G	F7L	0.974
1:74738754:T:A	V107E	0.974
1:74748761:C:A	A122E	0.974
1:74752326:T:C	L154S	0.973
1:74733396:G:A	G51D	0.972
1:74748760:G:C	A122P	0.971
1:74752385:G:C	A174P	0.970
1:74748784:T:C	S130P	0.969

dbSNP variants (sampled 300 via entrez): RS1000022571 (1:74732099 G>T), RS1000052765 (1:74742023 T>C), RS1000198582 (1:74763966 A>C), RS1000223268 (1:74735655 A>G), RS1000271426 (1:74746631 G>T), RS1000371648 (1:74742063 T>G), RS1000532074 (1:74737220 A>G), RS1000532374 (1:74750927 C>T), RS1000560687 (1:74747299 T>G), RS1000648395 (1:74751327 C>G), RS1000685765 (1:74757357 G>A), RS1000848384 (1:74765853 CTAATCTG>C), RS1000967971 (1:74737590 A>G), RS1001090255 (1:74765626 A>T), RS1001206697 (1:74733889 G>A,T)

Disease associations

OMIM: gene MIM:611245 | 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
GCST001525_9	Visceral fat	7.000000e-06
GCST001620_2	Resistin levels	6.000000e-12
GCST002541_29	Menarche (age at onset)	2.000000e-16
GCST004158_3	Self-reported tiredness	6.000000e-08
GCST005950_6	Body mass index x sex x age interaction (4df test)	1.000000e-15
GCST005951_197	Body mass index	4.000000e-13
GCST005953_11	Body mass index (age <50)	3.000000e-15
GCST005954_3	Body mass index x age interaction	3.000000e-06
GCST90000047_7	Age at first sexual intercourse	3.000000e-11

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0004819	resistin measurement
EFO:0004703	age at menarche
EFO:0007946	tiredness measurement
EFO:0004340	body mass index
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement
EFO:0009749	age at first sexual intercourse measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

26 total (human), top 26 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	3
Tetrachlorodibenzodioxin	decreases expression	2
FR900359	increases phosphorylation	1
TAK-243	increases sumoylation	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
trichostatin A	affects expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	increases abundance, increases expression	1
4-aminophenylarsenoxide	decreases reaction, affects binding	1
jinfukang	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Arsenic Trioxide	decreases reaction, affects binding	1
Acetaminophen	decreases expression	1
Arsenic	increases expression, increases abundance	1
Atrazine	decreases expression	1
Benzo(a)pyrene	decreases methylation	1
Caffeine	increases phosphorylation	1
Doxorubicin	decreases expression	1
Hydralazine	affects cotreatment, increases expression	1
Plant Extracts	affects cotreatment, increases expression	1
Quercetin	decreases expression	1
Tretinoin	decreases expression	1
Cyclosporine	increases expression	1
Aflatoxin B1	decreases methylation	1
Cadmium Chloride	increases expression	1

Clinical trials (associated diseases)

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