TRMT61B

protein-coding

tRNA methyltransferase 61B, the group of 7BS DNA/RNA methyltransferases

Gene summary

Enables mRNA (adenine-N1-)-methyltransferase activity; rRNA (adenine) methyltransferase activity; and tRNA (adenine(58)-N1)-methyltransferase activity. Involved in mRNA processing and mitochondrial tRNA processing. Located in mitochondrial matrix. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_017910.4

Inheritance

—

ClinVar variants

U:94B:4

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.66

Max pathogenic AF

—

Genomic locus

chr2:28,849,821-28,870,309

External References & Databases

Ensembl (ENSG00000171103)

Transcript & Mutation Effects

hg38 • Region Span ~20.5 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 TRMT61B variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 96

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_017910.4. 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			93 clinvar	4 clinvar		97
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	94	4	0	98

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 52 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_017910.4	RefSeq	NP_060380.3	7	MANE Select
ENST00000306108.10	Ensembl	ENSP00000302801.5	7	MANE Select
ENST00000419999.5	Ensembl	ENSP00000405467.1	3	Standard
ENST00000439947.1	Ensembl	ENSP00000389617.1	5	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

tRNA processing
tRNA modification in the mitochondrion
Metabolism of RNA

Biological Process

tRNA methylation
rRNA methylation
protein homooligomerization
mitochondrial tRNA methylation
mRNA methylation

Molecular Function

protein binding
tRNA (adenine-N1-)-methyltransferase activity
rRNA (adenine) methyltransferase activity
mRNA (adenine-N1-)-methyltransferase activity

Cellular Component

mitochondrion
mitochondrial matrix
tRNA (m1A) methyltransferase complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000306108
Coding exons: 7
Length: 20481
Individuals with no LoFs: 125686
Homozygous LoFs: 0
Heterozygous LoFs: 31
Defined: 125717
p: 0.000123

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.644	282	253	1.11	0.0000117	3081
Missense (PolyPhen)		59	63.055	0.93569		815
Synonymous	-0.451	106	100	1.06	0.00000479	945
Loss of Function	1.51	15	22.8	0.659	0.00000115	273

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000053	0.000053	rare
South Asian	0.00076	0.00075	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Methyltransferase that catalyzes the formation of N(1)- methyladenine at position 58 (m1A58) in various tRNAs in mitochondrion, including tRNA(Leu) (deciphering codons UUA or UUG), tRNA(Lys) and tRNA(Ser) (deciphering codons UCA, UCU, UCG or UCC) (PubMed:23097428). Catalyzes the formation of 1- methyladenosine at position 947 of mitochondrial 16S ribosomal RNA and this modification is most likely important for mitoribosomal structure and function (PubMed:27631568). In addition to tRNA N(1)-methyltransferase activity, also acts as a mRNA N(1)- methyltransferase by mediating methylation of adenosine residues at the N(1) position of MT-ND5 mRNA, leading to interfere with mitochondrial translation (PubMed:29107537). {ECO:0000269|PubMed:23097428, ECO:0000269|PubMed:27631568, ECO:0000269|PubMed:29107537}.;

Recessive Scores

pRec: 0.0722

Intolerance Scores

LoFtool: 0.904
RVIS EVS: 0.2
RVIS percentile EVS: 67.36

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.788

Gene Damage Prediction

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