METTL14methyltransferase 14, N6-adenosine-methyltransferase non-catalytic subunit
Autism Reports / Total Reports
6 / 8Rare Variants / Common Variants
6 / 0Aliases
-Associated Syndromes
-Chromosome Band
4q26Associated Disorders
-Relevance to Autism
In a report demonstrating that modification of APC with N6-methyladenosine faciliated its translation in neuronal somata via YTH domain-containing family M6A reader proteins, Broix et al. 2025 found that overexpression of the M6A writer METTL14 containing human missense variants associated with autism or schizophrenia impaired the transport and local translation of APC-regulated target mRNA beta-actin in axons and growth cones, which subsequently hindered axon development. In addition to the functionally validated ASD-associated missense variant (originally identified in an ASD proband from the Autism Sequencing Consortium in Neale et al., 2012), three additional de novo missense variants have been identified in ASD probands, including a variant predicted to be damaging by CADD and REVEL in an MSSNG proband (Zhou et al., 2022; Fu et al., 2022; Yuan et al., 2023). Depletion by Mettl14 knockout in embryonic mouse brains was previously reported to prolong the cell cycle of radial glia cells and extend cortical neurogenesis into postnatal stages, demonstrating its importance in the regulation of mammalian brain development (Yoon et al., 2017).
Molecular Function
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.
External Links
SFARI Genomic Platforms
Reports related to METTL14 (8 Reports)
| # | Type | Title | Author, Year | Autism Report | Associated Disorders |
|---|---|---|---|---|---|
| 1 | Support | Patterns and rates of exonic de novo mutations in autism spectrum disorders | Neale BM , et al. (2012) | Yes | - |
| 2 | Support | De novo mutations in schizophrenia implicate synaptic networks | Fromer M , et al. (2014) | No | - |
| 3 | Support | - | Ki-Jun Yoon et al. (2017) | No | - |
| 4 | Support | Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks | Ruzzo EK , et al. (2019) | Yes | - |
| 5 | Support | - | Zhou X et al. (2022) | Yes | - |
| 6 | Support | - | Fu JM et al. (2022) | Yes | - |
| 7 | Support | - | Yuan B et al. (2023) | Yes | - |
| 8 | Primary | - | Loic Broix et al. () | Yes | - |
Rare Variants (6)
| Status | Allele Change | Residue Change | Variant Type | Inheritance Pattern | Parental Transmission | Family Type | PubMed ID | Author, Year |
|---|---|---|---|---|---|---|---|---|
| c.117T>A | p.Asp39Glu | missense_variant | De novo | - | - | 35982160 | Fu JM et al. (2022) | |
| c.1247G>A | p.Gly416Glu | missense_variant | De novo | - | - | 36881370 | Yuan B et al. (2023) | |
| c.1028G>A | p.Arg343His | missense_variant | De novo | - | Simplex | 35982159 | Zhou X et al. (2022) | |
| c.931A>G | p.Ile311Val | missense_variant | De novo | - | Simplex | 22495311 | Neale BM , et al. (2012) | |
| c.1196C>T | p.Ser399Leu | missense_variant | De novo | - | Simplex | 24463507 | Fromer M , et al. (2014) | |
| c.739-1G>T | p.? | splice_site_variant | Familial | Paternal | Simplex | 31398340 | Ruzzo EK , et al. (2019) |
Common Variants
No common variants reported.