Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTT30ZON)

• DOT Name: Synaptosomal-associated protein 29 (SNAP29)
• Synonyms: SNAP-29; Soluble 29 kDa NSF attachment protein; Vesicle-membrane fusion protein SNAP-29
• Gene Name: SNAP29
• Related Disease:
  Retinitis pigmentosa
  Spinocerebellar ataxia type 3
  CEDNIK syndrome
  Epithelial ovarian cancer
  Hepatitis B virus infection
  Neurocutaneous syndrome
  Non-syndromic ichthyosis
  Obesity
  Ovarian cancer
  Ovarian neoplasm
  Palmoplantar keratosis
  Sturge-Weber syndrome
  Velocardiofacial syndrome
  Isolated congenital microcephaly
  Bacterial infection
  Schizophrenia
• UniProt ID: SNP29_HUMAN
• PDB ID: 4WY4; 7BV6
• Sequence:
  MSAYPKSYNPFDDDGEDEGARPAPWRDARDLPDGPDAPADRQQYLRQEVLRRAEATAAST
  SRSLALMYESEKVGVASSEELARQRGVLERTEKMVDKMDQDLKISQKHINSIKSVFGGLV
  NYFKSKPVETPPEQNGTLTSQPNNRLKEAISTSKEQEAKYQASHPNLRKLDDTDPVPRGA
  GSAMSTDAYPKNPHLRAYHQKIDSNLDELSMGLGRLKDIALGMQTEIEEQDDILDRLTTK
  VDKLDVNIKSTERKVRQL
• Function: SNAREs, soluble N-ethylmaleimide-sensitive factor-attachment protein receptors, are essential proteins for fusion of cellular membranes. SNAREs localized on opposing membranes assemble to form a trans-SNARE complex, an extended, parallel four alpha-helical bundle that drives membrane fusion. SNAP29 is a SNARE involved in autophagy through the direct control of autophagosome membrane fusion with the lysososome membrane. Also plays a role in ciliogenesis by regulating membrane fusions.
• Tissue Specificity: Found in brain, heart, kidney, liver, lung, placenta, skeletal muscle, spleen and pancreas.
• KEGG Pathway:
  S.RE interactions in vesicular transport (hsa04130)
  Autophagy - animal (hsa04140)
• Reactome Pathway:
  Intra-Golgi traffic (R-HSA-6811438)
  Neutrophil degranulation (R-HSA-6798695)

Molecular Interaction Atlas (MIA) of This DOT

16 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Retinitis pigmentosa	DISCGPY8	Definitive	Altered Expression	[1]
Spinocerebellar ataxia type 3	DISQBQID	Definitive	Biomarker	[1]
CEDNIK syndrome	DIS8AB7V	Strong	Autosomal recessive	[2]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[3]
Hepatitis B virus infection	DISLQ2XY	Strong	Biomarker	[4]
Neurocutaneous syndrome	DISNC82H	Strong	Genetic Variation	[5]
Non-syndromic ichthyosis	DISZ9QBQ	Strong	Genetic Variation	[6]
Obesity	DIS47Y1K	Strong	Biomarker	[7]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[3]
Ovarian neoplasm	DISEAFTY	Strong	Biomarker	[3]
Palmoplantar keratosis	DISYQGFB	Strong	Genetic Variation	[5]
Sturge-Weber syndrome	DISL0WMD	Strong	Genetic Variation	[5]
Velocardiofacial syndrome	DISOSBTY	Strong	Biomarker	[8]
Isolated congenital microcephaly	DISUXHZ6	moderate	Biomarker	[9]
Bacterial infection	DIS5QJ9S	Limited	Biomarker	[10]
Schizophrenia	DISSRV2N	Limited	Biomarker	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Synaptosomal-associated protein 29 (SNAP29).	[12]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Synaptosomal-associated protein 29 (SNAP29).	[13]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Synaptosomal-associated protein 29 (SNAP29).	[14]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Synaptosomal-associated protein 29 (SNAP29).	[15]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil increases the expression of Synaptosomal-associated protein 29 (SNAP29).	[14]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of Synaptosomal-associated protein 29 (SNAP29).	[16]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate increases the expression of Synaptosomal-associated protein 29 (SNAP29).	[17]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Synaptosomal-associated protein 29 (SNAP29).	[18]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Synaptosomal-associated protein 29 (SNAP29).	[19]

References

• [1] Diverse mechanisms of autophagy dysregulation and their therapeutic implications: does the shoe fit?.Autophagy. 2019 Feb;15(2):368-371. doi: 10.1080/15548627.2018.1509609. Epub 2018 Sep 13.
• [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] Down-regulation of OGT promotes cisplatin resistance by inducing autophagy in ovarian cancer.Theranostics. 2018 Oct 6;8(19):5200-5212. doi: 10.7150/thno.27806. eCollection 2018.
• [4] Synaptosomal-associated protein 29 is required for the autophagic degradation of hepatitis B virus.FASEB J. 2019 May;33(5):6023-6034. doi: 10.1096/fj.201801995RR. Epub 2019 Feb 11.
• [5] A mutation in SNAP29, coding for a SNARE protein involved in intracellular trafficking, causes a novel neurocutaneous syndrome characterized by cerebral dysgenesis, neuropathy, ichthyosis, and palmoplantar keratoderma. Am J Hum Genet. 2005 Aug;77(2):242-51. doi: 10.1086/432556. Epub 2005 Jun 20.
• [6] CEDNIK syndrome results from loss-of-function mutations in SNAP29. Br J Dermatol. 2011 Mar;164(3):610-6. doi: 10.1111/j.1365-2133.2010.10133.x. Epub 2011 Feb 17.
• [7] Identification of genetic loci associated with different responses to high-fat diet-induced obesity in C57BL/6N and C57BL/6J substrains.Physiol Genomics. 2014 Jun 1;46(11):377-84. doi: 10.1152/physiolgenomics.00014.2014. Epub 2014 Apr 1.
• [8] Polymorphism in SNAP29 gene promoter region associated with schizophrenia.Mol Psychiatry. 2001 Mar;6(2):193-201. doi: 10.1038/sj.mp.4000825.
• [9] A genetic model of CEDNIK syndrome in zebrafish highlights the role of the SNARE protein Snap29 in neuromotor and epidermal development.Sci Rep. 2019 Feb 4;9(1):1211. doi: 10.1038/s41598-018-37780-4.
• [10] A novel function for SNAP29 (synaptosomal-associated protein of 29 kDa) in mast cell phagocytosis.PLoS One. 2012;7(11):e49886. doi: 10.1371/journal.pone.0049886. Epub 2012 Nov 21.
• [11] Synaptic and Gene Regulatory Mechanisms in Schizophrenia, Autism, and 22q11.2 Copy Number Variant-Mediated Risk for Neuropsychiatric Disorders.Biol Psychiatry. 2020 Jan 15;87(2):150-163. doi: 10.1016/j.biopsych.2019.06.029. Epub 2019 Jul 11.
• [12] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [13] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [14] Analysis of the in vitro synergistic effect of 5-fluorouracil and cisplatin on cervical carcinoma cells. Int J Gynecol Cancer. 2006 May-Jun;16(3):1321-9.
• [15] 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.
• [16] Transcriptional profiling of testosterone-regulated genes in the skeletal muscle of human immunodeficiency virus-infected men experiencing weight loss. J Clin Endocrinol Metab. 2007 Jul;92(7):2793-802. doi: 10.1210/jc.2006-2722. Epub 2007 Apr 17.
• [17] Application of the adverse outcome pathway concept for investigating developmental neurotoxicity potential of Chinese herbal medicines by using human neural progenitor cells in vitro. Cell Biol Toxicol. 2023 Feb;39(1):319-343. doi: 10.1007/s10565-022-09730-4. Epub 2022 Jun 15.
• [18] Isobaric tags for relative and absolute quantitation-based proteomics analysis of the effect of ginger oil on bisphenol A-induced breast cancer cell proliferation. Oncol Lett. 2021 Feb;21(2):101. doi: 10.3892/ol.2020.12362. Epub 2020 Dec 8.
• [19] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.