Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT4L2BNR)

DOT Name	Sodium-dependent phosphate transport protein 2C (SLC34A3)
Synonyms	Sodium-phosphate transport protein 2C; Na(+)-dependent phosphate cotransporter 2C; Sodium/inorganic phosphate cotransporter IIC; Sodium/phosphate cotransporter 2C; Na(+)/Pi cotransporter 2C; NaPi-2c; Solute carrier family 34 member 3
Gene Name	SLC34A3
Related Disease	Hereditary hypophosphatemic rickets with hypercalciuria ( )
UniProt ID	NPT2C_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
Pfam ID	PF02690
Sequence	MPSSLPGSQVPHPTLDAVDLVEKTLRNEGTSSSAPVLEEGDTDPWTLPQLKDTSQPWKEL RVAGRLRRVAGSVLKACGLLGSLYFFICSLDVLSSAFQLLGSKVAGDIFKDNVVLSNPVA GLVIGVLVTALVQSSSTSSSIVVSMVAAKLLTVRVSVPIIMGVNVGTSITSTLVSMAQSG DRDEFQRAFSGSAVHGIFNWLTVLVLLPLESATALLERLSELALGAASLTPRAQAPDILK VLTKPLTHLIVQLDSDMIMSSATGNATNSSLIKHWCGTTGQPTQENSSCGAFGPCTEKNS TAPADRLPCRHLFAGTELTDLAVGCILLAGSLLVLCGCLVLIVKLLNSVLRGRVAQVVRT VINADFPFPLGWLGGYLAVLAGAGLTFALQSSSVFTAAVVPLMGVGVISLDRAYPLLLGS NIGTTTTALLAALASPADRMLSALQVALIHFFFNLAGILLWYLVPALRLPIPLARHFGVV TARYRWVAGVYLLLGFLLLPLAAFGLSLAGGMELAAVGGPLVGLVLLVILVTVLQRRRPA WLPVRLRSWAWLPVWLHSLEPWDRLVTRCCPCNVCSPPKATTKEAYCYENPEILASQQL
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 2:1 and is electroneutral.
Tissue Specificity	Expressed only in the kidney.
KEGG Pathway	Parathyroid hormone synthesis, secretion and action (hsa04928 ) Mineral absorption (hsa04978 )
Reactome Pathway	Defective SLC34A3 causes Hereditary hypophosphatemic rickets with hypercalciuria (HHRH) (R-HSA-5619097 ) Type II Na+/Pi cotransporters (R-HSA-427589 )

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance		REF
Hereditary hypophosphatemic rickets with hypercalciuria	DISJ2YQQ	Strong	Autosomal recessive	[1]
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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the methylation of Sodium-dependent phosphate transport protein 2C (SLC34A3).	[2]
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1 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Sodium-dependent phosphate transport protein 2C (SLC34A3).	[3]
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References

1	SLC34A3 mutations in patients with hereditary hypophosphatemic rickets with hypercalciuria predict a key role for the sodium-phosphate cotransporter NaPi-IIc in maintaining phosphate homeostasis. Am J Hum Genet. 2006 Feb;78(2):179-92. doi: 10.1086/499409. Epub 2005 Dec 9.
2	Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
3	Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.