Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT1DNGXL)

• DOT Name: Acid ceramidase (ASAH1)
• Synonyms: AC; ACDase; Acid CDase; EC 3.5.1.23; Acylsphingosine deacylase; N-acylethanolamine hydrolase ASAH1; EC 3.5.1.-; N-acylsphingosine amidohydrolase; Putative 32 kDa heart protein; PHP32
• Gene Name: ASAH1
• Related Disease:
  ASAH1-related sphingolipidosis
  Farber lipogranulomatosis
  Parkinson disease
  Spinal muscular atrophy-progressive myoclonic epilepsy syndrome
  Advanced cancer
  Atrial fibrillation
  Breast neoplasm
  Childhood epilepsy with centrotemporal spikes
  Colitis
  Colon cancer
  Colon carcinoma
  Colorectal carcinoma
  Congenital hypothyroidism
  Cystic fibrosis
  Epilepsy
  Hydrops fetalis
  Hyperglycemia
  Hypoparathyroidism
  Intellectual disability
  Lung cancer
  Lung carcinoma
  Lysosomal lipid storage disorder
  Lysosomal storage disease
  Neoplasm
  Non-immune hydrops fetalis
  Pancreatic cancer
  Progressive myoclonus epilepsy
  Prostate neoplasm
  Pseudohypoparathyroidism
  Pseudohypoparathyroidism type 1A
  Pseudopseudohypoparathyroidism
  Schizophrenia
  Spinal muscular atrophy
  Thyroid tumor
  Unverricht-Lundborg syndrome
  Acute myelogenous leukaemia
  Alzheimer disease
  Head and neck cancer
  Head and neck carcinoma
  Glioblastoma multiforme
  Rheumatoid arthritis
  Adult glioblastoma
  Arthritis
  Breast cancer
  Breast carcinoma
  Familial atrial fibrillation
  Melanoma
  Obesity
  Prostate cancer
  Prostate carcinoma
• UniProt ID: ASAH1_HUMAN
• PDB ID: 5U7Z; 6MHM
• EC Number: 3.5.1.-; 3.5.1.23
• Pfam ID: PF02275 ; PF15508
• Sequence:
  MPGRSCVALVLLAAAVSCAVAQHAPPWTEDCRKSTYPPSGPTYRGAVPWYTINLDLPPYK
  RWHELMLDKAPVLKVIVNSLKNMINTFVPSGKIMQVVDEKLPGLLGNFPGPFEEEMKGIA
  AVTDIPLGEIISFNIFYELFTICTSIVAEDKKGHLIHGRNMDFGVFLGWNINNDTWVITE
  QLKPLTVNLDFQRNNKTVFKASSFAGYVGMLTGFKPGLFSLTLNERFSINGGYLGILEWI
  LGKKDVMWIGFLTRTVLENSTSYEEAKNLLTKTKILAPAYFILGGNQSGEGCVITRDRKE
  SLDVYELDAKQGRWYVVQTNYDRWKHPFFLDDRRTPAKMCLNRTSQENISFETMYDVLST
  KPVLNKLTVYTTLIDVTKGQFETYLRDCPDPCIGW
• Function: Lysosomal ceramidase that hydrolyzes sphingolipid ceramides into sphingosine and free fatty acids at acidic pH. Ceramides, sphingosine, and its phosphorylated form sphingosine-1-phosphate are bioactive lipids that mediate cellular signaling pathways regulating several biological processes including cell proliferation, apoptosis and differentiation. Has a higher catalytic efficiency towards C12-ceramides versus other ceramides. Also catalyzes the reverse reaction allowing the synthesis of ceramides from fatty acids and sphingosine. For the reverse synthetic reaction, the natural sphingosine D-erythro isomer is more efficiently utilized as a substrate compared to D-erythro-dihydrosphingosine and D-erythro-phytosphingosine, while the fatty acids with chain lengths of 12 or 14 carbons are the most efficiently used. Has also an N-acylethanolamine hydrolase activity. By regulating the levels of ceramides, sphingosine and sphingosine-1-phosphate in the epidermis, mediates the calcium-induced differentiation of epidermal keratinocytes. Also indirectly regulates tumor necrosis factor/TNF-induced apoptosis. By regulating the intracellular balance between ceramides and sphingosine, in adrenocortical cells, probably also acts as a regulator of steroidogenesis ; [Isoform 2]: May directly regulate steroidogenesis by binding the nuclear receptor NR5A1 and negatively regulating its transcriptional activity.
• Tissue Specificity: Broadly expressed with higher expression in heart.
• KEGG Pathway:
  Sphingolipid metabolism (hsa00600)
  Metabolic pathways (hsa01100)
  Sphingolipid sig.ling pathway (hsa04071)
  Lysosome (hsa04142)
• Reactome Pathway:
  Glycosphingolipid catabolism (R-HSA-9840310)
  Neutrophil degranulation (R-HSA-6798695)

Molecular Interaction Atlas (MIA) of This DOT

50 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
ASAH1-related sphingolipidosis	DIS1MTJJ	Definitive	Autosomal recessive	[1]
Farber lipogranulomatosis	DISYBNUG	Definitive	Autosomal recessive	[2]
Parkinson disease	DISQVHKL	Definitive	Altered Expression	[3]
Spinal muscular atrophy-progressive myoclonic epilepsy syndrome	DISN54P4	Definitive	Autosomal recessive	[4]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[5]
Atrial fibrillation	DIS15W6U	Strong	Genetic Variation	[6]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[7]
Childhood epilepsy with centrotemporal spikes	DISKT2L5	Strong	CausalMutation	[8]
Colitis	DISAF7DD	Strong	Biomarker	[9]
Colon cancer	DISVC52G	Strong	Biomarker	[10]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[10]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[11]
Congenital hypothyroidism	DISL5XVU	Strong	Genetic Variation	[12]
Cystic fibrosis	DIS2OK1Q	Strong	Biomarker	[13]
Epilepsy	DISBB28L	Strong	Genetic Variation	[14]
Hydrops fetalis	DISD9BBF	Strong	Biomarker	[14]
Hyperglycemia	DIS0BZB5	Strong	Biomarker	[15]
Hypoparathyroidism	DISICS0V	Strong	Biomarker	[16]
Intellectual disability	DISMBNXP	Strong	Biomarker	[14]
Lung cancer	DISCM4YA	Strong	Biomarker	[17]
Lung carcinoma	DISTR26C	Strong	Biomarker	[17]
Lysosomal lipid storage disorder	DISXQRTX	Strong	Biomarker	[18]
Lysosomal storage disease	DIS6QM6U	Strong	Biomarker	[19]
Neoplasm	DISZKGEW	Strong	Altered Expression	[5]
Non-immune hydrops fetalis	DISPUY8C	Strong	Biomarker	[20]
Pancreatic cancer	DISJC981	Strong	Biomarker	[21]
Progressive myoclonus epilepsy	DISAMCNS	Strong	Genetic Variation	[22]
Prostate neoplasm	DISHDKGQ	Strong	Biomarker	[23]
Pseudohypoparathyroidism	DIS183OJ	Strong	Biomarker	[24]
Pseudohypoparathyroidism type 1A	DISSOR3M	Strong	Genetic Variation	[25]
Pseudopseudohypoparathyroidism	DISRRO5I	Strong	Genetic Variation	[26]
Schizophrenia	DISSRV2N	Strong	Biomarker	[27]
Spinal muscular atrophy	DISTLKOB	Strong	Biomarker	[22]
Thyroid tumor	DISLVKMD	Strong	Altered Expression	[28]
Unverricht-Lundborg syndrome	DISG4WLX	Strong	Genetic Variation	[22]
Acute myelogenous leukaemia	DISCSPTN	moderate	Altered Expression	[29]
Alzheimer disease	DISF8S70	moderate	Altered Expression	[30]
Head and neck cancer	DISBPSQZ	moderate	Biomarker	[31]
Head and neck carcinoma	DISOU1DS	moderate	Biomarker	[31]
Glioblastoma multiforme	DISK8246	Disputed	Biomarker	[32]
Rheumatoid arthritis	DISTSB4J	Disputed	Genetic Variation	[33]
Adult glioblastoma	DISVP4LU	Limited	Biomarker	[32]
Arthritis	DIST1YEL	Limited	Genetic Variation	[34]
Breast cancer	DIS7DPX1	Limited	Biomarker	[7]
Breast carcinoma	DIS2UE88	Limited	Biomarker	[7]
Familial atrial fibrillation	DISL4AGF	Limited	Biomarker	[6]
Melanoma	DIS1RRCY	Limited	Altered Expression	[35]
Obesity	DIS47Y1K	Limited	Biomarker	[24]
Prostate cancer	DISF190Y	Limited	Biomarker	[36]
Prostate carcinoma	DISMJPLE	Limited	Biomarker	[36]

This DOT Affected the Drug Response of 3 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Fluorouracil	DMUM7HZ	Approved	Acid ceramidase (ASAH1) affects the response to substance of Fluorouracil.	[59]
Etoposide	DMNH3PG	Approved	Acid ceramidase (ASAH1) affects the response to substance of Etoposide.	[59]
Mitomycin	DMH0ZJE	Approved	Acid ceramidase (ASAH1) affects the response to substance of Mitomycin.	[59]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Acid ceramidase (ASAH1).	[37]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Acid ceramidase (ASAH1).	[57]

34 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 Acid ceramidase (ASAH1).	[38]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Acid ceramidase (ASAH1).	[39]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Acid ceramidase (ASAH1).	[40]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Acid ceramidase (ASAH1).	[41]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Acid ceramidase (ASAH1).	[42]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Acid ceramidase (ASAH1).	[43]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Acid ceramidase (ASAH1).	[44]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the expression of Acid ceramidase (ASAH1).	[45]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Acid ceramidase (ASAH1).	[46]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol increases the expression of Acid ceramidase (ASAH1).	[47]
Clozapine	DMFC71L	Approved	Clozapine increases the expression of Acid ceramidase (ASAH1).	[48]
Acocantherin	DM7JT24	Approved	Acocantherin affects the expression of Acid ceramidase (ASAH1).	[49]
Fluoxetine	DM3PD2C	Approved	Fluoxetine increases the expression of Acid ceramidase (ASAH1).	[48]
Beta-carotene	DM0RXBT	Approved	Beta-carotene increases the expression of Acid ceramidase (ASAH1).	[50]
Sertraline	DM0FB1J	Approved	Sertraline increases the expression of Acid ceramidase (ASAH1).	[48]
Thioridazine	DM35M8J	Approved	Thioridazine increases the expression of Acid ceramidase (ASAH1).	[51]
Gamolenic acid	DMQN30Z	Approved	Gamolenic acid increases the expression of Acid ceramidase (ASAH1).	[52]
Imipramine	DM2NUH3	Approved	Imipramine increases the expression of Acid ceramidase (ASAH1).	[48]
Erythromycin	DM4K7GQ	Approved	Erythromycin increases the expression of Acid ceramidase (ASAH1).	[51]
Flecainide	DMSQDLE	Approved	Flecainide increases the expression of Acid ceramidase (ASAH1).	[48]
Perhexiline	DMINO7Z	Approved	Perhexiline increases the expression of Acid ceramidase (ASAH1).	[48]
Ofloxacin	DM0VQN3	Approved	Ofloxacin increases the expression of Acid ceramidase (ASAH1).	[51]
Clarithromycin	DM4M1SG	Approved	Clarithromycin increases the expression of Acid ceramidase (ASAH1).	[48]
Disopyramide	DM5SYZP	Approved	Disopyramide increases the expression of Acid ceramidase (ASAH1).	[48]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Acid ceramidase (ASAH1).	[53]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Acid ceramidase (ASAH1).	[54]
Chlorpromazine	DMBGZI3	Phase 3 Trial	Chlorpromazine increases the expression of Acid ceramidase (ASAH1).	[51]
Fenfluramine	DM0762O	Phase 3	Fenfluramine increases the expression of Acid ceramidase (ASAH1).	[55]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Acid ceramidase (ASAH1).	[54]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of Acid ceramidase (ASAH1).	[48]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the mutagenesis of Acid ceramidase (ASAH1).	[56]
Chlorcyclizine	DM3L52Q	Phase 1	Chlorcyclizine increases the expression of Acid ceramidase (ASAH1).	[48]
ZIMELIDINE	DMNI3U2	Withdrawn from market	ZIMELIDINE increases the expression of Acid ceramidase (ASAH1).	[48]
PP-242	DM2348V	Investigative	PP-242 decreases the expression of Acid ceramidase (ASAH1).	[58]

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