XPOT

protein-coding

exportin for tRNA, the group of Exportins

Gene summary

This gene encodes a protein belonging to the RAN-GTPase exportin family that mediates export of tRNA from the nucleus to the cytoplasm. Translocation of tRNA to the cytoplasm occurs once exportin has bound both tRNA and GTP-bound RAN. [provided by RefSeq, Jul 2008]

MANE transcript

NM_007235.6

Inheritance

—

ClinVar variants

U:90

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.16

Max pathogenic AF

—

Genomic locus

chr12:64,404,392-64,451,125

External References & Databases

Ensembl (ENSG00000184575)

Transcript & Mutation Effects

hg38 • Region Span ~46.7 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 XPOT variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 78

not providedTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_007235.6. 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			2 clinvar			2
missense			79 clinvar			79
nonsense			3 clinvar			3
start loss						0
frameshift			2 clinvar			2
splice donor/acceptor (+/-2bp)			4 clinvar			4
Total	0	0	90	0	0	90

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 67 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_007235.6	RefSeq	NP_009166.2	24	MANE Select
ENST00000332707.10	Ensembl	ENSP00000327821.5	24	MANE Select
ENST00000400935.2	Ensembl	ENSP00000383722.2	6	Standard
ENST00000538086.5	Ensembl	ENSP00000444345.2	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

RNA transport - Homo sapiens (human)
tRNA processing
Metabolism of RNA
tRNA processing in the nucleus

Biological Process

tRNA export from nucleus
tRNA re-export from nucleus

Molecular Function

tRNA binding
Ran GTPase binding

Cellular Component

nuclear pore
nucleoplasm
cytoplasm
cytosol
nuclear matrix

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000332707
Coding exons: 24
Length: 46778
Individuals with no LoFs: 125726
Homozygous LoFs: 0
Heterozygous LoFs: 17
Defined: 125743
p: 0.0000676

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.05	369	497	0.742	0.0000249	6335
Missense (PolyPhen)		62	118.77	0.52202		1523
Synonymous	1.13	162	181	0.893	0.00000948	1786
Loss of Function	5.88	9	56.9	0.158	0.00000282	669

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.000089	0.000087	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00012	0.00011	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000081	0.000079	rare
South Asian	0.000033	0.000033	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Mediates the nuclear export of aminoacylated tRNAs. In the nucleus binds to tRNA and to the GTPase Ran in its active GTP- bound form. Docking of this trimeric complex to the nuclear pore complex (NPC) is mediated through binding to nucleoporins. Upon transit of a nuclear export complex into the cytoplasm, disassembling of the complex and hydrolysis of Ran-GTP to Ran-GDP (induced by RANBP1 and RANGAP1, respectively) cause release of the tRNA from the export receptor. XPOT then return to the nuclear compartment and mediate another round of transport. The directionality of nuclear export is thought to be conferred by an asymmetric distribution of the GTP- and GDP-bound forms of Ran between the cytoplasm and nucleus. {ECO:0000269|PubMed:12138183, ECO:0000269|PubMed:9512417, ECO:0000269|PubMed:9660920}.;

Recessive Scores

pRec: 0.383

Intolerance Scores

LoFtool: 0.517
RVIS EVS: -0.69
RVIS percentile EVS: 15.2

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.942

Gene Damage Prediction

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