Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTNOMLU2)

DOT Name Sodium-dependent phosphate transport protein 2A (SLC34A1)
Synonyms Sodium-phosphate transport protein 2A; Na(+)-dependent phosphate cotransporter 2A; NaPi-3; Sodium/phosphate cotransporter 2A; Na(+)/Pi cotransporter 2A; NaPi-2a; Solute carrier family 34 member 1
Gene Name SLC34A1
Related Disease
Hypercalcemia, infantile, 2 ( )
Obsolete autosomal recessive infantile hypercalcemia ( )
Obsolete dominant hypophosphatemia with nephrolithiasis or osteoporosis ( )
Primary Fanconi syndrome ( )
Fanconi renotubular syndrome 2 ( )
Hypophosphatemic nephrolithiasis/osteoporosis 1 ( )
UniProt ID
NPT2A_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Pfam ID
PF02690
Sequence
MLSYGERLGSPAVSPLPVRGGHVMRGTAFAYVPSPQVLHRIPGTSAYAFPSLGPVALAEH
TCPCGEVLERHEPLPAKLALEEEQKPESRLVPKLRQAGAMLLKVPLMLTFLYLFVCSLDM
LSSAFQLAGGKVAGDIFKDNAILSNPVAGLVVGILVTVLVQSSSTSTSIIVSMVSSGLLE
VSSAIPIIMGSNIGTSVTNTIVALMQAGDRTDFRRAFAGATVHDCFNWLSVLVLLPLEAA
TGYLHHITRLVVASFNIHGGRDAPDLLKIITEPFTKLIIQLDESVITSIATGDESLRNHS
LIQIWCHPDSLQAPTSMSRAEANSSQTLGNATMEKCNHIFVDTGLPDLAVGLILLAGSLV
LLCTCLILLVKMLNSLLKGQVAKVIQKVINTDFPAPFTWVTGYFAMVVGASMTFVVQSSS
VFTSAITPLIGLGVISIERAYPLTLGSNIGTTTTAILAALASPREKLSSAFQIALCHFFF
NISGILLWYPVPCTRLPIRMAKALGKRTAKYRWFAVLYLLVCFLLLPSLVFGISMAGWQV
MVGVGTPFGALLAFVVLINVLQSRSPGHLPKWLQTWDFLPRWMHSLKPLDHLITRATLCC
ARPEPRSPPLPPRVFLEELPPATPSPRLALPAHHNATRL
Function Involved in actively transporting phosphate into cells via Na(+) cotransport in the renal brush border membrane. The cotransport has a Na(+):Pi stoichiometry of 3:1 and is electrogenic.
Tissue Specificity Kidney and lung.
KEGG Pathway
Parathyroid hormone synthesis, secretion and action (hsa04928 )
Mineral absorption (hsa04978 )
Reactome Pathway
Defective SLC34A1 causes hypophosphatemic nephrolithiasis/osteoporosis 1 (NPHLOP1) (R-HSA-5619040 )
Surfactant metabolism (R-HSA-5683826 )
Type II Na+/Pi cotransporters (R-HSA-427589 )

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Hypercalcemia, infantile, 2 DISOWEH7 Definitive Autosomal recessive [1]
Obsolete autosomal recessive infantile hypercalcemia DISWWUR1 Supportive Autosomal recessive [2]
Obsolete dominant hypophosphatemia with nephrolithiasis or osteoporosis DISGRJU9 Supportive Autosomal dominant [3]
Primary Fanconi syndrome DISR144Y Supportive Autosomal dominant [4]
Fanconi renotubular syndrome 2 DIS1I0AV Disputed Autosomal recessive [1]
Hypophosphatemic nephrolithiasis/osteoporosis 1 DIS1VBL1 Limited Autosomal dominant [5]
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⏷ Show the Full List of 6 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
4 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Sodium-dependent phosphate transport protein 2A (SLC34A1). [6]
Testosterone DM7HUNW Approved Testosterone decreases the expression of Sodium-dependent phosphate transport protein 2A (SLC34A1). [7]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the expression of Sodium-dependent phosphate transport protein 2A (SLC34A1). [8]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the expression of Sodium-dependent phosphate transport protein 2A (SLC34A1). [9]
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References

1 Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
2 Autosomal-Recessive Mutations in SLC34A1 Encoding Sodium-Phosphate Cotransporter 2A Cause Idiopathic Infantile Hypercalcemia. J Am Soc Nephrol. 2016 Feb;27(2):604-14. doi: 10.1681/ASN.2014101025. Epub 2015 Jun 5.
3 Nephrolithiasis and osteoporosis associated with hypophosphatemia caused by mutations in the type 2a sodium-phosphate cotransporter. N Engl J Med. 2002 Sep 26;347(13):983-91. doi: 10.1056/NEJMoa020028.
4 A loss-of-function mutation in NaPi-IIa and renal Fanconi's syndrome. N Engl J Med. 2010 Mar 25;362(12):1102-9. doi: 10.1056/NEJMoa0905647.
5 Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
6 Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
7 The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
8 Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
9 Isobaric tags for relative and absolute quantitation-based proteomics analysis of the effect of ginger oil on bisphenol A-induced breast cancer cell proliferation. Oncol Lett. 2021 Feb;21(2):101. doi: 10.3892/ol.2020.12362. Epub 2020 Dec 8.