SLC20A2

Summary

SLC20A2 (solute carrier family 20 member 2, HGNC:10947) is a protein-coding gene on chromosome 8p11.21, encoding Sodium-dependent phosphate transporter 2 (Q08357). Sodium-phosphate symporter which preferentially transports the monovalent form of phosphate with a stoichiometry of two sodium ions per phosphate ion.

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.

Source: NCBI Gene 6575 — RefSeq curated summary.

At a glance

• Gene–disease (curated): basal ganglia calcification, idiopathic, 1 (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 12
• Clinical variants (ClinVar): 439 total — 58 pathogenic, 26 likely-pathogenic
• Phenotypes (HPO): 54
• Druggable target: yes
• MANE Select transcript: NM_001257180

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10947
Approved symbol	SLC20A2
Name	solute carrier family 20 member 2
Location	8p11.21
Locus type	gene with protein product
Status	Approved
Aliases	PiT-2, Glvr-2, Ram-1, PIT2
Ensembl gene	ENSG00000168575
Ensembl biotype	protein_coding
OMIM	158378
Entrez	6575

Gene structure

Transcript identifiers

Ensembl transcripts: 63 — 54 protein_coding, 6 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay, 1 retained_intron

ENST00000342228, ENST00000517366, ENST00000518384, ENST00000518660, ENST00000518717, ENST00000519463, ENST00000520179, ENST00000520262, ENST00000521455, ENST00000522401, ENST00000522707, ENST00000523340, ENST00000524211, ENST00000524237, ENST00000713988, ENST00000713989, ENST00000908098, ENST00000908099, ENST00000908100, ENST00000908101, ENST00000908102, ENST00000908103, ENST00000908104, ENST00000908105, ENST00000908106, ENST00000908107, ENST00000908108, ENST00000908109, ENST00000908110, ENST00000908111, ENST00000908112, ENST00000908113, ENST00000908114, ENST00000908115, ENST00000908116, ENST00000908117, ENST00000908118, ENST00000908119, ENST00000908120, ENST00000908121, ENST00000926756, ENST00000926757, ENST00000926758, ENST00000926759, ENST00000926760, ENST00000926761, ENST00000926762, ENST00000926763, ENST00000965913, ENST00000965914, ENST00000965915, ENST00000965916, ENST00000965917, ENST00000965918, ENST00000965919, ENST00000965920, ENST00000965921, ENST00000965922, ENST00000965923, ENST00000965924, ENST00000965925, ENST00000965926, ENST00000965927

RefSeq mRNA: 3 — MANE Select: NM_001257180 NM_001257180, NM_001257181, NM_006749

CCDS: CCDS6132

Canonical transcript exons

ENST00000520262 — 11 exons

Exon	Start	End
ENSE00001128408	42430064	42430249
ENSE00001128418	42436989	42437577
ENSE00001240969	42428758	42428842
ENSE00001299605	42416475	42417967
ENSE00001383472	42472102	42472654
ENSE00002117862	42501031	42501231
ENSE00003467563	42465777	42465917
ENSE00003528807	42459896	42459992
ENSE00003574787	42439450	42439653
ENSE00003624920	42444646	42444762
ENSE00003683234	42463005	42463090

Expression profiles

Bgee: expression breadth ubiquitous, 276 present calls, max score 96.24.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 37.7177 / max 655.5137, expressed in 1819 samples.

FANTOM5 promoters (14 alternative TSS)

Promoter ID	TPM avg	Samples expressed
92915	22.7624	1805
92912	4.4420	1558
92908	4.2272	653
92913	1.3962	830
92917	1.2906	845
92914	1.2506	746
92907	0.7525	292
92916	0.6281	349
92906	0.3508	173
92919	0.3291	162

Top tissues by expression

289 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
left lobe of thyroid gland	UBERON:0001120	96.24	gold quality
right lobe of thyroid gland	UBERON:0001119	96.20	gold quality
thyroid gland	UBERON:0002046	96.01	gold quality
popliteal artery	UBERON:0002250	95.93	gold quality
hindlimb stylopod muscle	UBERON:0004252	95.92	gold quality
tibial artery	UBERON:0007610	95.92	gold quality
right atrium auricular region	UBERON:0006631	94.96	gold quality
aorta	UBERON:0000947	94.87	gold quality
vena cava	UBERON:0004087	94.20	gold quality
corpus callosum	UBERON:0002336	94.16	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	94.06	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	94.01	gold quality
muscle of leg	UBERON:0001383	93.89	gold quality
right coronary artery	UBERON:0001625	93.89	gold quality
gastrocnemius	UBERON:0001388	93.86	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	93.56	gold quality
thoracic aorta	UBERON:0001515	93.53	gold quality
ascending aorta	UBERON:0001496	93.47	gold quality
lower esophagus muscularis layer	UBERON:0035833	93.47	gold quality
lower esophagus	UBERON:0013473	93.46	gold quality
buccal mucosa cell	CL:0002336	93.43	gold quality
right hemisphere of cerebellum	UBERON:0014890	93.42	gold quality
cerebellar cortex	UBERON:0002129	93.31	gold quality
cerebellar hemisphere	UBERON:0002245	93.30	gold quality
descending thoracic aorta	UBERON:0002345	93.30	gold quality
right uterine tube	UBERON:0001302	93.29	gold quality
heart left ventricle	UBERON:0002084	93.28	gold quality
cardiac atrium	UBERON:0002081	93.21	gold quality
left coronary artery	UBERON:0001626	93.07	gold quality
cardiac ventricle	UBERON:0002082	93.06	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-HCAD-35	yes	6.62
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

132 targeting SLC20A2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-3148	99.97	75.06	6478
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-767-5P	99.95	70.85	993
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-424-5P	99.89	71.90	2641

Literature-anchored findings (GeneRIF, showing 40)

• NOT linked in indiopathic basal ganglia calcinosis (PMID:11810290)
• forms assemblies at cell surface (PMID:11932396)
• Two highly conserved glutamate residues critical for sodium-dependent phosphate transport are revealed by uncoupling transport function from retroviral receptor function. (PMID:12205090)
• structure activity relationship of deletion mutants of Pit2 retroviral receptor [Pit2] (PMID:15308749)
• the presence of an aspartic acid in either of the PiT family signature sequences is critical for the Na+-dependent P(i) transport function of human PiT2 (PMID:15955065)
• Results describe the characterization of transport mechanisms and determinants critical for sodium-dependent phosphate symport of the PiT family paralogs human PiT1 and PiT2. (PMID:16790504)
• Analysis of kinetics and substrate specificity of SLC20A2. (PMID:17494632)
• the human PiT2 histidine, H(502), and the human PiT1 glutamate, E(70),–both conserved in eukaryotic PiT family members–are critical for P(i) transport function (PMID:21586110)
• Mutations in SLC20A2 link familial idiopathic basal ganglia calcification with phosphate homeostasis. (PMID:22327515)
• Mutations in the underlying disease genes ENPP1, ABCC6, NT5E, and SLC20A2, respectively, lead to arterial media calcification. (PMID:23122642)
• Our screen in a large series expands the catalog of SLC20A2 mutations identified to date and demonstrates that mutations in SLC20A2 are a major cause of familial idiopathic basal ganglia calcification. (PMID:23334463)
• This finding reinforces the relevance of the SLC20A2 gene to the etiopathogeny of familial idiopathic basal ganglia calcification (PMID:23406454)
• we identified a novel SLC20A2 mutation, which causes a significant decrease in SLC20A2 mRNA expression. (PMID:23437308)
• Our study supports the hypothesis that SLC20A2 is a causative gene of Idiopathic basal ganglia calcification. (PMID:23939468)
• SLC20A2 and PDGFRB mutations result in different idiopathic basal ganglia calcification phenotypes. (PMID:24065723)
• deletion of SLC20A2 and THAP1 may have a role in familial basal ganglia calcification with dystonia [case report and family study] (PMID:24135862)
• SLC20A2 mutations are a major cause of familial idiopathic basal ganglia calcification in Japan (PMID:24463626)
• The mutation of SLC20A2 cause primary familial brain calcifications. (PMID:25212438)
• This molecular analysis expands the mutational spectrum of SLC20A2, which remains the major causative gene of primary familial brain calcification. (PMID:25284758)
• clinical, neuroimaging and genetic findings in an Italian family with idiopathic basal ganglia calcification; 2 affected family members harbored a novel missense mutation, G1618A leading to gly540-to-arg (G540R) substitution in a highly conserved residue (PMID:25348593)
• Familial idiopathic basal ganglia calcification caused by the SLC20A2 gene mutation can manifest as juvenile onset paroxysmal kinesigenic dyskinesia. (PMID:25636102)
• The SLC20A2 mutation leading to the accumulation of calcium salts in the brain. (PMID:25686613)
• A summary of SLC20A2 variants reported in patients with primary familial brain calcification (review). (PMID:25726928)
• Currently, mutations in SLC20A2 gene have been identified as pathogenic for Familial idiopathic basal ganglia calcification. (PMID:25906927)
• Mutations in SLC20A2 are a major cause of familial idiopathic basal ganglia calcification. (PMID:25958344)
• Lessons from SLC20A2, PDGFB, and PDGFRB mutation carriers. Three causative genes have been identified: SLC20A2, PDGFRB and, recently, PDGFB, whose associated phenotype has not yet been extensively studied. (PMID:26129893)
• SLC20A2 variant was identified in a family with CHRNB2 mutation, brain calcifications and generalized tonic-clonic seizures. (PMID:26475232)
• This study presented the Primary familial brain calcification in a Norwegian family, caused by a novel SLC20A2 gene mutation. (PMID:26860091)
• Deletions of exon 2 of SLC20A2 identified in two unrelated patients segregated with primary brain calcification. (PMID:27245298)
• The identified SLC20A2 mutation resolves the genetic cause of primary familial brain calcification in the ‘IBGC2’ kindred, collapsing ‘IBGC2’ into IBGC1. (PMID:27671522)
• Deletion of 5’ noncoding region of SLC20A2 was associated with primary familial brain calcification in a Finnish family with three affected memebers. (PMID:27726124)
• In mouse cells, the SLC20A2 brain calcification causal missense mutations exert their effect in a dominant negative manner resulting in decreased wild-type PiT2 Pi transport. (PMID:27943094)
• This review showed that SLC20A2 was the most common gene involved with 75 out of 137 cases included with brain calcification. (PMID:28162874)
• SLC20A2 expression is reduced in the primary brain familiar calcification patients carrying SLC20A2 mutation. (PMID:28578517)
• Report sub-cellular expression analysis of mutant PiT-2 in primary cultured fibroblasts from a primary familial brain calcification patient, showing that p.Trp626_Thr629dup in SLC20A2 alters PiT-2 sub-cellular localization and reduces Pi-uptake, leading to onset of PFBC in our patient. (PMID:28722801)
• The established IBGC-iPSCs carried SLC20A2 c.1848G>A mutation (p.W616* of translated protein PiT2), and also showed typical iPSC morphology, pluripotency markers, normal karyotype, and the ability of in vitro differentiation into three-germ layers. (PMID:29034894)
• This study demonstrated that the frequently mutated gene is SLC20A2 caused primary familial brain calcifications where mutations can affect any domain of the protein. (PMID:29325620)
• A Novel SLC20A2 Mutation Associated with Familial Idiopathic Basal Ganglia Calcification and Analysis of the Genotype-Phenotype Association in Chinese Patients (PMID:29578123)
• identified an SLC20A2 (c.509delT, p.(Leu170*)) variant in three affected members over three generations (PMID:29680161)
• SLC20A2 variants cause the loss of function of the Pi transport activity in both Flp-In CHO cells and disease-specific human Idiopathic Basal Ganglia Calcification induced pluripotent stem cells (PMID:30704756)

Cross-species orthologs

9 orthologs

Organism	Symbol	Gene ID
danio_rerio	slc20a2	ENSDARG00000060796
mus_musculus	Slc20a2	ENSMUSG00000037656
rattus_norvegicus	Slc20a2	ENSRNOG00000019490
drosophila_melanogaster	NaPi-III	FBGN0260795
caenorhabditis_elegans		WBGENE00012285
caenorhabditis_elegans		WBGENE00015054
caenorhabditis_elegans		WBGENE00015055
caenorhabditis_elegans		WBGENE00016739
caenorhabditis_elegans		WBGENE00017312

Paralogs (1): SLC20A1 (ENSG00000144136)

Protein

Protein identifiers

Sodium-dependent phosphate transporter 2 — Q08357 (reviewed: Q08357)

Alternative names: Gibbon ape leukemia virus receptor 2, Phosphate transporter 2, Solute carrier family 20 member 2

All UniProt accessions (7): A0A384MR38, E5RGG8, E5RGJ6, E5RGM8, E5RIX1, E5RJW9, Q08357

UniProt curated annotations — full annotation on UniProt →

Function. Sodium-phosphate symporter which preferentially transports the monovalent form of phosphate with a stoichiometry of two sodium ions per phosphate ion. Plays a critical role in the determination of bone quality and strength by providing phosphate for bone mineralization. Required to maintain normal cerebrospinal fluid phosphate levels. Mediates phosphate-induced calcification of vascular smooth muscle cells (VCMCs) and can functionally compensate for loss of SLC20A1 in VCMCs. (Microbial infection) 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.

Subunit / interactions. Homodimer.

Subcellular location. Cell membrane. Apical cell membrane.

Tissue specificity. Ubiquitously expressed.

Disease relevance. 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. The disease is caused by variants affecting the gene represented in this entry.

Induction. Increased by phosphate depletion in osteosarcoma cell lines.

Similarity. Belongs to the inorganic phosphate transporter (PiT) (TC 2.A.20) family.

RefSeq proteins (3): NP_001244109, NP_001244110, NP_006740 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001204	Phos_transporter	Family

Pfam: PF01384

Catalyzed reactions (Rhea), 1 shown:

• 2 Na(+)(out) + phosphate(out) = 2 Na(+)(in) + phosphate(in) (RHEA:71259)

UniProt features (64 total): sequence variant 21, topological domain 13, transmembrane region 12, mutagenesis site 7, modified residue 6, region of interest 2, chain 1, compositionally biased region 1, glycosylation site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q08357-F1	72.63	0.46

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (6): 253, 256, 259, 268, 316, 385

Glycosylation sites (1): 81

Mutagenesis-validated functional residues (7):

Position	Phenotype
55	abolishes sodium-dependent phosphate transport; no effect on retroviral receptor function.
55	abolishes phosphate but not sodium uptake; when associated with q-91 and q-575.
81	abolishes n-glycosylation.
91	abolishes phosphate but not sodium uptake; when associated with q-55 and q-575.
506	impairs phosphate transport; no effect on retroviral receptor function.
575	abolishes sodium-dependent phosphate transport; no effect on retroviral receptor function.
575	abolishes phosphate but not sodium uptake; when associated with q-55 and q-91.

Function

Pathways and Gene Ontology

Reactome pathways

8 pathways

ID	Pathway
R-HSA-427652	Sodium-coupled phosphate cotransporters
R-HSA-5619111	Defective SLC20A2 causes idiopathic basal ganglia calcification 1 (IBGC1)
R-HSA-1643685	Disease
R-HSA-382551	Transport of small molecules
R-HSA-425393
R-HSA-425407	SLC-mediated transmembrane transport
R-HSA-5619102	SLC transporter disorders
R-HSA-5619115	Disorders of transmembrane transporters

MSigDB gene sets: 282 (showing top): GRUETZMANN_PANCREATIC_CANCER_DN, GOBP_SODIUM_ION_TRANSMEMBRANE_TRANSPORT, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, ACEVEDO_NORMAL_TISSUE_ADJACENT_TO_LIVER_TUMOR_DN, GOBP_INORGANIC_ANION_TRANSPORT, CHANDRAN_METASTASIS_DN, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_BONE_MINERALIZATION, KINSEY_TARGETS_OF_EWSR1_FLII_FUSION_DN, GOBP_PHOSPHATE_ION_TRANSPORT, E4F1_Q6, GOBP_BIOLOGICAL_PROCESS_INVOLVED_IN_INTERACTION_WITH_HOST, GENTILE_UV_HIGH_DOSE_DN, GOBP_VIRAL_LIFE_CYCLE, GOBP_OSSIFICATION

GO Biological Process (8): monoatomic ion transport (GO:0006811), positive regulation of bone mineralization (GO:0030501), phosphate ion transmembrane transport (GO:0035435), sodium ion transport (GO:0006814), phosphate ion transport (GO:0006817), sodium ion transmembrane transport (GO:0035725), symbiont entry into host cell (GO:0046718), transmembrane transport (GO:0055085)

GO Molecular Function (5): virus receptor activity (GO:0001618), phosphate transmembrane transporter activity (GO:0005315), sodium:phosphate symporter activity (GO:0005436), signaling receptor activity (GO:0038023), symporter activity (GO:0015293)

GO Cellular Component (5): plasma membrane (GO:0005886), membrane (GO:0016020), apical plasma membrane (GO:0016324), brush border membrane (GO:0031526), extracellular exosome (GO:0070062)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
SLC-mediated transport of inorganic anions	1
SLC transporter disorders	1
Transport of small molecules	1
Disorders of transmembrane transporters	1
Disease	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transport	2
secondary active transmembrane transporter activity	2
bone mineralization	1
regulation of bone mineralization	1
positive regulation of ossification	1
positive regulation of biomineral tissue development	1
phosphate ion transport	1
transmembrane transport	1
metal ion transport	1
inorganic anion transport	1
sodium ion transport	1
monoatomic cation transmembrane transport	1
viral life cycle	1
symbiont entry into host	1
cellular process	1
symbiont entry into host cell	1
exogenous protein binding	1
phosphate transmembrane transporter activity	1
solute:sodium symporter activity	1
molecular transducer activity	1
membrane	1
cell periphery	1
cellular anatomical structure	1
apical part of cell	1
plasma membrane region	1
brush border	1
apical plasma membrane	1
cell projection membrane	1
extracellular vesicle	1

Protein interactions and networks

STRING

1736 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLC20A2	XPR1	Q9UBH6	892
SLC20A2	RMC1	Q96DM3	825
SLC20A2	MYORG	Q6NSJ0	813
SLC20A2	SLC34A3	Q8N130	805
SLC20A2	SLC34A2	O95436	738
SLC20A2	PTH	P01270	714
SLC20A2	SLC34A1	Q06495	684
SLC20A2	FGF23	Q9GZV9	652
SLC20A2	NFIC	P08651	636
SLC20A2	SLC20A1	Q8WUM9	630
SLC20A2	PDGFB	P01127	627
SLC20A2	POU1F1	P28069	610
SLC20A2	SLC17A1	Q14916	605
SLC20A2	PDGFRB	P09619	590
SLC20A2	KL	Q9UEF7	590

IntAct

44 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
SLC20A1	LIN7A	psi-mi:“MI:0914”(association)	0.640
TOR1AIP2	TMEM223	psi-mi:“MI:0914”(association)	0.530
HAVCR2	TCAF2	psi-mi:“MI:0914”(association)	0.530
GGT5	POTEI	psi-mi:“MI:0914”(association)	0.530
SYP	APBB1	psi-mi:“MI:0914”(association)	0.530
ARMC6	SLC27A2	psi-mi:“MI:0914”(association)	0.530
SLC20A2	CCR5	psi-mi:“MI:0915”(physical association)	0.370
SLC20A1	MPP2	psi-mi:“MI:0914”(association)	0.350
SYP	APBB1	psi-mi:“MI:0914”(association)	0.350
ARMC6	SLC27A2	psi-mi:“MI:0914”(association)	0.350
AIFM1	NR2F2	psi-mi:“MI:0914”(association)	0.350
SLC22A6	GK	psi-mi:“MI:0914”(association)	0.350
PTGFR	ATP12A	psi-mi:“MI:0914”(association)	0.350
BMI1	HMGB1P1	psi-mi:“MI:0914”(association)	0.350
FURIN	ESYT2	psi-mi:“MI:0914”(association)	0.350
PTH2R	METTL15	psi-mi:“MI:0914”(association)	0.350
OPRL1	METTL15	psi-mi:“MI:0914”(association)	0.350
RNF149	CCDC85C	psi-mi:“MI:0914”(association)	0.350
NRSN1	FAM171A2	psi-mi:“MI:0914”(association)	0.350
SLC31A2	PLSCR1	psi-mi:“MI:0914”(association)	0.350
SLC22A2	FADS1	psi-mi:“MI:0914”(association)	0.350
SLC22A6	YIF1A	psi-mi:“MI:0914”(association)	0.350
SPAG6	MT-ND1	psi-mi:“MI:0914”(association)	0.350

BioGRID (143): SLC20A2 (Affinity Capture-RNA), SLC20A2 (Affinity Capture-RNA), SLC20A2 (Affinity Capture-MS), SLC20A2 (Proximity Label-MS), SLC20A2 (Proximity Label-MS), SLC20A2 (Affinity Capture-MS), SLC20A2 (Affinity Capture-MS), SLC20A2 (Affinity Capture-MS), SLC20A2 (Affinity Capture-MS), SLC20A2 (Affinity Capture-MS), SLC20A2 (Affinity Capture-MS), SLC20A2 (Affinity Capture-MS), SLC20A2 (Affinity Capture-MS), SLC20A2 (Affinity Capture-MS), SLC20A2 (Affinity Capture-RNA)

ESM2 similar proteins: A1A4I1, B0UYF2, O77750, O94300, O95436, O97596, P15710, P38361, P47863, P55088, Q08357, Q27960, Q28620, Q28677, Q28E01, Q2UVJ5, Q38954, Q5BL44, Q5I4F9, Q5R9L5, Q5REV9, Q5RK27, Q5XHF9, Q61609, Q63488, Q63632, Q63633, Q657W3, Q68F35, Q6NV12, Q6PB26, Q6PFM1, Q6Z0E2, Q7YRU6, Q80UP8, Q8WUM9, Q91V14, Q923J4, Q924N4, Q95L97

Diamond homologs: A1A4I1, O26024, O28476, O30499, O34436, O97596, P0AFJ7, P0AFJ8, P0AFJ9, P43676, P59950, P9WIA6, P9WIA7, Q08357, Q28E01, Q5BL44, Q5R9L5, Q5XHF9, Q61609, Q63488, Q68F35, Q6NV12, Q6PB26, Q6PFM1, Q80UP8, Q8WUM9, Q95L97, Q9ES44, Q9JJP0, Q9ZJC8, B6KFA9, O58374, O84698, P15710, P45268, P65713, P9WIA4, P9WIA5, Q38954, Q58047

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
SLC20A2	“up-regulates quantity”	phosphate(3-)	relocalization

Disease & clinical

Clinical variants and AI predictions

ClinVar

439 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	58
Likely pathogenic	26
Uncertain significance	191
Likely benign	74
Benign	37

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1176885	NM_001257180.2(SLC20A2):c.1440_1443dup (p.Glu482fs)	Pathogenic
1176886	NM_001257180.2(SLC20A2):c.1423A>T (p.Lys475Ter)	Pathogenic
1210018	NM_001257180.2(SLC20A2):c.1158C>A (p.Tyr386Ter)	Pathogenic
1299114	NM_001257180.2(SLC20A2):c.1523+1G>T	Pathogenic
1447088	NM_001257180.2(SLC20A2):c.1223C>A (p.Ser408Ter)	Pathogenic
1456623	NM_001257180.2(SLC20A2):c.23G>A (p.Trp8Ter)	Pathogenic
1460189	NM_001257180.2(SLC20A2):c.1117C>T (p.Gln373Ter)	Pathogenic
1676262	NM_001257180.2(SLC20A2):c.1144C>T (p.Arg382Ter)	Pathogenic
1691845	NM_001257180.2(SLC20A2):c.80_92del (p.Asn27fs)	Pathogenic
1702969	NM_001257180.2(SLC20A2):c.731-18_738del	Pathogenic
1705290	NM_001257180.2(SLC20A2):c.1637_1638del (p.Thr546fs)	Pathogenic
1805266	NM_001257180.2(SLC20A2):c.1438_1439del (p.Ala480fs)	Pathogenic
2087831	NM_001257180.2(SLC20A2):c.617_618dup (p.Gly207fs)	Pathogenic
2098481	NM_001257180.2(SLC20A2):c.687dup (p.Val230fs)	Pathogenic
2118110	NM_001257180.2(SLC20A2):c.943_944del (p.Leu315fs)	Pathogenic
2121489	NM_001257180.2(SLC20A2):c.1239_1242del (p.Ser413fs)	Pathogenic
2428501	NM_001257180.2(SLC20A2):c.185T>C (p.Leu62Pro)	Pathogenic
2441711	NM_001257180.2(SLC20A2):c.1158C>G (p.Tyr386Ter)	Pathogenic
2499074	NM_001257180.2(SLC20A2):c.730_730+1del	Pathogenic
2575891	NM_001257180.2(SLC20A2):c.58_62del (p.Ala21fs)	Pathogenic
2582091	NM_001257180.2(SLC20A2):c.1794+1G>A	Pathogenic
2583065	NM_001257180.2(SLC20A2):c.1681A>T (p.Lys561Ter)	Pathogenic
2685308	GRCh37/hg19 8p11.21(chr8:42274264-42307548)x1	Pathogenic
2735161	NM_001257180.2(SLC20A2):c.1652G>A (p.Trp551Ter)	Pathogenic
2735162	NM_001257180.2(SLC20A2):c.935-1G>A	Pathogenic
2735163	NM_001257180.2(SLC20A2):c.344C>T (p.Thr115Met)	Pathogenic
280118	NM_001257180.2(SLC20A2):c.509del (p.Ile169_Leu170insTer)	Pathogenic
280122	NM_001257180.2(SLC20A2):c.338C>G (p.Ser113Ter)	Pathogenic
280572	NM_001257180.2(SLC20A2):c.971C>A (p.Ser324Ter)	Pathogenic
2821960	NM_001257180.2(SLC20A2):c.783_786del (p.Ser261fs)	Pathogenic

SpliceAI

3410 predictions. Top by Δscore:

Variant	Effect	Δscore
8:42417963:CCCAC:C	acceptor_gain	1.0000
8:42417964:CCAC:C	acceptor_gain	1.0000
8:42417964:CCACC:C	acceptor_gain	1.0000
8:42417965:CAC:C	acceptor_gain	1.0000
8:42417965:CACC:C	acceptor_gain	1.0000
8:42417966:ACC:A	acceptor_loss	1.0000
8:42417968:C:CG	acceptor_loss	1.0000
8:42417969:T:G	acceptor_loss	1.0000
8:42428840:CCG:C	acceptor_gain	1.0000
8:42428841:CG:C	acceptor_gain	1.0000
8:42428841:CGC:C	acceptor_gain	1.0000
8:42428843:C:CC	acceptor_gain	1.0000
8:42430058:GCTTA:G	donor_loss	1.0000
8:42430059:CTTA:C	donor_loss	1.0000
8:42430060:TTA:T	donor_loss	1.0000
8:42430062:ACCT:A	donor_loss	1.0000
8:42430063:C:A	donor_loss	1.0000
8:42430245:CATTA:C	acceptor_gain	1.0000
8:42430246:ATTA:A	acceptor_gain	1.0000
8:42430247:T:TC	acceptor_gain	1.0000
8:42430248:TA:T	acceptor_gain	1.0000
8:42430249:ACTGG:A	acceptor_loss	1.0000
8:42430250:C:CA	acceptor_loss	1.0000
8:42430250:C:CC	acceptor_gain	1.0000
8:42430251:T:C	acceptor_loss	1.0000
8:42437578:CTGAA:C	acceptor_loss	1.0000
8:42444763:C:CC	acceptor_gain	1.0000
8:42459890:CCTTA:C	donor_loss	1.0000
8:42459891:CTTA:C	donor_loss	1.0000
8:42459892:TTACC:T	donor_loss	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000006776 (8:42425569 G>A,T), RS1000084926 (8:42523769 C>T), RS1000095817 (8:42510886 TA>T,TAA), RS1000105907 (8:42439341 G>A), RS1000111559 (8:42442002 C>A,T), RS1000164632 (8:42526394 CTGGG>C), RS1000164935 (8:42512070 T>C), RS1000203255 (8:42491285 C>T), RS1000221063 (8:42431231 T>A), RS1000254358 (8:42473960 C>T), RS1000265967 (8:42447647 A>C), RS1000275350 (8:42491532 A>G,T), RS1000327684 (8:42478947 C>T), RS1000341150 (8:42487042 T>A), RS1000367122 (8:42480297 T>C)

Disease associations

OMIM: gene MIM:158378 | disease phenotypes: MIM:213600, MIM:606656

GenCC curated gene-disease

Disease	Classification	Inheritance
basal ganglia calcification, idiopathic, 1	Strong	Autosomal dominant
bilateral striopallidodentate calcinosis	Supportive	Autosomal dominant

Mondo (3): basal ganglia calcification, idiopathic, 1 (MONDO:0024538), vascular dementia (MONDO:0004648), bilateral striopallidodentate calcinosis (MONDO:0008947)

Orphanet (1): Bilateral striopallidodentate calcinosis (Orphanet:1980)

HPO phenotypes

54 total (30 of 54 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000012	Urinary urgency
HP:0000020	Urinary incontinence
HP:0000298	Mask-like facies
HP:0000709	Psychosis
HP:0000716	Depression
HP:0000726	Dementia
HP:0000739	Anxiety
HP:0000751	Personality changes
HP:0000802	Impotence
HP:0000822	Hypertension
HP:0001250	Seizure
HP:0001260	Dysarthria
HP:0001263	Global developmental delay
HP:0001266	Choreoathetosis
HP:0001268	Mental deterioration
HP:0001288	Gait disturbance
HP:0001300	Parkinsonism
HP:0001332	Dystonia
HP:0001337	Tremor
HP:0001347	Hyperreflexia
HP:0001350	Slurred speech
HP:0002015	Dysphagia
HP:0002063	Rigidity
HP:0002067	Bradykinesia
HP:0002072	Chorea
HP:0002075	Dysdiadochokinesis
HP:0002135	Basal ganglia calcification
HP:0002172	Postural instability
HP:0002305	Athetosis

GWAS associations

12 associations (top):

Study	Trait	p-value
GCST004278_37	Pulse pressure	1.000000e-08
GCST004602_68	Mean corpuscular volume	1.000000e-19
GCST005992_14	Mean corpuscular hemoglobin concentration	1.000000e-22
GCST006011_74	Mean corpuscular volume	1.000000e-09
GCST007096_194	Pulse pressure	1.000000e-10
GCST007269_222	Pulse pressure	2.000000e-12
GCST007954_17	Glycated hemoglobin levels	4.000000e-08
GCST010083_246	Hemoglobin levels	8.000000e-26
GCST010703_179	Brain morphology (MOSTest)	5.000000e-11
GCST90000025_356	Appendicular lean mass	4.000000e-12
GCST90002383_447	Hematocrit	4.000000e-14
GCST90002403_629	Red blood cell count	3.000000e-31

EFO canonical traits (8, from GWAS)

EFO ID	Trait name
EFO:0005763	pulse pressure measurement
EFO:0004528	mean corpuscular hemoglobin concentration
EFO:0004541	HbA1c measurement
EFO:0004509	hemoglobin measurement
EFO:0004346	neuroimaging measurement
EFO:0004980	appendicular lean mass
EFO:0004348	hematocrit
EFO:0004305	erythrocyte count

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D015140	Dementia, Vascular	C10.228.140.300.400; C10.228.140.300.510.800.500; C10.228.140.380.230; C10.228.140.695.500; C14.907.137.126.372.500; C14.907.253.560.350.500; F03.615.400.350
C537657	Basal ganglia calcification, idiopathic 2 (supp.)
C536275	Fahr’s disease (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4295806 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: transporter — SLC20 family of sodium-dependent phosphate transporters

ChEMBL bioactivities

1 potent at pChembl≥5 of 1 total, top 1 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.21	IC50	6200	nM	CHEMBL4170023

PubChem BioAssay actives

1 with measured affinity, of 12 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
N-(4-chlorophenyl)-5-methoxy-2-[[3-(trifluoromethyl)phenyl]sulfonylamino]benzamide	1354858: Inhibition of human Pit-2 expressed in HEK293 cells coexpressing tetracyclin assessed as reduction in uptake of 33P-radiolabeled Pi incubated for 20 to 30 mins prior to substrate addition	ic50	6.2000	uM

CTD chemical–gene interactions

49 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression	3
bisphenol A	decreases methylation, increases expression	2
Ozone	affects cotreatment, increases expression, increases abundance, decreases expression	2
Phosphates	increases reaction, increases uptake, decreases reaction, increases expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
Cyclosporine	decreases expression	2
Aflatoxin B1	decreases methylation, increases methylation	2
FR900359	affects phosphorylation	1
bisphenol F	affects cotreatment, increases methylation	1
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases expression, increases abundance	1
beta-lapachone	increases expression	1
sodium arsenite	increases expression	1
benzo(e)pyrene	increases methylation	1
coumarin	decreases phosphorylation	1
methacrylaldehyde	affects cotreatment, increases expression, increases abundance	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment	1
dorsomorphin	affects cotreatment, increases expression	1
bisphenol S	increases methylation	1
Sunitinib	decreases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Leflunomide	increases expression	1
Acrolein	affects cotreatment, increases expression, increases abundance	1
Air Pollutants	affects cotreatment, increases abundance, increases expression	1
Arsenic	affects methylation	1
Cadmium	increases expression	1
Caffeine	affects phosphorylation	1
Choline	increases reaction, increases uptake	1
Dimethyl Sulfoxide	increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4149755	Binding	Inhibition of human Pit-2 expressed in HEK293 cells coexpressing tetracyclin assessed as reduction in uptake of 33P-radiolabeled Pi incubated for 20 to 30 mins prior to substrate addition	Discovery of Orally Bioavailable Selective Inhibitors of the Sodium-Phosphate Cotransporter NaPi2a (SLC34A1). — ACS Med Chem Lett

Cellosaurus cell lines

12 cell lines: 8 cancer cell line, 4 induced pluripotent stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A1SX	HPS1705	Induced pluripotent stem cell	Male
CVCL_B2FL	Abcam HeLa SLC20A2 KO	Cancer cell line	Female
CVCL_D0I4	METUi002-A	Induced pluripotent stem cell	Male
CVCL_D4IU	HCT116-SLC20A2-KO-c6	Cancer cell line	Male
CVCL_D4IV	HCT116-SLC20A2-KO-c8	Cancer cell line	Male
CVCL_QX86	CIRAi003-A	Induced pluripotent stem cell	Male
CVCL_TL91	HAP1 SLC20A2 (-) 1	Cancer cell line	Male
CVCL_UL86	ZZUi012-A	Induced pluripotent stem cell	Male
CVCL_XS92	HAP1 SLC20A2 (-) 2	Cancer cell line	Male
CVCL_XS93	HAP1 SLC20A2 (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

89 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00165763	PHASE4	COMPLETED	Efficacy and Safety of Donepezil Hydrochloride (Aricept) in Vascular Dementia
NCT00847860	PHASE4	COMPLETED	Cilostazol Verse Asprin for Vascular Dementia in Poststroke Patients With White Matter Lesions
NCT00947531	PHASE4	COMPLETED	A Clinical Trial to Evaluate the Safety and Efficacy of 20 ml Cerebrolysin in Patients With Vascular Dementia
NCT00950430	PHASE4	ENROLLING_BY_INVITATION	Imaging of Brain Amyloid Plaques in the Aging Population
NCT00099216	PHASE3	COMPLETED	Efficacy and Safety of Rivastigmine Capsules in Patients With Probable Vascular Dementia
NCT00130338	PHASE3	COMPLETED	Rivastigmine Capsules in Patients With Probable Vascular Dementia
NCT00209456	PHASE3	COMPLETED	Dopamine Transporter Scintigraphy Imaging (DAT-Imaging) in Patients With Lewy Body Dementia
NCT00249158	PHASE3	COMPLETED	A Study of the Effectiveness and Safety of Risperidone in the Treatment of Behavioral Disturbances in Patients With Dementia
NCT00261573	PHASE3	COMPLETED	A Study of the Safety and Effectiveness of Galantamine Versus Placebo in the Treatment of Patients With Vascular Dementia or Mixed Dementia
NCT00621647	PHASE3	COMPLETED	Seroquel- Agitation Associated With Dementia
NCT02453932	PHASE3	COMPLETED	Efficacy and Safety of Tianzhi Granule in Mild to Moderate Vascular Dementia
NCT03682185	PHASE3	COMPLETED	The Healthy Patterns Sleep Study
NCT03789760	PHASE3	COMPLETED	The Clinical Trial of Chinese Herbal Medicine (SaiLuoTong) Capsule
NCT03804229	PHASE3	ACTIVE_NOT_RECRUITING	Efficacy and Safety of Butylphthalide Soft Capsule for the Treatment of Vascular Dementia
NCT03986424	PHASE3	COMPLETED	Local Study of Akatinol Memantine in VaD in Russia
NCT04552041	PHASE3	COMPLETED	Prospekta in the Treatment of Cognitive, Behavioral and Psychiatric Disorders in Patients With Vascular Dementia.
NCT05662111	PHASE2	RECRUITING	Treatment of Ectopic Calcification in Fahr’s Disease or Syndrome
NCT01466543	PHASE2	UNKNOWN	Effect of Zydena (Udenafil) on Cerebral Blood Flow and Peripheral Blood Viscosity
NCT01475578	PHASE2	COMPLETED	Study of STA-1 Capsule in Patients With Vascular Dementia (Marrow-Sea Deficiency)
NCT01608217	PHASE2	COMPLETED	Delta-THC in Dementia
NCT01761227	PHASE2	COMPLETED	Efficacy and Safety of Fufangdanshen Tablets in Mild to Moderate Vascular Dementia
NCT01953705	PHASE2	UNKNOWN	n-3 PUFA for Vascular Cognitive Aging
NCT01965756	PHASE2	COMPLETED	Effect of Insulin Sensitizer Metformin on AD Biomarkers
NCT01978730	PHASE2	UNKNOWN	The Clinical Trial of Chinese Herbal Medicine SaiLuoTong Capsule
NCT02467413	PHASE2	WITHDRAWN	BAC in Patient With Alzheimer’s Disease or Vascular Dementia
NCT03230071	PHASE2	COMPLETED	Efficacy and Safety of TMBCZG in Mild to Moderate Vascular Dementia
NCT04109963	PHASE2	UNKNOWN	Trial of Remote Ischemic Pre-conditioning in Vascular Cognitive Impairment
NCT05371639	PHASE2	UNKNOWN	Efficacy and Safety of Tian Ma Bian Chun Zhi Gan Tablets in Mild to Moderate Vascular Dementia
NCT00457769	PHASE1	UNKNOWN	Aricept to Improve Functional Tasks in Vascular Dementia
NCT03702543	PHASE1	UNKNOWN	Managing Vascular Dementia Risk Factors With SymTrend
NCT04567745	PHASE1	COMPLETED	Automated Retinal Image Analysis System (EyeQuant) for Computation of Vascular Biomarkers
NCT02098824	PHASE2/PHASE3	UNKNOWN	Symptomatic Treatment of Vascular Cognitive Impairment
NCT04248270	PHASE1/PHASE2	UNKNOWN	A Noval Tau Tracer in Young Onset Dementia
NCT00172900	Not specified	UNKNOWN	MRS and DTI of White Matter in Alzheimer’s Disease
NCT00506818	Not specified	COMPLETED	Cognitive and Emotional Impairment After Stroke
NCT00889603	Not specified	COMPLETED	Non-Interventional Study With Aricept® Evess
NCT01208675	Not specified	COMPLETED	The Swedish BioFINDER Study
NCT01345110	Not specified	COMPLETED	A Longitudinal Multidimensional Population Study on Brain Aging
NCT01370954	Not specified	COMPLETED	NAC-003 P.L.U.S. Program (Progress Through Learning Understanding & Support)
NCT01465360	Not specified	COMPLETED	Performance of AclarusDx™, a Blood-Based Transcriptomic Test for AD, in US Patients Newly Referred to a Memory Center