SLC20A2

Chr 8AD

solute carrier family 20 member 2

Also known as: GLVR-2, GLVR2, IBGC1, IBGC2, IBGC3, MLVAR, PIT-2, PIT2

NCBI Gene: 6575ENSG00000168575UniProt: Q08357

This gene encodes a member of the inorganic phosphate transporter family. The encoded protein is a type 3 sodium-dependent phosphate symporter that plays an important role in phosphate homeostasis by mediating cellular phosphate uptake. The encoded protein also confers susceptibility to viral infection as a gamma-retroviral receptor. Mutations in this gene may play a role in familial idiopathic basal ganglia calcification. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Mar 2012]

Primary Disease Associations & Inheritance

Basal ganglia calcification, idiopathic, 1MIM #213600
AD
484
ClinVar variants
130
Pathogenic / LP
0.97
pLI score· haploinsufficient
0
Active trials
Clinical Summary— SLC20A2
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.97). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
130 Pathogenic / Likely Pathogenic· 208 VUS of 484 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.33LOEUF
pLI 0.965
Z-score 4.21
OE 0.14 (0.07–0.33)
Highly constrained

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

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
2.63Z-score
OE missense 0.63 (0.57–0.70)
261 obs / 411.2 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.14 (0.07–0.33)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.63 (0.57–0.70)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.14
0≤1.21.6
LoF obs/exp: 4 / 28.1Missense obs/exp: 261 / 411.2Syn Z: -1.46

ClinVar Variant Classifications

484 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic97
Likely Pathogenic33
VUS208
Likely Benign92
Benign40
Conflicting14
97
Pathogenic
33
Likely Pathogenic
208
VUS
92
Likely Benign
40
Benign
14
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
28
2
67
0
97
Likely Pathogenic
12
10
11
0
33
VUS
2
153
49
4
208
Likely Benign
0
9
25
58
92
Benign
0
3
30
7
40
Conflicting
—14
Total4217718269484

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

SLC20A2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Basal ganglia calcification, idiopathic, 1

MIM #213600

Molecular basis of disorder known

Autosomal dominant
📖
GeneReview available — SLC20A2
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Basal ganglia calcification: 'Fahr's disease'.
Magrinelli F et al.·Pract Neurol
2025Review
Basal ganglia calcifications (Fahr's syndrome): related conditions and clinical features.
Donzuso G et al.·Neurol Sci
2019Review
Antisense oligonucleotides enhance SLC20A2 expression and suppress brain calcification in a humanized mouse model.
Zhao M et al.·Neuron
2024Functional
The clinical and genetic spectrum of primary familial brain calcification.
Carecchio M et al.·J Neurol
2023
The Genetics of Primary Familial Brain Calcification: A Literature Review.
Chen SY et al.·Int J Mol Sci
2023Review
Primary familial brain calcifications.
Quintáns B et al.·Handb Clin Neurol
2018Review
Brain Calcifications: Genetic, Molecular, and Clinical Aspects.
Monfrini E et al.·Int J Mol Sci
2023Review
Homozygous SLC20A2 mutations cause congenital CMV infection-like phenotype.
Ceylan AC et al.·Acta Neurol Belg
2023
Primary familial brain calcifications: genetic and clinical update.
Westenberger A et al.·Curr Opin Neurol
2019Review
The Genetic and Phenotypic Spectrum of Primary Brain Calcification in a Large Cohort from China.
Lin Z et al.·Mov Disord
2025Cohort
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Rare Presentation of Homozygous SLC20A2 Mutations Causing Intra-Arterial Cerebral Vasculopathy and Stroke in Infancy: Case Report and Review of the Literature.
Baker L et al.·Case Rep Genet
2025🔓 Open AccessReview
Early-onset Fahr's disease with acute psychosis in a 20-year-old male with SLC20A2 mutation: A case report and literature review.
Alhasan MS et al.·Radiol Case Rep
2026🔓 Open AccessReview
Slc20a2 Deficiency Increases Susceptibility to CNS Demyelination Possibly Through Th17 Cells.
Zhang Y et al.·J Neurosci Res
2025
Co-occurrence of primary familial brain calcification from a likely pathogenic SLC20A2 variant and Alzheimer's disease biology.
Lee HJ et al.·Neurocase
2025
Generation of a new Slc20a2 knockout mouse line as in vivo model for primary brain calcification.
Kurita H et al.·Mol Brain
2025🔓 Open AccessFunctional
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools