Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTLFMBB0)

• DOT Name: Sodium-dependent phosphate transport protein 2B (SLC34A2)
• Synonyms: Sodium-phosphate transport protein 2B; Na(+)-dependent phosphate cotransporter 2B; NaPi3b; Sodium/phosphate cotransporter 2B; Na(+)/Pi cotransporter 2B; NaPi-2b; Solute carrier family 34 member 2
• Gene Name: SLC34A2
• Related Disease: Pulmonary alveolar microlithiasis
• UniProt ID: NPT2B_HUMAN
• Pfam ID: PF02690
• Sequence:
  MAPWPELGDAQPNPDKYLEGAAGQQPTAPDKSKETNKTDNTEAPVTKIELLPSYSTATLI
  DEPTEVDDPWNLPTLQDSGIKWSERDTKGKILCFFQGIGRLILLLGFLYFFVCSLDILSS
  AFQLVGGKMAGQFFSNSSIMSNPLLGLVIGVLVTVLVQSSSTSTSIVVSMVSSSLLTVRA
  AIPIIMGANIGTSITNTIVALMQVGDRSEFRRAFAGATVHDFFNWLSVLVLLPVEVATHY
  LEIITQLIVESFHFKNGEDAPDLLKVITKPFTKLIVQLDKKVISQIAMNDEKAKNKSLVK
  IWCKTFTNKTQINVTVPSTANCTSPSLCWTDGIQNWTMKNVTYKENIAKCQHIFVNFHLP
  DLAVGTILLILSLLVLCGCLIMIVKILGSVLKGQVATVIKKTINTDFPFPFAWLTGYLAI
  LVGAGMTFIVQSSSVFTSALTPLIGIGVITIERAYPLTLGSNIGTTTTAILAALASPGNA
  LRSSLQIALCHFFFNISGILLWYPIPFTRLPIRMAKGLGNISAKYRWFAVFYLIIFFFLI
  PLTVFGLSLAGWRVLVGVGVPVVFIIILVLCLRLLQSRCPRVLPKKLQNWNFLPLWMRSL
  KPWDAVVSKFTGCFQMRCCCCCRVCCRACCLLCDCPKCCRCSKCCEDLEEAQEGQDVPVK
  APETFDNITISREAQGEVPASDSKTECTAL
• Function: Involved in actively transporting phosphate into cells via Na(+) cotransport.
• Tissue Specificity: Highly expressed in lung. Also detected in pancreas, kidney, small intestine, ovary, testis, prostate and mammary gland. In lung, it is found in alveolar type II cells but not in bronchiolar epithelium.
• KEGG Pathway:
  Parathyroid hormone synthesis, secretion and action (hsa04928)
  Mineral absorption (hsa04978)
• Reactome Pathway:
  Defective SLC34A2 causes pulmonary alveolar microlithiasis (PALM) (R-HSA-5619045)
  Surfactant metabolism (R-HSA-5683826)
  Defective SLC34A2 causes PALM (R-HSA-5687583)
  Type II Na+/Pi cotransporters (R-HSA-427589)
• BioCyc Pathway: MetaCyc:ENSG00000157765-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Pulmonary alveolar microlithiasis	DISY2U8W	Definitive	Autosomal recessive	[1]

This DOT Affected the Regulation of Drug Effects of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Sodium-dependent phosphate transport protein 2B (SLC34A2) increases the transport of Arsenic.	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Sodium-dependent phosphate transport protein 2B (SLC34A2).	[2]
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of Sodium-dependent phosphate transport protein 2B (SLC34A2).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Sodium-dependent phosphate transport protein 2B (SLC34A2).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Sodium-dependent phosphate transport protein 2B (SLC34A2).	[8]

6 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin affects the expression of Sodium-dependent phosphate transport protein 2B (SLC34A2).	[3]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Sodium-dependent phosphate transport protein 2B (SLC34A2).	[4]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Sodium-dependent phosphate transport protein 2B (SLC34A2).	[5]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Sodium-dependent phosphate transport protein 2B (SLC34A2).	[6]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Sodium-dependent phosphate transport protein 2B (SLC34A2).	[7]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Sodium-dependent phosphate transport protein 2B (SLC34A2).	[10]

References

• [1] 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.
• [2] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [3] Molecular characterization of a toxicological tipping point during human stem cell differentiation. Reprod Toxicol. 2020 Jan;91:1-13. doi: 10.1016/j.reprotox.2019.10.001. Epub 2019 Oct 7.
• [4] Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
• [5] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [6] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [7] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [8] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [9] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [10] Cellular reactions to long-term volatile organic compound (VOC) exposures. Sci Rep. 2016 Dec 1;6:37842. doi: 10.1038/srep37842.
• [11] In vitro study of transporters involved in intestinal absorption of inorganic arsenic. Chem Res Toxicol. 2012 Feb 20;25(2):446-53. doi: 10.1021/tx200491f. Epub 2012 Jan 26.