METTL14
protein-codingmethyltransferase 14, N6-adenosine-methyltransferase subunit, the group of 7BS N6-adenosine DNA/RNA methyltransferases|m6A methyltransferase complex
Gene summary
Enables mRNA binding activity and mRNA m(6)A methyltransferase activity. Involved in mRNA modification; mRNA splicing, via spliceosome; and mRNA stabilization. Located in nucleoplasm. Part of RNA N6-methyladenosine methyltransferase complex. [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 ~30.0 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 METTL14 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_020961.4. 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 | 2 | |||
| missense | 28 | 28 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 30 | 1 | 0 | 31 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_066012.1 | 11 | MANE Select | |
| Ensembl | ENSP00000373474.3 | 11 | MANE Select | |
| Ensembl | ENSP00000424111.2 | 4 | Standard | |
| Ensembl | ENSP00000425460.1 | 4 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Metabolism of RNA
- Processing of Capped Intron-Containing Pre-mRNA
Biological Process
- mRNA splicing, via spliceosome
- mRNA catabolic process
- spermatogenesis
- stem cell population maintenance
- forebrain radial glial cell differentiation
Molecular Function
- mRNA binding
- protein binding
- mRNA (2'-O-methyladenosine-N6-)-methyltransferase activity
- S-adenosyl-L-methionine binding
Cellular Component
- nucleus
- nucleoplasm
- RNA N6-methyladenosine methyltransferase complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000388822
- Coding exons
- 11
- Length
- 30066
- Individuals with no LoFs
- 125709
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 38
- Defined
- 125747
- p
- 0.000151
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.74 | 124 | 245 | 0.507 | 0.0000124 | 2981 |
| Missense (PolyPhen) | 32 | 95.98 | 0.3334 | 1208 | ||
| Synonymous | 0.359 | 77 | 81.1 | 0.949 | 0.00000401 | 844 |
| Loss of Function | 3.15 | 10 | 27.9 | 0.358 | 0.00000173 | 321 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00020 | 0.00018 | rare |
| Latino/Admixed American | 0.000067 | 0.000058 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.0011 | 0.0011 | notable |
| European (Non-Finnish) | 0.000084 | 0.000079 | rare |
| South Asian | 0.000045 | 0.000033 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: The METTL3-METTL14 heterodimer forms a N6- methyltransferase complex that methylates adenosine residues at the N(6) position of some mRNAs and regulates the circadian clock, differentiation of embryonic stem cells and cortical neurogenesis (PubMed:24316715, PubMed:24407421, PubMed:25719671, PubMed:29348140, PubMed:27373337, PubMed:27281194). In the heterodimer formed with METTL3, METTL14 constitutes the RNA- binding scaffold that recognizes the substrate rather than the catalytic core (PubMed:27627798, PubMed:27373337, PubMed:27281194, PubMed:29348140). N6-methyladenosine (m6A), which takes place at the 5'-[AG]GAC-3' consensus sites of some mRNAs, plays a role in mRNA stability and processing (PubMed:24316715, PubMed:24407421, PubMed:25719671). M6A acts as a key regulator of mRNA stability by promoting mRNA destabilization and degradation (By similarity). In embryonic stem cells (ESCs), m6A methylation of mRNAs encoding key naive pluripotency-promoting transcripts results in transcript destabilization (By similarity). M6A regulates spermatogonial differentiation and meiosis and is essential for male fertility and spermatogenesis (By similarity). M6A also regulates cortical neurogenesis: m6A methylation of transcripts related to transcription factors, neural stem cells, the cell cycle and neuronal differentiation during brain development promotes their destabilization and decay, promoting differentiation of radial glial cells (By similarity). {ECO:0000250|UniProtKB:Q3UIK4, ECO:0000269|PubMed:24316715, ECO:0000269|PubMed:24407421, ECO:0000269|PubMed:25719671, ECO:0000269|PubMed:27281194, ECO:0000269|PubMed:27373337, ECO:0000269|PubMed:27627798, ECO:0000269|PubMed:29348140}.;
Intolerance Scores
- RVIS EVS
- -0.27
- RVIS percentile EVS
- 33.97
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- S
- Essential (gene trap)
- E
- Indispensability pred.
- N
- Indispensability score
- 0.307
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |