TARBP1

Chr 1

tRNA guanosine 2 -O-methyltransferase TARBP1

Also known as: TRM3, TRMT3, TRP-185, TRP185

NCBI Gene: 6894 ENSG00000059588 UniProt: Q13395 OMIM: 605052

This gene encodes an S-adenosyl-L-methionine-dependent methyltransferase that catalyzes 2'-O-methylation at position 18 in specific tRNAs, enhancing their stability. Based on current databases, no definitive human genetic disorders have been established for TARBP1 mutations. The gene shows low constraint against loss-of-function variants (pLI near 0), suggesting it may be more tolerant to such changes than highly constrained developmental genes.

OMIM ResearchSummary from RefSeq, UniProt

HIV-1, the causative agent of acquired immunodeficiency syndrome (AIDS), contains an RNA genome that produces a chromosomally integrated DNA during the replicative cycle. Activation of HIV-1 gene expression by the transactivator Tat is dependent on an RNA regulatory element (TAR) located downstream of the transcription initiation site. This element forms a stable stem-loop structure and can be bound by either the protein encoded by this gene or by RNA polymerase II. This protein may act to disengage RNA polymerase II from TAR during transcriptional elongation. Alternatively spliced transcripts of this gene may exist, but their full-length natures have not been determined. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

Active trials

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Pubs (1 yr)

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P/LP submissions

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P/LP missense

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LOEUF

Mechanism· predicted

Some data sources returned errors (1)

gnomad: Error: Service overloaded

Population Genetics & Constraint

gnomAD

Constraint data not available from gnomAD.

Background carrier burden — how many people carry a rare variant somewhere in TARBP1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 26

2,223 rare PASS variants

Rare truncating (LoF)

1 in 340

432 rare PASS variants

Rare synonymous (reference)

1 in 66

843 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for TARBP1. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 40	1 in 430
South Asian	~43k	1 in 21	1 in 210
Remaining (unassigned)	~30k	1 in 22	1 in 190
European (Finnish)	~27k	1 in 180	1 in 670
Admixed American	~22k	1 in 21	1 in 250
African / African American	~21k	1 in 28	1 in 170
East Asian	~20k	1 in 28	1 in 170
Ashkenazi Jewish	~13k	1 in 110	1 in 1,500
Middle Eastern	~2,884	1 in 30	1 in 130

Each group is summed over the variants that are rare in that group. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 21 of 30 coding exons well covered in gnomAD exomes; exons 1, 3, 5, 6, 13 and 4 more marginal. Genomes: 29 of 30 (exon 5 below).? see exons ↓