SLC20A1

Summary

SLC20A1 (solute carrier family 20 member 1, HGNC:10946) is a protein-coding gene on chromosome 2q14.1, encoding Sodium-dependent phosphate transporter 1 (Q8WUM9). Sodium-phosphate symporter which preferentially transports the monovalent form of phosphate with a stoichiometry of two sodium ions per phosphate ion. It is a selective cancer dependency (DepMap: 15.1% of cell lines).

The protein encoded by this gene is a sodium-phosphate symporter that absorbs phosphate from interstitial fluid for use in cellular functions such as metabolism, signal transduction, and nucleic acid and lipid synthesis. The encoded protein is also a retroviral receptor, causing human cells to be susceptible to infection by gibbon ape leukemia virus, simian sarcoma-associated virus, feline leukemia virus subgroup B, and 10A1 murine leukemia virus.

Source: NCBI Gene 6574 — RefSeq curated summary.

At a glance

• Gene–disease (curated): exstrophy-epispadias complex (Strong, GenCC)
• GWAS associations: 1
• Clinical variants (ClinVar): 89 total
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 15.1% of screened cell lines
• MANE Select transcript: NM_005415

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10946
Approved symbol	SLC20A1
Name	solute carrier family 20 member 1
Location	2q14.1
Locus type	gene with protein product
Status	Approved
Aliases	PiT-1, Glvr-1, PiT1
Ensembl gene	ENSG00000144136
Ensembl biotype	protein_coding
OMIM	137570
Entrez	6574

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 10 protein_coding, 3 protein_coding_CDS_not_defined, 3 retained_intron

ENST00000272542, ENST00000413135, ENST00000423633, ENST00000433924, ENST00000456264, ENST00000480984, ENST00000490674, ENST00000492076, ENST00000498224, ENST00000922295, ENST00000922296, ENST00000922297, ENST00000922298, ENST00000922299, ENST00000922300, ENST00000943734

RefSeq mRNA: 1 — MANE Select: NM_005415 NM_005415

CCDS: CCDS2099

Canonical transcript exons

ENST00000272542 — 11 exons

Exon	Start	End
ENSE00000963745	112647324	112647464
ENSE00000963746	112647653	112647738
ENSE00000963750	112659204	112659762
ENSE00000963751	112660387	112660572
ENSE00000963752	112661142	112661226
ENSE00001000613	112646563	112647162
ENSE00001145417	112645939	112646129
ENSE00001923899	112662864	112663825
ENSE00003526119	112658825	112659094
ENSE00003592497	112657122	112657241
ENSE00003680433	112652702	112652798

Expression profiles

Bgee: expression breadth ubiquitous, 296 present calls, max score 96.54.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 170.4023 / max 2324.0381, expressed in 1826 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
21998	166.4490	1826
21997	2.8880	1236
21996	1.0653	642

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of transverse colon	UBERON:0004991	96.54	gold quality
granulocyte	CL:0000094	96.49	gold quality
cartilage tissue	UBERON:0002418	96.45	gold quality
trachea	UBERON:0003126	96.36	gold quality
pigmented layer of retina	UBERON:0001782	95.91	gold quality
retina	UBERON:0000966	95.89	gold quality
mucosa of urinary bladder	UBERON:0001259	95.79	gold quality
trabecular bone tissue	UBERON:0002483	95.10	gold quality
parietal pleura	UBERON:0002400	94.84	gold quality
vermiform appendix	UBERON:0001154	94.73	gold quality
mucosa of paranasal sinus	UBERON:0005030	94.70	gold quality
leukocyte	CL:0000738	94.59	gold quality
placenta	UBERON:0001987	94.59	gold quality
mononuclear cell	CL:0000842	94.53	gold quality
colonic mucosa	UBERON:0000317	94.51	gold quality
monocyte	CL:0000576	94.48	gold quality
pleura	UBERON:0000977	94.22	gold quality
lymph node	UBERON:0000029	94.04	gold quality
ileal mucosa	UBERON:0000331	94.02	gold quality
blood	UBERON:0000178	93.98	gold quality
mucosa of sigmoid colon	UBERON:0004993	93.63	gold quality
bone element	UBERON:0001474	93.61	gold quality
bone marrow	UBERON:0002371	93.30	gold quality
transverse colon	UBERON:0001157	93.26	gold quality
embryo	UBERON:0000922	93.18	gold quality
caecum	UBERON:0001153	93.10	gold quality
small intestine Peyer’s patch	UBERON:0003454	93.01	gold quality
upper lobe of left lung	UBERON:0008952	92.97	gold quality
urinary bladder	UBERON:0001255	92.95	gold quality
ganglionic eminence	UBERON:0004023	92.91	gold quality

Single-cell (SCXA)

Detected in 8 experiment(s), a significant marker in 7.

Experiment	Marker?	Max mean expression
E-MTAB-6505	yes	1687.83
E-GEOD-124858	yes	993.00
E-GEOD-125970	yes	17.36
E-CURD-122	yes	15.21
E-HCAD-10	yes	9.01
E-MTAB-9801	yes	6.27
E-MTAB-6075	no	1056.92
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ATF1, CREB1, HNF4A, TGFB1

miRNA regulators (miRDB)

73 targeting SLC20A1, 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-4500	99.99	72.72	2367
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-548AW	99.99	72.57	3559
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-12136	99.98	72.81	5713
HSA-LET-7D-5P	99.96	71.76	1632
HSA-MIR-4458	99.96	71.64	1650
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-3682-5P	99.93	67.97	1163
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-5682	99.89	72.56	1005
HSA-LET-7A-2-3P	99.87	70.53	1921
HSA-LET-7G-3P	99.85	70.43	1929
HSA-MIR-6515-3P	99.82	68.19	1933

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 15.1% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 22)

• propose that region A of Pit1 confers competence for viral entry by influencing the topology of the authentic binding site in the membrane and hence its accessibility to a viral envelope protein (PMID:12097582)
• Two highly conserved glutamate residues critical for sodium-dependent phosphate transport are revealed by uncoupling transport function from retroviral receptor function. (PMID:12205090)
• Our results link low-grade IL-8-mediated cartilaginous inflammation in OA to altered chondrocyte differentiation and disease progression through PiT-1 expression and sodium-dependent Pi uptake mediated by CXCR1 signaling. (PMID:15641067)
• Phosphate uptake through Pit-1 is essential for vascular smooth muscle cell calcification and phenotypic modulation in response to elevated phosphate. (PMID:16527991)
• 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 SLC20A1. (PMID:17494632)
• An overexpression of Pit-1 seems to play a key role in the formation of soft tissue calcification in Werner syndrome. (PMID:18729813)
• PiT1 depletion markedly reduces cell proliferation, delays cell cycle, and impairs mitosis and cytokinesis. (PMID:19726692)
• Identification of a novel transport-independent function of PiT1/SLC20A1 in the regulation of TNF-induced apoptosis. (PMID:20817733)
• 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)
• Allelic variations in SLC20A1 were associated with the levels of Sodium-lithium countertransport. (PMID:21796222)
• Overexpression of SLC20A1 promotes apoptosis and mineralization by altering the level of Akt-1. (PMID:23308213)
• Ox-LDL induces an osteogenic change in human aortic valve interstitial cells marked by the induction of PiT-1. (PMID:23849774)
• indoxyl sulfate promotes Pit-1 expression in part by activation of the JNK pathway in vascular smooth muscle cells (PMID:27001263)
• Overexpression of SLC20A1 is associated with Estrogen Receptor-positive Breast Cancer. (PMID:27986439)
• Targeted sequencing of two candidate genes, SLC20A1 and SLC15A4, of the solute carrier membrane transport protein family in 200 additional patients demonstrated two further variants predicted as damaging for combined hormone deficiency. (PMID:29261175)
• The present data suggested that SLC20A1 levels are positively associated with tumor size, invasive behavior and tumor recurrence in somatotroph adenomas. Furthermore, SLC20A1 may be associated with the activation of the Wnt/betacatenin signaling pathway. (PMID:31432167)
• Genome-wide methylation association with current suicidal ideation in schizophrenia. (PMID:32661777)
• Long Noncoding RNA SLC20A1-1 Induces Nucleus Pulposus Apoptosis by Sponging miR-146a-5p. (PMID:35349375)
• Cellular abundance of sodium phosphate cotransporter SLC20A1/PiT1 and phosphate uptake are controlled post-transcriptionally by ESCRT. (PMID:35447110)
• Pit 1 transporter (SLC20A1) as a key factor in the NPP1-mediated inhibition of insulin signaling in human podocytes. (PMID:37269459)
• Spitz Melanoma With SLC20A1::ALK Fusion: A Novel Fusion Previously Undescribed in Spitz Melanocytic Neoplasm. (PMID:38941542)

Cross-species orthologs

10 orthologs

Organism	Symbol	Gene ID
danio_rerio	slc20a1b	ENSDARG00000010641
danio_rerio	slc20a1a	ENSDARG00000020114
mus_musculus	Slc20a1	ENSMUSG00000027397
rattus_norvegicus	Slc20a1	ENSRNOG00000018567
drosophila_melanogaster	NaPi-III	FBGN0260795
caenorhabditis_elegans		WBGENE00012285
caenorhabditis_elegans		WBGENE00015054
caenorhabditis_elegans		WBGENE00015055
caenorhabditis_elegans		WBGENE00016739
caenorhabditis_elegans		WBGENE00017312

Paralogs (1): SLC20A2 (ENSG00000168575)

Protein

Protein identifiers

Sodium-dependent phosphate transporter 1 — Q8WUM9 (reviewed: Q8WUM9)

Alternative names: Gibbon ape leukemia virus receptor 1, Leukemia virus receptor 1 homolog, Phosphate transporter 1, Solute carrier family 20 member 1

All UniProt accessions (4): Q8WUM9, A7LNJ1, H7BZK4, H7BZY1

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. May play a role in extracellular matrix and cartilage calcification as well as in vascular calcification. Essential for cell proliferation but this function is independent of its phosphate transporter activity. (Microbial infection) May function as a retroviral receptor as it confers human cells susceptibility to infection to Gibbon Ape Leukemia Virus (GaLV), Simian sarcoma-associated virus (SSAV) and Feline leukemia virus subgroup B (FeLV-B) as well as 10A1 murine leukemia virus (10A1 MLV).

Subcellular location. Cell membrane.

Tissue specificity. Ubiquitously expressed.

Domain organisation. Region A confers human cells susceptibility to infection by Gibbon Ape Leukemia Virus (GaLV) and Feline leukemia virus subgroup B (FeLV-B). Substitution of Human SLC20A1 region A by region A of murine SLC20A1 prevents viral infection.

Induction. By phosphate deprivation as well as by IL8/interleukin-8 in hypertrophic chondrocytes.

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

RefSeq proteins (1): NP_005406* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001204	Phos_transporter	Family

Pfam: PF01384

Enzyme classification (BRENDA):

• EC 7.3.2.1 — ABC-type phosphate transporter (BRENDA: 48 organisms, 39 substrates, 25 inhibitors, 44 Km, 0 kcat entries)

Substrate kinetics (BRENDA)

5 substrates with measured Km, best-characterized 5. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
PHOSPHATE	0.0002–6.3	23
PHOSPHATE/OUT	0.0019–0.385	9
ATP	0.0239–0.654	4
CTP	0.13	1
GTP	0.211	1

Catalyzed reactions (Rhea), 1 shown:

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

UniProt features (21 total): transmembrane region 10, mutagenesis site 4, sequence conflict 3, modified residue 2, chain 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8WUM9-F1	70.02	0.47

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 (2): 265, 269

Mutagenesis-validated functional residues (4):

Position	Phenotype
128	loss of sodium-dependent phosphate transporter activity. able to restore cell proliferation in slc20a1-deficient hela ce
550–558	loss of virus infectibility.
550	drastic reduction of virus infectibility, but conserved virus binding ability.
550	loss of virus infectibility.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-427652	Sodium-coupled phosphate cotransporters
R-HSA-382551	Transport of small molecules
R-HSA-425393
R-HSA-425407	SLC-mediated transmembrane transport

MSigDB gene sets: 365 (showing top): GSE45365_NK_CELL_VS_CD11B_DC_DN, TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_MONOCYTE_UP, GOBP_SODIUM_ION_TRANSMEMBRANE_TRANSPORT, AMIT_EGF_RESPONSE_60_HELA, GOBP_CANONICAL_NF_KAPPAB_SIGNAL_TRANSDUCTION, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GTCTACC_MIR379, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, GAUSSMANN_MLL_AF4_FUSION_TARGETS_A_UP, LANG_MYB_FAMILY_TARGETS, GOBP_INORGANIC_ANION_TRANSPORT, CACCAGC_MIR138, USF_C, MODULE_503, GOBP_MONOATOMIC_CATION_TRANSPORT

GO Biological Process (10): phosphate-containing compound metabolic process (GO:0006796), monoatomic ion transport (GO:0006811), cell population proliferation (GO:0008283), biomineral tissue development (GO:0031214), phosphate ion transmembrane transport (GO:0035435), positive regulation of canonical NF-kappaB signal transduction (GO:0043123), sodium ion transport (GO:0006814), phosphate ion transport (GO:0006817), sodium ion transmembrane transport (GO:0035725), transmembrane transport (GO:0055085)

GO Molecular Function (5): phosphate transmembrane transporter activity (GO:0005315), high-affinity phosphate:sodium symporter activity (GO:0005316), sodium:phosphate symporter activity (GO:0005436), signaling receptor activity (GO:0038023), symporter activity (GO:0015293)

GO Cellular Component (2): plasma membrane (GO:0005886), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
SLC-mediated transport of inorganic anions	1
Transport of small molecules	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transport	2
cellular process	2
secondary active transmembrane transporter activity	2
metabolic process	1
tissue development	1
animal organ development	1
phosphate ion transport	1
transmembrane transport	1
canonical NF-kappaB signal transduction	1
regulation of canonical NF-kappaB signal transduction	1
positive regulation of intracellular signal transduction	1
metal ion transport	1
inorganic anion transport	1
sodium ion transport	1
monoatomic cation transmembrane transport	1
sodium:phosphate symporter activity	1
phosphate transmembrane transporter activity	1
solute:sodium symporter activity	1
molecular transducer activity	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1702 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLC20A1	RAD1	O60671	826
SLC20A1	RAD51B	O15315	676
SLC20A1	SLC34A3	Q8N130	671
SLC20A1	SLC34A2	O95436	647
SLC20A1	SLC17A1	Q14916	638
SLC20A1	SLC17A2	O00624	637
SLC20A1	SLC34A1	Q06495	633
SLC20A1	SLC20A2	Q08357	630
SLC20A1	SLC15A4	Q8N697	615
SLC20A1	SERPINB2	P05120	588
SLC20A1	FECH	P22830	588
SLC20A1	ALPL	P05186	529
SLC20A1	SLC37A4	O43826	526
SLC20A1	FGF23	Q9GZV9	525
SLC20A1	SP3	Q02447	503

IntAct

63 interactions, top by confidence:

A	B	Type	Score
LIN7A	CASK	psi-mi:“MI:0914”(association)	0.830
TSPAN5	ADAM10	psi-mi:“MI:0914”(association)	0.800
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
SLC20A1	LIN7A	psi-mi:“MI:0914”(association)	0.640
PDGFRB	PIK3R2	psi-mi:“MI:0914”(association)	0.610
ARRDC4	WWP2	psi-mi:“MI:0914”(association)	0.530
TMEM9	ESYT2	psi-mi:“MI:0914”(association)	0.530
ARMC6	SLC27A2	psi-mi:“MI:0914”(association)	0.530
KCNE3	RIOK3	psi-mi:“MI:0914”(association)	0.530
NRAS	ESYT2	psi-mi:“MI:2364”(proximity)	0.480
SLC20A1	RAPGEF1	psi-mi:“MI:0915”(physical association)	0.370
SLC20A1	MAPK6	psi-mi:“MI:0915”(physical association)	0.370
SLC20A1	BCL10	psi-mi:“MI:0915”(physical association)	0.370
	SNAP23	psi-mi:“MI:0914”(association)	0.350
SLC20A1	MPP2	psi-mi:“MI:0914”(association)	0.350
TNFRSF10B	SCAMP1	psi-mi:“MI:0914”(association)	0.350
	SHTN1	psi-mi:“MI:0914”(association)	0.350
KCNE3	PIK3R2	psi-mi:“MI:0914”(association)	0.350
GPR12	TLCD2	psi-mi:“MI:0914”(association)	0.350
FFAR1	SLC12A8	psi-mi:“MI:0914”(association)	0.350
KLRB1	ESYT2	psi-mi:“MI:0914”(association)	0.350
TSPAN15	TMEM223	psi-mi:“MI:0914”(association)	0.350
PCDHB7	TMEM131L	psi-mi:“MI:0914”(association)	0.350
UPK2	TMEM131L	psi-mi:“MI:0914”(association)	0.350
SLC22A9	TMEM131L	psi-mi:“MI:0914”(association)	0.350
KCNE3	TMEM131L	psi-mi:“MI:0914”(association)	0.350
SLC1A1	UBXN8	psi-mi:“MI:0914”(association)	0.350
SYP	HAS3	psi-mi:“MI:0914”(association)	0.350
TGFBR2	TNFRSF10A	psi-mi:“MI:0914”(association)	0.350

BioGRID (153): SLC20A1 (Affinity Capture-RNA), SLC20A1 (Affinity Capture-MS), SLC20A1 (Affinity Capture-MS), SLC20A1 (Proximity Label-MS), MPP6 (Affinity Capture-MS), MPP2 (Affinity Capture-MS), UGCG (Affinity Capture-MS), FLVCR1 (Affinity Capture-MS), SLC20A2 (Affinity Capture-MS), ADCY9 (Affinity Capture-MS), MFAP3 (Affinity Capture-MS), LIN7A (Affinity Capture-MS), LRP10 (Affinity Capture-MS), BMPR1A (Affinity Capture-MS), SLC9A1 (Affinity Capture-MS)

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

2 interactions.

A	Effect	B	Mechanism
TGFB1	“up-regulates quantity by expression”	SLC20A1	“transcriptional regulation”
SLC20A1	“up-regulates quantity”	phosphate(3-)	relocalization

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 87 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants	5	42.5×	2e-05
Downstream signal transduction	6	37.4×	4e-06
Signaling by SCF-KIT	5	20.4×	5e-04
RAF/MAP kinase cascade	6	6.0×	9e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	64
Likely benign	7
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

2034 predictions. Top by Δscore:

Variant	Effect	Δscore
2:112647158:GTTTG:G	donor_gain	1.0000
2:112647162:GGTA:G	donor_loss	1.0000
2:112647163:G:GG	donor_gain	1.0000
2:112647651:A:AG	acceptor_gain	1.0000
2:112647651:AGT:A	acceptor_gain	1.0000
2:112647652:G:GC	acceptor_gain	1.0000
2:112647652:GT:G	acceptor_gain	1.0000
2:112647652:GTG:G	acceptor_gain	1.0000
2:112647652:GTGAT:G	acceptor_gain	1.0000
2:112652794:ACCGT:A	donor_gain	1.0000
2:112652795:CCGT:C	donor_gain	1.0000
2:112652797:GT:G	donor_gain	1.0000
2:112652798:TG:T	donor_loss	1.0000
2:112652799:G:GA	donor_loss	1.0000
2:112652799:G:GG	donor_gain	1.0000
2:112652800:TA:T	donor_loss	1.0000
2:112652801:AAG:A	donor_loss	1.0000
2:112652802:AGT:A	donor_loss	1.0000
2:112659758:GTAAG:G	donor_loss	1.0000
2:112659759:TAAG:T	donor_loss	1.0000
2:112659760:AAG:A	donor_loss	1.0000
2:112659762:GGT:G	donor_loss	1.0000
2:112659763:G:GA	donor_loss	1.0000
2:112660385:A:AG	acceptor_gain	1.0000
2:112660386:G:GG	acceptor_gain	1.0000
2:112660386:GC:G	acceptor_gain	1.0000
2:112660386:GCA:G	acceptor_gain	1.0000
2:112660386:GCAAT:G	acceptor_gain	1.0000
2:112660571:AGGTA:A	donor_loss	1.0000
2:112660572:GGTA:G	donor_loss	1.0000

AlphaMissense

4441 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:112646946:G:A	G40R	1.000
2:112646946:G:C	G40R	1.000
2:112646947:G:A	G40E	1.000
2:112646954:T:A	N42K	1.000
2:112646954:T:G	N42K	1.000
2:112646955:G:C	D43H	1.000
2:112646955:G:T	D43Y	1.000
2:112646956:A:C	D43A	1.000
2:112646956:A:G	D43G	1.000
2:112646956:A:T	D43V	1.000
2:112646957:T:A	D43E	1.000
2:112646957:T:G	D43E	1.000
2:112646966:T:A	N46K	1.000
2:112646966:T:G	N46K	1.000
2:112646974:G:A	G49D	1.000
2:112647025:C:A	A66D	1.000
2:112647027:A:C	S67R	1.000
2:112647029:C:A	S67R	1.000
2:112647029:C:G	S67R	1.000
2:112647045:G:C	G73R	1.000
2:112647046:G:A	G73D	1.000
2:112647335:T:A	W116R	1.000
2:112647335:T:C	W116R	1.000
2:112647348:C:A	A120D	1.000
2:112647363:T:C	L125P	1.000
2:112647366:C:A	P126H	1.000
2:112647385:T:G	C132W	1.000
2:112647392:G:C	G135R	1.000
2:112647393:G:A	G135D	1.000
2:112647661:T:A	W162R	1.000

dbSNP variants (sampled 300 via entrez): RS1000154671 (2:112652083 G>C,T), RS1000218492 (2:112652430 G>A), RS1000231411 (2:112646556 C>G,T), RS1000265554 (2:112646489 G>A,T), RS1000267899 (2:112664060 C>T), RS1000280337 (2:112648941 A>G), RS1000563683 (2:112648031 A>G), RS1000613016 (2:112647522 A>C,G), RS1000747332 (2:112653999 T>C,G), RS1001597756 (2:112659017 T>C,G), RS1001684214 (2:112659421 C>A,G), RS1001755033 (2:112653688 G>A), RS1001821256 (2:112664324 C>G), RS1002019739 (2:112660989 A>C,T), RS1002159203 (2:112654759 A>G)

Disease associations

OMIM: gene MIM:137570 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
exstrophy-epispadias complex	Strong	Autosomal dominant

Mondo (1): exstrophy-epispadias complex (MONDO:0017919)

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST002541_49	Menarche (age at onset)	3.000000e-16

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004703	age at menarche

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4295909 (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

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.82	IC50	1500	nM	CHEMBL4170023
5.27	IC50	5400	nM	CHEMBL4159390

PubChem BioAssay actives

2 with measured affinity, of 12 total; 2 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	1354857: Inhibition of human Pit-1 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	1.5000	uM
5-chloro-2-[[3-(2,3-dihydroxypropylsulfanylmethyl)benzoyl]amino]-N-[(E)-(3-fluorophenyl)methylideneamino]benzamide	1354857: Inhibition of human Pit-1 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	5.4000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	decreases expression, increases expression, affects cotreatment, increases abundance, increases oxidation (+1 more)	4
methylmercuric chloride	increases expression	3
Benzo(a)pyrene	decreases expression, increases expression	3
Phosphates	decreases reaction, increases uptake, increases reaction, increases expression, affects reaction (+2 more)	3
Tobacco Smoke Pollution	increases expression	3
Valproic Acid	decreases expression, decreases methylation, increases expression	3
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	affects expression, decreases expression	3
Cyclosporine	increases expression	3
Particulate Matter	decreases expression, increases abundance, increases expression, affects cotreatment	3
bisphenol A	affects cotreatment, decreases expression, affects expression	2
sodium arsenite	decreases expression, affects cotreatment, increases abundance	2
Cisplatin	affects response to substance, decreases expression	2
Estradiol	affects expression, increases expression	2
Lipopolysaccharides	affects cotreatment, decreases expression	2
Ozone	affects cotreatment, increases oxidation, increases abundance, affects expression	2
Plant Extracts	increases expression	2
Tetrachlorodibenzodioxin	increases expression	2
Tretinoin	affects cotreatment, decreases expression	2
Aflatoxin B1	decreases methylation, increases expression	2
Foscarnet	decreases reaction, increases expression, decreases activity	2
FR900359	decreases phosphorylation	1
alpha-pinene	increases oxidation, increases abundance, affects cotreatment	1
pirinixic acid	increases activity, increases expression, affects binding	1
tris(2-butoxyethyl) phosphate	affects expression	1
beta-lapachone	increases expression	1
methylparaben	increases expression	1
sulforaphane	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
cobaltous chloride	increases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	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
CHEMBL4149754	Binding	Inhibition of human Pit-1 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

4 cell lines: 4 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D4IS	HCT116-SLC20A1-KO-c11	Cancer cell line	Male
CVCL_D4IT	HCT116-SLC20A1-KO-c7	Cancer cell line	Male
CVCL_TL89	HAP1 SLC20A1 (-) 1	Cancer cell line	Male
CVCL_TL90	HAP1 SLC20A1 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04760028	PHASE4	COMPLETED	Study on the Influencing Factors of Electroencephalogram Parameters Under Anesthesia
NCT06106425	Not specified	UNKNOWN	Diagnostic and Prognostic Criteria of EEG in Neonatal Convulsions at Assiut University Children Hospital