METTL6
protein-codingmethyltransferase 6, methylcytidine, the group of 7BS DNA/RNA methyltransferases
Gene summary
Enables enzyme binding activity and tRNA (cytidine-N3)-methyltransferase activity. Involved in tRNA C3-cytosine methylation. Located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Jun 2026]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~59.3 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 METTL6 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_152396.4. 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 | 48 | 48 | ||||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 49 | 1 | 0 | 50 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_689609.2 | 5 | MANE Select | |
| Ensembl | ENSP00000373300.3 | 5 | MANE Select | |
| RefSeq | NP_001288719.1 | 4 | Standard | |
| RefSeq | NP_001288720.1 | 5 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Selenoamino Acid Metabolism
Biological Process
- tRNA C5-cytosine methylation
Molecular Function
- tRNA (cytosine-5-)-methyltransferase activity
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000443029
- Coding exons
- 5
- Length
- 59292
- Individuals with no LoFs
- 124761
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 32
- Defined
- 124793
- p
- 0.000128
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.705 | 120 | 144 | 0.835 | 0.00000676 | 1887 |
| Missense (PolyPhen) | 21 | 30.457 | 0.6895 | 410 | ||
| Synonymous | 0.574 | 49 | 54.4 | 0.901 | 0.00000278 | 516 |
| Loss of Function | 1.09 | 9 | 13.3 | 0.678 | 6.24e-7 | 179 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00026 | 0.00026 | rare |
| Latino/Admixed American | 0.000058 | 0.000058 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000056 | 0.000056 | rare |
| Finnish | 0.000047 | 0.000046 | rare |
| European (Non-Finnish) | 0.00015 | 0.00015 | rare |
| South Asian | 0.00020 | 0.00020 | rare |
| Other | 0.00017 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Probable methyltransferase. {ECO:0000250}.;
Recessive Scores
- pRec
- 0.0996
Intolerance Scores
- LoFtool
- 0.645
- RVIS EVS
- -0.21
- RVIS percentile EVS
- 38.28
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.785
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |