Details of Drug Off-Target (DOT)

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

• DOT Name: Maspardin (SPG21)
• Synonyms: Acid cluster protein 33; Spastic paraplegia 21 autosomal recessive Mast syndrome protein; Spastic paraplegia 21 protein
• Gene Name: SPG21
• Related Disease:
  Alcohol use disorder
  Advanced cancer
  Alcohol dependence
  Cystic fibrosis
  Gonorrhea
  Hereditary spastic paraplegia
  Mast syndrome
  Prostate cancer
  Prostate carcinoma
  Breast cancer
  Breast carcinoma
  Autism
  Dementia
  Immune system disorder
  Paraplegia
• UniProt ID: SPG21_HUMAN
• Pfam ID: PF00561
• Sequence:
  MGEIKVSPDYNWFRGTVPLKKIIVDDDDSKIWSLYDAGPRSIRCPLIFLPPVSGTADVFF
  RQILALTGWGYRVIALQYPVYWDHLEFCDGFRKLLDHLQLDKVHLFGASLGGFLAQKFAE
  YTHKSPRVHSLILCNSFSDTSIFNQTWTANSFWLMPAFMLKKIVLGNFSSGPVDPMMADA
  IDFMVDRLESLGQSELASRLTLNCQNSYVEPHKIRDIPVTIMDVFDQSALSTEAKEEMYK
  LYPNARRAHLKTGGNFPYLCRSAEVNLYVQIHLLQFHGTKYAAIDPSMVSAEELEVQKGS
  LGISQEEQ
• Function: May play a role as a negative regulatory factor in CD4-dependent T-cell activation.
• Tissue Specificity: Expressed in all tissues tested, including heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas. Expressed in J.CaM1.6, HuT 78 and HeLa cell lines (at protein level).
• KEGG Pathway: Endocytosis (hsa04144)

Molecular Interaction Atlas (MIA) of This DOT

15 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Alcohol use disorder	DISMB65Y	Definitive	Biomarker	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
Alcohol dependence	DIS4ZSCO	Strong	Biomarker	[3]
Cystic fibrosis	DIS2OK1Q	Strong	Genetic Variation	[4]
Gonorrhea	DISQ5AO6	Strong	Biomarker	[5]
Hereditary spastic paraplegia	DISGZQV1	Strong	Genetic Variation	[6]
Mast syndrome	DIS78QKW	Strong	Autosomal recessive	[7]
Prostate cancer	DISF190Y	Strong	Biomarker	[8]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[8]
Breast cancer	DIS7DPX1	moderate	Genetic Variation	[9]
Breast carcinoma	DIS2UE88	moderate	Genetic Variation	[9]
Autism	DISV4V1Z	Limited	Biomarker	[10]
Dementia	DISXL1WY	Limited	Genetic Variation	[11]
Immune system disorder	DISAEGPH	Limited	Genetic Variation	[10]
Paraplegia	DISSKWBI	Limited	Genetic Variation	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Maspardin (SPG21).	[12]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Maspardin (SPG21).	[13]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Maspardin (SPG21).	[14]
Fluoxetine	DM3PD2C	Approved	Fluoxetine increases the expression of Maspardin (SPG21).	[15]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Maspardin (SPG21).	[17]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Maspardin (SPG21).	[18]

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 decreases the methylation of Maspardin (SPG21).	[16]

References

• [1] The influence of gender on selected risk factors for chronic non-communicable diseases in patients hospitalized in surgical wards: A cross-sectional study.Adv Clin Exp Med. 2018 Apr;27(4):515-523. doi: 10.17219/acem/68741.
• [2] Evaluation of a telehealth psychological support intervention for people with primary brain tumour and their family members: Study protocol for a randomised controlled trial.Eur J Cancer Care (Engl). 2019 Jul;28(4):e13132. doi: 10.1111/ecc.13132. Epub 2019 Jul 10.
• [3] Occurrence of alcohol addiction in the adult population living in rural areas.Ann Agric Environ Med. 2018 Dec 20;25(4):659-664. doi: 10.26444/aaem/80796. Epub 2018 Jan 9.
• [4] Epidemiology of Burkholderia cepacia complex colonisation in cystic fibrosis patients.Eur Respir J. 2004 Jun;23(6):851-6. doi: 10.1183/09031936.04.00118804.
• [5] Increase in Gonorrhea Incidence Associated With Enhanced Partner Notification Strategy.Sex Transm Dis. 2019 Nov;46(11):706-712. doi: 10.1097/OLQ.0000000000001060.
• [6] Hereditary spastic paraplegias with autosomal dominant, recessive, X-linked, or maternal trait of inheritance.J Neurol Sci. 2012 Jul 15;318(1-2):1-18. doi: 10.1016/j.jns.2012.03.025. Epub 2012 May 1.
• [7] Cloning of ACP33 as a novel intracellular ligand of CD4. J Biol Chem. 2001 Mar 23;276(12):9123-32. doi: 10.1074/jbc.M009270200. Epub 2000 Dec 11.
• [8] Entering an era of radiogenomics in prostate cancer risk stratification.Transl Androl Urol. 2018 Sep;7(Suppl 4):S443-S452. doi: 10.21037/tau.2018.07.04.
• [9] MAST2 and NOTCH1 translocations in breast carcinoma and associated pre-invasive lesions.Hum Pathol. 2013 Dec;44(12):2837-44. doi: 10.1016/j.humpath.2013.08.001. Epub 2013 Oct 18.
• [10] Mathematical Models for Possible Roles of Oxytocin and Oxytocin Receptors in Autism.Comput Math Methods Med. 2019 Nov 11;2019:7308197. doi: 10.1155/2019/7308197. eCollection 2019.
• [11] Maspardin is mutated in mast syndrome, a complicated form of hereditary spastic paraplegia associated with dementia.Am J Hum Genet. 2003 Nov;73(5):1147-56. doi: 10.1086/379522. Epub 2003 Oct 16.
• [12] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [13] 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.
• [14] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [15] Screening autism-associated environmental factors in differentiating human neural progenitors with fractional factorial design-based transcriptomics. Sci Rep. 2023 Jun 29;13(1):10519. doi: 10.1038/s41598-023-37488-0.
• [16] 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.
• [17] 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.
• [18] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.