METTL8

Chr 2

methyltransferase 8, tRNA N3-cytidine

Also known as: TIP

NCBI Gene: 79828 ENSG00000123600 UniProt: Q9H825 OMIM: 609525

Enables mRNA methyltransferase activity and tRNA (cytidine-3-)-methyltransferase activity. Involved in RNA metabolic process and positive regulation of mitochondrial translation. Is active in mitochondrial matrix. [provided by Alliance of Genome Resources, Jul 2025]

OMIM Research

OMIM ResearchGenerating clinical summary…

LOEUF 1.33

Clinical Summary— METTL8

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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

9 unique Pathogenic / Likely Pathogenic· 78 VUS of 146 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.33LOEUF

pLI 0.000

Z-score 0.44

OE 0.89 (0.61–1.33)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.46Z-score

OE missense 0.91 (0.80–1.03)

170 obs / 187.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.89 (0.61–1.33)

0≤0.351.4

Missense OE?0.91 (0.80–1.03)

0≤0.61.4

Synonymous OE?0.92

0≤1.21.6

LoF obs/exp: 17 / 19.1Missense obs/exp: 170 / 187.5Syn Z: 0.51

ClinVar Variant Classifications

146 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic6

Likely Pathogenic3

VUS78

Likely Benign35

Benign5

Conflicting3

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	2	2	2	0	6
Likely Pathogenic	2	1	0	0	3
VUS	2	65	11	0	78
Likely Benign	0	5	9	21	35
Benign	0	1	3	1	5
Conflicting	—				3
Total	6	74	25	22	130

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

View in ClinVar →

21 pathogenic / likely-pathogenic (of 23) ClinVar copy-number / structural variants overlap METTL8 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →