TYW5
protein-codingtRNA-yW synthesizing protein 5, the group of JmjC hydroxylases
Gene summary
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]
- C2orf60
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~26.8 kbGenCC 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 TYW5 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001039693.3. 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 | 0 | |||||
| missense | 37 | 1 | 38 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 37 | 1 | 0 | 38 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001034782.1 | 8 | MANE Select | |
| Ensembl | ENSP00000346627.4 | 8 | MANE Select | |
| Ensembl | ENSP00000398447.1 | 5 | Standard | |
| Ensembl | ENSP00000420024.1 | 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
Biological Process
- tRNA modification
- wybutosine biosynthetic process
- oxidation-reduction process
Molecular Function
- tRNA binding
- iron ion binding
- 2-oxoglutarate-dependent dioxygenase activity
- protein homodimerization activity
- tRNAPhe (7-(3-amino-3-carboxypropyl)wyosine37-C2)-hydroxylase activity
Cellular Component
- cytoplasm
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000354611
- Coding exons
- 8
- Length
- 25762
- Individuals with no LoFs
- 124718
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 76
- Defined
- 124794
- p
- 0.000305
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.120 | 158 | 162 | 0.974 | 0.00000760 | 2061 |
| Missense (PolyPhen) | 52 | 50.982 | 1.02 | 636 | ||
| Synonymous | 1.19 | 46 | 57.4 | 0.801 | 0.00000256 | 572 |
| Loss of Function | 0.740 | 17 | 20.6 | 0.824 | 0.00000120 | 238 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00039 | 0.00039 | rare |
| Latino/Admixed American | 0.000059 | 0.000058 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00017 | 0.00017 | rare |
| Finnish | 0.00075 | 0.00074 | rare |
| European (Non-Finnish) | 0.00029 | 0.00029 | rare |
| South Asian | 0.00043 | 0.00042 | rare |
| Other | 0.00050 | 0.00049 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: tRNA hydroxylase that acts as a 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 hydroxylation of 7-(a-amino-a-carboxypropyl)wyosine (yW-72) into undermodified hydroxywybutosine (OHyW*). OHyW* being further transformed into hydroxywybutosine (OHyW) by LCMT2/TYW4. OHyW is a derivative of wybutosine found in higher eukaryotes. {ECO:0000269|PubMed:20739293}.;
Recessive Scores
- pRec
- 0.113
Intolerance Scores
- RVIS EVS
- -0.18
- RVIS percentile EVS
- 39.95
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.114
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |