METTL1
protein-codingmethyltransferase 1, tRNA methylguanosine, the group of 7BS DNA/RNA methyltransferases
Gene summary
This gene is similar in sequence to the S. cerevisiae YDL201w gene. The gene product contains a conserved S-adenosylmethionine-binding motif and is inactivated by phosphorylation. Alternative splice variants encoding different protein isoforms have been described for this gene. A pseudogene has been identified on chromosome X. [provided by RefSeq, Jul 2008]
- C12orf1
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~3.6 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 METTL1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_005371.6. 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 | 8 | 8 | ||||
| missense | 50 | 50 | ||||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 53 | 8 | 0 | 61 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_005362.3 | 6 | MANE Select | |
| Ensembl | ENSP00000314441.7 | 6 | MANE Select | |
| RefSeq | NP_075422.3 | 4 | Standard | |
| Ensembl | ENSP00000257848.7 | 4 | Standard |
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
Biological Process
- tRNA modification
- tRNA methylation
- RNA (guanine-N7)-methylation
- tRNA (guanine-N7)-methylation
Molecular Function
- tRNA binding
- protein binding
- tRNA (guanine-N7-)-methyltransferase activity
Cellular Component
- nucleus
- nucleoplasm
- nucleolus
- cytosol
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000324871
- Coding exons
- 6
- Length
- 4323
- Individuals with no LoFs
- 125741
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 7
- Defined
- 125748
- p
- 0.0000278
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.239 | 157 | 166 | 0.948 | 0.00000960 | 1782 |
| Missense (PolyPhen) | 50 | 57.192 | 0.87424 | 585 | ||
| Synonymous | -0.207 | 67 | 64.9 | 1.03 | 0.00000374 | 559 |
| Loss of Function | 1.52 | 6 | 11.6 | 0.518 | 4.90e-7 | 146 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00012 | 0.00012 | rare |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000036 | 0.000035 | rare |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Catalyzes the formation of N(7)-methylguanine at position 46 (m7G46) in tRNA. {ECO:0000255|HAMAP-Rule:MF_03055, ECO:0000269|PubMed:12403464}.;
Recessive Scores
- pRec
- 0.139
Intolerance Scores
- LoFtool
- 0.409
- RVIS EVS
- -0.63
- RVIS percentile EVS
- 17.03
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- E
- Essential (gene trap)
- E
- Indispensability pred.
- E
- Indispensability score
- 0.810
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |