Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTSB55D2)

• DOT Name: 17-beta-hydroxysteroid dehydrogenase type 6 (HSD17B6)
• Synonyms: 17-beta-HSD 6; 17-beta-HSD6; EC 1.1.1.105; EC 1.1.1.209; EC 1.1.1.239; EC 1.1.1.53; EC 1.1.1.62; 3-alpha->beta-hydroxysteroid epimerase; 3-alpha->beta-HSE; Oxidative 3-alpha hydroxysteroid dehydrogenase; Short chain dehydrogenase/reductase family 9C member 6
• Gene Name: HSD17B6
• Related Disease:
  Non-insulin dependent diabetes
  Spinocerebellar ataxia type 1
  Advanced cancer
  Alzheimer disease
  Bacillary dysentery
  Bullous pemphigoid
  Coffin-Lowry syndrome
  Congenital vertical talus
  Dengue
  Exocrine pancreatic insufficiency
  Huntington disease
  Inherited retinal dystrophy
  Melioidosis
  Metastatic malignant neoplasm
  Multiple sclerosis
  Neoplasm
  Non-syndromic ichthyosis
  Parkinson disease
  Retinitis pigmentosa
  Sjogren-Larsson syndrome
  Systemic lupus erythematosus
  Tuberculosis
  Chronic obstructive pulmonary disease
  Clear cell renal carcinoma
  Leber congenital amaurosis
  Neuroblastoma
  Prostate cancer
  Prostate carcinoma
  Congenital adrenal hyperplasia due to 11-beta-hydroxylase deficiency
  Lung cancer
  Lung carcinoma
  Breast cancer
  Breast carcinoma
  Endometrial cancer
  Endometrial carcinoma
  Neurofibromatosis type 1
• UniProt ID: H17B6_HUMAN
• EC Number: 1.1.1.105; 1.1.1.209; 1.1.1.239; 1.1.1.53; 1.1.1.62
• Pfam ID: PF00106
• Sequence:
  MWLYLAAFVGLYYLLHWYRERQVVSHLQDKYVFITGCDSGFGNLLARQLDARGLRVLAAC
  LTEKGAEQLRGQTSDRLETVTLDVTKMESIAAATQWVKEHVGDRGLWGLVNNAGILTPIT
  LCEWLNTEDSMNMLKVNLIGVIQVTLSMLPLVRRARGRIVNVSSILGRVAFFVGGYCVSK
  YGVEAFSDILRREIQHFGVKISIVEPGYFRTGMTNMTQSLERMKQSWKEAPKHIKETYGQ
  QYFDALYNIMKEGLLNCSTNLNLVTDCMEHALTSVHPRTRYSAGWDAKFFFIPLSYLPTS
  LADYILTRSWPKPAQAV
• Function: NAD-dependent oxidoreductase with broad substrate specificity that shows both oxidative and reductive activity (in vitro). Has 17-beta-hydroxysteroid dehydrogenase activity towards various steroids (in vitro). Converts 5-alpha-androstan-3-alpha,17-beta-diol to androsterone and estradiol to estrone (in vitro). Has 3-alpha-hydroxysteroid dehydrogenase activity towards androsterone (in vitro). Has retinol dehydrogenase activity towards all-trans-retinol (in vitro). Can convert androsterone to epi-androsterone. Androsterone is first oxidized to 5-alpha-androstane-3,17-dione and then reduced to epi-andosterone. Can act on both C-19 and C-21 3-alpha-hydroxysteroids.
• Tissue Specificity: Detected in liver and prostate (at protein level). Detected in adult liver, lung, brain, placenta, prostate, adrenal gland, testis, mammary gland, spleen, spinal cord and uterus. Detected in caudate nucleus, and at lower levels in amygdala, corpus callosum, hippocampus, substantia nigra and thalamus. Detected in fetal lung, liver and brain.
• KEGG Pathway:
  Steroid hormone biosynthesis (hsa00140)
  Retinol metabolism (hsa00830)
  Metabolic pathways (hsa01100)
  Biosynthesis of cofactors (hsa01240)
• Reactome Pathway: The canonical retinoid cycle in rods (twilight vision) (R-HSA-2453902)

Molecular Interaction Atlas (MIA) of This DOT

36 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Non-insulin dependent diabetes	DISK1O5Z	Definitive	Altered Expression	[1]
Spinocerebellar ataxia type 1	DISF7BO2	Definitive	Biomarker	[2]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[3]
Alzheimer disease	DISF8S70	Strong	Biomarker	[4]
Bacillary dysentery	DISFZHKN	Strong	Biomarker	[5]
Bullous pemphigoid	DISOJLKV	Strong	Genetic Variation	[6]
Coffin-Lowry syndrome	DISMTBDA	Strong	Altered Expression	[7]
Congenital vertical talus	DISZF3HD	Strong	Biomarker	[8]
Dengue	DISKH221	Strong	Altered Expression	[9]
Exocrine pancreatic insufficiency	DISCZYU2	Strong	Biomarker	[10]
Huntington disease	DISQPLA4	Strong	Biomarker	[11]
Inherited retinal dystrophy	DISGGL77	Strong	Genetic Variation	[12]
Melioidosis	DISB13HR	Strong	Biomarker	[13]
Metastatic malignant neoplasm	DIS86UK6	Strong	Altered Expression	[14]
Multiple sclerosis	DISB2WZI	Strong	Biomarker	[15]
Neoplasm	DISZKGEW	Strong	Biomarker	[16]
Non-syndromic ichthyosis	DISZ9QBQ	Strong	Genetic Variation	[17]
Parkinson disease	DISQVHKL	Strong	Biomarker	[18]
Retinitis pigmentosa	DISCGPY8	Strong	Genetic Variation	[19]
Sjogren-Larsson syndrome	DISP943Y	Strong	Genetic Variation	[20]
Systemic lupus erythematosus	DISI1SZ7	Strong	Biomarker	[15]
Tuberculosis	DIS2YIMD	Strong	Biomarker	[21]
Chronic obstructive pulmonary disease	DISQCIRF	moderate	Altered Expression	[22]
Clear cell renal carcinoma	DISBXRFJ	moderate	Biomarker	[23]
Leber congenital amaurosis	DISMGH8F	moderate	Biomarker	[24]
Neuroblastoma	DISVZBI4	moderate	Biomarker	[25]
Prostate cancer	DISF190Y	moderate	Biomarker	[26]
Prostate carcinoma	DISMJPLE	moderate	Biomarker	[26]
Congenital adrenal hyperplasia due to 11-beta-hydroxylase deficiency	DISBTYRN	Disputed	Genetic Variation	[27]
Lung cancer	DISCM4YA	Disputed	Genetic Variation	[28]
Lung carcinoma	DISTR26C	Disputed	Genetic Variation	[28]
Breast cancer	DIS7DPX1	Limited	Genetic Variation	[29]
Breast carcinoma	DIS2UE88	Limited	Genetic Variation	[29]
Endometrial cancer	DISW0LMR	Limited	Altered Expression	[30]
Endometrial carcinoma	DISXR5CY	Limited	Altered Expression	[30]
Neurofibromatosis type 1	DIS53JH9	Limited	Altered Expression	[31]

16 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 17-beta-hydroxysteroid dehydrogenase type 6 (HSD17B6).	[32]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of 17-beta-hydroxysteroid dehydrogenase type 6 (HSD17B6).	[33]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of 17-beta-hydroxysteroid dehydrogenase type 6 (HSD17B6).	[34]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of 17-beta-hydroxysteroid dehydrogenase type 6 (HSD17B6).	[35]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of 17-beta-hydroxysteroid dehydrogenase type 6 (HSD17B6).	[33]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of 17-beta-hydroxysteroid dehydrogenase type 6 (HSD17B6).	[36]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of 17-beta-hydroxysteroid dehydrogenase type 6 (HSD17B6).	[37]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of 17-beta-hydroxysteroid dehydrogenase type 6 (HSD17B6).	[38]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of 17-beta-hydroxysteroid dehydrogenase type 6 (HSD17B6).	[39]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of 17-beta-hydroxysteroid dehydrogenase type 6 (HSD17B6).	[40]
Mifepristone	DMGZQEF	Approved	Mifepristone decreases the expression of 17-beta-hydroxysteroid dehydrogenase type 6 (HSD17B6).	[41]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of 17-beta-hydroxysteroid dehydrogenase type 6 (HSD17B6).	[42]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of 17-beta-hydroxysteroid dehydrogenase type 6 (HSD17B6).	[43]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of 17-beta-hydroxysteroid dehydrogenase type 6 (HSD17B6).	[38]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of 17-beta-hydroxysteroid dehydrogenase type 6 (HSD17B6).	[44]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of 17-beta-hydroxysteroid dehydrogenase type 6 (HSD17B6).	[45]

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