XPO5

protein-coding

exportin 5, the group of Exportins

Gene summary

This gene encodes a member of the karyopherin family that is required for the transport of small RNAs and double-stranded RNA-binding proteins from the nucleus to the cytoplasm. The encoded protein translocates cargo through the nuclear pore complex in a RanGTP-dependent process. [provided by RefSeq, Aug 2011]

MANE transcript

NM_020750.3

Inheritance

ClinVar variants

U:185B:82

Top phenotype

XPO5-related disorder

gnomAD constraint

pLI —, LoF o/e 0.15

Max pathogenic AF

—

Genomic locus

chr6:43,522,334-43,576,038

External References & Databases

Ensembl (ENSG00000124571)

Transcript & Mutation Effects

hg38 • Region Span ~53.7 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

nephrotic syndromeLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0005377

Submitter: PanelApp Australia

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to XPO5 variants in ClinVar

4 Conditions Cataloged

not providedTotal: 269

not specifiedTotal: 112

XPO5-related disorderTotal: 35

POLR1C-related disorderTotal: 4

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_020750.3. 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	65 clinvar	4 clinvar	73
missense			167 clinvar	11 clinvar	2 clinvar	180
nonsense			1 clinvar			1
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			12 clinvar			12
Total	0	0	185	76	6	267

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 28 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_020750.3	RefSeq	NP_065801.1	32	MANE Select
ENST00000265351.12	Ensembl	ENSP00000265351.7	32	MANE Select
ENST00000398799.2	Ensembl	ENSP00000381779.2	2	Standard
ENST00000398835.7	Ensembl	ENSP00000381816.3	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

RNA transport - Homo sapiens (human)
miRNA Biogenesis
RNA interference
Gene expression (Transcription)
MicroRNA (miRNA) biogenesis

Biological Process

protein export from nucleus
miRNA metabolic process
pre-miRNA export from nucleus
regulation of protein export from nucleus
positive regulation of RNA interference

Molecular Function

tRNA binding
RNA binding
mRNA binding
nuclear export signal receptor activity
protein binding

Cellular Component

nucleus
nucleoplasm
cytoplasm
cytosol
micro-ribonucleoprotein complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000265351
Coding exons: 32
Length: 53741
Individuals with no LoFs: 124972
Homozygous LoFs: 0
Heterozygous LoFs: 25
Defined: 124997
p: 0.000100

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	3.11	422	644	0.655	0.0000333	7897
Missense (PolyPhen)		68	169.07	0.40221		2074
Synonymous	-0.625	245	233	1.05	0.0000122	2290
Loss of Function	6.65	11	71.8	0.153	0.00000410	804

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00020	0.00019	rare
Latino/Admixed American	0.00038	0.00023	rare
Ashkenazi Jewish	0.00021	0.00020	rare
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.00011	0.00011	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Mediates the nuclear export of proteins bearing a double-stranded RNA binding domain (dsRBD) and double-stranded RNAs (cargos). XPO5 in the nucleus binds cooperatively to the RNA and to the GTPase Ran in its active GTP-bound form. Proteins containing dsRBDs can associate with this trimeric complex through the RNA. Docking of this complex to the nuclear pore complex (NPC) is mediated through binding to nucleoporins. Upon transit of a nuclear export complex into the cytoplasm, hydrolysis of Ran-GTP to Ran-GDP (induced by RANBP1 and RANGAP1, respectively) cause disassembly of the complex and release of the cargo from the export receptor. XPO5 then returns to the nuclear compartment by diffusion through the nuclear pore complex, to 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. Overexpression may in some circumstances enhance RNA-mediated gene silencing (RNAi). Mediates nuclear export of isoform 5 of ADAR/ADAR1 in a RanGTP-dependent manner.; FUNCTION: (Microbial infection) Mediates the nuclear export of adenovirus VA1 dsRNA. {ECO:0000269|PubMed:12509441}.;

Recessive Scores

pRec: 0.235

Intolerance Scores

RVIS EVS: -0.82
RVIS percentile EVS: 12.01

Essentials

Essential (CRISPR): E
Essential (CRISPR2): E
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.982

Gene Damage Prediction

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