TYW1B

gene

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Also known as RSAFD2MGC87315NCRNA00069LINC00069

Summary

TYW1B (tRNA-yW synthesizing protein 1 homolog B, HGNC:33908) is a protein-coding gene on chromosome 7q11.22-q11.23, encoding S-adenosyl-L-methionine-dependent tRNA 4-demethylwyosine synthase TYW1B (Q6NUM6). Probable component of the wybutosine biosynthesis pathway.

Wybutosine is a hypermodified guanosine found in phenylalanine tRNA. Wybutosine functions to stabilize codon-anticodon interactions during ribosome decoding and therefore supports the maintenance of the reading frame. In yeast, the homolog of this gene is essential for the synthesis of wybutosine. The human genome contains two closely related genes that putatively function in wybutosine synthesis. The open reading frame of this locus is disrupted in some individuals. Thus, this locus appears to be an evolving pseudogene, but may still be functional in some members of the population.

Source: NCBI Gene 441250 — RefSeq curated summary.

At a glance

GWAS associations: 8
Clinical variants (ClinVar): 85 total
MANE Select transcript: NM_001145440

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:33908
Approved symbol	TYW1B
Name	tRNA-yW synthesizing protein 1 homolog B
Location	7q11.22-q11.23
Locus type	gene with protein product
Status	Approved
Aliases	RSAFD2, MGC87315, NCRNA00069, LINC00069
Ensembl gene	ENSG00000277149
Ensembl biotype	protein_coding
Entrez	441250

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

ENST00000610600, ENST00000612372, ENST00000620995, ENST00000902318

RefSeq mRNA: 3 — MANE Select: NM_001145440 NM_001145440, NM_001412179, NM_001412180

CCDS: CCDS69309

Canonical transcript exons

ENST00000620995 — 14 exons

Exon	Start	End
ENSE00003717112	72807066	72807356
ENSE00003723148	72694687	72694822
ENSE00003724262	72826855	72826985
ENSE00003726063	72713621	72713798
ENSE00003728695	72828072	72828200
ENSE00003729832	72777416	72777533
ENSE00003735223	72802400	72802522
ENSE00003735267	72574513	72575719
ENSE00003739660	72616672	72616839
ENSE00003742589	72728822	72728931
ENSE00003744820	72628887	72628997
ENSE00003747077	72815380	72815481
ENSE00003753156	72744484	72744601
ENSE00003753188	72810471	72810665

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 92.09.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 6.4695 / max 110.6306, expressed in 1486 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
84280	5.7925	1452
84279	0.6770	341

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	92.09	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.95	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	83.56	gold quality
calcaneal tendon	UBERON:0003701	76.72	gold quality
bone marrow cell	CL:0002092	74.86	gold quality
tonsil	UBERON:0002372	74.36	gold quality
granulocyte	CL:0000094	73.54	gold quality
skeletal muscle tissue	UBERON:0001134	73.31	gold quality
gastrocnemius	UBERON:0001388	72.72	gold quality
ventricular zone	UBERON:0003053	72.58	gold quality
bone marrow	UBERON:0002371	72.50	gold quality
muscle of leg	UBERON:0001383	71.79	gold quality
corpus callosum	UBERON:0002336	71.61	gold quality
muscle tissue	UBERON:0002385	71.24	gold quality
endocervix	UBERON:0000458	71.22	gold quality
uterine cervix	UBERON:0000002	71.16	gold quality
ectocervix	UBERON:0012249	70.63	gold quality
urinary bladder	UBERON:0001255	70.23	gold quality
adrenal tissue	UBERON:0018303	70.21	gold quality
right ovary	UBERON:0002118	70.17	gold quality
ovary	UBERON:0000992	69.52	gold quality
liver	UBERON:0002107	68.92	gold quality
left ovary	UBERON:0002119	68.78	gold quality
leukocyte	CL:0000738	68.54	gold quality
placenta	UBERON:0001987	68.37	gold quality
mucosa of transverse colon	UBERON:0004991	68.29	gold quality
lower esophagus mucosa	UBERON:0035834	68.20	gold quality
popliteal artery	UBERON:0002250	68.00	gold quality
tibial artery	UBERON:0007610	67.99	gold quality
vagina	UBERON:0000996	67.97	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.09
E-MTAB-4850	no	6.82

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

39 targeting TYW1B, 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-4795-3P	100.00	74.62	4024
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-570-3P	99.96	72.41	4910
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-369-3P	99.85	70.52	2264
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-6749-3P	99.00	65.73	1443
HSA-MIR-6876-3P	98.97	65.69	765
HSA-MIR-455-3P	98.94	67.68	878
HSA-MIR-626	98.89	66.21	762
HSA-MIR-3149	98.77	67.13	1639
HSA-MIR-496	98.66	69.80	931

Cross-species orthologs

3 orthologs

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

Paralogs (1): TYW1 (ENSG00000198874)

Protein

Protein identifiers

S-adenosyl-L-methionine-dependent tRNA 4-demethylwyosine synthase TYW1B — Q6NUM6 (reviewed: Q6NUM6)

Alternative names: Radical S-adenosyl methionine and flavodoxin domain-containing protein 2, tRNA wybutosine-synthesizing protein 1 homolog B

All UniProt accessions (3): Q6NUM6, A0A087WWV6, A0A087X1V1

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?
Q6NUM6-1	1	yes
Q6NUM6-2	2

RefSeq proteins (3): NP_001138912, NP_001399108, NP_001399109 (=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 (14 total): binding site 5, compositionally biased region 3, domain 2, chain 1, splice variant 1, sequence conflict 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6NUM6-F1	76.40	0.44

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): 356; 359; 43–47; 130–162; 352

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 47 (showing top): GOBP_TRNA_METABOLIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_RNA_MODIFICATION, GOBP_CARBOHYDRATE_DERIVATIVE_BIOSYNTHETIC_PROCESS, chr7q11, GOBP_GLYCOSYL_COMPOUND_BIOSYNTHETIC_PROCESS, GOBP_TRNA_PROCESSING, GOBP_TRNA_MODIFICATION, GOMF_FMN_BINDING, GOMF_CARBON_CARBON_LYASE_ACTIVITY, GOMF_METAL_CLUSTER_BINDING, GOMF_4_IRON_4_SULFUR_CLUSTER_BINDING, GOMF_OXO_ACID_LYASE_ACTIVITY, GOMF_CATALYTIC_ACTIVITY_ACTING_ON_RNA, GOMF_CATALYTIC_ACTIVITY_ACTING_ON_A_TRNA

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

GO Molecular Function (9): 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), protein binding (GO:0005515), lyase activity (GO:0016829), iron-sulfur cluster binding (GO:0051536)

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

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
binding	1
catalytic activity	1
metal cluster binding	1
cellular anatomical structure	1

Protein interactions and networks

STRING

538 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TYW1B	OSBPL7	Q9BZF2	571
TYW1B	MTARC1	Q5VT66	519
TYW1B	COBLL1	Q53SF7	447
TYW1B	NBPF9	P0DPF3	431
TYW1B	ABCA8	O94911	419
TYW1B	DEFB132	Q7Z7B7	402
TYW1B	DPY19L3	Q6ZPD9	399
TYW1B	FAM110A	Q9BQ89	395
TYW1B	KLF14	Q8TD94	380
TYW1B	DIPK1A	Q5T7M9	371
TYW1B	ANGPTL3	Q9Y5C1	370
TYW1B	IQCE	Q6IPM2	366
TYW1B	IL6R	P08887	365
TYW1B	SP6	Q3SY56	352
TYW1B	JMJD1C	Q15652	350
TYW1B	EML5	Q05BV3	350

IntAct

26 interactions, top by confidence:

A	B	Type	Score
RANBP6	SLC27A2	psi-mi:“MI:0914”(association)	0.640
TAS2R19	TYW1B	psi-mi:“MI:0915”(physical association)	0.560
POMK	TMEM120B	psi-mi:“MI:0914”(association)	0.530
PTGER3	PIK3R2	psi-mi:“MI:0914”(association)	0.530
SPACA1	GOLIM4	psi-mi:“MI:0914”(association)	0.530
TEX264	PER1	psi-mi:“MI:0914”(association)	0.530
ARL15	SLC25A20	psi-mi:“MI:0914”(association)	0.530
TCIRG1	AP3D1	psi-mi:“MI:0914”(association)	0.530
HEATR3	SLC27A2	psi-mi:“MI:0914”(association)	0.530
	HTATSF1	psi-mi:“MI:0915”(physical association)	0.400
SLC18A1	LIMK2	psi-mi:“MI:0914”(association)	0.350
EDNRB	EXOC5	psi-mi:“MI:0914”(association)	0.350
CDKAL1	CIAO1	psi-mi:“MI:0914”(association)	0.350
ENTPD4	TYW1B	psi-mi:“MI:0914”(association)	0.350
SPACA1	ESYT2	psi-mi:“MI:0914”(association)	0.350
KLRC4	RAP1BL	psi-mi:“MI:0914”(association)	0.350
HFE	PODXL	psi-mi:“MI:0914”(association)	0.350
CD3D	CLGN	psi-mi:“MI:0914”(association)	0.350
KCNE3	TMEM131L	psi-mi:“MI:0914”(association)	0.350
TAS2R19	TYW1B	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (34): TYW1B (Affinity Capture-MS), TYW1B (Affinity Capture-MS), TYW1B (Affinity Capture-MS), TYW1B (Affinity Capture-MS), TYW1B (Affinity Capture-MS), TYW1B (Affinity Capture-MS), TYW1B (Affinity Capture-MS), TYW1B (Affinity Capture-MS), TYW1B (Affinity Capture-MS), TYW1B (Affinity Capture-MS), TYW1B (Affinity Capture-MS), TYW1B (Affinity Capture-MS), TYW1B (Affinity Capture-MS), TYW1B (Affinity Capture-MS), TYW1B (Affinity Capture-MS)

ESM2 similar proteins: A0A0K3AXH1, A0A125YYR0, A0A7J6K9S4, B5SNZ6, B8PYG1, B9EHT4, C5E2E7, D0Z5N4, F1RD40, F4I2J8, F4IIZ9, F4J6F6, F4KFS5, F5HB62, G5EG86, O04064, O19132, O48767, O48791, O64953, P23915, P26358, P32351, P34335, P49584, Q0WUY1, Q2PAY3, Q5R4R7, Q60JJ0, Q66654, Q6NUM6, Q6X4W1, Q6XL73, Q755A9, Q75QN6, Q80TL4, Q86ME2, Q8BFX3, Q8GX05, Q8SVC0

Diamond homologs: A0A2U1KZS6, A0A2U1LIM9, A0A7T9QPQ1, A2QS05, A2WZT1, A2Y8E0, A5F3I4, C5YJG8, O04397, O04977, O08336, O08394, O19114, O32214, O54705, O62699, P00388, P00389, P00454, P00455, P04175, P10933, P16435, P16603, P19618, P21890, P29477, P35228, P36587, P37039, P37040, P37116, P37201, P41343, P41344, P41346, P47169, P50126, P79290, Q00141

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	66
Likely benign	4
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

3647 predictions. Top by Δscore:

Variant	Effect	Δscore
7:72575715:TTAAA:T	acceptor_gain	1.0000
7:72575716:TAAA:T	acceptor_gain	1.0000
7:72575717:AAACT:A	acceptor_loss	1.0000
7:72575718:AACTG:A	acceptor_loss	1.0000
7:72575719:ACTG:A	acceptor_loss	1.0000
7:72575720:C:CC	acceptor_gain	1.0000
7:72575720:C:CG	acceptor_loss	1.0000
7:72575721:T:G	acceptor_loss	1.0000
7:72616666:TCTTA:T	donor_loss	1.0000
7:72616667:CTTA:C	donor_loss	1.0000
7:72616668:TTACC:T	donor_loss	1.0000
7:72616669:TAC:T	donor_loss	1.0000
7:72616670:ACCT:A	donor_loss	1.0000
7:72616671:C:G	donor_loss	1.0000
7:72616671:CCTTT:C	donor_gain	1.0000
7:72628881:GCTTA:G	donor_loss	1.0000
7:72628882:CTTA:C	donor_loss	1.0000
7:72628883:TTAC:T	donor_loss	1.0000
7:72628884:TACCT:T	donor_loss	1.0000
7:72628885:A:AC	donor_gain	1.0000
7:72628885:A:C	donor_loss	1.0000
7:72628886:C:CC	donor_gain	1.0000
7:72628886:CCTT:C	donor_gain	1.0000
7:72628993:TGTTG:T	acceptor_gain	1.0000
7:72628994:GTTG:G	acceptor_gain	1.0000
7:72628995:TTG:T	acceptor_gain	1.0000
7:72628995:TTGCT:T	acceptor_loss	1.0000
7:72628996:TG:T	acceptor_gain	1.0000
7:72628997:GC:G	acceptor_loss	1.0000
7:72628998:C:A	acceptor_loss	1.0000

