XPR1

Chr 1AD

xenotropic and polytropic retrovirus receptor 1

Also known as: IBGC6, SLC53A1, SYG1, X3

NCBI Gene: 9213 ENSG00000143324 UniProt: Q9UBH6 OMIM: 605237

XPR1 encodes an inorganic phosphate transporter that mediates phosphate export across the plasma membrane, playing a major role in cellular phosphate homeostasis and preventing intracellular phosphate accumulation. Mutations cause autosomal dominant idiopathic basal ganglia calcification-6, which primarily affects the brain's basal ganglia structures. The gene is highly constrained against loss-of-function variants (pLI 1.0, LOEUF 0.156), indicating intolerance to protein-truncating mutations.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Basal ganglia calcification, idiopathic, 6MIM #616413

Clinical highlights

Gene–disease validity

Not independently assessedOMIM lists Basal ganglia calcification, idiopathic; no ClinGen or GenCC tier

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.16

LOEUF· LoF intol.

Multiple*

Mechanism· predicted

📖

GeneReview available — XPR1

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Dual constrained — LoF & missense intolerant

LoF Constraint?

0.16LOEUF

pLI 1.000

Z-score 5.60

OE 0.05 (0.02–0.16)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

3.23Z-score

OE missense 0.55 (0.49–0.61)

218 obs / 400.0 exp

Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?

LoF OE?0.05 (0.02–0.16)

0≤0.351.4

Missense OE?0.55 (0.49–0.61)

0≤0.61.4

Synonymous OE?0.92

0≤1.21.6

LoF obs/exp: 2 / 40.4Missense obs/exp: 218 / 400.0Syn Z: 0.72

Background carrier burden — how many people carry a rare variant somewhere in XPR1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 160

602 rare PASS variants

Rare truncating (LoF)

1 in 6,200

44 rare PASS variants

Rare synonymous (reference)

1 in 210

317 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for XPR1. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 160	1 in 5,700
South Asian	~43k	1 in 120	1 in 5,900
Remaining (unassigned)	~30k	1 in 150	≈ 1 in 30,000
European (Finnish)	~27k	1 in 580	≈ 1 in 26,000
Admixed American	~22k	1 in 200	1 in 3,100
African / African American	~21k	1 in 140	≈ 1 in 5,200
East Asian	~20k	1 in 130	≈ 1 in 6,600
Ashkenazi Jewish	~13k	1 in 670	1 in 1,400
Middle Eastern	~2,884	1 in 160	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 15 coding exons well covered in gnomAD exomes and genomes.? see exons ↓