Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT4J48JJ)

DOT Name Hemoglobin subunit gamma-2 (HBG2)
Synonyms Gamma-2-globin; Hb F Ggamma; Hemoglobin gamma-2 chain; Hemoglobin gamma-G chain
Gene Name HBG2
Related Disease
Acute megakaryoblastic leukemia ( )
Hereditary gingival fibromatosis ( )
Hyperglycemia ( )
Metabolic disorder ( )
Spondylocarpotarsal synostosis syndrome ( )
Acute kidney injury ( )
Alpha thalassemia ( )
Alzheimer disease ( )
B-cell neoplasm ( )
Beta-thalassemia intermedia ( )
Beta-thalassemia major ( )
Cardiac arrest ( )
Cardiac disease ( )
Dyskeratosis congenita ( )
Fanconi's anemia ( )
G6PD deficiency ( )
Granulomatous disease, chronic, X-linked ( )
Hemoglobinopathy ( )
Hemolytic anemia ( )
Heritable pulmonary arterial hypertension ( )
High blood pressure ( )
Immunodeficiency ( )
Leukemia ( )
Melorheostosis ( )
Myeloid leukaemia ( )
Polycythemia ( )
Prostate cancer ( )
Prostate neoplasm ( )
Sweetener ( )
Synovial sarcoma ( )
Thalassemia ( )
Triple negative breast cancer ( )
Acute erythroid leukemia ( )
Type-1/2 diabetes ( )
Hemoglobinopathy Toms River ( )
Hereditary persistence of fetal hemoglobin-beta-thalassemia syndrome ( )
Hereditary persistence of fetal hemoglobin-sickle cell disease syndrome ( )
Anemia ( )
Chronic myelomonocytic leukaemia ( )
Coronary heart disease ( )
Cyanosis, transient neonatal ( )
Hematologic disease ( )
IRIDA syndrome ( )
Malaria ( )
Myelodysplastic syndrome ( )
UniProt ID
HBG2_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
PDB ID
1FDH; 4MQJ; 4MQK; 7QU4
Pfam ID
PF00042
Sequence
MGHFTEEDKATITSLWGKVNVEDAGGETLGRLLVVYPWTQRFFDSFGNLSSASAIMGNPK
VKAHGKKVLTSLGDAIKHLDDLKGTFAQLSELHCDKLHVDPENFKLLGNVLVTVLAIHFG
KEFTPEVQASWQKMVTGVASALSSRYH
Function Gamma chains make up the fetal hemoglobin F, in combination with alpha chains.
Tissue Specificity Red blood cells.
Reactome Pathway
Factors involved in megakaryocyte development and platelet production (R-HSA-983231 )

Molecular Interaction Atlas (MIA) of This DOT

45 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Acute megakaryoblastic leukemia DIS0JX3M Definitive Altered Expression [1]
Hereditary gingival fibromatosis DISN1ML3 Definitive Genetic Variation [2]
Hyperglycemia DIS0BZB5 Definitive Biomarker [3]
Metabolic disorder DIS71G5H Definitive Altered Expression [4]
Spondylocarpotarsal synostosis syndrome DISF9VP3 Definitive Genetic Variation [5]
Acute kidney injury DISXZG0T Strong Biomarker [6]
Alpha thalassemia DIS5XGK0 Strong Genetic Variation [7]
Alzheimer disease DISF8S70 Strong Genetic Variation [8]
B-cell neoplasm DISVY326 Strong Altered Expression [9]
Beta-thalassemia intermedia DISYQ0NL Strong Biomarker [10]
Beta-thalassemia major DISW06BV Strong Biomarker [11]
Cardiac arrest DIS9DIA4 Strong Biomarker [12]
Cardiac disease DISVO1I5 Strong Biomarker [13]
Dyskeratosis congenita DISSXV0K Strong Genetic Variation [14]
Fanconi's anemia DISGW6Q8 Strong Biomarker [14]
G6PD deficiency DISYF1GO Strong Biomarker [15]
Granulomatous disease, chronic, X-linked DISNTTS3 Strong Biomarker [16]
Hemoglobinopathy DISCT4GX Strong Genetic Variation [17]
Hemolytic anemia DIS803XQ Strong Altered Expression [18]
Heritable pulmonary arterial hypertension DISD1Y94 Strong Biomarker [19]
High blood pressure DISY2OHH Strong Biomarker [4]
Immunodeficiency DIS093I0 Strong Biomarker [20]
Leukemia DISNAKFL Strong Altered Expression [21]
Melorheostosis DISIMCL3 Strong Altered Expression [22]
Myeloid leukaemia DISMN944 Strong Biomarker [23]
Polycythemia DIS8B6VW Strong Genetic Variation [24]
Prostate cancer DISF190Y Strong Biomarker [25]
Prostate neoplasm DISHDKGQ Strong Biomarker [25]
Sweetener DISDGALM Strong Genetic Variation [26]
Synovial sarcoma DISEZJS7 Strong Genetic Variation [26]
Thalassemia DIS76XZB Strong Biomarker [17]
Triple negative breast cancer DISAMG6N Strong Biomarker [27]
Acute erythroid leukemia DISZFC1O moderate Altered Expression [28]
Type-1/2 diabetes DISIUHAP moderate Biomarker [29]
Hemoglobinopathy Toms River DISCXLXP Supportive Autosomal dominant [30]
Hereditary persistence of fetal hemoglobin-beta-thalassemia syndrome DISD21FA Supportive Autosomal dominant [31]
Hereditary persistence of fetal hemoglobin-sickle cell disease syndrome DISK38J4 Supportive Autosomal recessive [32]
Anemia DISTVL0C Limited Biomarker [20]
Chronic myelomonocytic leukaemia DISDN5P7 Limited Altered Expression [33]
Coronary heart disease DIS5OIP1 Limited Altered Expression [34]
Cyanosis, transient neonatal DISJ9H0Z Limited Unknown [35]
Hematologic disease DIS9XD9A Limited Biomarker [36]
IRIDA syndrome DISPN8YW Limited Biomarker [17]
Malaria DISQ9Y50 Limited Altered Expression [37]
Myelodysplastic syndrome DISYHNUI Limited Biomarker [38]
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⏷ Show the Full List of 45 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
9 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Ciclosporin DMAZJFX Approved Ciclosporin increases the expression of Hemoglobin subunit gamma-2 (HBG2). [39]
Quercetin DM3NC4M Approved Quercetin decreases the expression of Hemoglobin subunit gamma-2 (HBG2). [40]
Aspirin DM672AH Approved Aspirin increases the expression of Hemoglobin subunit gamma-2 (HBG2). [41]
Testosterone enanthate DMB6871 Approved Testosterone enanthate affects the expression of Hemoglobin subunit gamma-2 (HBG2). [42]
Primaquine DMWQ16I Approved Primaquine increases the expression of Hemoglobin subunit gamma-2 (HBG2). [43]
Resveratrol DM3RWXL Phase 3 Resveratrol increases the expression of Hemoglobin subunit gamma-2 (HBG2). [44]
Tocopherol DMBIJZ6 Phase 2 Tocopherol increases the expression of Hemoglobin subunit gamma-2 (HBG2). [45]
Disulfiram DMCL2OK Phase 2 Trial Disulfiram increases the expression of Hemoglobin subunit gamma-2 (HBG2). [43]
Butanoic acid DMTAJP7 Investigative Butanoic acid increases the expression of Hemoglobin subunit gamma-2 (HBG2). [47]
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⏷ Show the Full List of 9 Drug(s)
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 affects the methylation of Hemoglobin subunit gamma-2 (HBG2). [46]
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References

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3 Physical and Chemical Processes and the Morphofunctional Characteristics of Human Erythrocytes in Hyperglycaemia.Front Physiol. 2017 Aug 30;8:606. doi: 10.3389/fphys.2017.00606. eCollection 2017.
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12 Sickle Cell Trait and Renal Function in Hispanics in the United States: The Northern Manhattan Study.Ethn Dis. 2017 Jan 19;27(1):11-14. doi: 10.18865/ed.27.1.11.
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17 Characterization of deletional and non-deletional alpha globin variants in a large cohort from Spain between 2009 and 2014.Ann Hematol. 2019 Jul;98(7):1537-1545. doi: 10.1007/s00277-019-03696-w. Epub 2019 Apr 25.
18 Orthopaedic Manifestations of Sickle Cell Disease.J Am Acad Orthop Surg. 2018 Feb 1;26(3):94-101. doi: 10.5435/JAAOS-D-16-00255.
19 Familial association of primary pulmonary hypertension and a new low-oxygen affinity beta-chain hemoglobinopathy, Hb Washtenaw.Chest. 1996 Mar;109(3):848-50. doi: 10.1378/chest.109.3.848.
20 Lentiviral Transfer of -Globin with Fusion Gene NUP98-HOXA10HD Expands Hematopoietic Stem Cells and Ameliorates Murine -Thalassemia.Mol Ther. 2017 Mar 1;25(3):593-605. doi: 10.1016/j.ymthe.2017.01.019. Epub 2017 Feb 9.
21 Rapamycin-mediated induction of gamma-globin mRNA accumulation in human erythroid cells.Br J Haematol. 2004 Aug;126(4):612-21. doi: 10.1111/j.1365-2141.2004.05083.x.
22 Comparison of expression of human globin genes transferred into mouse erythroleukemia cells and in transgenic mice.Blood. 1998 Nov 1;92(9):3416-21.
23 5-Aminolevulinate synthase expression and hemoglobin synthesis in a human myelogenous leukemia cell line.J Biochem. 1997 Mar;121(3):487-95. doi: 10.1093/oxfordjournals.jbchem.a021613.
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25 Microarray comparison of prostate tumor gene expression in African-American and Caucasian American males: a pilot project study.Infect Agent Cancer. 2009 Feb 10;4 Suppl 1(Suppl 1):S3. doi: 10.1186/1750-9378-4-S1-S3.
26 Certain mutations observed in the 5' sequences of the G gamma- and A gamma-globin genes of beta S chromosomes are specific for chromosomes with major haplotypes.Acta Haematol. 1991;85(2):79-87. doi: 10.1159/000204862.
27 Probing the interaction between the histone methyltransferase/deacetylase subunit RBBP4/7 and the transcription factor BCL11A in epigenetic complexes.J Biol Chem. 2018 Feb 9;293(6):2125-2136. doi: 10.1074/jbc.M117.811463. Epub 2017 Dec 20.
28 CARM1-mediated methylation of protein arginine methyltransferase 5 represses human -globin gene expression in erythroleukemia cells.J Biol Chem. 2018 Nov 9;293(45):17454-17463. doi: 10.1074/jbc.RA118.004028. Epub 2018 Sep 26.
29 Leukocyte-endothelial interaction is augmented by high glucose concentrations and hyperglycemia in a NF-kB-dependent fashion.J Clin Invest. 1998 May 1;101(9):1905-15. doi: 10.1172/JCI656.
30 A hemoglobin variant associated with neonatal cyanosis and anemia. N Engl J Med. 2011 May 12;364(19):1837-43. doi: 10.1056/NEJMoa1013579.
31 The Hellenic type of nondeletional hereditary persistence of fetal hemoglobin results from a novel mutation (g.-109G>T) in the HBG2 gene promoter. Ann Hematol. 2009 Jun;88(6):549-55. doi: 10.1007/s00277-008-0643-0. Epub 2008 Dec 3.
32 Role of the duplicated CCAAT box region in gamma-globin gene regulation and hereditary persistence of fetal haemoglobin. EMBO J. 1996 Jan 2;15(1):143-9.
33 Epigenetic dysregulation of the erythropoietic transcription factor KLF1 and the -like globin locus in juvenile myelomonocytic leukemia.Epigenetics. 2017 Aug;12(8):715-723. doi: 10.1080/15592294.2017.1356959. Epub 2017 Jul 27.
34 Upward trend of dapsone-induced methemoglobinemia in renal transplant community?"Salim SA. Palabindala V
35 Transient neonatal cyanosis associated with a new Hb F variant: Hb F viseu. J Pediatr Hematol Oncol. 2013 Mar;35(2):e77-80. doi: 10.1097/MPH.0b013e3182667be3.
36 Stability of postmortem methemoglobin: Artifactual changes caused by storage conditions.Forensic Sci Int. 2018 Feb;283:21-28. doi: 10.1016/j.forsciint.2017.12.009. Epub 2017 Dec 8.
37 Primaquine in Plasma and Methemoglobinemia in Patients with Malaria Due to Plasmodium vivax in the Brazilian Amazon Basin.Am J Trop Med Hyg. 2017 May;96(5):1171-1175. doi: 10.4269/ajtmh.15-0368. Epub 2017 Apr 5.
38 In vivo effects of decitabine in myelodysplasia and acute myeloid leukemia: review of cytogenetic and molecular studies.Ann Hematol. 2005 Dec;84 Suppl 1:32-8. doi: 10.1007/s00277-005-0004-1.
39 Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
40 Protein expression profiling identifies molecular targets of quercetin as a major dietary flavonoid in human colon cancer cells. Proteomics. 2004 Jul;4(7):2160-74.
41 Effects of aspirin on metastasis-associated gene expression detected by cDNA microarray. Acta Pharmacol Sin. 2004 Oct;25(10):1327-33.
42 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.
43 Cytochrome P(450)-dependent toxic effects of primaquine on human erythrocytes. Toxicol Appl Pharmacol. 2009 Nov 15;241(1):14-22. doi: 10.1016/j.taap.2009.07.012. Epub 2009 Jul 17.
44 Resveratrol induces human K562 cell apoptosis, erythroid differentiation, and autophagy. Tumour Biol. 2014 Jun;35(6):5381-8. doi: 10.1007/s13277-014-1701-y. Epub 2014 Feb 15.
45 Effect of alpha-tocopherol on peroxidative membrane damage caused by doxorubicin: an in vitro study in human erythrocytes. Indian J Exp Biol. 1989 Mar;27(3):274-8.
46 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.
47 O-Linked N-Acetylglucosamine (O-GlcNAc) Transferase and O-GlcNAcase Interact with Mi2 Protein at the A-Globin Promoter. J Biol Chem. 2016 Jul 22;291(30):15628-40. doi: 10.1074/jbc.M116.721928. Epub 2016 May 26.