METTL14
methyltransferase 14, N6-adenosine-methyltransferase subunit, the group of 7BS N6-adenosine DNA/RNA methyltransferases|m6A methyltransferase complex
Basic information
Region (hg38): 4:118685392-118715433
Links
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
- not_specified (25 variants)
- not_provided (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the METTL14 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000020961.4. Only rare variants are included in the table.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | |||||
| missense | 25 | 25 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 25 | 1 | 0 |
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| METTL14 | protein_coding | protein_coding | ENST00000388822 | 11 | 30066 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.00133 | 0.998 | 125709 | 0 | 38 | 125747 | 0.000151 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 2.74 | 124 | 245 | 0.507 | 0.0000124 | 2981 |
| Missense in 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 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.000265 | 0.000251 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00107 | 0.00106 |
| European (Non-Finnish) | 0.0000837 | 0.0000791 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.0000449 | 0.0000327 |
| Other | 0.00 | 0.00 |
dbNSFP
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}.;
- Pathway
- Metabolism of RNA;Processing of Capped Intron-Containing Pre-mRNA
(Consensus)
Intolerance Scores
- loftool
- rvis_EVS
- -0.27
- rvis_percentile_EVS
- 33.97
Haploinsufficiency Scores
- pHI
- hipred
- Y
- hipred_score
- 0.613
- ghis
- 0.694
Essentials
- essential_gene_CRISPR
- E
- essential_gene_CRISPR2
- S
- essential_gene_gene_trap
- E
- gene_indispensability_pred
- N
- gene_indispensability_score
- 0.307
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Mettl14
- Phenotype
Gene ontology
- Biological process
- mRNA splicing, via spliceosome;mRNA catabolic process;spermatogenesis;stem cell population maintenance;forebrain radial glial cell differentiation;gliogenesis;mRNA destabilization;mRNA methylation
- Cellular component
- nucleus;nucleoplasm;RNA N6-methyladenosine methyltransferase complex
- Molecular function
- mRNA binding;protein binding;mRNA (2'-O-methyladenosine-N6-)-methyltransferase activity;S-adenosyl-L-methionine binding