Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTV6I4Z0)

• DOT Name: Transmembrane protein 132D (TMEM132D)
• Synonyms: Mature oligodendrocytes transmembrane protein; Mature OL transmembrane protein
• Gene Name: TMEM132D
• Related Disease:
  Acute myelogenous leukaemia
  Breast cancer
  Breast carcinoma
  Colon cancer
  Colon carcinoma
  Kidney cancer
  Melanoma
  Non-small-cell lung cancer
  Renal carcinoma
  T-cell leukaemia
  Acute leukaemia
  Acute lymphocytic leukaemia
  Acute monocytic leukemia
  Acute myelomonocytic leukemia M4
  Advanced cancer
  Anxiety
  B-cell neoplasm
  Bruton-type agammaglobulinemia
  Carcinoma
  Childhood acute lymphoblastic leukemia
  leukaemia
  Leukemia
  Liver cancer
  Lymphoid leukemia
  Major depressive disorder
  Mental disorder
  Neoplasm
  Neuroblastoma
  Panic disorder
  Precancerous condition
  Schizophrenia
  Sjogren syndrome
  T-cell acute lymphoblastic leukaemia
  T-cell lymphoma
  Anxiety disorder
  Small lymphocytic lymphoma
  Burkitt lymphoma
  Intellectual disability
  Small-cell lung cancer
• UniProt ID: T132D_HUMAN
• Pfam ID: PF16070 ; PF15706 ; PF15705
• Sequence:
  MCPSEMGTLWHHWSPVLISLAALFSKVTEGRGILESIQRFSLLPTYLPVTYHINNADVSF
  FLKEANQDIMRNSSLQSRVESFLIYKSRRLPVLNASYGPFSIEQVVPQDLMLPSNPFGFT
  NKFSLNWKLKAHILRDKVYLSRPKVQVLFHIMGRDWDDRSAGEKLPCLRVFAFRETREVR
  GSCRLQGDLGLCVAELELLSSWFSPPTVVAGRRKSVDQPEGTPVELYYTVHPGGERGDCV
  REDARRSNGIRTGHSDIDESGPPLQRIGSIFLYQTHRKPSLRELRLDNSVAIHYIPKTVR
  KGDVLTFPVSISRNSTEDRFTLRAKVKKGVNIIGVRASSPSIWDVKERTDYTGKYAPAVI
  VCQKKAAGSENSADGASYEVMQIDVEVEEPGDLPATQLVTWQVEYPGEITSDLGVSKIYV
  SPKDLIGVVPLAMEAEILNTAILTGKTVAVPVKVVSVEDDGTVTELLESVECRSSDEDVI
  KVSDRCDYVFVNGKEMKGKVNVVVNFTYQHLSSPLEMTVWVPRLPLQIEVSDTELNQIKG
  WRVPIVSSRRPAGDSEEEEDDERRGRGCTLQYQHAMVRVLTQFVAEAAGPGGHLAHLLGS
  DWQVDITELINDFMQVEEPRIAKLQGGQILMGQELGMTTIQILSPLSDTILAEKTITVLD
  EKVTITDLGVQLVTGLSLSLQLSPGSNRAIFATAVAQELLQRPKQEAAISCWVQFSDGSV
  TPLDIYDGKDFSLMATSLDEKVVSIHQDPKFKWPIIAAETEGQGTLVKVEMVISESCQKS
  KRKSVLAVGTANIKVKFGQNDANPNTSDSRHTGAGVHMENNVSDRRPKKPSQEWGSQEGQ
  YYGSSSMGLMEGRGTTTDRSILQKKKGQESLLDDNSHLQTIPSDLTSFPAQVDLPRSNGE
  MDGNDLMQASKGLSDLEIGMYALLGVFCLAILVFLINCVTFALKYRHKQVPFEEQEGMSH
  SHDWVGLSNRTELLENHINFASSQDEQITAIDRGMDFEESKYLLSTNSQKSINGQLFKPL
  GPIIIDGKDQKSEPPTSPTSKRKRVKFTTFTAVSSDDEYPTRNSIVMSSEDDIKWVCQDL
  DPGDCKELHNYMERLHENV
• Function: Regulate neuronals morphology via inhibition of the WAVE regulatory complex (WCR), a complex that controls F-actin cytoskeletal dynamics.
• Tissue Specificity: Expressed in mature oligodendrocytes. Detected in the brain, lung, pancreas and testis . Highly expressed in mature neurons of the adult nervous system .

Molecular Interaction Atlas (MIA) of This DOT

39 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute myelogenous leukaemia	DISCSPTN	Definitive	Genetic Variation	[1]
Breast cancer	DIS7DPX1	Definitive	Genetic Variation	[2]
Breast carcinoma	DIS2UE88	Definitive	Genetic Variation	[2]
Colon cancer	DISVC52G	Definitive	Biomarker	[2]
Colon carcinoma	DISJYKUO	Definitive	Biomarker	[2]
Kidney cancer	DISBIPKM	Definitive	Biomarker	[2]
Melanoma	DIS1RRCY	Definitive	Biomarker	[2]
Non-small-cell lung cancer	DIS5Y6R9	Definitive	Biomarker	[2]
Renal carcinoma	DISER9XT	Definitive	Biomarker	[2]
T-cell leukaemia	DISJ6YIF	Definitive	Altered Expression	[3]
Acute leukaemia	DISDQFDI	Strong	Genetic Variation	[4]
Acute lymphocytic leukaemia	DISPX75S	Strong	Biomarker	[5]
Acute monocytic leukemia	DIS28NEL	Strong	Biomarker	[6]
Acute myelomonocytic leukemia M4	DISRRMV2	Strong	Biomarker	[6]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[7]
Anxiety	DISIJDBA	Strong	Biomarker	[8]
B-cell neoplasm	DISVY326	Strong	Biomarker	[9]
Bruton-type agammaglobulinemia	DISQ5ZYP	Strong	Biomarker	[10]
Carcinoma	DISH9F1N	Strong	Biomarker	[11]
Childhood acute lymphoblastic leukemia	DISJ5D6U	Strong	Biomarker	[12]
leukaemia	DISS7D1V	Strong	Genetic Variation	[13]
Leukemia	DISNAKFL	Strong	Genetic Variation	[13]
Liver cancer	DISDE4BI	Strong	Biomarker	[14]
Lymphoid leukemia	DIS65TYQ	Strong	Biomarker	[15]
Major depressive disorder	DIS4CL3X	Strong	Genetic Variation	[16]
Mental disorder	DIS3J5R8	Strong	Genetic Variation	[17]
Neoplasm	DISZKGEW	Strong	Biomarker	[18]
Neuroblastoma	DISVZBI4	Strong	Genetic Variation	[19]
Panic disorder	DISD3VNY	Strong	Genetic Variation	[8]
Precancerous condition	DISV06FL	Strong	Biomarker	[14]
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[20]
Sjogren syndrome	DISUBX7H	Strong	Genetic Variation	[21]
T-cell acute lymphoblastic leukaemia	DIS17AI2	Strong	Biomarker	[18]
T-cell lymphoma	DISSXRTQ	Strong	Biomarker	[22]
Anxiety disorder	DISBI2BT	moderate	Biomarker	[8]
Small lymphocytic lymphoma	DIS30POX	moderate	Biomarker	[23]
Burkitt lymphoma	DIS9D5XU	Limited	Genetic Variation	[24]
Intellectual disability	DISMBNXP	Limited	Autosomal recessive	[25]
Small-cell lung cancer	DISK3LZD	Limited	Biomarker	[26]

3 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 Transmembrane protein 132D (TMEM132D).	[27]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Transmembrane protein 132D (TMEM132D).	[30]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the methylation of Transmembrane protein 132D (TMEM132D).	[31]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Transmembrane protein 132D (TMEM132D).	[28]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Transmembrane protein 132D (TMEM132D).	[29]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Transmembrane protein 132D (TMEM132D).	[28]

References

• [1] Genome-wide haplotype association study identify the FGFR2 gene as a risk gene for acute myeloid leukemia.Oncotarget. 2017 Jan 31;8(5):7891-7899. doi: 10.18632/oncotarget.13631.
• [2] Design, synthesis and evaluation of novel sulfonamides as potential anticancer agents.Comput Biol Chem. 2018 Jun;74:294-303. doi: 10.1016/j.compbiolchem.2018.04.006. Epub 2018 Apr 10.
• [3] SAR study of 5-alkynyl substituted quinazolin-4(3H)-ones as phosphoinositide 3-kinase delta (PI3K) inhibitors.Eur J Med Chem. 2017 Jan 5;125:1156-1171. doi: 10.1016/j.ejmech.2016.11.014. Epub 2016 Nov 9.
• [4] Expression of BRCA1 and BRCA2 in male breast cancers and gynecomastias.Anticancer Res. 2003 Jan-Feb;23(1B):661-7.
• [5] Time dependent response of daunorubicin on cytotoxicity, cell cycle and DNA repair in acute lymphoblastic leukaemia.BMC Cancer. 2019 Feb 27;19(1):179. doi: 10.1186/s12885-019-5377-y.
• [6] The cytotoxic potential of interleukin-15-stimulated cytokine-induced killer cells against leukemia cells.Cytotherapy. 2012 Jan;14(1):91-103. doi: 10.3109/14653249.2011.613931. Epub 2011 Oct 6.
• [7] Vernodalidimer L, a sesquiterpene lactone dimer from Vernonia extensa and anti-tumor effects of vernodalin, vernolepin, and vernolide on HepG2 liver cancer cells.Bioorg Chem. 2019 Nov;92:103197. doi: 10.1016/j.bioorg.2019.103197. Epub 2019 Aug 16.
• [8] Polymorphism in Tmem132d regulates expression and anxiety-related behavior through binding of RNA polymerase II complex.Transl Psychiatry. 2018 Jan 10;8(1):1. doi: 10.1038/s41398-017-0025-2.
• [9] A developed antibody-drug conjugate rituximab-vcMMAE shows a potent cytotoxic activity against CD20-positive cell line.Artif Cells Nanomed Biotechnol. 2018;46(sup2):1-8. doi: 10.1080/21691401.2018.1449119. Epub 2018 Mar 9.
• [10] Cellular origins of serum complement receptor type 2 in normal individuals and in hypogammaglobulinaemia.Clin Exp Immunol. 1991 Apr;84(1):16-22. doi: 10.1111/j.1365-2249.1991.tb08117.x.
• [11] Lack of rearranged Tpr-met mRNA expression in human gastric cancer cell lines and gastric mucosa and carcinoma.Anticancer Res. 1996 Sep-Oct;16(5A):2881-4.
• [12] Antiproliferative Effect of Gaillardin from Inula oculus-christi in Human Leukemic Cells.Nutr Cancer. 2020;72(6):1043-1056. doi: 10.1080/01635581.2019.1665188. Epub 2019 Sep 23.
• [13] Synthesis of New Derivatives of Benzofuran as Potential Anticancer Agents.Molecules. 2019 Apr 18;24(8):1529. doi: 10.3390/molecules24081529.
• [14] Multiple genes exhibit phenobarbital-induced constitutive active/androstane receptor-mediated DNA methylation changes during liver tumorigenesis and in liver tumors.Toxicol Sci. 2009 Apr;108(2):273-89. doi: 10.1093/toxsci/kfp031. Epub 2009 Feb 20.
• [15] Long Chain Alkyl Esters of Hydroxycinnamic Acids as Promising Anticancer Agents: Selective Induction of Apoptosis in Cancer Cells.J Agric Food Chem. 2017 Aug 23;65(33):7228-7239. doi: 10.1021/acs.jafc.7b01388. Epub 2017 Aug 8.
• [16] Association of TMEM132D, COMT, and GABRA6 genotypes with cingulate, frontal cortex and hippocampal emotional processing in panic and major depressive disorder.Int J Psychiatry Clin Pract. 2015;19(3):192-200. doi: 10.3109/13651501.2015.1043133. Epub 2015 May 14.
• [17] Genome-wide significant loci for addiction and anxiety.Eur Psychiatry. 2016 Aug;36:47-54. doi: 10.1016/j.eurpsy.2016.03.004. Epub 2016 Jun 16.
• [18] CD47 agonist peptide PKHB1 induces immunogenic cell death in T-cell acute lymphoblastic leukemia cells.Cancer Sci. 2019 Jan;110(1):256-268. doi: 10.1111/cas.13885. Epub 2018 Dec 14.
• [19] Platelet-activating factor activates HIV promoter in transfected SH-SY5Y neuroblastoma cells and MOLT-4 T lymphocytes.J Mol Neurosci. 1990;2(2):79-84. doi: 10.1007/BF02876914.
• [20] Genome-wide association study identifies five new schizophrenia loci.Nat Genet. 2011 Sep 18;43(10):969-76. doi: 10.1038/ng.940.
• [21] Initial human T-cell leukemia virus type 1 infection of the salivary gland epithelial cells requires a biofilm-like structure.Virus Res. 2019 Aug;269:197643. doi: 10.1016/j.virusres.2019.197643. Epub 2019 Jun 21.
• [22] Leptin and its receptor in glucose metabolism of T-cell lymphoma.Oncol Lett. 2018 Nov;16(5):5838-5846. doi: 10.3892/ol.2018.9356. Epub 2018 Aug 23.
• [23] A new disulfide-linked dimer of a single-chain antibody fragment against human CD47 induces apoptosis in lymphoid malignant cells via the hypoxia inducible factor-1 pathway.Cancer Sci. 2011 Jun;102(6):1208-15. doi: 10.1111/j.1349-7006.2011.01925.x. Epub 2011 May 3.
• [24] Biallelic deletion and loss of expression analysis of genes at FRA2G common fragile site in tumor-derived cell lines.Cancer Genet Cytogenet. 2005 Sep;161(2):181-6. doi: 10.1016/j.cancergencyto.2005.01.018.
• [25] 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.
• [26] Expression and clinical significance of genes frequently mutated in small cell lung cancers defined by whole exome/RNA sequencing.Carcinogenesis. 2015 Jun;36(6):616-21. doi: 10.1093/carcin/bgv026. Epub 2015 Apr 11.
• [27] 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.
• [28] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [29] 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.
• [30] 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.
• [31] 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.