Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTV57BZD)

• DOT Name: Alpha-aminoadipic semialdehyde dehydrogenase (ALDH7A1)
• Synonyms: Alpha-AASA dehydrogenase; EC 1.2.1.31; Aldehyde dehydrogenase family 7 member A1; EC 1.2.1.3; Antiquitin-1; Betaine aldehyde dehydrogenase; EC 1.2.1.8; Delta1-piperideine-6-carboxylate dehydrogenase; P6c dehydrogenase
• Gene Name: ALDH7A1
• Related Disease:
  Erectile dysfunction
  Pyridoxine-dependent epilepsy
  Pyridoxine-dependent epilepsy caused by ALDH7A1 mutant
  Advanced cancer
  Alzheimer disease
  Atopic dermatitis
  Benign prostatic hyperplasia
  Bone disease
  Cardiac failure
  Cardiovascular disease
  Cerebral infarction
  Coloboma
  Colon cancer
  Colon carcinoma
  Congestive heart failure
  Depression
  Dilated cardiomyopathy 1A
  Esophageal squamous cell carcinoma
  Gastric cancer
  Gastric neoplasm
  Hepatitis C virus infection
  Hereditary diffuse gastric adenocarcinoma
  High blood pressure
  Huntington disease
  Major depressive disorder
  Matthew-Wood syndrome
  Melanoma
  Mental disorder
  Osteoporosis
  Pendred syndrome
  Pneumonia
  Pneumonitis
  Schizophrenia
  Small lymphocytic lymphoma
  Breast carcinoma
  Gastrointestinal stromal tumour
  Prostate cancer
  Prostate carcinoma
  Epilepsy
  Adult glioblastoma
  Asthma
  Carcinoma
  Carcinoma of liver and intrahepatic biliary tract
  Glioblastoma multiforme
  Liver cancer
  Non-insulin dependent diabetes
  Pulmonary disease
  Rectal carcinoma
  Squamous cell carcinoma
• UniProt ID: AL7A1_HUMAN
• PDB ID: 2J6L; 4X0T; 4X0U; 4ZUK; 4ZUL; 4ZVW; 4ZVX; 4ZVY; 6O4B; 6O4C; 6O4D; 6O4E; 6O4F; 6O4G; 6O4H; 6O4I; 6O4K; 6O4L; 6U2X; 6V0Z
• EC Number: 1.2.1.3; 1.2.1.31; 1.2.1.8
• Pfam ID: PF00171
• Sequence:
  MWRLPRALCVHAAKTSKLSGPWSRPAAFMSTLLINQPQYAWLKELGLREENEGVYNGSWG
  GRGEVITTYCPANNEPIARVRQASVADYEETVKKAREAWKIWADIPAPKRGEIVRQIGDA
  LREKIQVLGSLVSLEMGKILVEGVGEVQEYVDICDYAVGLSRMIGGPILPSERSGHALIE
  QWNPVGLVGIITAFNFPVAVYGWNNAIAMICGNVCLWKGAPTTSLISVAVTKIIAKVLED
  NKLPGAICSLTCGGADIGTAMAKDERVNLLSFTGSTQVGKQVGLMVQERFGRSLLELGGN
  NAIIAFEDADLSLVVPSALFAAVGTAGQRCTTARRLFIHESIHDEVVNRLKKAYAQIRVG
  NPWDPNVLYGPLHTKQAVSMFLGAVEEAKKEGGTVVYGGKVMDRPGNYVEPTIVTGLGHD
  ASIAHTETFAPILYVFKFKNEEEVFAWNNEVKQGLSSSIFTKDLGRIFRWLGPKGSDCGI
  VNVNIPTSGAEIGGAFGGEKHTGGGRESGSDAWKQYMRRSTCTINYSKDLPLAQGIKFQ
• Function: Multifunctional enzyme mediating important protective effects. Metabolizes betaine aldehyde to betaine, an important cellular osmolyte and methyl donor. Protects cells from oxidative stress by metabolizing a number of lipid peroxidation-derived aldehydes. Involved in lysine catabolism.
• Tissue Specificity: Abundant in hepatoma cells and fetal cochlea, ovary, eye, heart, adrenal gland, liver and kidney. Low levels present in adult peripheral blood leukocytes and fetal brain, thymus, spleen, skeletal muscle, lung and tongue.
• KEGG Pathway:
  Glycolysis / Gluconeogenesis (hsa00010)
  Ascorbate and aldarate metabolism (hsa00053)
  Fatty acid degradation (hsa00071)
  Glycine, serine and threonine metabolism (hsa00260)
  Valine, leucine and isoleucine degradation (hsa00280)
  Lysine degradation (hsa00310)
  Arginine and proline metabolism (hsa00330)
  Histidine metabolism (hsa00340)
  Tryptophan metabolism (hsa00380)
  beta-Alanine metabolism (hsa00410)
  Glycerolipid metabolism (hsa00561)
  Pyruvate metabolism (hsa00620)
  Metabolic pathways (hsa01100)
  Alcoholic liver disease (hsa04936)
• Reactome Pathway:
  Lysine catabolism (R-HSA-71064)
  Choline catabolism (R-HSA-6798163)
• BioCyc Pathway: MetaCyc:HS09157-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

49 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Erectile dysfunction	DISD8MTH	Definitive	Biomarker	[1]
Pyridoxine-dependent epilepsy	DISVYADQ	Definitive	Autosomal recessive	[2]
Pyridoxine-dependent epilepsy caused by ALDH7A1 mutant	DIS93J7H	Definitive	Autosomal dominant	[3]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[4]
Alzheimer disease	DISF8S70	Strong	Biomarker	[5]
Atopic dermatitis	DISTCP41	Strong	Altered Expression	[6]
Benign prostatic hyperplasia	DISI3CW2	Strong	Biomarker	[7]
Bone disease	DISE1F82	Strong	Biomarker	[8]
Cardiac failure	DISDC067	Strong	Biomarker	[9]
Cardiovascular disease	DIS2IQDX	Strong	Biomarker	[10]
Cerebral infarction	DISR1WNP	Strong	Genetic Variation	[11]
Coloboma	DISP39N5	Strong	Biomarker	[8]
Colon cancer	DISVC52G	Strong	Biomarker	[12]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[12]
Congestive heart failure	DIS32MEA	Strong	Biomarker	[9]
Depression	DIS3XJ69	Strong	Biomarker	[13]
Dilated cardiomyopathy 1A	DIS0RK9Z	Strong	Biomarker	[14]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Genetic Variation	[15]
Gastric cancer	DISXGOUK	Strong	Biomarker	[16]
Gastric neoplasm	DISOKN4Y	Strong	Biomarker	[16]
Hepatitis C virus infection	DISQ0M8R	Strong	Biomarker	[17]
Hereditary diffuse gastric adenocarcinoma	DISUIBYS	Strong	Biomarker	[16]
High blood pressure	DISY2OHH	Strong	Genetic Variation	[18]
Huntington disease	DISQPLA4	Strong	Biomarker	[19]
Major depressive disorder	DIS4CL3X	Strong	Genetic Variation	[20]
Matthew-Wood syndrome	DISA7HR7	Strong	Biomarker	[21]
Melanoma	DIS1RRCY	Strong	Altered Expression	[22]
Mental disorder	DIS3J5R8	Strong	Biomarker	[13]
Osteoporosis	DISF2JE0	Strong	Biomarker	[23]
Pendred syndrome	DISZ1MU8	Strong	Genetic Variation	[24]
Pneumonia	DIS8EF3M	Strong	Biomarker	[25]
Pneumonitis	DIS88E0K	Strong	Biomarker	[25]
Schizophrenia	DISSRV2N	Strong	Biomarker	[26]
Small lymphocytic lymphoma	DIS30POX	Strong	Altered Expression	[27]
Breast carcinoma	DIS2UE88	moderate	Altered Expression	[28]
Gastrointestinal stromal tumour	DIS6TJYS	moderate	Biomarker	[29]
Prostate cancer	DISF190Y	moderate	Biomarker	[30]
Prostate carcinoma	DISMJPLE	moderate	Biomarker	[30]
Epilepsy	DISBB28L	Disputed	Genetic Variation	[31]
Adult glioblastoma	DISVP4LU	Limited	Biomarker	[30]
Asthma	DISW9QNS	Limited	Altered Expression	[32]
Carcinoma	DISH9F1N	Limited	Biomarker	[4]
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	Limited	Altered Expression	[4]
Glioblastoma multiforme	DISK8246	Limited	Biomarker	[30]
Liver cancer	DISDE4BI	Limited	Altered Expression	[4]
Non-insulin dependent diabetes	DISK1O5Z	Limited	Biomarker	[33]
Pulmonary disease	DIS6060I	Limited	Biomarker	[34]
Rectal carcinoma	DIS8FRR7	Limited	Biomarker	[35]
Squamous cell carcinoma	DISQVIFL	Limited	Biomarker	[36]

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Hydrogen peroxide	DM1NG5W	Approved	Alpha-aminoadipic semialdehyde dehydrogenase (ALDH7A1) decreases the response to substance of Hydrogen peroxide.	[57]
4-hydroxy-2-nonenal	DM2LJFZ	Investigative	Alpha-aminoadipic semialdehyde dehydrogenase (ALDH7A1) decreases the response to substance of 4-hydroxy-2-nonenal.	[57]

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 Alpha-aminoadipic semialdehyde dehydrogenase (ALDH7A1).	[37]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A decreases the acetylation of Alpha-aminoadipic semialdehyde dehydrogenase (ALDH7A1).	[53]

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 Alpha-aminoadipic semialdehyde dehydrogenase (ALDH7A1).	[38]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Alpha-aminoadipic semialdehyde dehydrogenase (ALDH7A1).	[39]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Alpha-aminoadipic semialdehyde dehydrogenase (ALDH7A1).	[40]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Alpha-aminoadipic semialdehyde dehydrogenase (ALDH7A1).	[41]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Alpha-aminoadipic semialdehyde dehydrogenase (ALDH7A1).	[42]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Alpha-aminoadipic semialdehyde dehydrogenase (ALDH7A1).	[43]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Alpha-aminoadipic semialdehyde dehydrogenase (ALDH7A1).	[44]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Alpha-aminoadipic semialdehyde dehydrogenase (ALDH7A1).	[45]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Alpha-aminoadipic semialdehyde dehydrogenase (ALDH7A1).	[46]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of Alpha-aminoadipic semialdehyde dehydrogenase (ALDH7A1).	[47]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Alpha-aminoadipic semialdehyde dehydrogenase (ALDH7A1).	[49]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Alpha-aminoadipic semialdehyde dehydrogenase (ALDH7A1).	[50]
chloropicrin	DMSGBQA	Investigative	chloropicrin decreases the expression of Alpha-aminoadipic semialdehyde dehydrogenase (ALDH7A1).	[51]
Deguelin	DMXT7WG	Investigative	Deguelin decreases the expression of Alpha-aminoadipic semialdehyde dehydrogenase (ALDH7A1).	[52]
Paraquat	DMR8O3X	Investigative	Paraquat decreases the expression of Alpha-aminoadipic semialdehyde dehydrogenase (ALDH7A1).	[54]
BRN-3548355	DM4KXT0	Investigative	BRN-3548355 increases the expression of Alpha-aminoadipic semialdehyde dehydrogenase (ALDH7A1).	[55]
biochanin A	DM0HPWY	Investigative	biochanin A decreases the expression of Alpha-aminoadipic semialdehyde dehydrogenase (ALDH7A1).	[56]

1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Dihydroartemisinin	DMBXVMZ	Approved	Dihydroartemisinin affects the binding of Alpha-aminoadipic semialdehyde dehydrogenase (ALDH7A1).	[48]

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