Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT1HG3HG)

• DOT Name: Delta(14)-sterol reductase LBR (LBR)
• Synonyms: Delta-14-SR; EC 1.3.1.70; 3-beta-hydroxysterol Delta (14)-reductase; C-14 sterol reductase; C14SR; Integral nuclear envelope inner membrane protein; LMN2R; Lamin-B receptor; Sterol C14-reductase
• Gene Name: LBR
• Related Disease:
  B-cell neoplasm
  Greenberg dysplasia
  Multiple sclerosis
  Acute myelogenous leukaemia
  Adenocarcinoma
  Alzheimer disease
  Arteriosclerosis
  Atherosclerosis
  Autoimmune disease
  Bloom syndrome
  Brain neoplasm
  Breast cancer
  Breast carcinoma
  Colon cancer
  Colon carcinoma
  Colorectal carcinoma
  Endometriosis
  Hepatocellular carcinoma
  Ichthyosis vulgaris
  Leukemia
  Pancreatic cancer
  Pelger-Huet anomaly
  Polydactyly
  Prostate cancer
  Prostate carcinoma
  Regressive spondylometaphyseal dysplasia
  Rheumatoid arthritis
  Severe combined immunodeficiency
  Small lymphocytic lymphoma
  Spondyloepimetaphyseal dysplasia, Strudwick type
  Squamous cell carcinoma
  Systemic lupus erythematosus
  T-cell leukaemia
  Tuberculosis
  Adult lymphoma
  B-cell lymphoma
  Cervical carcinoma
  Lymphoma
  Neoplasm
  Non-syndromic ichthyosis
  Pediatric lymphoma
  Asthma
  Acute lymphocytic leukaemia
  Advanced cancer
  Blast phase chronic myelogenous leukemia, BCR-ABL1 positive
  Chromosomal disorder
  Hepatitis C virus infection
  Neuroblastoma
  Thyroid gland papillary carcinoma
  Type-1 diabetes
• UniProt ID: LBR_HUMAN
• PDB ID: 2DIG
• EC Number: 1.3.1.70
• Pfam ID: PF01222 ; PF09465
• Sequence:
  MPSRKFADGEVVRGRWPGSSLYYEVEILSHDSTSQLYTVKYKDGTELELKENDIKPLTSF
  RQRKGGSTSSSPSRRRGSRSRSRSRSPGRPPKSARRSASASHQADIKEARREVEVKLTPL
  ILKPFGNSISRYNGEPEHIERNDAPHKNTQEKFSLSQESSYIATQYSLRPRREEVKLKEI
  DSKEEKYVAKELAVRTFEVTPIRAKDLEFGGVPGVFLIMFGLPVFLFLLLLMCKQKDPSL
  LNFPPPLPALYELWETRVFGVYLLWFLIQVLFYLLPIGKVVEGTPLIDGRRLKYRLNGFY
  AFILTSAVIGTSLFQGVEFHYVYSHFLQFALAATVFCVVLSVYLYMRSLKAPRNDLSPAS
  SGNAVYDFFIGRELNPRIGTFDLKYFCELRPGLIGWVVINLVMLLAEMKIQDRAVPSLAM
  ILVNSFQLLYVVDALWNEEALLTTMDIIHDGFGFMLAFGDLVWVPFIYSFQAFYLVSHPN
  EVSWPMASLIIVLKLCGYVIFRGANSQKNAFRKNPSDPKLAHLKTIHTSTGKNLLVSGWW
  GFVRHPNYLGDLIMALAWSLPCGFNHILPYFYIIYFTMLLVHREARDEYHCKKKYGVAWE
  KYCQRVPYRIFPYIY
• Function: Catalyzes the reduction of the C14-unsaturated bond of lanosterol, as part of the metabolic pathway leading to cholesterol biosynthesis. Plays a critical role in myeloid cell cholesterol biosynthesis which is essential to both myeloid cell growth and functional maturation. Mediates the activation of NADPH oxidases, perhaps by maintaining critical levels of cholesterol required for membrane lipid raft formation during neutrophil differentiation. Anchors the lamina and the heterochromatin to the inner nuclear membrane.
• Tissue Specificity: Expressed in the bone marrow, liver, heart, adrenal gland, lung, placenta and uterus . Expressed in osteoclasts and osteoblast-like cells .
• KEGG Pathway:
  Steroid biosynthesis (hsa00100)
  Metabolic pathways (hsa01100)
  Cytoskeleton in muscle cells (hsa04820)
• Reactome Pathway:
  Initiation of Nuclear Envelope (NE) Reformation (R-HSA-2995383)
  RHOA GTPase cycle (R-HSA-8980692)
  RHOC GTPase cycle (R-HSA-9013106)
  CDC42 GTPase cycle (R-HSA-9013148)
  RAC1 GTPase cycle (R-HSA-9013149)
  RAC2 GTPase cycle (R-HSA-9013404)
  RHOD GTPase cycle (R-HSA-9013405)
  RHOG GTPase cycle (R-HSA-9013408)
  RAC3 GTPase cycle (R-HSA-9013423)
  Regulation of MECP2 expression and activity (R-HSA-9022692)
  Cholesterol biosynthesis (R-HSA-191273)
• BioCyc Pathway: MetaCyc:HS07110-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

50 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
B-cell neoplasm	DISVY326	Definitive	Biomarker	[1]
Greenberg dysplasia	DISITZBA	Definitive	Autosomal recessive	[2]
Multiple sclerosis	DISB2WZI	Definitive	Biomarker	[3]
Acute myelogenous leukaemia	DISCSPTN	Strong	Genetic Variation	[4]
Adenocarcinoma	DIS3IHTY	Strong	Altered Expression	[5]
Alzheimer disease	DISF8S70	Strong	Biomarker	[6]
Arteriosclerosis	DISK5QGC	Strong	Altered Expression	[7]
Atherosclerosis	DISMN9J3	Strong	Altered Expression	[7]
Autoimmune disease	DISORMTM	Strong	Biomarker	[8]
Bloom syndrome	DISKXQ7J	Strong	Biomarker	[9]
Brain neoplasm	DISY3EKS	Strong	Biomarker	[10]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[11]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[11]
Colon cancer	DISVC52G	Strong	Biomarker	[12]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[12]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[13]
Endometriosis	DISX1AG8	Strong	Biomarker	[14]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[15]
Ichthyosis vulgaris	DISTRF9L	Strong	Biomarker	[16]
Leukemia	DISNAKFL	Strong	Genetic Variation	[17]
Pancreatic cancer	DISJC981	Strong	Altered Expression	[12]
Pelger-Huet anomaly	DISCW4OI	Strong	Autosomal dominant	[18]
Polydactyly	DIS25BMZ	Strong	Biomarker	[19]
Prostate cancer	DISF190Y	Strong	Altered Expression	[20]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[20]
Regressive spondylometaphyseal dysplasia	DISFMT9Y	Strong	Autosomal recessive	[21]
Rheumatoid arthritis	DISTSB4J	Strong	Altered Expression	[22]
Severe combined immunodeficiency	DIS6MF4Q	Strong	Biomarker	[23]
Small lymphocytic lymphoma	DIS30POX	Strong	Biomarker	[24]
Spondyloepimetaphyseal dysplasia, Strudwick type	DISNRAF6	Strong	Biomarker	[25]
Squamous cell carcinoma	DISQVIFL	Strong	Biomarker	[26]
Systemic lupus erythematosus	DISI1SZ7	Strong	Biomarker	[8]
T-cell leukaemia	DISJ6YIF	Strong	Biomarker	[27]
Tuberculosis	DIS2YIMD	Strong	Genetic Variation	[28]
Adult lymphoma	DISK8IZR	moderate	Biomarker	[29]
B-cell lymphoma	DISIH1YQ	moderate	Biomarker	[30]
Cervical carcinoma	DIST4S00	moderate	Biomarker	[31]
Lymphoma	DISN6V4S	moderate	Biomarker	[29]
Neoplasm	DISZKGEW	moderate	Biomarker	[32]
Non-syndromic ichthyosis	DISZ9QBQ	moderate	Biomarker	[16]
Pediatric lymphoma	DIS51BK2	moderate	Biomarker	[29]
Asthma	DISW9QNS	Disputed	Biomarker	[33]
Acute lymphocytic leukaemia	DISPX75S	Limited	Biomarker	[4]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[34]
Blast phase chronic myelogenous leukemia, BCR-ABL1 positive	DIS3KLUX	Limited	Genetic Variation	[35]
Chromosomal disorder	DISM5BB5	Limited	Biomarker	[36]
Hepatitis C virus infection	DISQ0M8R	Limited	Biomarker	[37]
Neuroblastoma	DISVZBI4	Limited	Biomarker	[38]
Thyroid gland papillary carcinoma	DIS48YMM	Limited	Altered Expression	[39]
Type-1 diabetes	DIS7HLUB	Limited	Biomarker	[40]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Delta(14)-sterol reductase LBR (LBR).	[41]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Delta(14)-sterol reductase LBR (LBR).	[42]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Delta(14)-sterol reductase LBR (LBR).	[43]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Delta(14)-sterol reductase LBR (LBR).	[44]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Delta(14)-sterol reductase LBR (LBR).	[45]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Delta(14)-sterol reductase LBR (LBR).	[46]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide decreases the expression of Delta(14)-sterol reductase LBR (LBR).	[47]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Delta(14)-sterol reductase LBR (LBR).	[48]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Delta(14)-sterol reductase LBR (LBR).	[48]
Menadione	DMSJDTY	Approved	Menadione decreases the expression of Delta(14)-sterol reductase LBR (LBR).	[47]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Delta(14)-sterol reductase LBR (LBR).	[49]
Piroxicam	DMTK234	Approved	Piroxicam increases the expression of Delta(14)-sterol reductase LBR (LBR).	[50]
Obeticholic acid	DM3Q1SM	Approved	Obeticholic acid decreases the expression of Delta(14)-sterol reductase LBR (LBR).	[51]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Delta(14)-sterol reductase LBR (LBR).	[52]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Delta(14)-sterol reductase LBR (LBR).	[53]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Delta(14)-sterol reductase LBR (LBR).	[56]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Delta(14)-sterol reductase LBR (LBR).	[57]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Delta(14)-sterol reductase LBR (LBR).	[54]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Delta(14)-sterol reductase LBR (LBR).	[55]

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