METTL16
protein-codingmethyltransferase 16, N6-methyladenosine, the group of 7BS N6-adenosine DNA/RNA methyltransferases
Gene summary
Enables RNA binding activity and RNA methyltransferase activity. Involved in RNA processing and regulation of mRNA metabolic process. Located in cytoplasm and nucleoplasm. [provided by Alliance of Genome Resources, Jun 2026]
- METT10D
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~106.3 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 METTL16 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_024086.4. 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 | 47 | 3 | 50 | |||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 0 | 0 | 51 | 4 | 0 | 55 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_076991.3 | 9 | MANE Select | |
| Ensembl | ENSP00000263092.5 | 9 | MANE Select | |
| Ensembl | ENSP00000465733.1 | 3 | Standard | |
| Ensembl | ENSP00000460207.1 | 4 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- mRNA catabolic process
- S-adenosylmethionine biosynthetic process
- posttranscriptional regulation of gene expression
- regulation of mRNA splicing, via spliceosome
- mRNA destabilization
Molecular Function
- mRNA (N6-adenosine)-methyltransferase activity
- RNA binding
- U6 snRNA 3'-end binding
- RNA stem-loop binding
- 23S rRNA (adenine(1618)-N(6))-methyltransferase activity
Cellular Component
- nucleus
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000263092
- Coding exons
- 9
- Length
- 106330
- Individuals with no LoFs
- 124781
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 13
- Defined
- 124794
- p
- 0.0000521
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.35 | 194 | 310 | 0.625 | 0.0000177 | 3670 |
| Missense (PolyPhen) | 17 | 97.743 | 0.17392 | 1282 | ||
| Synonymous | 0.559 | 114 | 122 | 0.936 | 0.00000798 | 1079 |
| Loss of Function | 3.98 | 6 | 29.2 | 0.205 | 0.00000176 | 333 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000056 | 0.000056 | rare |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.000063 | 0.000062 | rare |
| South Asian | 0.00010 | 0.000098 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: RNA N6-methyltransferase that methylates adenosine residues of a subset of RNAs and plays a key role in S-adenosyl-L- methionine homeostasis by regulating expression of MAT2A transcripts (PubMed:28525753). Able to N6-methylate a subset of mRNAs and U6 small nuclear RNAs (U6 snRNAs) (PubMed:28525753). In contrast to the METTL3-METTL14 heterodimer, only able to methylate a limited number of RNAs: requires both a 5'UACAGAGAA-3' nonamer sequence and a specific RNA structure (PubMed:28525753). In presence of S-adenosyl-L-methionine, binds the 3'-UTR region of MAT2A mRNA and specifically N6-methylates the first hairpin of MAT2A mRNA, impairing MAT2A expression (PubMed:28525753). In S- adenosyl-L-methionine-limiting conditions, binds the 3'-UTR region of MAT2A mRNA but stalls due to the lack of a methyl donor, preventing N6-methylation and promoting expression of MAT2A (PubMed:28525753). In addition to mRNAs, also able to mediate N6- methylation of U6 small nuclear RNA (U6 snRNA): specifically N6- methylates adenine in position 43 of U6 snRNAs (PubMed:28525753, PubMed:29051200). Also able to bind various lncRNAs (PubMed:29051200). Specifically binds the 3'-end of the MALAT1 long non-coding RNA (PubMed:27872311). {ECO:0000269|PubMed:27872311, ECO:0000269|PubMed:28525753, ECO:0000269|PubMed:29051200}.;
Recessive Scores
- pRec
- 0.0984
Intolerance Scores
- RVIS EVS
- -0.07
- RVIS percentile EVS
- 48.54
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- E
- Essential (gene trap)
- E
- Indispensability pred.
- N
- Indispensability score
- 0.114
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |