TYW1

protein-coding

tRNA-yW synthesizing protein 1 homolog, the group of Radical S-adenosylmethionine domain containing

Gene summary

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. [provided by RefSeq, Dec 2015]

Previous symbols:

RSAFD1

MANE transcript

NM_018264.4

Inheritance

—

ClinVar variants

U:101B:4

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.53

Max pathogenic AF

—

Genomic locus

chr7:66,995,173-67,239,514

External References & Databases

Ensembl (ENSG00000198874)

Transcript & Mutation Effects

hg38 • Region Span ~244.3 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TYW1 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 97

not providedTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_018264.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar	1 clinvar		3
missense			95 clinvar	3 clinvar		98
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			4 clinvar			4
Total	0	0	101	4	0	105

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 45 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_018264.4	RefSeq	NP_060734.2	16	MANE Select
ENST00000359626.10	Ensembl	ENSP00000352645.5	16	MANE Select
ENST00000361660.8	Ensembl	ENSP00000354795.4	9	Standard
ENST00000442959.5	Ensembl	ENSP00000398897.1	5	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Synthesis of wybutosine at G37 of tRNA(Phe)
tRNA modification in the nucleus and cytosol
tRNA processing
Metabolism of RNA
wybutosine biosynthesis

Biological Process

tRNA processing
oxidation-reduction process

Molecular Function

FMN binding
metal ion binding
4 iron, 4 sulfur cluster binding
tRNA-4-demethylwyosine synthase activity

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000359626
Coding exons: 16
Length: 244342
Individuals with no LoFs: 125674
Homozygous LoFs: 0
Heterozygous LoFs: 73
Defined: 125747
p: 0.000290

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.978	358	414	0.865	0.0000226	4874
Missense (PolyPhen)		120	133.96	0.89581		1480
Synonymous	0.906	144	159	0.908	0.0000103	1285
Loss of Function	2.85	23	43.2	0.532	0.00000223	490

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.00032	0.00032	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0.000092	0.000092	rare
European (Non-Finnish)	0.00039	0.00039	rare
South Asian	0.00043	0.00042	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: 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 (By similarity). {ECO:0000250}.;

Recessive Scores

pRec: 0.0869

Intolerance Scores

LoFtool: 0.513
RVIS EVS: -1.17
RVIS percentile EVS: 5.99

Essentials

Essential (CRISPR): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.622

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	High
Cancer	Medium	Medium	Medium