Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTO7TNDD)

• DOT Name: GDH/6PGL endoplasmic bifunctional protein (H6PD)
• Gene Name: H6PD
• Related Disease:
  B-cell neoplasm
  Central diabetes insipidus
  Hyperinsulinemic hypoglycemia
  Leishmaniasis
  Multiple sclerosis
  Primary hyperoxaluria
  Advanced cancer
  Arteriosclerosis
  Atherosclerosis
  Beta thalassemia
  Beta-thalassemia major
  Breast neoplasm
  Cardiovascular disease
  Colorectal neoplasm
  Cone-rod dystrophy 2
  Cortisone reductase deficiency 1
  Fatty liver disease
  Giardiasis
  Hypoglycemia
  Intrahepatic cholangiocarcinoma
  Obesity
  Fetal growth restriction
  Type-1/2 diabetes
  Cortisone reductase deficiency
  Neoplasm
  Breast cancer
  Breast carcinoma
  Hemolytic anemia
  Hyperinsulinemia
  Malaria
• UniProt ID: G6PE_HUMAN
• PDB ID: 8EM2
• EC Number: 1.1.1.363; 1.1.1.47; 3.1.1.31
• Pfam ID: PF02781 ; PF00479 ; PF01182
• Sequence:
  MWNMLIVAMCLALLGCLQAQELQGHVSIILLGATGDLAKKYLWQGLFQLYLDEAGRGHSF
  SFHGAALTAPKQGQELMAKALESLSCPKDMAPSHCAEHKDQFLQLSQYRQLKTAEDYQAL
  NKDIEAQLQHAGLREAGRIFYFSVPPFAYEDIARNINSSCRPGPGAWLRVVLEKPFGHDH
  FSAQQLATELGTFFQEEEMYRVDHYLGKQAVAQILPFRDQNRKALDGLWNRHHVERVEII
  MKETVDAEGRTSFYEEYGVIRDVLQNHLTEVLTLVAMELPHNVSSAEAVLRHKLQVFQAL
  RGLQRGSAVVGQYQSYSEQVRRELQKPDSFHSLTPTFAAVLVHIDNLRWEGVPFILMSGK
  ALDERVGYARILFKNQACCVQSEKHWAAAQSQCLPRQLVFHIGHGDLGSPAVLVSRNLFR
  PSLPSSWKEMEGPPGLRLFGSPLSDYYAYSPVRERDAHSVLLSHIFHGRKNFFITTENLL
  ASWNFWTPLLESLAHKAPRLYPGGAENGRLLDFEFSSGRLFFSQQQPEQLVPGPGPAPMP
  SDFQVLRAKYRESPLVSAWSEELISKLANDIEATAVRAVRRFGQFHLALSGGSSPVALFQ
  QLATAHYGFPWAHTHLWLVDERCVPLSDPESNFQGLQAHLLQHVRIPYYNIHPMPVHLQQ
  RLCAEEDQGAQIYAREISALVANSSFDLVLLGMGADGHTASLFPQSPTGLDGEQLVVLTT
  SPSQPHRRMSLSLPLINRAKKVAVLVMGRMKREITTLVSRVGHEPKKWPISGVLPHSGQL
  VWYMDYDAFLG
• Function: Bifunctional enzyme localized in the lumen of the endoplasmic reticulum that catalyzes the first two steps of the oxidative branch of the pentose phosphate pathway/shunt, an alternative to glycolysis and a major source of reducing power and metabolic intermediates for biosynthetic processes. Has a hexose-6-phosphate dehydrogenase activity, with broad substrate specificity compared to glucose-6-phosphate 1-dehydrogenase/G6PD, and catalyzes the first step of the pentose phosphate pathway. In addition, acts as a 6-phosphogluconolactonase and catalyzes the second step of the pentose phosphate pathway. May have a dehydrogenase activity for alternative substrates including glucosamine 6-phosphate and glucose 6-sulfate. The main function of this enzyme is to provide reducing equivalents such as NADPH to maintain the adequate levels of reductive cofactors in the oxidizing environment of the endoplasmic reticulum. By producing NADPH that is needed by reductases of the lumen of the endoplasmic reticulum like corticosteroid 11-beta-dehydrogenase isozyme 1/HSD11B1, indirectly regulates their activity.
• Tissue Specificity: Present in most tissues examined, strongest in liver.
• KEGG Pathway:
  Pentose phosphate pathway (hsa00030)
  Metabolic pathways (hsa01100)
  Carbon metabolism (hsa01200)
• BioCyc Pathway: MetaCyc:HS00614-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

30 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
B-cell neoplasm	DISVY326	Definitive	Altered Expression	[1]
Central diabetes insipidus	DISJ4P9O	Definitive	Biomarker	[2]
Hyperinsulinemic hypoglycemia	DIS3KP5D	Definitive	Biomarker	[3]
Leishmaniasis	DISABTW7	Definitive	Altered Expression	[4]
Multiple sclerosis	DISB2WZI	Definitive	Biomarker	[5]
Primary hyperoxaluria	DIS0L16N	Definitive	Biomarker	[6]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[7]
Arteriosclerosis	DISK5QGC	Strong	Biomarker	[8]
Atherosclerosis	DISMN9J3	Strong	Biomarker	[8]
Beta thalassemia	DIS5RCQK	Strong	Altered Expression	[9]
Beta-thalassemia major	DISW06BV	Strong	Altered Expression	[9]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[7]
Cardiovascular disease	DIS2IQDX	Strong	Genetic Variation	[8]
Colorectal neoplasm	DISR1UCN	Strong	Altered Expression	[10]
Cone-rod dystrophy 2	DISX2RWY	Strong	Genetic Variation	[11]
Cortisone reductase deficiency 1	DISKWH38	Strong	Autosomal recessive	[12]
Fatty liver disease	DIS485QZ	Strong	Altered Expression	[13]
Giardiasis	DISWUNWK	Strong	Genetic Variation	[14]
Hypoglycemia	DISRCKR7	Strong	Genetic Variation	[15]
Intrahepatic cholangiocarcinoma	DIS6GOC8	Strong	Biomarker	[16]
Obesity	DIS47Y1K	Strong	Altered Expression	[17]
Fetal growth restriction	DIS5WEJ5	moderate	Altered Expression	[18]
Type-1/2 diabetes	DISIUHAP	moderate	Altered Expression	[17]
Cortisone reductase deficiency	DIS88XDM	Supportive	Autosomal dominant	[19]
Neoplasm	DISZKGEW	Disputed	Altered Expression	[20]
Breast cancer	DIS7DPX1	Limited	Altered Expression	[20]
Breast carcinoma	DIS2UE88	Limited	Altered Expression	[20]
Hemolytic anemia	DIS803XQ	Limited	Biomarker	[21]
Hyperinsulinemia	DISIDWT6	Limited	Altered Expression	[17]
Malaria	DISQ9Y50	Limited	Biomarker	[22]

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 GDH/6PGL endoplasmic bifunctional protein (H6PD).	[23]
Arsenic	DMTL2Y1	Approved	Arsenic increases the methylation of GDH/6PGL endoplasmic bifunctional protein (H6PD).	[28]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of GDH/6PGL endoplasmic bifunctional protein (H6PD).	[36]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of GDH/6PGL endoplasmic bifunctional protein (H6PD).	[24]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of GDH/6PGL endoplasmic bifunctional protein (H6PD).	[25]
Estradiol	DMUNTE3	Approved	Estradiol affects the expression of GDH/6PGL endoplasmic bifunctional protein (H6PD).	[26]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of GDH/6PGL endoplasmic bifunctional protein (H6PD).	[27]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of GDH/6PGL endoplasmic bifunctional protein (H6PD).	[29]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of GDH/6PGL endoplasmic bifunctional protein (H6PD).	[30]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of GDH/6PGL endoplasmic bifunctional protein (H6PD).	[31]
Selenium	DM25CGV	Approved	Selenium increases the expression of GDH/6PGL endoplasmic bifunctional protein (H6PD).	[32]
Bortezomib	DMNO38U	Approved	Bortezomib decreases the expression of GDH/6PGL endoplasmic bifunctional protein (H6PD).	[33]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol increases the expression of GDH/6PGL endoplasmic bifunctional protein (H6PD).	[34]
Zidovudine	DM4KI7O	Approved	Zidovudine affects the expression of GDH/6PGL endoplasmic bifunctional protein (H6PD).	[35]
Hydrocortisone	DMGEMB7	Approved	Hydrocortisone increases the expression of GDH/6PGL endoplasmic bifunctional protein (H6PD).	[31]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of GDH/6PGL endoplasmic bifunctional protein (H6PD).	[32]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of GDH/6PGL endoplasmic bifunctional protein (H6PD).	[37]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of GDH/6PGL endoplasmic bifunctional protein (H6PD).	[38]
4-hydroxy-2-nonenal	DM2LJFZ	Investigative	4-hydroxy-2-nonenal decreases the activity of GDH/6PGL endoplasmic bifunctional protein (H6PD).	[39]
CH-223191	DMMJZYC	Investigative	CH-223191 increases the expression of GDH/6PGL endoplasmic bifunctional protein (H6PD).	[40]

References

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