METTL16

Chr 17

methyltransferase 16, RNA N6-adenosine

Also known as: METT10D

NCBI Gene: 79066 ENSG00000127804 UniProt: Q86W50

METTL16 encodes an RNA N6-methyltransferase that methylates specific adenosine residues in mRNAs and U6 small nuclear RNAs, playing a critical role in S-adenosyl-L-methionine homeostasis by regulating MAT2A transcript expression. Mutations cause autosomal recessive intellectual disability with developmental delay and seizures, typically presenting in infancy or early childhood. The gene shows significant constraint against loss-of-function variants (LOEUF 0.405), indicating that complete loss of protein function is poorly tolerated.

ResearchSummary from RefSeq, UniProt

Enables RNA binding activity and RNA methyltransferase activity. Involved in RNA processing and regulation of mRNA metabolic process. Located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

LOEUF 0.41

Clinical Summary— METTL16

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Population Constraint (gnomAD)

Moderately constrained gene (pLI 0.61) — some intolerance to loss-of-function variants.

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ClinVar Variants

47 VUS of 61 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.41LOEUF

pLI 0.612

Z-score 3.98

OE 0.21 (0.11–0.41)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

2.35Z-score

OE missense 0.63 (0.56–0.70)

194 obs / 310.2 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.21 (0.11–0.41)

0≤0.351.4

Missense OE?0.63 (0.56–0.70)

0≤0.61.4

Synonymous OE?0.94

0≤1.21.6

LoF obs/exp: 6 / 29.2Missense obs/exp: 194 / 310.2Syn Z: 0.56

ClinVar Variant Classifications

61 submitted variants in ClinVar

ClinVar

Classification Summary

VUS47

Likely Benign4

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	47	0	47
Likely Benign	3	1	4
Benign	0	0	0
Total	50	1	51

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

69 pathogenic / likely-pathogenic (of 88) ClinVar copy-number / structural variants overlap METTL16 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →