TYW1

Summary

TYW1 (tRNA-yW synthesizing protein 1 homolog, HGNC:25598) is a protein-coding gene on chromosome 7q11.21, encoding S-adenosyl-L-methionine-dependent tRNA 4-demethylwyosine synthase TYW1 (Q9NV66). Probable component of the wybutosine biosynthesis pathway.

Wybutosine (yW) is a hypermodified guanosine found in phenylalanine tRNA adjacent to the anticodon that stabilizes codon-anticodon interactions in the ribosome. In yeast, the homolog of this gene is essential for the synthesis of wybutosine. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 55253 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 116 total
• MANE Select transcript: NM_018264

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25598
Approved symbol	TYW1
Name	tRNA-yW synthesizing protein 1 homolog
Location	7q11.21
Locus type	gene with protein product
Status	Approved
Aliases	FLJ10900, MGC23001, MGC60291, YPL207W, TYW1A
Ensembl gene	ENSG00000198874
Ensembl biotype	protein_coding
OMIM	611243
Entrez	55253

Gene structure

Transcript identifiers

Ensembl transcripts: 18 — 14 protein_coding, 2 retained_intron, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000359626, ENST00000361660, ENST00000442959, ENST00000475392, ENST00000491969, ENST00000495971, ENST00000860520, ENST00000860521, ENST00000860522, ENST00000935194, ENST00000935195, ENST00000935196, ENST00000935197, ENST00000960945, ENST00000960946, ENST00000960947, ENST00000960948, ENST00000960949

RefSeq mRNA: 1 — MANE Select: NM_018264 NM_018264

CCDS: CCDS5538

Canonical transcript exons

ENST00000359626 — 16 exons

Exon	Start	End
ENSE00001086879	67055835	67055887
ENSE00001821375	67238308	67239514
ENSE00001947681	66996833	66996982
ENSE00002437264	67049949	67050066
ENSE00002455444	67009583	67009684
ENSE00002487255	67024900	67025022
ENSE00002509045	67017853	67018143
ENSE00002518578	67014367	67014561
ENSE00003519485	66998065	66998195
ENSE00003539568	67067285	67067403
ENSE00003541079	67117483	67117618
ENSE00003585657	66998817	66998954
ENSE00003631643	67098541	67098718
ENSE00003634106	67083430	67083539
ENSE00003647261	67195170	67195337
ENSE00003652078	67183126	67183236

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 87.99.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 20.3303 / max 272.7187, expressed in 1795 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
78899	17.9549	1790
78900	1.9139	1092
78898	0.3809	114
78902	0.0806	35

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sural nerve	UBERON:0015488	87.99	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.56	gold quality
bone marrow cell	CL:0002092	87.41	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.97	gold quality
ectocervix	UBERON:0012249	86.86	gold quality
left ovary	UBERON:0002119	86.70	gold quality
ovary	UBERON:0000992	86.57	gold quality
gastrocnemius	UBERON:0001388	86.49	gold quality
endocervix	UBERON:0000458	86.33	gold quality
muscle of leg	UBERON:0001383	85.83	gold quality
skeletal muscle tissue	UBERON:0001134	85.76	gold quality
bone marrow	UBERON:0002371	85.68	gold quality
right ovary	UBERON:0002118	85.36	gold quality
uterine cervix	UBERON:0000002	85.27	gold quality
ventricular zone	UBERON:0003053	84.73	gold quality
islet of Langerhans	UBERON:0000006	84.67	gold quality
left adrenal gland cortex	UBERON:0035825	84.30	gold quality
muscle tissue	UBERON:0002385	84.14	gold quality
left adrenal gland	UBERON:0001234	84.08	gold quality
hindlimb stylopod muscle	UBERON:0004252	84.03	gold quality
right adrenal gland	UBERON:0001233	83.95	gold quality
adrenal gland	UBERON:0002369	83.93	gold quality
popliteal artery	UBERON:0002250	83.88	gold quality
tibial artery	UBERON:0007610	83.88	gold quality
right adrenal gland cortex	UBERON:0035827	83.84	gold quality
calcaneal tendon	UBERON:0003701	83.73	gold quality
duodenum	UBERON:0002114	83.53	gold quality
corpus callosum	UBERON:0002336	83.53	gold quality
urinary bladder	UBERON:0001255	83.52	gold quality
adrenal tissue	UBERON:0018303	83.52	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-9543	yes	25.50
E-CURD-112	yes	8.87
E-ANND-3	yes	5.45

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

49 targeting TYW1, 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-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-433-3P	99.98	69.37	1203
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-454-3P	99.91	74.01	1925
HSA-MIR-130A-3P	99.90	73.31	1861
HSA-MIR-130B-3P	99.90	73.27	1850
HSA-MIR-301A-3P	99.90	73.15	1839
HSA-MIR-301B-3P	99.90	73.19	1836
HSA-MIR-3666	99.90	73.24	1833
HSA-MIR-4295	99.90	73.11	1838
HSA-MIR-129-5P	99.88	70.26	3273
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-369-3P	99.85	70.52	2264
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-3680-3P	99.75	72.51	3095
HSA-MIR-3059-5P	99.70	69.93	2491
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-325	99.58	66.55	358
HSA-MIR-6716-5P	99.56	68.62	1244
HSA-MIR-297	99.40	69.58	1418
HSA-MIR-1244	99.33	68.38	832
HSA-MIR-877-3P	99.09	68.10	1637
HSA-MIR-670-3P	99.03	68.88	2404
HSA-MIR-6749-3P	99.00	65.73	1443
HSA-MIR-6876-3P	98.97	65.69	765

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	tyw1	ENSDARG00000062987
mus_musculus	Tyw1	ENSMUSG00000056310
rattus_norvegicus	Tyw1	ENSRNOG00000024352

Paralogs (1): TYW1B (ENSG00000277149)

Protein

Protein identifiers

S-adenosyl-L-methionine-dependent tRNA 4-demethylwyosine synthase TYW1 — Q9NV66 (reviewed: Q9NV66)

Alternative names: Radical S-adenosyl methionine and flavodoxin domain-containing protein 1, tRNA wybutosine-synthesizing protein 1 homolog, tRNA-yW-synthesizing protein

All UniProt accessions (2): Q9NV66, C9J9Q4

UniProt curated annotations — full annotation on UniProt →

Function. Probable 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. Catalyzes the condensation of N-methylguanine with 2 carbon atoms from pyruvate to form the tricyclic 4-demethylwyosine, an intermediate in wybutosine biosynthesis.

Cofactor. Binds 1 [4Fe-4S] cluster. The cluster is coordinated with 3 cysteines and an exchangeable S-adenosyl-L-methionine.

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

Similarity. Belongs to the TYW1 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9NV66-1	1	yes
Q9NV66-2	2

RefSeq proteins (1): NP_060734* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001094	Flavdoxin-like	Domain
IPR007197	rSAM	Domain
IPR008254	Flavodoxin/NO_synth	Domain
IPR013785	Aldolase_TIM	Homologous_superfamily
IPR013917	tRNA_wybutosine-synth	Domain
IPR029039	Flavoprotein-like_sf	Homologous_superfamily
IPR034556	tRNA_wybutosine-synthase	Family
IPR058240	rSAM_sf	Homologous_superfamily

Pfam: PF00258, PF04055, PF08608

Catalyzed reactions (Rhea), 1 shown:

• N(1)-methylguanosine(37) in tRNA(Phe) + pyruvate + S-adenosyl-L-methionine = 4-demethylwyosine(37) in tRNA(Phe) + 5’-deoxyadenosine + L-methionine + CO2 + H2O (RHEA:36347)

UniProt features (20 total): binding site 5, sequence conflict 4, sequence variant 3, domain 2, splice variant 2, compositionally biased region 2, chain 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NV66-F1	80.43	0.59

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 (5): 423; 85–89; 176–208; 416; 420

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: 97 (showing top): GOBP_TRNA_METABOLIC_PROCESS, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_RNA_MODIFICATION, GOBP_CARBOHYDRATE_DERIVATIVE_BIOSYNTHETIC_PROCESS, chr7q11, MODULE_207, MILI_PSEUDOPODIA_CHEMOTAXIS_DN, GOBP_GLYCOSYL_COMPOUND_BIOSYNTHETIC_PROCESS, GOBP_TRNA_PROCESSING, REACTOME_METABOLISM_OF_RNA, GOBP_TRNA_MODIFICATION, MARSON_BOUND_BY_E2F4_UNSTIMULATED, GOMF_FMN_BINDING, GOMF_CARBON_CARBON_LYASE_ACTIVITY

GO Biological Process (2): wybutosine biosynthetic process (GO:0031591), tRNA processing (GO:0008033)

GO Molecular Function (8): FMN binding (GO:0010181), metal ion binding (GO:0046872), 4 iron, 4 sulfur cluster binding (GO:0051539), tRNA-4-demethylwyosine synthase activity (GO:0102521), nucleotide binding (GO:0000166), catalytic activity (GO:0003824), lyase activity (GO:0016829), iron-sulfur cluster binding (GO:0051536)

GO Cellular Component (1): membrane (GO:0016020)

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	1
glycosyl compound biosynthetic process	1
RNA processing	1
tRNA metabolic process	1
ribonucleotide binding	1
anion binding	1
cation binding	1
iron-sulfur cluster binding	1
oxo-acid-lyase activity	1
catalytic activity, acting on a tRNA	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
molecular_function	1
catalytic activity	1
metal cluster binding	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1112 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TYW1	TYW3	Q6IPR3	873
TYW1	TYW2	Q53H54	871
TYW1	TRMT5	Q32P41	858
TYW1	LCMT2	O60294	858
TYW1	TYW5	A2RUC4	759
TYW1	ISCA1	Q9BUE6	698
TYW1	GLRX3	O76003	693
TYW1	MOCS1	Q9NZB8	622
TYW1	FTSJ1	Q9UET6	594
TYW1	PWP1	Q13610	575
TYW1	ABCE1	P61221	552
TYW1	CDK5RAP1	Q96SZ6	520
TYW1	ELP3	Q9H9T3	520
TYW1	RSAD1	Q9HA92	505
TYW1	MYBBP1A	Q9BQG0	493

IntAct

120 interactions, top by confidence:

A	B	Type	Score
ENTREP1	WWP2	psi-mi:“MI:0914”(association)	0.850
CEP20	OFD1	psi-mi:“MI:0914”(association)	0.710
MMS19	ERCC2	psi-mi:“MI:0914”(association)	0.690
GPR156	PLD2	psi-mi:“MI:0914”(association)	0.640
MPPED1	CLUH	psi-mi:“MI:0914”(association)	0.640
BTN2A1	POTEF	psi-mi:“MI:0914”(association)	0.530
GDPD5	GOLIM4	psi-mi:“MI:0914”(association)	0.530
SPINT2	UPK3BL1	psi-mi:“MI:0914”(association)	0.530
EVA1C	UPK3BL1	psi-mi:“MI:0914”(association)	0.530
ZNRF4	UPK3BL1	psi-mi:“MI:0914”(association)	0.530
KCNS3	UPK3BL1	psi-mi:“MI:0914”(association)	0.530
TSPAN17	UPK3BL1	psi-mi:“MI:0914”(association)	0.530
KLHL40	CBX4	psi-mi:“MI:0914”(association)	0.530
ATP6V0A2	B4GALT3	psi-mi:“MI:0914”(association)	0.530
ADAM33	LRP5	psi-mi:“MI:0914”(association)	0.530
RNF170	ERLIN1	psi-mi:“MI:0914”(association)	0.530
BTNL3	FAM171A2	psi-mi:“MI:0914”(association)	0.530
LRRTM1	UPK3BL1	psi-mi:“MI:0914”(association)	0.530
GPIHBP1	ADAM10	psi-mi:“MI:0914”(association)	0.530
CIAO2B	ELP1	psi-mi:“MI:0914”(association)	0.350

