Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTHJFW2G)

• DOT Name: Sodium-dependent neutral amino acid transporter SLC6A17 (SLC6A17)
• Synonyms: Sodium-dependent neurotransmitter transporter NTT4; Solute carrier family 6 member 17
• Gene Name: SLC6A17
• Related Disease:
  Progressive essential tremor-speech impairment-facial dysmorphism-intellectual disability-abnormal behavior syndrome
  Schizophrenia
• UniProt ID: S6A17_HUMAN
• Pfam ID: PF00209
• Sequence:
  MPKNSKVTQREHSSEHVTESVADLLALEEPVDYKQSVLNVAGEAGGKQKAVEEELDAEDR
  PAWNSKLQYILAQIGFSVGLGNIWRFPYLCQKNGGGAYLVPYLVLLIIIGIPLFFLELAV
  GQRIRRGSIGVWHYICPRLGGIGFSSCIVCLFVGLYYNVIIGWSIFYFFKSFQYPLPWSE
  CPVVRNGSVAVVEAECEKSSATTYFWYREALDISDSISESGGLNWKMTLCLLVAWSIVGM
  AVVKGIQSSGKVMYFSSLFPYVVLACFLVRGLLLRGAVDGILHMFTPKLDKMLDPQVWRE
  AATQVFFALGLGFGGVIAFSSYNKQDNNCHFDAALVSFINFFTSVLATLVVFAVLGFKAN
  IMNEKCVVENAEKILGYLNTNVLSRDLIPPHVNFSHLTTKDYMEMYNVIMTVKEDQFSAL
  GLDPCLLEDELDKSVQGTGLAFIAFTEAMTHFPASPFWSVMFFLMLINLGLGSMIGTMAG
  ITTPIIDTFKVPKEMFTVGCCVFAFLVGLLFVQRSGNYFVTMFDDYSATLPLTLIVILEN
  IAVAWIYGTKKFMQELTEMLGFRPYRFYFYMWKFVSPLCMAVLTTASIIQLGVTPPGYSA
  WIKEEAAERYLYFPNWAMALLITLIVVATLPIPVVFVLRHFHLLSDGSNTLSVSYKKGRM
  MKDISNLEENDETRFILSKVPSEAPSPMPTHRSYLGPGSTSPLETSGNPNGRYGSGYLLA
  STPESEL
• Function: Synaptic vesicle transporter with apparent selectivity for neutral amino acids. The transport is sodium-coupled but chloride-independent, likely driven by the proton electrochemical gradient generated by vacuolar H(+)-ATPase in an overall electrogenic mechanism. May contribute to the synaptic uptake of neurotransmitter precursors in a process coupled in part to vesicle exocytosis.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Progressive essential tremor-speech impairment-facial dysmorphism-intellectual disability-abnormal behavior syndrome	DISGBLN0	Strong	Autosomal recessive	[1]
Schizophrenia	DISSRV2N	No Known	Unknown	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Sodium-dependent neutral amino acid transporter SLC6A17 (SLC6A17).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Sodium-dependent neutral amino acid transporter SLC6A17 (SLC6A17).	[4]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Sodium-dependent neutral amino acid transporter SLC6A17 (SLC6A17).	[5]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Sodium-dependent neutral amino acid transporter SLC6A17 (SLC6A17).	[7]

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 increases the methylation of Sodium-dependent neutral amino acid transporter SLC6A17 (SLC6A17).	[6]

References

• [1] Homozygous SLC6A17 mutations cause autosomal-recessive intellectual disability with progressive tremor, speech impairment, and behavioral problems. Am J Hum Genet. 2015 Mar 5;96(3):386-96. doi: 10.1016/j.ajhg.2015.01.010. Epub 2015 Feb 19.
• [2] The Gene Curation Coalition: A global effort to harmonize gene-disease evidence resources. Genet Med. 2022 Aug;24(8):1732-1742. doi: 10.1016/j.gim.2022.04.017. Epub 2022 May 4.
• [3] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [4] 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.
• [5] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [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.
• [7] 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.