AlphaMissense

4498 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:72575672:G:C	F611L	0.881
7:72575672:G:T	F611L	0.881
7:72575674:A:G	F611L	0.881
7:72575717:A:C	F596L	0.874
7:72575717:A:T	F596L	0.874
7:72575719:A:G	F596L	0.874
7:72713656:G:C	F445L	0.874
7:72713656:G:T	F445L	0.874
7:72713658:A:G	F445L	0.874
7:72575624:G:C	F627L	0.873
7:72575624:G:T	F627L	0.873
7:72575626:A:G	F627L	0.873
7:72713659:G:C	S444R	0.872
7:72713659:G:T	S444R	0.872
7:72713661:T:G	S444R	0.872
7:72713635:A:C	F452L	0.861
7:72713635:A:T	F452L	0.861
7:72713637:A:G	F452L	0.861
7:72575701:A:G	W602R	0.854
7:72575701:A:T	W602R	0.854
7:72810510:A:C	F131L	0.853
7:72810510:A:T	F131L	0.853
7:72810512:A:G	F131L	0.853
7:72616759:A:C	F566L	0.843
7:72616759:A:T	F566L	0.843
7:72616761:A:G	F566L	0.843
7:72810477:G:C	F142L	0.811
7:72810477:G:T	F142L	0.811
7:72810479:A:G	F142L	0.811
7:72744492:G:C	F358L	0.805

dbSNP variants (sampled 300 via entrez): RS1000025959 (7:72753047 C>T), RS1000305732 (7:72754704 C>T), RS1001067332 (7:72759678 T>A), RS1001346729 (7:72761361 T>C,G), RS1001579949 (7:72756093 A>T), RS1003070739 (7:72762672 T>C), RS1003356005 (7:72805709 G>C), RS1003408486 (7:72805317 A>G), RS1003525608 (7:72752383 T>C), RS1003808607 (7:72752676 A>G), RS1003857949 (7:72756965 C>A,G), RS1004442123 (7:72751200 G>A), RS1005401654 (7:72763993 A>T), RS1005586305 (7:72757906 C>T), RS1005761993 (7:72805267 C>A)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST000758_32	Triglycerides	1.000000e-09
GCST002216_8	Triglycerides	3.000000e-06
GCST004237_20	Triglyceride levels	2.000000e-08
GCST008151_111	Waist circumference	3.000000e-06
GCST008160_63	Waist circumference	3.000000e-06
GCST009363_14	Triglyceride levels x short total sleep time interaction (2df test)	1.000000e-56
GCST009364_13	Triglyceride levels x long total sleep time interaction (2df test)	2.000000e-57
GCST009364_14	Triglyceride levels x long total sleep time interaction (2df test)	8.000000e-11

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004530	triglyceride measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

9 total (human), top 9 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression	1
abrine	increases expression	1
licochalcone B	increases expression	1
Sunitinib	decreases expression	1
Benzo(a)pyrene	increases methylation	1
Urethane	increases expression	1
Aflatoxin B1	increases methylation	1
Okadaic Acid	increases expression	1
Acrylamide	increases expression	1

Clinical trials (associated diseases)

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

No linked Atlas pages yet — the cross-entity mesh grows as the corpus expands.