TRDMT1
protein-codingtRNA aspartic acid methyltransferase 1, the group of 7BS C5-cytosine DNA/RNA methyltransferases
Gene summary
This gene encodes a protein responsible for the methylation of aspartic acid transfer RNA, specifically at the cytosine-38 residue in the anticodon loop. This enzyme also possesses residual DNA-(cytosine-C5) methyltransferase activity. While similar in sequence and structure to DNA cytosine methyltransferases, this gene is distinct and highly conserved in its function among taxa. [provided by RefSeq, Jun 2010]
- DNMT2
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~64.7 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 TRDMT1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_004412.7. 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 | 2 | |||
| missense | 55 | 3 | 1 | 59 | ||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 58 | 3 | 2 | 63 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_004403.1 | 11 | MANE Select | |
| Ensembl | ENSP00000367030.3 | 11 | MANE Select | |
| RefSeq | NP_001307935.1 | 8 | Standard | |
| RefSeq | NP_001307936.1 | 9 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| trdmt1 | Danio rerio | Structure: post-vent region Quality: malformed abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- tRNA modification in the nucleus and cytosol
- tRNA processing
- Metabolism of RNA
- Methionine and cysteine metabolism
Biological Process
- response to amphetamine
- tRNA modification
- tRNA methylation
Molecular Function
- RNA binding
- tRNA methyltransferase activity
- tRNA (cytosine-5-)-methyltransferase activity
Cellular Component
- nucleoplasm
- cytoplasm
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000377799
- Coding exons
- 11
- Length
- 59801
- Individuals with no LoFs
- 125689
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 45
- Defined
- 125734
- p
- 0.000179
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.822 | 224 | 192 | 1.17 | 0.00000965 | 2527 |
| Missense (PolyPhen) | 61 | 72.279 | 0.84395 | 956 | ||
| Synonymous | -1.16 | 83 | 70.6 | 1.18 | 0.00000363 | 717 |
| Loss of Function | 0.883 | 17 | 21.4 | 0.794 | 0.00000117 | 271 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00012 | 0.00012 | rare |
| Latino/Admixed American | 0.00029 | 0.00029 | rare |
| Ashkenazi Jewish | 0.00030 | 0.00030 | rare |
| East Asian | 0.000055 | 0.000054 | rare |
| Finnish | 0.00033 | 0.00032 | rare |
| European (Non-Finnish) | 0.00015 | 0.00015 | rare |
| South Asian | 0.00013 | 0.00013 | rare |
| Other | 0.00017 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Specifically methylates cytosine 38 in the anticodon loop of tRNA(Asp). {ECO:0000269|PubMed:16424344}.;
Recessive Scores
- pRec
- 0.163
Intolerance Scores
- LoFtool
- 0.438
- RVIS EVS
- 0.09
- RVIS percentile EVS
- 60.47
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.864
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |