METTL5

Chr 2AR

methyltransferase 5, N6-adenosine

Also known as: HSPC133, MRT72

NCBI Gene: 29081 ENSG00000138382 UniProt: Q9NRN9 OMIM: 618628

Enables S-adenosyl-L-methionine binding activity and rRNA (adenine-N6-)-methyltransferase activity. Involved in positive regulation of translation and rRNA methylation. Located in several cellular components, including fibrillar center; postsynapse; and presynapse. Implicated in autosomal recessive intellectual developmental disorder 72. [provided by Alliance of Genome Resources, Jul 2025]

OMIM Research

OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 1.261 OMIM phenotype

Clinical Summary— METTL5

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

10 unique Pathogenic / Likely Pathogenic· 38 VUS of 71 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.26LOEUF

pLI 0.000

Z-score 0.94

OE 0.70 (0.41–1.26)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.56Z-score

OE missense 0.85 (0.72–1.01)

94 obs / 110.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.70 (0.41–1.26)

0≤0.351.4

Missense OE?0.85 (0.72–1.01)

0≤0.61.4

Synonymous OE?0.87

0≤1.21.6

LoF obs/exp: 8 / 11.4Missense obs/exp: 94 / 110.5Syn Z: 0.61

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

strongMETTL5-related intellectual disability and microcephalyLOFAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

0.6549th %ile

GOF

0.4085th %ile

LOF

0.3649th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

71 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic4

Likely Pathogenic6

VUS38

Likely Benign1

Benign2

Conflicting2

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	4	0	0	0	4
Likely Pathogenic	6	0	0	0	6
VUS	5	31	2	0	38
Likely Benign	0	0	0	1	1
Benign	0	0	1	1	2
Conflicting	—				2
Total	15	31	3	2	53

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

View in ClinVar →

15 pathogenic / likely-pathogenic (of 19) ClinVar copy-number / structural variants overlap METTL5 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →