Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTEC7EP7)

• DOT Name: Very-long-chain (HACD1)
• Synonyms: 3R)-3-hydroxyacyl-CoA dehydratase 1 (EC 4.2.1.134; 3-hydroxyacyl-CoA dehydratase 1; HACD1; Cementum-attachment protein; CAP; Protein-tyrosine phosphatase-like member A
• Gene Name: HACD1
• Related Disease:
  Congenital myopathy
  Non-insulin dependent diabetes
  Tuberculosis
  Acute leukaemia
  Arrhythmia
  Bacteremia
  Beta thalassemia
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Chromosomal disorder
  Colitis
  Cryptococcosis
  Epilepsy
  Fatty liver disease
  Hepatitis B virus infection
  Hepatocellular carcinoma
  Huntington disease
  Lyme disease
  Mantle cell lymphoma
  Neoplasm
  Non-alcoholic fatty liver disease
  Perry syndrome
  Pneumonia
  Polycystic ovarian syndrome
  Prostate cancer
  Prostate carcinoma
  Prostate neoplasm
  Thalassemia
  Type-1/2 diabetes
  Adult glioblastoma
  Female hypogonadism
  Glioblastoma multiforme
  Influenza
  Invasive breast carcinoma
  Methicillin-resistant staphylococci infection
  Congenital fiber-type disproportion myopathy
  Aplastic anemia
  Epithelial ovarian cancer
  Advanced cancer
  Asthma
  Bone osteosarcoma
  Gastric cancer
  Osteosarcoma
  Stomach cancer
  Stroke
• UniProt ID: HACD1_HUMAN
• EC Number: 4.2.1.134
• Pfam ID: PF04387
• Sequence:
  MGRLTEAAAAGSGSRAAGWAGSPPTLLPLSPTSPRCAATMASSDEDGTNGGASEAGEDRE
  APGERRRLGVLATAWLTFYDIAMTAGWLVLAIAMVRFYMEKGTHRGLYKSIQKTLKFFQT
  FALLEIVHCLIGIVPTSVIVTGVQVSSRIFMVWLITHSIKPIQNEESVVLFLVAWTVTEI
  TRYSFYTFSLLDHLPYFIKWARYNFFIILYPVGVAGELLTIYAALPHVKKTGMFSIRLPN
  KYNVSFDYYYFLLITMASYIPLFPQLYFHMLRQRRKVLHGEVIVEKDD
• Function: [Isoform 1]: Catalyzes the third of the four reactions of the long-chain fatty acids elongation cycle. This endoplasmic reticulum-bound enzymatic process, allows the addition of two carbons to the chain of long- and very long-chain fatty acids/VLCFAs per cycle. This enzyme catalyzes the dehydration of the 3-hydroxyacyl-CoA intermediate into trans-2,3-enoyl-CoA, within each cycle of fatty acid elongation. Thereby, it participates in the production of VLCFAs of different chain lengths that are involved in multiple biological processes as precursors of membrane lipids and lipid mediators; [Isoform 2]: In tooth development, may play a role in the recruitment and the differentiation of cells that contribute to cementum formation. May also bind hydroxyapatite and regulate its crystal nucleation to form cementum.
• Tissue Specificity: Isoform 1 is highly expressed in the myocardium, and to a lesser extent in skeletal and smooth muscular tissues including those from stomach, jejunum, and bladder. Also detected in gingival fibroblasts, periodontal ligament cells, osteoblasts and cementoblasts . Isoform 2 is specifically expressed by cementoblasts but also detected in periodontal ligament cells, heart, liver and kidney (at protein level) .
• KEGG Pathway:
  Fatty acid elongation (hsa00062)
  Biosynthesis of unsaturated fatty acids (hsa01040)
  Metabolic pathways (hsa01100)
  Fatty acid metabolism (hsa01212)
• Reactome Pathway: Synthesis of very long-chain fatty acyl-CoAs (R-HSA-75876)

Molecular Interaction Atlas (MIA) of This DOT

46 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Congenital myopathy	DISLSK9G	Definitive	Autosomal recessive	[1]
Non-insulin dependent diabetes	DISK1O5Z	Definitive	Biomarker	[2]
Tuberculosis	DIS2YIMD	Definitive	Biomarker	[3]
Acute leukaemia	DISDQFDI	Strong	Biomarker	[4]
Arrhythmia	DISFF2NI	Strong	Genetic Variation	[5]
Bacteremia	DIS6N9RZ	Strong	Genetic Variation	[6]
Beta thalassemia	DIS5RCQK	Strong	Genetic Variation	[7]
Breast cancer	DIS7DPX1	Strong	Biomarker	[8]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[9]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[10]
Chromosomal disorder	DISM5BB5	Strong	Biomarker	[11]
Colitis	DISAF7DD	Strong	Genetic Variation	[12]
Cryptococcosis	DISDYDTK	Strong	Biomarker	[13]
Epilepsy	DISBB28L	Strong	Biomarker	[14]
Fatty liver disease	DIS485QZ	Strong	Biomarker	[15]
Hepatitis B virus infection	DISLQ2XY	Strong	Biomarker	[16]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[17]
Huntington disease	DISQPLA4	Strong	Biomarker	[18]
Lyme disease	DISO70G5	Strong	Biomarker	[19]
Mantle cell lymphoma	DISFREOV	Strong	Biomarker	[20]
Neoplasm	DISZKGEW	Strong	Biomarker	[21]
Non-alcoholic fatty liver disease	DISDG1NL	Strong	Biomarker	[22]
Perry syndrome	DIS8YKKM	Strong	Genetic Variation	[23]
Pneumonia	DIS8EF3M	Strong	Biomarker	[24]
Polycystic ovarian syndrome	DISZ2BNG	Strong	Biomarker	[25]
Prostate cancer	DISF190Y	Strong	Biomarker	[26]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[26]
Prostate neoplasm	DISHDKGQ	Strong	Genetic Variation	[27]
Thalassemia	DIS76XZB	Strong	Genetic Variation	[28]
Type-1/2 diabetes	DISIUHAP	Strong	Biomarker	[29]
Adult glioblastoma	DISVP4LU	moderate	Biomarker	[30]
Female hypogonadism	DISWASB4	moderate	Altered Expression	[31]
Glioblastoma multiforme	DISK8246	moderate	Biomarker	[30]
Influenza	DIS3PNU3	moderate	Biomarker	[32]
Invasive breast carcinoma	DISANYTW	moderate	Biomarker	[33]
Methicillin-resistant staphylococci infection	DIS6DRDZ	moderate	Biomarker	[34]
Congenital fiber-type disproportion myopathy	DISU9T2M	Supportive	Autosomal dominant	[35]
Aplastic anemia	DISJRSC0	Disputed	Biomarker	[36]
Epithelial ovarian cancer	DIS56MH2	Disputed	Genetic Variation	[37]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[38]
Asthma	DISW9QNS	Limited	Biomarker	[39]
Bone osteosarcoma	DIST1004	Limited	Biomarker	[40]
Gastric cancer	DISXGOUK	Limited	Genetic Variation	[41]
Osteosarcoma	DISLQ7E2	Limited	Biomarker	[40]
Stomach cancer	DISKIJSX	Limited	Genetic Variation	[41]
Stroke	DISX6UHX	Limited	Biomarker	[42]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Fluorouracil	DMUM7HZ	Approved	Very-long-chain (HACD1) affects the response to substance of Fluorouracil.	[54]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Very-long-chain (HACD1).	[43]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Very-long-chain (HACD1).	[44]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Very-long-chain (HACD1).	[45]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Very-long-chain (HACD1).	[46]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Very-long-chain (HACD1).	[47]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Very-long-chain (HACD1).	[48]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Very-long-chain (HACD1).	[49]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Very-long-chain (HACD1).	[50]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Very-long-chain (HACD1).	[48]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Very-long-chain (HACD1).	[51]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Very-long-chain (HACD1).	[52]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Very-long-chain (HACD1).	[48]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Very-long-chain (HACD1).	[53]

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