METTL2A

protein-coding

methyltransferase 2A, methylcytidine, the group of 7BS DNA/RNA methyltransferases

Gene summary

Enables tRNA (cytidine-N3)-methyltransferase activity. Involved in tRNA methylation. Located in cytoplasm. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_181725.4

Inheritance

—

ClinVar variants

U:61B:2

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.93

Max pathogenic AF

—

Genomic locus

chr17:62,423,875-62,453,385

External References & Databases

Ensembl (ENSG00000087995)

Transcript & Mutation Effects

hg38 • Region Span ~29.5 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 METTL2A variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 60

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_181725.4. 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						0
missense			60 clinvar	2 clinvar		62
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	61	2	0	63

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 18 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_181725.4	RefSeq	NP_859076.3	9	MANE Select
ENST00000311506.10	Ensembl	ENSP00000309610.6	9	MANE Select
ENST00000616852.1	Ensembl	ENSP00000479905.1	8	Standard
ENST00000616852.2	Ensembl	ENSP00000479905.1	8	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

tRNA methylation

Molecular Function

tRNA (cytosine) methyltransferase activity
tRNA (cytosine-3-)-methyltransferase activity

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000311506
Coding exons: 9
Length: 26227
Individuals with no LoFs: 125441
Homozygous LoFs: 0
Heterozygous LoFs: 307
Defined: 125748
p: 0.00122

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.0738	199	202	0.985	0.0000103	2492
Missense (PolyPhen)		51	55.66	0.91628		588
Synonymous	0.912	66	76.1	0.867	0.00000407	690
Loss of Function	0.297	20	21.5	0.931	0.00000115	239

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0080	0.0080	notable
Latino/Admixed American	0.0032	0.0032	notable
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0.00032	0.00032	rare
European (Non-Finnish)	0.00023	0.00023	rare
South Asian	0.00083	0.00082	rare
Other	0.0012	0.0011	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Probable S-adenosyl-L-methionine-dependent methyltransferase that mediates 3-methylcytidine modification of some tRNAs. {ECO:0000250}.;

Recessive Scores

pRec: 0.105

Intolerance Scores

LoFtool: 0.694
RVIS EVS: 0.19
RVIS percentile EVS: 67.03

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.201

Gene Damage Prediction

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