SLC20A2

protein-coding

solute carrier family 20 member 2, the group of Solute carrier family 20

Gene summary

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]

Previous symbols:

MLVAR
GLVR2

MANE transcript

NM_001257180.2

Inheritance

ClinVar variants

P:90U:194B:95

Top phenotype

Basal ganglia calcification, idiopathic, 1

gnomAD constraint

pLI —, LoF o/e 0.14

Max pathogenic AF

—

Genomic locus

chr8:42,416,475-42,541,926

External References & Databases

Ensembl (ENSG00000168575)

Transcript & Mutation Effects

hg38 • Region Span ~125.5 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

basal ganglia calcification, idiopathic, 1STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0024538

Submitter: Genomics England PanelApp

bilateral striopallidodentate calcinosisSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0008947

Submitter: Orphanet

basal ganglia calcification, idiopathic, 1STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0024538

Submitter: PanelApp Australia

basal ganglia calcification, idiopathic, 1STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0024538

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Basal ganglia calcification, idiopathic, 1AD

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: 20552677; 22327515; 24463626

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SLC20A2 variants in ClinVar

7 Conditions Cataloged

not providedTotal: 298

Idiopathic basal ganglia calcification 1Total: 102

Inborn genetic diseasesTotal: 88

not specifiedTotal: 47

SLC20A2-related disorderTotal: 39

Vascular dementiaTotal: 1

Basal ganglia calcification, idiopathic, childhood-onsetTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001257180.2. 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			5 clinvar	71 clinvar	6 clinvar	82
missense	4 clinvar	15 clinvar	183 clinvar	17 clinvar	1 clinvar	220
nonsense	21 clinvar	5 clinvar				26
start loss			1 clinvar			1
frameshift	22 clinvar	6 clinvar	1 clinvar			29
splice donor/acceptor (+/-2bp)	8 clinvar	9 clinvar	4 clinvar			21
Total	55	35	194	88	7	379

Highest pathogenic variant AF is 0.000022304916

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 143 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001257180.2	RefSeq	NP_001244109.1	10	MANE Select
ENST00000520262.6	Ensembl	ENSP00000429754.1	10	MANE Select
NM_001257181.2	RefSeq	NP_001244110.1	10	Standard
NM_006749.5	RefSeq	NP_006740.1	10	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Transport of inorganic cations/anions and amino acids/oligopeptides
SLC-mediated transmembrane transport
Transport of small molecules
Sodium-coupled phosphate cotransporters

Biological Process

ion transport
phosphate ion transmembrane transport
sodium ion transmembrane transport
sodium-dependent phosphate transport
viral entry into host cell

Molecular Function

virus receptor activity
inorganic phosphate transmembrane transporter activity
sodium:phosphate symporter activity
sodium:inorganic phosphate symporter activity
sodium-dependent phosphate transmembrane transporter activity

Cellular Component

plasma membrane
integral component of plasma membrane
membrane
extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000342228
Coding exons: 10
Length: 123077
Individuals with no LoFs: 125736
Homozygous LoFs: 0
Heterozygous LoFs: 10
Defined: 125746
p: 0.0000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.63	261	411	0.635	0.0000257	4193
Missense (PolyPhen)		91	162.83	0.55885		1661
Synonymous	-1.46	210	185	1.14	0.0000140	1389
Loss of Function	4.21	4	28.1	0.142	0.00000153	303

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000093	0.000087	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000035	0.000035	rare
South Asian	0	0.0	absent
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Sodium-phosphate symporter which seems to play a fundamental housekeeping role in phosphate transport by absorbing phosphate from interstitial fluid for normal cellular functions such as cellular metabolism, signal transduction, and nucleic acid and lipid synthesis. In vitro, sodium-dependent phosphate uptake is not siginificantly affected by acidic and alkaline conditions, however sodium-independent phosphate uptake occurs at acidic conditions. May play a role in extracellular matrix, cartilage and vascular calcification. Functions as a retroviral receptor and confers human cells susceptibility to infection to amphotropic murine leukemia virus (A-MuLV), 10A1 murine leukemia virus (10A1 MLV) and some feline leukemia virus subgroup B (FeLV-B) variants. {ECO:0000269|PubMed:11435563, ECO:0000269|PubMed:12205090, ECO:0000269|PubMed:15955065, ECO:0000269|PubMed:16790504, ECO:0000269|PubMed:8302848}.;
Disease: DISEASE: Basal ganglia calcification, idiopathic, 1 (IBGC1) [MIM:213600]: 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:15955065, ECO:0000269|PubMed:22327515, ECO:0000269|PubMed:23334463, ECO:0000269|PubMed:23406454, ECO:0000269|PubMed:23939468, ECO:0000269|PubMed:24065723, ECO:0000269|PubMed:24463626, ECO:0000269|PubMed:25284758}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.176

Intolerance Scores

LoFtool: 0.0451
RVIS EVS: -0.75
RVIS percentile EVS: 13.67

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.115

Gene Damage Prediction

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