Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTNZ6AO4)

• DOT Name: Cystatin-C (CST3)
• Synonyms: Cystatin-3; Gamma-trace; Neuroendocrine basic polypeptide; Post-gamma-globulin
• Gene Name: CST3
• Related Disease:
  Acute kidney injury
  Acute myelogenous leukaemia
  ACys amyloidosis
  Advanced cancer
  Age-related macular degeneration
  Amyotrophic lateral sclerosis type 1
  Arteriosclerosis
  Atherosclerosis
  Cerebral amyloid angiopathy
  Chronic kidney disease
  Familial Alzheimer disease
  Familial amyotrophic lateral sclerosis
  High blood pressure
  Intracerebral hemorrhage
  Intracranial meningioma
  Liver cirrhosis
  Neoplasm
  Nephropathy
  Non-insulin dependent diabetes
  Acute coronary syndrome
  Coronary heart disease
  ITM2B amyloidosis
  Meningioma
  Cardiac failure
  Dementia
  Diabetic kidney disease
  Stroke
• UniProt ID: CYTC_HUMAN
• PDB ID: 1G96; 1R4C; 1TIJ; 3GAX; 3NX0; 3PS8; 3QRD; 3S67; 3SVA; 6ROA; 6RPV
• Pfam ID: PF00031
• Sequence:
  MAGPLRAPLLLLAILAVALAVSPAAGSSPGKPPRLVGGPMDASVEEEGVRRALDFAVGEY
  NKASNDMYHSRALQVVRARKQIVAGVNYFLDVELGRTTCTKTQPNLDNCPFHDQPHLKRK
  AFCSFQIYAVPWQGTMTLSKSTCQDA
• Function: As an inhibitor of cysteine proteinases, this protein is thought to serve an important physiological role as a local regulator of this enzyme activity.
• Tissue Specificity: Expressed in submandibular and sublingual saliva but not in parotid saliva (at protein level). Expressed in various body fluids, such as the cerebrospinal fluid and plasma. Expressed in highest levels in the epididymis, vas deferens, brain, thymus, and ovary and the lowest in the submandibular gland.
• KEGG Pathway: Salivary secretion (hsa04970)
• Reactome Pathway:
  Neutrophil degranulation (R-HSA-6798695)
  Post-translational protein phosphorylation (R-HSA-8957275)
  Amyloid fiber formation (R-HSA-977225)
  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

27 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute kidney injury	DISXZG0T	Strong	Biomarker	[1]
Acute myelogenous leukaemia	DISCSPTN	Strong	Biomarker	[2]
ACys amyloidosis	DIS9H9YB	Strong	Autosomal dominant	[3]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[4]
Age-related macular degeneration	DIS0XS2C	Strong	Genetic Variation	[5]
Amyotrophic lateral sclerosis type 1	DIS5A2M0	Strong	Biomarker	[6]
Arteriosclerosis	DISK5QGC	Strong	Biomarker	[7]
Atherosclerosis	DISMN9J3	Strong	Biomarker	[7]
Cerebral amyloid angiopathy	DIS1KAQI	Strong	Biomarker	[8]
Chronic kidney disease	DISW82R7	Strong	Biomarker	[9]
Familial Alzheimer disease	DISE75U4	Strong	Biomarker	[10]
Familial amyotrophic lateral sclerosis	DISWZ9CJ	Strong	Biomarker	[6]
High blood pressure	DISY2OHH	Strong	Biomarker	[11]
Intracerebral hemorrhage	DISC81BT	Strong	Biomarker	[12]
Intracranial meningioma	DISD09EF	Strong	Biomarker	[13]
Liver cirrhosis	DIS4G1GX	Strong	Biomarker	[14]
Neoplasm	DISZKGEW	Strong	Biomarker	[15]
Nephropathy	DISXWP4P	Strong	Biomarker	[16]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Biomarker	[11]
Acute coronary syndrome	DIS7DYEW	moderate	Altered Expression	[17]
Coronary heart disease	DIS5OIP1	moderate	Biomarker	[18]
ITM2B amyloidosis	DISO8UGV	moderate	Genetic Variation	[19]
Meningioma	DISPT4TG	Disputed	Biomarker	[13]
Cardiac failure	DISDC067	Limited	Biomarker	[20]
Dementia	DISXL1WY	Limited	Biomarker	[21]
Diabetic kidney disease	DISJMWEY	Limited	Altered Expression	[22]
Stroke	DISX6UHX	Limited	Altered Expression	[23]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Cystatin-C (CST3).	[24]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Cystatin-C (CST3).	[25]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Cystatin-C (CST3).	[26]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Cystatin-C (CST3).	[27]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Cystatin-C (CST3).	[28]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Cystatin-C (CST3).	[29]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Cystatin-C (CST3).	[30]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Cystatin-C (CST3).	[31]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Cystatin-C (CST3).	[32]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Cystatin-C (CST3).	[33]
Selenium	DM25CGV	Approved	Selenium increases the expression of Cystatin-C (CST3).	[34]
Isotretinoin	DM4QTBN	Approved	Isotretinoin increases the expression of Cystatin-C (CST3).	[35]
Azacitidine	DMTA5OE	Approved	Azacitidine increases the expression of Cystatin-C (CST3).	[36]
Gentamicin	DMKINJO	Approved	Gentamicin increases the expression of Cystatin-C (CST3).	[37]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene increases the expression of Cystatin-C (CST3).	[26]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Cystatin-C (CST3).	[34]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Cystatin-C (CST3).	[38]
Scriptaid	DM9JZ21	Preclinical	Scriptaid affects the expression of Cystatin-C (CST3).	[39]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Cystatin-C (CST3).	[41]
chloropicrin	DMSGBQA	Investigative	chloropicrin decreases the expression of Cystatin-C (CST3).	[42]
Choline	DM5D9YK	Investigative	Choline affects the expression of Cystatin-C (CST3).	[43]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Cystatin-C (CST3).	[40]

References

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