TARBP1

protein-coding

TAR (HIV-1) RNA binding protein 1, the group of SPOUT methyltransferase domain containing|Armadillo like helical domain containing

Gene summary

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]

MANE transcript

NM_005646.4

Inheritance

—

ClinVar variants

U:311B:15

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.66

Max pathogenic AF

—

Genomic locus

chr1:234,391,313-234,479,179

External References & Databases

Ensembl (ENSG00000059588)

Transcript & Mutation Effects

hg38 • Region Span ~87.9 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 TARBP1 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 291

not providedTotal: 7

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_005646.4. 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			4 clinvar	3 clinvar	1 clinvar	8
missense			297 clinvar	10 clinvar	1 clinvar	308
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			10 clinvar			10
Total	0	0	311	13	2	326

Loading ClinVar variants...

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_005646.4	RefSeq	NP_005637.3	30	MANE Select
ENST00000040877.2	Ensembl	ENSP00000040877.1	30	MANE Select
ENST00000870825.1	Ensembl	ENSP00000540884.1	28	Standard
ENST00000870825.2	Ensembl	ENSP00000540884.1	28	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

regulation of transcription by RNA polymerase II
tRNA methylation

Molecular Function

RNA binding
tRNA (guanine) methyltransferase activity

Cellular Component

nucleus

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000040877
Coding exons: 30
Length: 87791
Individuals with no LoFs: 125573
Homozygous LoFs: 1
Heterozygous LoFs: 174
Defined: 125748
p: 0.000696

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.429	758	726	1.04	0.0000358	10415
Missense (PolyPhen)		216	243.1	0.88851		3580
Synonymous	0.881	254	273	0.932	0.0000139	3198
Loss of Function	2.68	48	72.6	0.661	0.00000335	960

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0017	0.0016	notable
Latino/Admixed American	0.00067	0.00061	rare
Ashkenazi Jewish	0.00041	0.00040	rare
East Asian	0.0010	0.00098	notable
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00076	0.00074	rare
South Asian	0.00065	0.00059	rare
Other	0.00050	0.00049	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Probable S-adenosyl-L-methionine-dependent methyltransferase which methylates RNA molecules such as tRNAs. In case of infection by HIV-1, it binds to the loop region of TAR RNA, a region also bound by RNA polymerase II. Binding of TARBP1 and RNA polymerase II to HIV-1 TAR RNA is mutually exclusive, suggesting that TARBP1 may function alone or in conjunction with HIV-1 Tat to disengage RNA polymerase II from HIV-1 TAR RNA. May act by methylating HIV-1 TAR RNA. {ECO:0000269|PubMed:7638159, ECO:0000269|PubMed:8626763, ECO:0000269|PubMed:8846792}.;

Recessive Scores

pRec: 0.107

Intolerance Scores

LoFtool: 0.993
RVIS EVS: -0.23
RVIS percentile EVS: 36.36

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.557

Gene Damage Prediction

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