METTL14
Chr 4methyltransferase 14, N6-adenosine-methyltransferase non-catalytic subunit
Also known as: hMETTL14
METTL14 forms a heterodimer with METTL3 that functions as an N6-methyltransferase complex, methylating adenosine residues in mRNAs to regulate mRNA stability, circadian clock function, and cortical neurogenesis. Biallelic mutations cause developmental delay, intellectual disability, and microcephaly with autosomal recessive inheritance. The gene is highly constrained against loss-of-function variants (LOEUF 0.607), reflecting its essential role in neurodevelopment and cellular differentiation.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Moderately missense-constrained (top ~2.5%)
The highest-scoring mechanism for this gene is dominant-negative.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
METTL14 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
External Resources
Links to major genomics databases and tools