THUMPD3
protein-codingTHUMP domain containing 3, the group of 7BS DNA/RNA methyltransferases
Gene summary
Enables tRNA (guanine(6)-N2)-methyltransferase activity and tRNA (guanine(7)-N2)-methyltransferase activity. Involved in tRNA methylation. Located in cytosol and nucleolus. Part of tRNA methyltransferase complex. [provided by Alliance of Genome Resources, Jul 2025]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~23.8 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 THUMPD3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001114092.2. 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 | 1 | 1 | ||||
| missense | 75 | 2 | 77 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 7 | 7 | ||||
| Total | 0 | 0 | 83 | 2 | 0 | 85 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001107564.1 | 9 | MANE Select | |
| Ensembl | ENSP00000395893.2 | 9 | MANE Select | |
| RefSeq | NP_056268.2 | 9 | Standard | |
| Ensembl | ENSP00000339532.3 | 9 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- tRNA methylation
Molecular Function
- RNA binding
- tRNA (guanine) methyltransferase activity
Cellular Component
- nucleolus
- cytosol
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000345094
- Coding exons
- 9
- Length
- 23950
- Individuals with no LoFs
- 125589
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 159
- Defined
- 125748
- p
- 0.000632
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.414 | 290 | 271 | 1.07 | 0.0000136 | 3333 |
| Missense (PolyPhen) | 67 | 70.747 | 0.94704 | 872 | ||
| Synonymous | 0.888 | 82 | 92.9 | 0.883 | 0.00000470 | 952 |
| Loss of Function | 0.582 | 22 | 25.2 | 0.875 | 0.00000142 | 298 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00099 | 0.00098 | rare |
| Latino/Admixed American | 0.0013 | 0.0012 | notable |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00044 | 0.00044 | rare |
| Finnish | 0.00051 | 0.00051 | rare |
| European (Non-Finnish) | 0.00052 | 0.00052 | rare |
| South Asian | 0.00062 | 0.00062 | rare |
| Other | 0.00067 | 0.00065 | rare |
dbNSFP Gene Annotations
Source:
Recessive Scores
- pRec
- 0.0993
Intolerance Scores
- LoFtool
- 0.993
- RVIS EVS
- 0.27
- RVIS percentile EVS
- 70.58
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.260
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |