Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTEOT8GI)

• DOT Name: GTP cyclohydrolase 1 feedback regulatory protein (GCHFR)
• Synonyms: GFRP; GTP cyclohydrolase I feedback regulatory protein; p35
• Gene Name: GCHFR
• Related Disease:
  Advanced cancer
  Alzheimer disease
  Amyloidosis
  Astrocytoma
  Behcet disease
  Bone osteosarcoma
  Brain disease
  Crohn disease
  Familial Alzheimer disease
  Hepatitis B virus infection
  Hepatitis C virus infection
  Hyperinsulinemia
  Idiopathic thrombocytopenic purpura
  Immunodeficiency
  Lung cancer
  Lung carcinoma
  Lyme disease
  Lymphoma, non-Hodgkin, familial
  Major depressive disorder
  Medullary thyroid gland carcinoma
  Mood disorder
  Non-hodgkin lymphoma
  Osteosarcoma
  Prostate carcinoma
  Psoriasis
  Rheumatoid arthritis
  Schizophrenia
  Spinal muscular atrophy
  Stroke
  Systemic lupus erythematosus
  Systemic sclerosis
  Fetal growth restriction
  Matthew-Wood syndrome
  Neoplasm
  Neuroblastoma
  Ovarian cancer
  Pancreatic ductal carcinoma
  Periodontitis
  Tuberous sclerosis
  Cognitive impairment
  Malaria
  Epithelial ovarian cancer
  Intellectual disability
  Nervous system disease
  Ovarian neoplasm
  Pancreatic cancer
  Type-1 diabetes
• UniProt ID: GFRP_HUMAN
• PDB ID: 6Z80; 6Z85; 7ACC; 7AL9; 7ALA; 7ALB; 7ALC; 7ALQ
• Pfam ID: PF06399
• Sequence:
  MPYLLISTQIRMEVGPTMVGDEQSDPELMQHLGASKRRALGNNFYEYYVDDPPRIVLDKL
  ERRGFRVLSMTGVGQTLVWCLHKE
• Function: Mediates tetrahydrobiopterin inhibition of GTP cyclohydrolase 1. This inhibition is reversed by L-phenylalanine.
• Tissue Specificity: In epidermis, expressed predominantly in basal undifferentiated keratinocytes and in some but not all melanocytes (at protein level).
• Reactome Pathway: Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation (R-HSA-1474151)

Molecular Interaction Atlas (MIA) of This DOT

47 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Alzheimer disease	DISF8S70	Strong	Biomarker	[2]
Amyloidosis	DISHTAI2	Strong	Genetic Variation	[3]
Astrocytoma	DISL3V18	Strong	Altered Expression	[4]
Behcet disease	DISSYMBS	Strong	Altered Expression	[5]
Bone osteosarcoma	DIST1004	Strong	Altered Expression	[1]
Brain disease	DIS6ZC3X	Strong	Biomarker	[6]
Crohn disease	DIS2C5Q8	Strong	Biomarker	[7]
Familial Alzheimer disease	DISE75U4	Strong	Biomarker	[3]
Hepatitis B virus infection	DISLQ2XY	Strong	Biomarker	[8]
Hepatitis C virus infection	DISQ0M8R	Strong	Altered Expression	[9]
Hyperinsulinemia	DISIDWT6	Strong	Biomarker	[10]
Idiopathic thrombocytopenic purpura	DISFKGJU	Strong	Altered Expression	[11]
Immunodeficiency	DIS093I0	Strong	Altered Expression	[12]
Lung cancer	DISCM4YA	Strong	Altered Expression	[13]
Lung carcinoma	DISTR26C	Strong	Altered Expression	[13]
Lyme disease	DISO70G5	Strong	Altered Expression	[14]
Lymphoma, non-Hodgkin, familial	DISCXYIZ	Strong	Biomarker	[15]
Major depressive disorder	DIS4CL3X	Strong	Genetic Variation	[16]
Medullary thyroid gland carcinoma	DISHBL3K	Strong	Altered Expression	[17]
Mood disorder	DISLVMWO	Strong	Genetic Variation	[16]
Non-hodgkin lymphoma	DISS2Y8A	Strong	Biomarker	[15]
Osteosarcoma	DISLQ7E2	Strong	Altered Expression	[1]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[18]
Psoriasis	DIS59VMN	Strong	Biomarker	[19]
Rheumatoid arthritis	DISTSB4J	Strong	Biomarker	[20]
Schizophrenia	DISSRV2N	Strong	Biomarker	[21]
Spinal muscular atrophy	DISTLKOB	Strong	Biomarker	[22]
Stroke	DISX6UHX	Strong	Biomarker	[23]
Systemic lupus erythematosus	DISI1SZ7	Strong	Biomarker	[24]
Systemic sclerosis	DISF44L6	Strong	Altered Expression	[25]
Fetal growth restriction	DIS5WEJ5	moderate	Biomarker	[26]
Matthew-Wood syndrome	DISA7HR7	moderate	Genetic Variation	[27]
Neoplasm	DISZKGEW	moderate	Biomarker	[28]
Neuroblastoma	DISVZBI4	moderate	Biomarker	[29]
Ovarian cancer	DISZJHAP	moderate	Altered Expression	[30]
Pancreatic ductal carcinoma	DIS26F9Q	moderate	Biomarker	[27]
Periodontitis	DISI9JOI	moderate	Altered Expression	[31]
Tuberous sclerosis	DISEMUGZ	moderate	Genetic Variation	[32]
Cognitive impairment	DISH2ERD	Disputed	Biomarker	[33]
Malaria	DISQ9Y50	Disputed	Biomarker	[34]
Epithelial ovarian cancer	DIS56MH2	Limited	Altered Expression	[30]
Intellectual disability	DISMBNXP	Limited	Genetic Variation	[35]
Nervous system disease	DISJ7GGT	Limited	Altered Expression	[36]
Ovarian neoplasm	DISEAFTY	Limited	Altered Expression	[30]
Pancreatic cancer	DISJC981	Limited	Altered Expression	[37]
Type-1 diabetes	DIS7HLUB	Limited	Altered Expression	[38]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Paclitaxel	DMLB81S	Approved	GTP cyclohydrolase 1 feedback regulatory protein (GCHFR) decreases the response to substance of Paclitaxel.	[56]

1 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 GTP cyclohydrolase 1 feedback regulatory protein (GCHFR).	[39]

18 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 GTP cyclohydrolase 1 feedback regulatory protein (GCHFR).	[40]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of GTP cyclohydrolase 1 feedback regulatory protein (GCHFR).	[41]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of GTP cyclohydrolase 1 feedback regulatory protein (GCHFR).	[42]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of GTP cyclohydrolase 1 feedback regulatory protein (GCHFR).	[43]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of GTP cyclohydrolase 1 feedback regulatory protein (GCHFR).	[44]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of GTP cyclohydrolase 1 feedback regulatory protein (GCHFR).	[45]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of GTP cyclohydrolase 1 feedback regulatory protein (GCHFR).	[46]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of GTP cyclohydrolase 1 feedback regulatory protein (GCHFR).	[47]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of GTP cyclohydrolase 1 feedback regulatory protein (GCHFR).	[48]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone decreases the expression of GTP cyclohydrolase 1 feedback regulatory protein (GCHFR).	[49]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of GTP cyclohydrolase 1 feedback regulatory protein (GCHFR).	[50]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of GTP cyclohydrolase 1 feedback regulatory protein (GCHFR).	[48]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of GTP cyclohydrolase 1 feedback regulatory protein (GCHFR).	[40]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of GTP cyclohydrolase 1 feedback regulatory protein (GCHFR).	[51]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of GTP cyclohydrolase 1 feedback regulatory protein (GCHFR).	[52]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of GTP cyclohydrolase 1 feedback regulatory protein (GCHFR).	[53]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of GTP cyclohydrolase 1 feedback regulatory protein (GCHFR).	[54]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of GTP cyclohydrolase 1 feedback regulatory protein (GCHFR).	[55]

References

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