Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT07YJW4)

• DOT Name: Solute carrier family 7 member 14 (SLC7A14)
• Synonyms: Gamma-aminobutyric acid transporter SLC7A14
• Gene Name: SLC7A14
• Related Disease:
  Inherited retinal dystrophy
  Leber congenital amaurosis
  Leber congenital amaurosis 1
  Retinitis pigmentosa 68
  Retinitis pigmentosa
  Mesothelioma
• UniProt ID: S7A14_HUMAN
• Pfam ID: PF13520 ; PF13906
• Sequence:
  MSGFFTSLDPRRVQWGAAWYAMHSRILRTKPVESMLEGTGTTTAHGTKLAQVLTTVDLIS
  LGVGSCVGTGMYVVSGLVAKEMAGPGVIVSFIIAAVASILSGVCYAEFGVRVPKTTGSAY
  TYSYVTVGEFVAFFIGWNLILEYLIGTAAGASALSSMFDSLANHTISRWMADSVGTLNGL
  GKGEESYPDLLALLIAVIVTIIVALGVKNSIGFNNVLNVLNLAVWVFIMIAGLFFINGKY
  WAEGQFLPHGWSGVLQGAATCFYAFIGFDIIATTGEEAKNPNTSIPYAITASLVICLTAY
  VSVSVILTLMVPYYTIDTESPLMEMFVAHGFYAAKFVVAIGSVAGLTVSLLGSLFPMPRV
  IYAMAGDGLLFRFLAHVSSYTETPVVACIVSGFLAALLALLVSLRDLIEMMSIGTLLAYT
  LVSVCVLLLRYQPESDIDGFVKFLSEEHTKKKEGILADCEKEACSPVSEGDEFSGPATNT
  CGAKNLPSLGDNEMLIGKSDKSTYNVNHPNYGTVDMTTGIEADESENIYLIKLKKLIGPH
  YYTMRIRLGLPGKMDRPTAATGHTVTICVLLLFILMFIFCSFIIFGSDYISEQSWWAILL
  VVLMVLLISTLVFVILQQPENPKKLPYMAPCLPFVPAFAMLVNIYLMLKLSTITWIRFAV
  WCFVGLLIYFGYGIWNSTLEISAREEALHQSTYQRYDVDDPFSVEEGFSYATEGESQEDW
  GGPTEDKGFYYQQMSDAKANGRTSSKAKSKSKHKQNSEALIANDELDYSPE
• Function: Imports 4-aminobutanoate (GABA) into lysosomes. May act as a GABA sensor that regulates mTORC2-dependent INS signaling and gluconeogenesis. The transport mechanism and substrate selectivity remain to be elucidated.
• Tissue Specificity: Expressed in skin fibroblasts.

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Inherited retinal dystrophy	DISGGL77	Strong	Genetic Variation	[1]
Leber congenital amaurosis	DISMGH8F	Strong	Genetic Variation	[1]
Leber congenital amaurosis 1	DISY2B33	Strong	Genetic Variation	[1]
Retinitis pigmentosa 68	DISBF5TV	Strong	Autosomal recessive	[2]
Retinitis pigmentosa	DISCGPY8	Supportive	Autosomal dominant	[2]
Mesothelioma	DISKWK9M	Limited	Genetic Variation	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
3-iodothyronamine	DM3L0F8	Investigative	Solute carrier family 7 member 14 (SLC7A14) affects the uptake of 3-iodothyronamine.	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Solute carrier family 7 member 14 (SLC7A14).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Solute carrier family 7 member 14 (SLC7A14).	[5]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Solute carrier family 7 member 14 (SLC7A14).	[7]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Solute carrier family 7 member 14 (SLC7A14).	[5]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Solute carrier family 7 member 14 (SLC7A14).	[9]

2 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 Solute carrier family 7 member 14 (SLC7A14).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Solute carrier family 7 member 14 (SLC7A14).	[8]

References

• [1] Phenotypic variability of SLC7A14 mutations in patients with inherited retinal dystrophy.Ophthalmic Genet. 2019 Apr;40(2):118-123. doi: 10.1080/13816810.2019.1586964. Epub 2019 Mar 29.
• [2] SLC7A14 linked to autosomal recessive retinitis pigmentosa. Nat Commun. 2014 Mar 27;5:3517. doi: 10.1038/ncomms4517.
• [3] Genetic variants associated with increased risk of malignant pleural mesothelioma: a genome-wide association study.PLoS One. 2013 Apr 23;8(4):e61253. doi: 10.1371/journal.pone.0061253. Print 2013.
• [4] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [5] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [6] 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.
• [7] Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
• [8] 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.
• [9] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [10] Identification and characterization of 3-iodothyronamine intracellular transport. Endocrinology. 2009 Apr;150(4):1991-9.