Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT3D9SA4)

• DOT Name: Pro-MCH (PMCH)
• Gene Name: PMCH
• Related Disease:
  Thalassemia
  Adrenal gland neoplasm
  Alcoholic hepatitis
  Alpha thalassemia
  Androgen insensitivity syndrome
  Anemia
  Attention deficit hyperactivity disorder
  Beta thalassemia
  Beta-thalassemia major
  Bipolar disorder
  Bone osteosarcoma
  Depression
  Hematologic disease
  Hemoglobin H disease
  Hypochromic microcytic anemia
  Mantle cell lymphoma
  Neuroblastoma
  Non-alcoholic fatty liver disease
  Non-small-cell lung cancer
  Obesity
  Osteosarcoma
  Pheochromocytoma
  Schizophrenia
  Sweetener
  Synovial sarcoma
  Mood disorder
  Asthma
  Bronchiolitis
  Follicular lymphoma
• UniProt ID: MCH_HUMAN
• Pfam ID: PF05824
• Sequence:
  MAKMNLSSYILILTFSLFSQGILLSASKSIRNLDDDMVFNTFRLGKGFQKEDTAEKSVIA
  PSLEQYKNDESSFMNEEENKVSKNTGSKHNFLNHGLPLNLAIKPYLALKGSVAFPAENGV
  QNTESTQEKREIGDEENSAKFPIGRRDFDMLRCMLGRVYRPCWQV
• Function: MCH may act as a neurotransmitter or neuromodulator in a broad array of neuronal functions directed toward the regulation of goal-directed behavior, such as food intake, and general arousal. May also have a role in spermatocyte differentiation.
• Tissue Specificity: Predominantly expressed in lateral hypothalamus, also detected in pallidum, neocortex and cerebellum. Also found in thymus, brown adipose tissue, duodenum and testis (spermatogonia, early spermatocytes and Sertoli cells). No expression in peripheral blood. In brain exclusively mature MCH and NEI peptides are present. In peripheral tissues a large product, encompassing the NEI and MCH domains of the precursor, is found predominantly.
• KEGG Pathway: Neuroactive ligand-receptor interaction (hsa04080)
• Reactome Pathway:
  G alpha (q) signalling events (R-HSA-416476)
  G alpha (i) signalling events (R-HSA-418594)
  Peptide ligand-binding receptors (R-HSA-375276)

Molecular Interaction Atlas (MIA) of This DOT

29 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Thalassemia	DIS76XZB	Definitive	Genetic Variation	[1]
Adrenal gland neoplasm	DISFK7RF	Strong	Altered Expression	[2]
Alcoholic hepatitis	DISA7SH0	Strong	Altered Expression	[3]
Alpha thalassemia	DIS5XGK0	Strong	Altered Expression	[4]
Androgen insensitivity syndrome	DISUZBBO	Strong	Altered Expression	[5]
Anemia	DISTVL0C	Strong	Biomarker	[6]
Attention deficit hyperactivity disorder	DISL8MX9	Strong	Biomarker	[7]
Beta thalassemia	DIS5RCQK	Strong	Genetic Variation	[8]
Beta-thalassemia major	DISW06BV	Strong	Biomarker	[9]
Bipolar disorder	DISAM7J2	Strong	Biomarker	[10]
Bone osteosarcoma	DIST1004	Strong	Altered Expression	[11]
Depression	DIS3XJ69	Strong	Genetic Variation	[12]
Hematologic disease	DIS9XD9A	Strong	Altered Expression	[13]
Hemoglobin H disease	DISHFWO5	Strong	Biomarker	[14]
Hypochromic microcytic anemia	DIS0RMTQ	Strong	Biomarker	[15]
Mantle cell lymphoma	DISFREOV	Strong	Genetic Variation	[16]
Neuroblastoma	DISVZBI4	Strong	Altered Expression	[2]
Non-alcoholic fatty liver disease	DISDG1NL	Strong	Biomarker	[17]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[18]
Obesity	DIS47Y1K	Strong	Biomarker	[19]
Osteosarcoma	DISLQ7E2	Strong	Altered Expression	[11]
Pheochromocytoma	DIS56IFV	Strong	Altered Expression	[2]
Schizophrenia	DISSRV2N	Strong	Biomarker	[20]
Sweetener	DISDGALM	Strong	Altered Expression	[21]
Synovial sarcoma	DISEZJS7	Strong	Altered Expression	[21]
Mood disorder	DISLVMWO	moderate	Biomarker	[22]
Asthma	DISW9QNS	Limited	Biomarker	[23]
Bronchiolitis	DISEE9BG	Limited	Biomarker	[24]
Follicular lymphoma	DISVEUR6	Limited	Altered Expression	[25]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Pro-MCH (PMCH).	[26]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Pro-MCH (PMCH).	[26]

References

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• [2] Expression of melanin-concentrating hormone receptor messenger ribonucleic acid in tumor tissues of pheochromocytoma, ganglioneuroblastoma, and neuroblastoma.J Clin Endocrinol Metab. 2001 Jan;86(1):369-74. doi: 10.1210/jcem.86.1.7158.
• [3] 4-Methylcoumarin-[5,6-g]-hesperetin attenuates inflammatory responses in alcoholic hepatitis through PPAR- activation.Toxicology. 2019 Jun 1;421:9-21. doi: 10.1016/j.tox.2019.04.004. Epub 2019 Apr 3.
• [4] Fetal hemoglobin and alpha thalassemia modulate the phenotypic expression of HbSD-Punjab.Int J Lab Hematol. 2014 Aug;36(4):444-50. doi: 10.1111/ijlh.12165. Epub 2013 Nov 19.
• [5] Abnormal red blood cell indices increase the risk of arterial ischemic stroke in children.J Clin Neurosci. 2019 Apr;62:117-120. doi: 10.1016/j.jocn.2018.12.005. Epub 2018 Dec 19.
• [6] Alpha-thalassaemia.Orphanet J Rare Dis. 2010 May 28;5:13. doi: 10.1186/1750-1172-5-13.
• [7] A study on association of iron deficiency with attention deficit hyperactivity disorder in a tertiary care center.Indian J Psychiatry. 2018 Jan-Mar;60(1):131-134. doi: 10.4103/psychiatry.IndianJPsychiatry_197_17.
• [8] Genotype and phenotype characterizations in a large cohort of -thalassemia heterozygote with different forms of -thalassemia in northeast Thailand.Blood Cells Mol Dis. 2011 Aug 15;47(2):120-4. doi: 10.1016/j.bcmd.2011.05.003. Epub 2011 Jun 12.
• [9] Clinical and haematological evaluation of beta thalassaemia intermedia characterised by unusually low Hb F and increased Hb A2: beta thalassaemia intermedia II.J Med Genet. 1985 Jun;22(3):213-21. doi: 10.1136/jmg.22.3.213.
• [10] Linkage analysis between manic depressive illness and the region on chromosome 12q involved in Darier's disease.Psychiatr Genet. 1994 Winter;4(4):195-200. doi: 10.1097/00041444-199400440-00001.
• [11] Divergent in vitro effects of recombinant interferons on human osteosarcoma cells.Bone. 1990;11(4):247-51. doi: 10.1016/8756-3282(90)90077-c.
• [12] Melanin-concentrating hormone in the Locus Coeruleus aggravates helpless behavior in stressed rats.Behav Brain Res. 2019 Nov 18;374:112120. doi: 10.1016/j.bbr.2019.112120. Epub 2019 Jul 31.
• [13] Excessive fluoride consumption increases haematological alteration in subjects with iron deficiency, thalassaemia, and glucose-6-phosphate dehydrogenase (G-6-PD) deficiency.Environ Geochem Health. 2017 Aug;39(4):751-758. doi: 10.1007/s10653-016-9845-x. Epub 2016 Jun 18.
• [14] Iranian patients with hemoglobin H disease: genotype-phenotype correlation.Mol Biol Rep. 2019 Oct;46(5):5041-5048. doi: 10.1007/s11033-019-04955-9. Epub 2019 Jul 4.
• [15] A case of ectopic pancreas in the ileum presenting as obscure gastrointestinal bleeding and abdominal pain.BMC Gastroenterol. 2019 Apr 17;19(1):57. doi: 10.1186/s12876-019-0971-7.
• [16] Mantle Cell Lymphoma Involving Skin: A Clinicopathologic Study of 37 Cases.Am J Surg Pathol. 2019 Oct;43(10):1421-1428. doi: 10.1097/PAS.0000000000001312.
• [17] Decreased Physical Working Capacity in Adolescents With Nonalcoholic Fatty Liver Disease Associates With Reduced Iron Availability.Clin Gastroenterol Hepatol. 2020 Jun;18(7):1584-1591. doi: 10.1016/j.cgh.2019.10.017. Epub 2019 Oct 16.
• [18] Antitumor activity of dual blockade of PD-L1 and MEK in NSCLC patients derived three-dimensional spheroid cultures.J Exp Clin Cancer Res. 2019 Jun 13;38(1):253. doi: 10.1186/s13046-019-1257-1.
• [19] Association between lifestyle and hematological parameters: A study of Chinese male steelworkers.J Clin Lab Anal. 2019 Sep;33(7):e22946. doi: 10.1002/jcla.22946. Epub 2019 Jun 26.
• [20] Melanin Concentrating Hormone Signaling Deficits in Schizophrenia: Association With Memory and Social Impairments and Abnormal Sensorimotor Gating.Int J Neuropsychopharmacol. 2020 Mar 10;23(1):53-65. doi: 10.1093/ijnp/pyz051.
• [21] A comparison of sickle cell syndromes in northern Greece.Br J Haematol. 1991 Mar;77(3):386-91. doi: 10.1111/j.1365-2141.1991.tb08589.x.
• [22] A study of the involvement of melanin-concentrating hormone receptor 1 (MCHR1) in murine models of depression.Biol Psychiatry. 2007 Jan 15;61(2):174-80. doi: 10.1016/j.biopsych.2006.03.076. Epub 2006 Aug 24.
• [23] Exhaled nitric oxide can't replace the methacholine challenge in suspected pediatric asthma.Respir Med. 2019 Oct;157:21-25. doi: 10.1016/j.rmed.2019.08.008. Epub 2019 Aug 27.
• [24] Increased incidence of bronchial reactivity in children with a history of bronchiolitis.J Pediatr. 1981 Apr;98(4):551-5. doi: 10.1016/s0022-3476(81)80758-5.
• [25] Follicular lymphoma cells induce changes in T-cell gene expression and function: potential impact on survival and risk of transformation.J Clin Oncol. 2013 Jul 20;31(21):2654-61. doi: 10.1200/JCO.2012.44.2137. Epub 2013 Jun 17.
• [26] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.