Details of Drug Off-Target (DOT)

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

• DOT Name: Sodium/hydrogen exchanger 7 (SLC9A7)
• Synonyms: Na(+)/H(+) exchanger 7; NHE-7; Solute carrier family 9 member 7
• Gene Name: SLC9A7
• Related Disease:
  Intellectual developmental disorder, X-linked 108
  Non-syndromic X-linked intellectual disability
• UniProt ID: SL9A7_HUMAN
• Pfam ID: PF00999
• Sequence:
  MEPGDAARPGSGRATGAPPPRLLLLPLLLGWGLRVAAAASASSSGAAAEDSSAMEELATE
  KEAEESHRQDSVSLLTFILLLTLTILTIWLFKHRRVRFLHETGLAMIYGLIVGVILRYGT
  PATSGRDKSLSCTQEDRAFSTLLVNVSGKFFEYTLKGEISPGKINSVEQNDMLRKVTFDP
  EVFFNILLPPIIFHAGYSLKKRHFFRNLGSILAYAFLGTAVSCFIIGNLMYGVVKLMKIM
  GQLSDKFYYTDCLFFGAIISATDPVTVLAIFNELHADVDLYALLFGESVLNDAVAIVLSS
  SIVAYQPAGLNTHAFDAAAFFKSVGIFLGIFSGSFTMGAVTGVNANVTKFTKLHCFPLLE
  TALFFLMSWSTFLLAEACGFTGVVAVLFCGITQAHYTYNNLSVESRSRTKQLFEVLHFLA
  ENFIFSYMGLALFTFQKHVFSPIFIIGAFVAIFLGRAAHIYPLSFFLNLGRRHKIGWNFQ
  HMMMFSGLRGAMAFALAIRDTASYARQMMFTTTLLIVFFTVWIIGGGTTPMLSWLNIRVG
  VEEPSEEDQNEHHWQYFRVGVDPDQDPPPNNDSFQVLQGDGPDSARGNRTKQESAWIFRL
  WYSFDHNYLKPILTHSGPPLTTTLPAWCGLLARCLTSPQVYDNQEPLREEDSDFILTEGD
  LTLTYGDSTVTANGSSSSHTASTSLEGSRRTKSSSEEVLERDLGMGDQKVSSRGTRLVFP
  LEDNA
• Function: Golgi Na(+), K(+)/(H+) antiporter. Mediates the electoneutral influx of Na(+) or K(+) in exchange for H(+). May contribute to the regulation of Golgi apparatus volume and pH.
• Tissue Specificity: Ubiquitously expressed.
• KEGG Pathway: Cardiac muscle contraction (hsa04260)
• Reactome Pathway: Sodium/Proton exchangers (R-HSA-425986)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Intellectual developmental disorder, X-linked 108	DISN3DUL	Strong	X-linked	[1]
Non-syndromic X-linked intellectual disability	DIS71AI3	Supportive	X-linked	[1]

This DOT Affected the Regulation of Drug Effects of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
AMG 386	DMQJXL4	Phase 3	Sodium/hydrogen exchanger 7 (SLC9A7) increases the uptake of AMG 386.	[6]
3-iodothyronamine	DM3L0F8	Investigative	Sodium/hydrogen exchanger 7 (SLC9A7) affects the uptake of 3-iodothyronamine.	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Sodium/hydrogen exchanger 7 (SLC9A7).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Sodium/hydrogen exchanger 7 (SLC9A7).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Sodium/hydrogen exchanger 7 (SLC9A7).	[4]
Quinine	DMSWYF5	Approved	Quinine decreases the activity of Sodium/hydrogen exchanger 7 (SLC9A7).	[6]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Sodium/hydrogen exchanger 7 (SLC9A7).	[9]
Benzamil	DM57SVW	Investigative	Benzamil decreases the activity of Sodium/hydrogen exchanger 7 (SLC9A7).	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Sodium/hydrogen exchanger 7 (SLC9A7).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Sodium/hydrogen exchanger 7 (SLC9A7).	[7]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Sodium/hydrogen exchanger 7 (SLC9A7).	[8]

References

• [1] A recurrent missense variant in SLC9A7 causes nonsyndromic X-linked intellectual disability with alteration of Golgi acidification and aberrant glycosylation. Hum Mol Genet. 2019 Feb 15;28(4):598-614. doi: 10.1093/hmg/ddy371.
• [2] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [3] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [4] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [5] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [6] Molecular cloning and characterization of a novel (Na+,K+)/H+ exchanger localized to the trans-Golgi network. J Biol Chem. 2001 May 18;276(20):17387-94. doi: 10.1074/jbc.M101319200. Epub 2001 Feb 26.
• [7] 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.
• [8] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [9] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [10] Identification and characterization of 3-iodothyronamine intracellular transport. Endocrinology. 2009 Apr;150(4):1991-9.