Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT861KCR)

• DOT Name: Solute carrier family 38 member 8 (SLC38A8)
• Synonyms: Amino acid transporter SLC38A8
• Gene Name: SLC38A8
• Related Disease: Foveal hypoplasia - optic nerve decussation defect - anterior segment dysgenesis syndrome
• UniProt ID: S38A8_HUMAN
• Pfam ID: PF01490
• Sequence:
  MEGQTPGSRGLPEKPHPATAAATLSSMGAVFILMKSALGAGLLNFPWAFSKAGGVVPAFL
  VELVSLVFLISGLVILGYAAAVSGQATYQGVVRGLCGPAIGKLCEACFLLNLLMISVAFL
  RVIGDQLEKLCDSLLSGTPPAPQPWYADQRFTLPLLSVLVILPLSAPREIAFQKYTSILG
  TLAACYLALVITVQYYLWPQGLVRESHPSLSPASWTSVFSVFPTICFGFQCHEAAVSIYC
  SMRKRSLSHWALVSVLSLLACCLIYSLTGVYGFLTFGTEVSADVLMSYPGNDMVIIVARV
  LFAVSIVTVYPIVLFLGRSVMQDFWRRSCLGGWGPSALADPSGLWVRMPLTILWVTVTLA
  MALFMPDLSEIVSIIGGISSFFIFIFPGLCLICAMGVEPIGPRVKCCLEVWGVVSVLVGT
  FIFGQSTAAAVWEMF
• Function: Electrogenic sodium-dependent amino acid transporter with a preference for L-glutamine, L-alanine, L-histidine, L-aspartate and L-arginine. May facilitate glutamine uptake in both excitatory and inhibitory neurons. The transport mechanism and stoichiometry remain to be elucidated.
• Tissue Specificity: Expressed in fetal and adult brain, and spinal cord. In the brain, it is localized in the cell body and axon of the majority of neuronal cells and in a subset of glial cells. Found throughout the neuronal retina, with higher expression levels in the inner and outer plexiform layers and the photoreceptor layer. Very weak expression is also present in the kidneys, thymus, and testes.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Foveal hypoplasia - optic nerve decussation defect - anterior segment dysgenesis syndrome	DISXOOPZ	Definitive	Autosomal recessive	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Solute carrier family 38 member 8 (SLC38A8).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Solute carrier family 38 member 8 (SLC38A8).	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Solute carrier family 38 member 8 (SLC38A8).	[3]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Solute carrier family 38 member 8 (SLC38A8).	[4]

References

• [1] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [2] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [3] 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.
• [4] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [5] 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.