Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTP8PAKU)

• DOT Name: VPS10 domain-containing receptor SorCS1 (SORCS1)
• Synonyms: hSorCS
• Gene Name: SORCS1
• Related Disease:
  Autism
  Nephropathy
  Non-insulin dependent diabetes
  Obesity
  Polycystic ovarian syndrome
  Type-1/2 diabetes
  Colorectal carcinoma
  Alzheimer disease
  Hypoglycemia
  Mental disorder
  Schizophrenia
• UniProt ID: SORC1_HUMAN
• Pfam ID: PF00801 ; PF15902 ; PF15901
• Sequence:
  MGKVGAGGGSQARLSALLAGAGLLILCAPGVCGGGSCCPSPHPSSAPRSASTPRGFSHQG
  RPGRAPATPLPLVVRPLFSVAPGDRALSLERARGTGASMAVAARSGRRRRSGADQEKAER
  GEGASRSPRGVLRDGGQQEPGTRERDPDKATRFRMEELRLTSTTFALTGDSAHNQAMVHW
  SGHNSSVILILTKLYDYNLGSITESSLWRSTDYGTTYEKLNDKVGLKTILSYLYVCPTNK
  RKIMLLTDPEIESSLLISSDEGATYQKYRLNFYIQSLLFHPKQEDWILAYSQDQKLYSSA
  EFGRRWQLIQEGVVPNRFYWSVMGSNKEPDLVHLEARTVDGHSHYLTCRMQNCTEANRNQ
  PFPGYIDPDSLIVQDHYVFVQLTSGGRPHYYVSYRRNAFAQMKLPKYALPKDMHVISTDE
  NQVFAAVQEWNQNDTYNLYISDTRGVYFTLALENVQSSRGPEGNIMIDLYEVAGIKGMFL
  ANKKIDNQVKTFITYNKGRDWRLLQAPDTDLRGDPVHCLLPYCSLHLHLKVSENPYTSGI
  IASKDTAPSIIVASGNIGSELSDTDISMFVSSDAGNTWRQIFEEEHSVLYLDQGGVLVAM
  KHTSLPIRHLWLSFDEGRSWSKYSFTSIPLFVDGVLGEPGEETLIMTVFGHFSHRSEWQL
  VKVDYKSIFDRRCAEEDYRPWQLHSQGEACIMGAKRIYKKRKSERKCMQGKYAGAMESEP
  CVCTEADFDCDYGYERHSNGQCLPAFWFNPSSLSKDCSLGQSYLNSTGYRKVVSNNCTDG
  VREQYTAKPQKCPGKAPRGLRIVTADGKLTAEQGHNVTLMVQLEEGDVQRTLIQVDFGDG
  IAVSYVNLSSMEDGIKHVYQNVGIFRVTVQVDNSLGSDSAVLYLHVTCPLEHVHLSLPFV
  TTKNKEVNATAVLWPSQVGTLTYVWWYGNNTEPLITLEGSISFRFTSEGMNTITVQVSAG
  NAILQDTKTIAVYEEFRSLRLSFSPNLDDYNPDIPEWRRDIGRVIKKSLVEATGVPGQHI
  LVAVLPGLPTTAELFVLPYQDPAGENKRSTDDLEQISELLIHTLNQNSVHFELKPGVRVL
  VHAAHLTAAPLVDLTPTHSGSAMLMLLSVVFVGLAVFVIYKFKRRVALPSPPSPSTQPGD
  SSLRLQRARHATPPSTPKRGSAGAQYAI
• Tissue Specificity: Detected in fetal and infant brain and in fetal retina.

Molecular Interaction Atlas (MIA) of This DOT

11 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Autism	DISV4V1Z	Definitive	Genetic Variation	[1]
Nephropathy	DISXWP4P	Definitive	Genetic Variation	[2]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Biomarker	[3]
Obesity	DIS47Y1K	Strong	Biomarker	[4]
Polycystic ovarian syndrome	DISZ2BNG	Strong	Genetic Variation	[5]
Type-1/2 diabetes	DISIUHAP	Strong	Biomarker	[3]
Colorectal carcinoma	DIS5PYL0	moderate	Biomarker	[6]
Alzheimer disease	DISF8S70	Limited	Biomarker	[3]
Hypoglycemia	DISRCKR7	Limited	Genetic Variation	[7]
Mental disorder	DIS3J5R8	Limited	Biomarker	[8]
Schizophrenia	DISSRV2N	No Known	Unknown	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of VPS10 domain-containing receptor SorCS1 (SORCS1).	[10]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of VPS10 domain-containing receptor SorCS1 (SORCS1).	[11]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of VPS10 domain-containing receptor SorCS1 (SORCS1).	[12]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of VPS10 domain-containing receptor SorCS1 (SORCS1).	[13]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of VPS10 domain-containing receptor SorCS1 (SORCS1).	[14]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of VPS10 domain-containing receptor SorCS1 (SORCS1).	[15]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of VPS10 domain-containing receptor SorCS1 (SORCS1).	[16]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of VPS10 domain-containing receptor SorCS1 (SORCS1).	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of VPS10 domain-containing receptor SorCS1 (SORCS1).	[17]

References

• [1] Individual common variants exert weak effects on the risk for autism spectrum disorders.Hum Mol Genet. 2012 Nov 1;21(21):4781-92. doi: 10.1093/hmg/dds301. Epub 2012 Jul 26.
• [2] SORCS1 contributes to the development of renal disease in rats and humans.Physiol Genomics. 2013 Aug 15;45(16):720-8. doi: 10.1152/physiolgenomics.00089.2013. Epub 2013 Jun 18.
• [3] Unexpected partial correction of metabolic and behavioral phenotypes of Alzheimer's APP/PSEN1 mice by gene targeting of diabetes/Alzheimer's-related Sorcs1.Acta Neuropathol Commun. 2016 Feb 25;4:16. doi: 10.1186/s40478-016-0282-y.
• [4] The genetic basis of obesity-associated type 2 diabetes (diabesity) in polygenic mouse models.Mamm Genome. 2014 Oct;25(9-10):401-12. doi: 10.1007/s00335-014-9514-2. Epub 2014 Apr 22.
• [5] SORCS1 polymorphism and insulin secretion in obese women with polycystic ovary syndrome.Gynecol Endocrinol. 2016;32(5):395-8. doi: 10.3109/09513590.2015.1126818. Epub 2016 Jan 6.
• [6] Decreased expression of SorCS1 in colorectal cancer: An independent predictor of poor prognosis.Neoplasma. 2020 Jan;67(1):119-128. doi: 10.4149/neo_2019_190221N146. Epub 2019 Dec 9.
• [7] A genome-wide association study identifies a novel major locus for glycemic control in type 1 diabetes, as measured by both A1C and glucose.Diabetes. 2010 Feb;59(2):539-49. doi: 10.2337/db09-0653. Epub 2009 Oct 29.
• [8] Structural insights into SorCS2-Nerve Growth Factor complex formation.Nat Commun. 2018 Jul 30;9(1):2979. doi: 10.1038/s41467-018-05405-z.
• [9] 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.
• [10] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [11] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [12] Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration. Arch Toxicol. 2016 Jan;90(1):159-80.
• [13] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [14] 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.
• [15] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [16] Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.
• [17] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.