BioGRID (180): TYW1 (Affinity Capture-MS), TYW1 (Affinity Capture-MS), TYW1 (Affinity Capture-MS), TYW1 (Affinity Capture-MS), TYW1 (Affinity Capture-MS), TYW1 (Affinity Capture-MS), TYW1 (Affinity Capture-MS), TYW1 (Affinity Capture-MS), TYW1 (Affinity Capture-MS), TYW1 (Affinity Capture-MS), TYW1 (Affinity Capture-MS), TYW1 (Affinity Capture-MS), TYW1 (Affinity Capture-MS), TYW1 (Affinity Capture-MS), TYW1 (Affinity Capture-MS)

ESM2 similar proteins: A1L251, A1YVX4, A3KGZ2, A4H7G5, A8QFQ3, C0SUU8, O60066, P0CB42, P0DO23, P34283, P49896, P70551, Q01F03, Q08C92, Q13686, Q28C22, Q2KHP8, Q30DN6, Q3ED68, Q3SWY8, Q4DCH3, Q4QFY1, Q4R4A2, Q57X81, Q5F3R2, Q5REF9, Q5U2S3, Q5XUN4, Q62240, Q6N063, Q6P158, Q6P5D3, Q75E61, Q7YTB0, Q80Y84, Q8BJM7, Q8MNT9, Q8UVX8, Q8VYB9, Q96AP4

Diamond homologs: A0A2U1KZS6, A0A2U1LIM9, A0A7T9QPQ1, A0KTH4, A1KU06, A2AI05, A2QS05, A2WZT1, A5F3I4, A8G9X6, A9LZ73, C5YJG8, O04397, O08336, O08394, O19114, O19132, O32214, O54705, O61309, O62699, P00388, P00389, P00455, P04175, P10933, P14779, P16435, P16603, P19618, P29473, P29474, P29476, P29477, P35228, P36587, P37039, P37040, P37116, P37201

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	95
Likely benign	7
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

3929 predictions. Top by Δscore:

Variant	Effect	Δscore
7:66995284:ACT:A	donor_loss	1.0000
7:66995285:CTCA:C	donor_loss	1.0000
7:66995287:CACA:C	donor_loss	1.0000
7:66995288:A:AC	donor_gain	1.0000
7:66995288:A:AT	donor_loss	1.0000
7:66995288:ACACG:A	donor_gain	1.0000
7:66995289:C:CC	donor_gain	1.0000
7:66995289:C:CT	donor_loss	1.0000
7:66995289:CA:C	donor_gain	1.0000
7:66995289:CACG:C	donor_gain	1.0000
7:66995289:CACGC:C	donor_gain	1.0000
7:66998815:A:G	acceptor_gain	1.0000
7:66998816:G:GG	acceptor_gain	1.0000
7:66998951:GAAG:G	donor_gain	1.0000
7:66998952:AAG:A	donor_gain	1.0000
7:66998953:AG:A	donor_gain	1.0000
7:66998953:AGGTA:A	donor_loss	1.0000
7:66998954:GG:G	donor_gain	1.0000
7:66998954:GGTAA:G	donor_loss	1.0000
7:66998955:G:GG	donor_gain	1.0000
7:66998956:T:G	donor_loss	1.0000
7:67009571:T:A	acceptor_gain	1.0000
7:67009578:ATTAG:A	acceptor_gain	1.0000
7:67009579:TTA:T	acceptor_loss	1.0000
7:67009580:TAGG:T	acceptor_loss	1.0000
7:67009581:AG:A	acceptor_gain	1.0000
7:67009581:AGGG:A	acceptor_loss	1.0000
7:67009582:G:GT	acceptor_loss	1.0000
7:67009582:GG:G	acceptor_gain	1.0000
7:67009682:GAG:G	donor_gain	1.0000

