Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTXI9C1E)

DOT Name Sorting nexin-14 (SNX14)
Gene Name SNX14
Related Disease
Autosomal recessive spinocerebellar ataxia 20 ( )
Intellectual disability ( )
Cerebellar ataxia ( )
UniProt ID
SNX14_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
PDB ID
4BGJ; 4PQO; 4PQP
Pfam ID
PF08628 ; PF00787 ; PF02194 ; PF00615
Sequence
MVPWVRTMGQKLKQRLRLDVGREICRQYPLFCFLLLCLSAASLLLNRYIHILMIFWSFVA
GVVTFYCSLGPDSLLPNIFFTIKYKPKQLGLQELFPQGHSCAVCGKVKCKRHRPSLLLEN
YQPWLDLKISSKVDASLSEVLELVLENFVYPWYRDVTDDESFVDELRITLRFFASVLIRR
IHKVDIPSIITKKLLKAAMKHIEVIVKARQKVKNTEFLQQAALEEYGPELHVALRSRRDE
LHYLRKLTELLFPYILPPKATDCRSLTLLIREILSGSVFLPSLDFLADPDTVNHLLIIFI
DDSPPEKATEPASPLVPFLQKFAEPRNKKPSVLKLELKQIREQQDLLFRFMNFLKQEGAV
HVLQFCLTVEEFNDRILRPELSNDEMLSLHEELQKIYKTYCLDESIDKIRFDPFIVEEIQ
RIAEGPYIDVVKLQTMRCLFEAYEHVLSLLENVFTPMFCHSDEYFRQLLRGAESPTRNSK
LNRGSLSLDDFRNTQKRGESFGISRIGSKIKGVFKSTTMEGAMLPNYGVAEGEDDFIEEG
IVVMEDDSPVEAVSTPNTPRNLAAWKISIPYVDFFEDPSSERKEKKERIPVFCIDVERND
RRAVGHEPEHWSVYRRYLEFYVLESKLTEFHGAFPDAQLPSKRIIGPKNYEFLKSKREEF
QEYLQKLLQHPELSNSQLLADFLSPNGGETQFLDKILPDVNLGKIIKSVPGKLMKEKGQH
LEPFIMNFINSCESPKPKPSRPELTILSPTSENNKKLFNDLFKNNANRAENTERKQNQNY
FMEVMTVEGVYDYLMYVGRVVFQVPDWLHHLLMGTRILFKNTLEMYTDYYLQCKLEQLFQ
EHRLVSLITLLRDAIFCENTEPRSLQDKQKGAKQTFEEMMNYIPDLLVKCIGEETKYESI
RLLFDGLQQPVLNKQLTYVLLDIVIQELFPELNKVQKEVTSVTSWM
Function
Plays a role in maintaining normal neuronal excitability and synaptic transmission. May be involved in several stages of intracellular trafficking. Required for autophagosome clearance, possibly by mediating the fusion of lysosomes with autophagosomes (Probable). Binds phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2), a key component of late endosomes/lysosomes. Does not bind phosphatidylinositol 3-phosphate (PtdIns(3P)).
Tissue Specificity Widely expressed both in fetal and adult tissues.

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Autosomal recessive spinocerebellar ataxia 20 DISLZ9M1 Strong Autosomal recessive [1]
Intellectual disability DISMBNXP Strong Genetic Variation [2]
Cerebellar ataxia DIS9IRAV Limited Biomarker [3]
------------------------------------------------------------------------------------
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
8 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate affects the expression of Sorting nexin-14 (SNX14). [4]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Sorting nexin-14 (SNX14). [5]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Sorting nexin-14 (SNX14). [6]
Quercetin DM3NC4M Approved Quercetin decreases the expression of Sorting nexin-14 (SNX14). [7]
Hydrogen peroxide DM1NG5W Approved Hydrogen peroxide affects the expression of Sorting nexin-14 (SNX14). [8]
Menadione DMSJDTY Approved Menadione affects the expression of Sorting nexin-14 (SNX14). [8]
Milchsaure DM462BT Investigative Milchsaure decreases the expression of Sorting nexin-14 (SNX14). [9]
Bilirubin DMI0V4O Investigative Bilirubin decreases the expression of Sorting nexin-14 (SNX14). [10]
------------------------------------------------------------------------------------
⏷ Show the Full List of 8 Drug(s)

References

1 Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
2 Congenital disorders of autophagy: an emerging novel class of inborn errors of neuro-metabolism.Brain. 2016 Feb;139(Pt 2):317-37. doi: 10.1093/brain/awv371. Epub 2015 Dec 29.
3 Cerebellar ataxia disease-associated Snx14 promotes lipid droplet growth at ER-droplet contacts.J Cell Biol. 2019 Apr 1;218(4):1335-1351. doi: 10.1083/jcb.201808133. Epub 2019 Feb 14.
4 Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
5 Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
6 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.
7 Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
8 Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
9 Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
10 Global changes in gene regulation demonstrate that unconjugated bilirubin is able to upregulate and activate select components of the endoplasmic reticulum stress response pathway. J Biochem Mol Toxicol. 2010 Mar-Apr;24(2):73-88.