Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTHHPC3C)

• DOT Name: Solute carrier family 25 member 44 (SLC25A44)
• Gene Name: SLC25A44
• Related Disease:
  Intracerebral hemorrhage
  Neoplasm of testis
  Testicular germ cell tumor
  Acute myelogenous leukaemia
• UniProt ID: S2544_HUMAN
• Pfam ID: PF00153
• Sequence:
  MEDKRNIQIIEWEHLDKKKFYVFGVAMTMMIRVSVYPFTLIRTRLQVQKGKSLYHGTFDA
  FIKILRADGITGLYRGFLVNTFTLISGQCYVTTYELTRKFVADYSQSNTVKSLVAGGSAS
  LVAQSITVPIDVVSQHLMMQRKGEKMGRFQVRGNPEGQGVVAFGQTKDIIRQILQADGLR
  GFYRGYVASLLTYIPNSAVWWPFYHFYAEQLSYLCPKECPHIVFQAVSGPLAAATASILT
  NPMDVIRTRVQVEGKNSIILTFRQLMAEEGPWGLMKGLSARIISATPSTIVIVVGYESLK
  KLSLRPELVDSRHW
• Function: Mitochondrial solute transporter which transports branched-chain amino acid (BCAA; valine, leucine and isoleucine) into mitochondria in brown adipose tissue (BAT). BAT is involved in BCAA catabolism and actively utilizes BCAA in the mitochondria for thermogenesis.
• Reactome Pathway: Branched-chain amino acid catabolism (R-HSA-70895)

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Intracerebral hemorrhage	DISC81BT	Strong	Genetic Variation	[1]
Neoplasm of testis	DISK4XHT	Strong	Genetic Variation	[2]
Testicular germ cell tumor	DIS5RN24	Strong	Genetic Variation	[3]
Acute myelogenous leukaemia	DISCSPTN	moderate	Genetic Variation	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Solute carrier family 25 member 44 (SLC25A44).	[5]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Solute carrier family 25 member 44 (SLC25A44).	[6]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Solute carrier family 25 member 44 (SLC25A44).	[7]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Solute carrier family 25 member 44 (SLC25A44).	[8]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Solute carrier family 25 member 44 (SLC25A44).	[9]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Solute carrier family 25 member 44 (SLC25A44).	[10]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Solute carrier family 25 member 44 (SLC25A44).	[11]

References

• [1] Meta-analysis of genome-wide association studies identifies 1q22 as a susceptibility locus for intracerebral hemorrhage.Am J Hum Genet. 2014 Apr 3;94(4):511-21. doi: 10.1016/j.ajhg.2014.02.012. Epub 2014 Mar 20.
• [2] Identification of nine new susceptibility loci for testicular cancer, including variants near DAZL and PRDM14.Nat Genet. 2013 Jun;45(6):686-9. doi: 10.1038/ng.2635. Epub 2013 May 12.
• [3] Identification of 19 new risk loci and potential regulatory mechanisms influencing susceptibility to testicular germ cell tumor.Nat Genet. 2017 Jul;49(7):1133-1140. doi: 10.1038/ng.3896. Epub 2017 Jun 12.
• [4] Genome-wide haplotype association study identify the FGFR2 gene as a risk gene for acute myeloid leukemia.Oncotarget. 2017 Jan 31;8(5):7891-7899. doi: 10.18632/oncotarget.13631.
• [5] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [6] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [7] Increased mitochondrial ROS formation by acetaminophen in human hepatic cells is associated with gene expression changes suggesting disruption of the mitochondrial electron transport chain. Toxicol Lett. 2015 Apr 16;234(2):139-50.
• [8] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [9] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [10] 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.
• [11] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.