AlphaMissense

4902 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:67055873:T:C	C381R	1.000
7:67055879:T:A	W383R	1.000
7:67055879:T:C	W383R	1.000
7:67055881:G:C	W383C	1.000
7:67055881:G:T	W383C	1.000
7:67067316:A:T	K396I	1.000
7:67067317:A:C	K396N	1.000
7:67067317:A:T	K396N	1.000
7:67067366:A:C	S413R	1.000
7:67067368:C:A	S413R	1.000
7:67067368:C:G	S413R	1.000
7:67067393:T:C	F422L	1.000
7:67067395:C:A	F422L	1.000
7:67067395:C:G	F422L	1.000
7:67067396:T:C	C423R	1.000
7:67067397:G:A	C423Y	1.000
7:67067399:T:A	W424R	1.000
7:67067399:T:C	W424R	1.000
7:67067401:G:C	W424C	1.000
7:67067401:G:T	W424C	1.000
7:67098607:T:A	L484H	1.000
7:67050055:T:C	L364P	0.999
7:67055837:T:C	Y369H	0.999
7:67055862:G:A	G377E	0.999
7:67055869:G:C	K379N	0.999
7:67055869:G:T	K379N	0.999
7:67055873:T:A	C381S	0.999
7:67055874:G:A	C381Y	0.999
7:67055874:G:C	C381S	0.999
7:67055875:C:G	C381W	0.999

dbSNP variants (sampled 300 via entrez): RS1000013008 (7:67171130 A>G,T), RS1000016716 (7:67129459 T>C), RS1000019136 (7:67001467 G>A,C), RS1000031590 (7:67168088 A>G), RS1000036079 (7:67210498 C>T), RS1000064753 (7:67046928 A>G), RS1000070642 (7:67008268 C>T), RS1000090292 (7:67082215 G>A), RS1000090515 (7:67001741 A>G), RS1000155732 (7:67173766 G>A,C), RS1000176567 (7:67010682 C>A,G,T), RS1000181982 (7:67013173 T>G), RS1000234638 (7:67217463 T>C), RS1000245392 (7:67135560 C>A), RS1000246646 (7:67161914 C>T)

Disease associations

OMIM: gene MIM:611243 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST006632_7	Decline in glucose metabolism in posterior cingulate cortex	7.000000e-06
GCST009391_1929	Metabolite levels	8.000000e-06
GCST009391_409	Metabolite levels	2.000000e-06
GCST011122_62	Walking pace	3.000000e-08

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0009392	glucose metabolism decline measurement
EFO:0010461	argininosuccinate measurement
EFO:0010387	phosphatidylcholine 38:5 measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

17 total (human), top 17 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression	4
Aflatoxin B1	affects expression, decreases methylation, increases methylation	3
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases expression, increases abundance	1
bisphenol A	affects cotreatment, increases methylation	1
beta-lapachone	increases expression	1
arsenite	affects binding, decreases reaction	1
methacrylaldehyde	affects cotreatment, increases expression, increases abundance	1
CGP 52608	affects binding, increases reaction	1
Fulvestrant	increases methylation, affects cotreatment	1
Acrolein	affects cotreatment, increases expression, increases abundance	1
Air Pollutants	affects cotreatment, increases abundance, increases expression	1
Cisplatin	decreases expression	1
Ozone	increases abundance, affects cotreatment, increases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	1
Cyclosporine	increases expression	1
Volatile Organic Compounds	affects cotreatment, increases expression	1

Cellosaurus cell lines

1 cell lines: 1 induced pluripotent stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_YT13	SYSUi004-A	Induced pluripotent stem cell	Male

Clinical trials (associated diseases)

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