TRMT6

protein-coding

tRNA methyltransferase 6 non-catalytic subunit

Gene summary

This gene encodes a member of the tRNA methyltransferase 6 protein family. A similar protein in yeast is part of a two component methyltransferase, which is involved in the posttranslational modification that produces the modified nucleoside 1-methyladenosine in tRNAs. Modified 1-methyladenosine influences initiator methionine stability and may be involved in the replication of human immunodeficiency virus type 1. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

MANE transcript

NM_015939.5

Inheritance

—

ClinVar variants

U:57B:3

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.46

Max pathogenic AF

—

Genomic locus

chr20:5,937,228-5,950,558

External References & Databases

Ensembl (ENSG00000089195)

Transcript & Mutation Effects

hg38 • Region Span ~13.3 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 TRMT6 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 56

not providedTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_015939.5. 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			55 clinvar	3 clinvar		58
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	57	3	0	60

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 20 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_015939.5	RefSeq	NP_057023.2	11	MANE Select
ENST00000203001.7	Ensembl	ENSP00000203001.2	11	MANE Select
NM_001281467.2	RefSeq	NP_001268396.1	7	Standard
ENST00000453074.6	Ensembl	ENSP00000392070.2	7	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

tRNA modification in the nucleus and cytosol
tRNA processing
Metabolism of RNA

Biological Process

tRNA methylation
mRNA methylation

Molecular Function

RNA binding
tRNA (adenine-N1-)-methyltransferase activity

Cellular Component

nucleus
nucleoplasm
tRNA (m1A) methyltransferase complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000203001
Coding exons: 11
Length: 13302
Individuals with no LoFs: 125725
Homozygous LoFs: 0
Heterozygous LoFs: 23
Defined: 125748
p: 0.0000915

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.03	224	272	0.824	0.0000139	3261
Missense (PolyPhen)		51	89.6	0.5692		1025
Synonymous	-0.691	107	98.3	1.09	0.00000540	933
Loss of Function	2.55	12	26.0	0.461	0.00000141	315

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.000087	0.000087	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.00022	0.00022	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.000053	0.000053	rare
South Asian	0.00017	0.00016	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Substrate-binding subunit of tRNA (adenine-N(1)-)- methyltransferase, which catalyzes the formation of N(1)- methyladenine at position 58 (m1A58) in initiator methionyl-tRNA (PubMed:16043508). Together with the TRMT61A catalytic subunit, part of a mRNA N(1)-methyltransferase complex that mediates methylation of adenosine residues at the N(1) position of a small subset of mRNAs: N(1) methylation takes place in tRNA T-loop-like structures of mRNAs and is only present at low stoichiometries (PubMed:29107537, PubMed:29072297). {ECO:0000269|PubMed:16043508, ECO:0000269|PubMed:29072297, ECO:0000269|PubMed:29107537}.;

Recessive Scores

pRec: 0.101

Intolerance Scores

LoFtool: 0.644
RVIS EVS: -0.56
RVIS percentile EVS: 19.54

Essentials

Essential (CRISPR): E
Essential (CRISPR2): E
Essential (gene trap): E
Indispensability pred.: N
Indispensability score: 0.302

Gene Damage Prediction

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