TYW5

Chr 2

tRNA-yW synthesizing protein 5

Also known as: C2orf60, hTYW5

NCBI Gene: 129450ENSG00000162971UniProt: A2RUC4

Enables several functions, including iron ion binding activity; protein homodimerization activity; and tRNA(Phe) (7-(3-amino-3-carboxypropyl)wyosine37-C2)-hydroxylase activity. Involved in wybutosine biosynthetic process. Predicted to be located in cytoplasm. [provided by Alliance of Genome Resources, Jul 2025]

73
ClinVar variants
34
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— TYW5
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
34 Pathogenic / Likely Pathogenic· 38 VUS of 73 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.24LOEUF
pLI 0.000
Z-score 0.74
OE 0.82 (0.56–1.24)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.12Z-score
OE missense 0.97 (0.85–1.11)
158 obs / 162.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.82 (0.56–1.24)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.97 (0.85–1.11)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.80
0≤1.21.6
LoF obs/exp: 17 / 20.6Missense obs/exp: 158 / 162.3Syn Z: 1.19

ClinVar Variant Classifications

73 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic33
Likely Pathogenic1
VUS38
Likely Benign1
33
Pathogenic
1
Likely Pathogenic
38
VUS
1
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
33
0
33
Likely Pathogenic
0
0
1
0
1
VUS
0
36
2
0
38
Likely Benign
0
1
0
0
1
Benign
0
0
0
0
0
Total03736073

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

TYW5 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Comprehensive and integrative analyses identify TYW5 as a schizophrenia risk gene.
Zhang C et al.·BMC Med
2022
The small members of the JMJD protein family: Enzymatic jewels or jinxes?
Oh S et al.·Biochim Biophys Acta Rev Cancer
2019Review
Brain transcriptome-wide association study implicates novel risk genes underlying schizophrenia risk.
Zhang C et al.·Psychol Med
2023
Crystal structure of a novel JmjC-domain-containing protein, TYW5, involved in tRNA modification.
Kato M et al.·Nucleic Acids Res
2011
Crystal structure and functional analysis of JMJD5 indicate an alternate specificity and function.
Del Rizzo PA et al.·Mol Cell Biol
2012Functional
Regulatory variants at 2q33.1 confer schizophrenia risk by modulating distal gene TYW5 expression.
Li S et al.·Brain
2022
Systematic Surveys of Iron Homeostasis Mechanisms Reveal Ferritin Superfamily and Nucleotide Surveillance Regulation to be Modified by PINK1 Absence.
Key J et al.·Cells
2020Functional
Expanding role of the jumonji C domain as an RNA hydroxylase.
Noma A et al.·J Biol Chem
2010
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC

No open access results found

Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools