Details of Drug Off-Target (DOT)

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

• DOT Name: Insulin-like growth factor-binding protein complex acid labile subunit (IGFALS)
• Synonyms: ALS
• Gene Name: IGFALS
• Related Disease:
  Hepatocellular carcinoma
  Primary progressive aphasia
  Advanced cancer
  Astrocytoma
  Autoimmune disease
  Breast neoplasm
  Cardiac arrest
  Cardiovascular disease
  Cerebellar ataxia
  Depression
  Epilepsy
  Frontotemporal dementia and/or amyotrophic lateral sclerosis 1
  Glioblastoma multiforme
  Huntington disease
  Immunodeficiency
  Lateral sclerosis
  Motor neurone disease
  Movement disorder
  Multiple sclerosis
  Myopathy
  Non-alcoholic fatty liver disease
  Obesity
  Oral candidiasis
  Papillon-Lefevre disease
  Parkinson disease
  Pick disease
  Prion disease
  Prostate cancer
  Respiratory failure
  Sarcoma
  Schizophrenia
  Short stature due to primary acid-labile subunit deficiency
  Spinal muscular atrophy, type 1
  Spinocerebellar ataxia type 2
  Stroke
  Systemic lupus erythematosus
  Type-1/2 diabetes
  Vascular purpura
  Amyotrophic lateral sclerosis-parkinsonism-dementia complex
  Kennedy disease
  Parkinsonian disorder
  Progressive bulbar palsy
  Spinal muscular atrophy
  Amyotrophic lateral sclerosis type 1
  Familial amyotrophic lateral sclerosis
  Fragile X-associated tremor/ataxia syndrome
  Nervous system disease
  Non-insulin dependent diabetes
• UniProt ID: ALS_HUMAN
• PDB ID: 7WRQ
• Pfam ID: PF00560 ; PF13855 ; PF01462
• Sequence:
  MALRKGGLALALLLLSWVALGPRSLEGADPGTPGEAEGPACPAACVCSYDDDADELSVFC
  SSRNLTRLPDGVPGGTQALWLDGNNLSSVPPAAFQNLSSLGFLNLQGGQLGSLEPQALLG
  LENLCHLHLERNQLRSLALGTFAHTPALASLGLSNNRLSRLEDGLFEGLGSLWDLNLGWN
  SLAVLPDAAFRGLGSLRELVLAGNRLAYLQPALFSGLAELRELDLSRNALRAIKANVFVQ
  LPRLQKLYLDRNLIAAVAPGAFLGLKALRWLDLSHNRVAGLLEDTFPGLLGLRVLRLSHN
  AIASLRPRTFKDLHFLEELQLGHNRIRQLAERSFEGLGQLEVLTLDHNQLQEVKAGAFLG
  LTNVAVMNLSGNCLRNLPEQVFRGLGKLHSLHLEGSCLGRIRPHTFTGLSGLRRLFLKDN
  GLVGIEEQSLWGLAELLELDLTSNQLTHLPHRLFQGLGKLEYLLLSRNRLAELPADALGP
  LQRAFWLDVSHNRLEALPNSLLAPLGRLRYLSLRNNSLRTFTPQPPGLERLWLEGNPWDC
  GCPLKALRDFALQNPSAVPRFVQAICEGDDCQPPAYTYNNITCASPPEVVGLDLRDLSEA
  HFAPC
• Function: Involved in protein-protein interactions that result in protein complexes, receptor-ligand binding or cell adhesion.
• Tissue Specificity: Plasma.
• KEGG Pathway: Growth hormone synthesis, secretion and action (hsa04935)
• Reactome Pathway: Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) (R-HSA-381426)

Molecular Interaction Atlas (MIA) of This DOT

48 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hepatocellular carcinoma	DIS0J828	Definitive	Biomarker	[1]
Primary progressive aphasia	DISLRYFE	Definitive	Biomarker	[2]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[3]
Astrocytoma	DISL3V18	Strong	Biomarker	[4]
Autoimmune disease	DISORMTM	Strong	Biomarker	[5]
Breast neoplasm	DISNGJLM	Strong	Genetic Variation	[6]
Cardiac arrest	DIS9DIA4	Strong	Genetic Variation	[7]
Cardiovascular disease	DIS2IQDX	Strong	Genetic Variation	[8]
Cerebellar ataxia	DIS9IRAV	Strong	Genetic Variation	[7]
Depression	DIS3XJ69	Strong	Genetic Variation	[9]
Epilepsy	DISBB28L	Strong	Genetic Variation	[4]
Frontotemporal dementia and/or amyotrophic lateral sclerosis 1	DIS8SB8X	Strong	Biomarker	[10]
Glioblastoma multiforme	DISK8246	Strong	Altered Expression	[4]
Huntington disease	DISQPLA4	Strong	Biomarker	[11]
Immunodeficiency	DIS093I0	Strong	Biomarker	[12]
Lateral sclerosis	DISH30B8	Strong	Biomarker	[13]
Motor neurone disease	DISUHWUI	Strong	Biomarker	[14]
Movement disorder	DISOJJ2D	Strong	Genetic Variation	[7]
Multiple sclerosis	DISB2WZI	Strong	Genetic Variation	[15]
Myopathy	DISOWG27	Strong	Biomarker	[16]
Non-alcoholic fatty liver disease	DISDG1NL	Strong	Biomarker	[17]
Obesity	DIS47Y1K	Strong	Biomarker	[17]
Oral candidiasis	DISAVKAH	Strong	Altered Expression	[18]
Papillon-Lefevre disease	DIS3R7KX	Strong	Biomarker	[19]
Parkinson disease	DISQVHKL	Strong	Genetic Variation	[20]
Pick disease	DISP6X50	Strong	Biomarker	[21]
Prion disease	DISOUMB0	Strong	Biomarker	[22]
Prostate cancer	DISF190Y	Strong	Biomarker	[23]
Respiratory failure	DISVMYJO	Strong	Biomarker	[24]
Sarcoma	DISZDG3U	Strong	Genetic Variation	[25]
Schizophrenia	DISSRV2N	Strong	Biomarker	[26]
Short stature due to primary acid-labile subunit deficiency	DISW3WR3	Strong	Autosomal recessive	[27]
Spinal muscular atrophy, type 1	DISYCWUG	Strong	Biomarker	[28]
Spinocerebellar ataxia type 2	DISF7WDI	Strong	Genetic Variation	[29]
Stroke	DISX6UHX	Strong	Biomarker	[30]
Systemic lupus erythematosus	DISI1SZ7	Strong	Genetic Variation	[31]
Type-1/2 diabetes	DISIUHAP	Strong	Biomarker	[32]
Vascular purpura	DIS6ZZMF	Strong	Biomarker	[7]
Amyotrophic lateral sclerosis-parkinsonism-dementia complex	DISTHQI1	moderate	Biomarker	[33]
Kennedy disease	DISXZVM1	moderate	Biomarker	[34]
Parkinsonian disorder	DISHGY45	moderate	Biomarker	[35]
Progressive bulbar palsy	DIS4SNUB	moderate	Genetic Variation	[36]
Spinal muscular atrophy	DISTLKOB	moderate	Biomarker	[37]
Amyotrophic lateral sclerosis type 1	DIS5A2M0	Limited	Genetic Variation	[38]
Familial amyotrophic lateral sclerosis	DISWZ9CJ	Limited	Genetic Variation	[39]
Fragile X-associated tremor/ataxia syndrome	DISKB25R	Limited	Genetic Variation	[40]
Nervous system disease	DISJ7GGT	Limited	Biomarker	[41]
Non-insulin dependent diabetes	DISK1O5Z	Limited	Biomarker	[42]

2 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 Insulin-like growth factor-binding protein complex acid labile subunit (IGFALS).	[43]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Insulin-like growth factor-binding protein complex acid labile subunit (IGFALS).	[53]

11 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 Insulin-like growth factor-binding protein complex acid labile subunit (IGFALS).	[44]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Insulin-like growth factor-binding protein complex acid labile subunit (IGFALS).	[45]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Insulin-like growth factor-binding protein complex acid labile subunit (IGFALS).	[46]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Insulin-like growth factor-binding protein complex acid labile subunit (IGFALS).	[47]
Menthol	DMG2KW7	Approved	Menthol increases the expression of Insulin-like growth factor-binding protein complex acid labile subunit (IGFALS).	[48]
Ethinyl estradiol	DMODJ40	Approved	Ethinyl estradiol decreases the expression of Insulin-like growth factor-binding protein complex acid labile subunit (IGFALS).	[46]
Obeticholic acid	DM3Q1SM	Approved	Obeticholic acid decreases the expression of Insulin-like growth factor-binding protein complex acid labile subunit (IGFALS).	[49]
Cenestin	DMXQS7K	Approved	Cenestin decreases the expression of Insulin-like growth factor-binding protein complex acid labile subunit (IGFALS).	[46]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Insulin-like growth factor-binding protein complex acid labile subunit (IGFALS).	[50]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of Insulin-like growth factor-binding protein complex acid labile subunit (IGFALS).	[51]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Insulin-like growth factor-binding protein complex acid labile subunit (IGFALS).	[52]

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