GeneBe

XPR1

protein-coding

xenotropic and polytropic retrovirus receptor 1, the group of Solute carrier family 53

Gene summary

The protein encoded by this gene is a receptor for the xenotropic and polytropic classes of murine leukemia viruses. The encoded protein is involved in phosphate homeostasis by mediating phosphate export from the cell. Defects in this gene have been associated with idiopathic basal ganglia calcification-6. [provided by RefSeq, Jun 2016]

MANE transcript

NM_004736.4

Inheritance

AD

ClinVar variants

P:7U:143B:77

Top phenotype

Basal ganglia calcification, idiopathic, 6

gnomAD constraint

pLI —, LoF o/e 0.05

Max pathogenic AF

—

Genomic locus

chr1:180,632,022-180,890,279

External References & Databases

Ensembl (ENSG00000143324)NCBI Gene (9213)OMIM (605237)HGNC:12827GenCCUniProt (Q9UBH6)AlphaFoldClinVar (XPR1)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~258.3 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

basal ganglia calcification, idiopathic, 6STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0014628

Submitter: Genomics England PanelApp

basal ganglia calcification, idiopathic, 6MODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0014628

Submitter: Ambry Genetics

bilateral striopallidodentate calcinosisSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0008947

Submitter: Orphanet

basal ganglia calcification, idiopathic, 6STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0014628

Submitter: PanelApp Australia

basal ganglia calcification, idiopathic, 6MODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0014628

Submitter: Illumina

basal ganglia calcification, idiopathic, 6STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0014628

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Basal ganglia calcification, idiopathic, 6AD

Manifestation: Neurologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 886353; 25938945Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to XPR1 variants in ClinVar

7 Conditions Cataloged
not providedTotal: 238
Inborn genetic diseasesTotal: 51
not specifiedTotal: 43
Basal ganglia calcification, idiopathic, 6Total: 20
XPR1-related disorderTotal: 9
XPR1-related primary familial brain calcificationTotal: 1
See casesTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_004736.4. 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.

EffectPLPVUSLBBSum
synonymous
3
clinvar
65
clinvar
4
clinvar
 72
missense
4
clinvar
2
clinvar
132
clinvar
8
clinvar
 146
nonsense
4
clinvar
 4
start loss
0
frameshift
2
clinvar
 2
splice donor/acceptor (+/-2bp)
1
clinvar
2
clinvar
 3
Total43143734227
Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 31 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_004736.4RefSeqNP_004727.215MANE Select
ENST00000367590.9EnsemblENSP00000356562.415MANE Select
NM_001135669.2RefSeqNP_001129141.114Standard
NM_001328662.2RefSeqNP_001315591.111Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / ModelOrganismObserved Phenotype
xpr1bDanio rerio

Structure: macrophage

Quality: has fewer parts of type

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

  • G protein-coupled receptor signaling pathway
  • response to virus
  • cellular phosphate ion homeostasis
  • phosphate ion transmembrane transport
  • viral entry into host cell

Molecular Function

  • inositol hexakisphosphate binding
  • virus receptor activity
  • transmembrane signaling receptor activity
  • G protein-coupled receptor activity
  • phosphate ion transmembrane transporter activity

Cellular Component

  • Golgi apparatus
  • plasma membrane
  • integral component of membrane
  • intrinsic component of plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000367590
Coding exons
15
Length
258248
Individuals with no LoFs
125743
Homozygous LoFs
0
Heterozygous LoFs
4
Defined
125747
p
0.0000159
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense3.232184000.5450.00002274583
Missense (PolyPhen)38161.230.235691775
Synonymous0.7191311420.9230.000007191331
Loss of Function5.60240.40.04950.00000236427

Population LoF Frequency

PopulationCAFp-valueStatus
African00.0absent
Latino/Admixed American00.0absent
Ashkenazi Jewish00.0absent
East Asian0.000110.00011rare
Finnish00.0absent
European (Non-Finnish)0.0000180.000018rare
South Asian00.0absent
Other00.0absent

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: Plays a role in phosphate homeostasis. Mediates phosphate export from the cell (PubMed:23791524, PubMed:25938945). Binds inositol hexakisphosphate (Ins6P) and similar inositol polyphosphates, such as 5-diphospho-inositol pentakisphosphate (5- InsP7); these are important intracellular signaling molecules (PubMed:27080106). {ECO:0000250|UniProtKB:Q9Z0U0, ECO:0000269|PubMed:23791524, ECO:0000269|PubMed:25938945, ECO:0000269|PubMed:27080106}.;
Disease
DISEASE: Basal ganglia calcification, idiopathic, 6 (IBGC6) [MIM:616413]: A form of basal ganglia calcification, an autosomal dominant condition characterized by symmetric calcification in the basal ganglia and other brain regions. Affected individuals can either be asymptomatic or show a wide spectrum of neuropsychiatric symptoms, including parkinsonism, dystonia, tremor, ataxia, dementia, psychosis, seizures, and chronic headache. Serum levels of calcium, phosphate, alkaline phosphatase and parathyroid hormone are normal. The neuropathological hallmark of the disease is vascular and pericapillary calcification, mainly of calcium phosphate, in the affected brain areas. {ECO:0000269|PubMed:25938945}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec
0.204

Intolerance Scores

LoFtool
0.144
RVIS EVS
-0.78
RVIS percentile EVS
12.77

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
E
Indispensability score
0.940

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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