TYW1

Chr 7

tRNA-yW synthesizing protein 1 homolog

Also known as: RSAFD1, TYW1A, YPL207W

NCBI Gene: 55253 ENSG00000198874 UniProt: Q9NV66 OMIM: 611243

This enzyme catalyzes the condensation of N-methylguanine with pyruvate to form 4-demethylwyosine, an intermediate in the biosynthesis of wybutosine, a hypermodified guanosine that stabilizes codon-anticodon interactions in phenylalanine tRNA. Disease associations and inheritance patterns have not been established for TYW1 mutations. The extremely low pLI score suggests this gene may tolerate loss-of-function variants in humans.

OMIM ResearchSummary from RefSeq, UniProt, Mechanism

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]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.75

LOEUF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.75LOEUF

pLI 0.000

Z-score 2.85

OE 0.53 (0.38–0.75)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.98Z-score

OE missense 0.86 (0.79–0.94)

358 obs / 414.0 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.53 (0.38–0.75)

0≤0.351.4

Missense OE?0.86 (0.79–0.94)

0≤0.61.4

Synonymous OE?0.91

0≤1.21.6

LoF obs/exp: 23 / 43.2Missense obs/exp: 358 / 414.0Syn Z: 0.91

Background carrier burden — how many people carry a rare variant somewhere in TYW1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 76

753 rare PASS variants

Rare truncating (LoF)

1 in 1,200

84 rare PASS variants

Rare synonymous (reference)

1 in 120

296 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for TYW1. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 74	1 in 900
South Asian	~43k	1 in 57	1 in 1,200
Remaining (unassigned)	~30k	1 in 64	1 in 2,300
European (Finnish)	~27k	1 in 210	1 in 2,700
Admixed American	~22k	1 in 83	1 in 1,400
African / African American	~21k	1 in 61	1 in 1,500
East Asian	~20k	1 in 60	1 in 980
Ashkenazi Jewish	~13k	1 in 640	none seen
Middle Eastern	~2,884	1 in 90	≈ 1 in 2,900

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 16 of 16 coding exons well covered in gnomAD exomes. Genomes: 15 of 16 (exon 15 below).? see exons ↓