XPR1

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

Basic information

Region (hg38): 1:180632021-180890279

Links

ENSG00000143324 ∙ NCBI:9213 ∙ OMIM:605237 ∙ HGNC:12827 ∙ Uniprot:Q9UBH6 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• basal ganglia calcification, idiopathic, 6 (Strong), mode of inheritance: AD
• basal ganglia calcification, idiopathic, 6 (Strong), mode of inheritance: AD
• basal ganglia calcification, idiopathic, 6 (Moderate), mode of inheritance: AD
• bilateral striopallidodentate calcinosis (Supportive), mode of inheritance: AD
• basal ganglia calcification, idiopathic, 6 (Moderate), mode of inheritance: AD
• basal ganglia calcification, idiopathic, 6 (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Basal ganglia calcification, idiopathic, 6	AD	General	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	Neurologic	886353; 25938945

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the XPR1 gene.

• not provided (181 variants)
• Inborn genetic diseases (12 variants)
• Basal ganglia calcification, idiopathic, 6 (6 variants)
• not specified (3 variants)
• XPR1-related primary familial brain calcification (1 variants)
• Seizure (1 variants)
• See cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the XPR1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				35	7	42
missense			70	2		72
nonsense			1			1
start loss						0
frameshift			1			1
inframe indel			1			1
splice donor/acceptor (+/-2bp)		1	2			3
splice region			7	2	3	12
non coding			1	20	39	60
Total	0	1	76	57	46

Variants in XPR1

This is a list of pathogenic ClinVar variants found in the XPR1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
1-180632070-G-A			Benign (Jul 17, 2018)
1-180632227-C-G			Uncertain significance (Apr 25, 2023)
1-180632267-T-C		Basal ganglia calcification, idiopathic, 6	Conflicting classifications of pathogenicity (May 13, 2022)
1-180632280-C-T			Likely benign (Mar 29, 2023)
1-180632288-G-C			Likely benign (Jul 05, 2023)
1-180632290-G-A			Likely benign (Dec 04, 2021)
1-180682347-T-A			Likely benign (Feb 11, 2023)
1-180682383-A-T			Likely benign (Jun 03, 2021)
1-180682478-G-A			Likely benign (Aug 11, 2018)
1-180682660-A-C			Likely benign (Mar 01, 2020)
1-180787733-A-G			Likely benign (May 31, 2023)
1-180787752-G-C			Uncertain significance (Jul 19, 2022)
1-180787761-G-A			Uncertain significance (Jun 27, 2023)
1-180787769-A-G			Likely benign (Jun 24, 2023)
1-180787774-A-G			Uncertain significance (Mar 05, 2023)
1-180787802-G-C			Uncertain significance (Oct 03, 2023)
1-180787813-C-G			Uncertain significance (Nov 21, 2022)
1-180787819-A-G			Uncertain significance (Jul 24, 2019)
1-180787853-A-G			Uncertain significance (May 23, 2023)
1-180787871-CT-C			Benign (Feb 08, 2022)
1-180787871-C-CT			Benign (Jan 30, 2024)
1-180787871-C-CTT			Benign (Jan 11, 2024)
1-180787920-A-G			Benign (Jul 30, 2018)
1-180787981-G-GT			Benign (Nov 14, 2019)
1-180788008-G-A			Benign (Jul 05, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
XPR1	protein_coding	protein_coding	ENST00000367590	15	258248

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.0000130	125743	0	4	125747	0.0000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.23	218	400	0.545	0.0000227	4583
Missense in Polyphen		38	161.23	0.23569		1775
Synonymous	0.719	131	142	0.923	0.00000719	1331
Loss of Function	5.60	2	40.4	0.0495	0.00000236	427

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.0000176	0.0000176
Middle Eastern	0.000109	0.000109
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

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

Haploinsufficiency Scores

• pHI: 0.423
• hipred: Y
• hipred_score: 0.713
• ghis: 0.557

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.940

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Xpr1
• Phenotype: immune system phenotype

Zebrafish Information Network

• Gene name: xpr1b
• Affected structure: macrophage
• Phenotype tag: abnormal
• Phenotype quality: has fewer parts of type

Gene ontology

• Biological process: G protein-coupled receptor signaling pathway;response to virus;cellular phosphate ion homeostasis;phosphate ion transmembrane transport;viral entry into host cell
• Cellular component: Golgi apparatus;plasma membrane;integral component of membrane;intrinsic component of plasma membrane
• Molecular function: inositol hexakisphosphate binding;virus receptor activity;transmembrane signaling receptor activity;G protein-coupled receptor activity;phosphate ion transmembrane transporter activity;efflux transmembrane transporter activity;signaling receptor activity