METTL8

protein-coding

methyltransferase 8, methylcytidine, the group of 7BS DNA/RNA methyltransferases

Gene summary

Enables mRNA methyltransferase activity and tRNA (cytidine-N3)-methyltransferase activity. Involved in RNA metabolic process and positive regulation of mitochondrial translation. Is active in mitochondrial matrix. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_001321154.2

Inheritance

—

ClinVar variants

U:64B:4

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.89

Max pathogenic AF

—

Genomic locus

chr2:171,315,746-171,434,802

External References & Databases

Ensembl (ENSG00000123600)

Transcript & Mutation Effects

hg38 • Region Span ~119.1 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to METTL8 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 59

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001321154.2. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous					1 clinvar	1
missense			58 clinvar	3 clinvar		61
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			6 clinvar			6
Total	0	0	64	3	1	68

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 49 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001321154.2	RefSeq	NP_001308083.1	9	MANE Select
ENST00000375258.9	Ensembl	ENSP00000364407.4	9	MANE Select
NM_001321155.2	RefSeq	NP_001308084.1	9	Standard
NM_001321156.2	RefSeq	NP_001308085.1	9	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

tRNA methylation

Molecular Function

tRNA (cytosine-3-)-methyltransferase activity

Cellular Component

nucleus
cytoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000375258
Coding exons: 9
Length: 117394
Individuals with no LoFs: 125533
Homozygous LoFs: 0
Heterozygous LoFs: 210
Defined: 125743
p: 0.000835

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.455	170	188	0.906	0.00000933	2484
Missense (PolyPhen)		62	72.837	0.85122		990
Synonymous	0.514	57	62.1	0.917	0.00000284	678
Loss of Function	0.443	17	19.1	0.890	9.94e-7	258

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00027	0.00025	rare
Latino/Admixed American	0.00054	0.00052	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00040	0.00038	rare
Finnish	0.0046	0.0046	notable
European (Non-Finnish)	0.00050	0.00047	rare
South Asian	0.00068	0.00062	rare
Other	0.0017	0.0016	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Probable methyltransferase. {ECO:0000250}.;

Recessive Scores

pRec: 0.0767

Essentials

Essential (CRISPR2): S
Indispensability pred.: N
Indispensability score: 0.0136

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium