Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT06IH3H)

• DOT Name: FXYD domain-containing ion transport regulator 4 (FXYD4)
• Gene Name: FXYD4
• Related Disease:
  Candidemia
  Candidiasis, invasive
  Invasive candidiasis
• UniProt ID: FXYD4_HUMAN
• Pfam ID: PF02038
• Sequence:
  MERVTLALLLLAGLTALEANDPFANKDDPFYYDWKNLQLSGLICGGLLAIAGIAAVLSGK
  CKCKSSQKQHSPVPEKAIPLITPGSATTC
• KEGG Pathway: Aldosterone-regulated sodium reabsorption (hsa04960)
• Reactome Pathway:
  Ion transport by P-type ATPases (R-HSA-936837)
  Potential therapeutics for SARS (R-HSA-9679191)
  Ion homeostasis (R-HSA-5578775)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Candidemia	DISVKFN7	Strong	Biomarker	[1]
Candidiasis, invasive	DIS5VDG3	Strong	Biomarker	[2]
Invasive candidiasis	DIS5EI0L	Strong	Biomarker	[2]

3 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 FXYD domain-containing ion transport regulator 4 (FXYD4).	[3]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of FXYD domain-containing ion transport regulator 4 (FXYD4).	[4]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of FXYD domain-containing ion transport regulator 4 (FXYD4).	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of FXYD domain-containing ion transport regulator 4 (FXYD4).	[6]

References

• [1] Development of fluconazole resistance in a series of Candida parapsilosis isolates from a persistent candidemia patient with prolonged antifungal therapy.BMC Infect Dis. 2015 Aug 18;15:340. doi: 10.1186/s12879-015-1086-6.
• [2] Five-Year National Surveillance of Invasive Candidiasis: Species Distribution and Azole Susceptibility from the China Hospital Invasive Fungal Surveillance Net (CHIF-NET) Study.J Clin Microbiol. 2018 Jun 25;56(7):e00577-18. doi: 10.1128/JCM.00577-18. Print 2018 Jul.
• [3] 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.
• [4] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [5] Endometrial receptivity is affected in women with high circulating progesterone levels at the end of the follicular phase: a functional genomics analysis. Hum Reprod. 2011 Jul;26(7):1813-25.
• [6] 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.