Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTDX9687)

• DOT Name: Mitochondrial import inner membrane translocase subunit Tim8 A (TIMM8A)
• Synonyms: Deafness dystonia protein 1; X-linked deafness dystonia protein
• Gene Name: TIMM8A
• Related Disease:
  Deafness dystonia syndrome
  Metastatic malignant neoplasm
  Non-insulin dependent diabetes
  Pancreatic cancer
  Acute lymphocytic leukaemia
  Acute myelogenous leukaemia
  Adenocarcinoma
  Advanced cancer
  Bone osteosarcoma
  Breast cancer
  Breast carcinoma
  Carcinoma of esophagus
  Cardiac failure
  Cervical cancer
  Cervical carcinoma
  Colon carcinoma
  Congestive heart failure
  Deafness
  Endometrial carcinoma
  Epithelial ovarian cancer
  Esophageal squamous cell carcinoma
  Fanconi anemia complementation group A
  Fanconi's anemia
  Gastric cancer
  Hepatocellular carcinoma
  Hyperglycemia
  Major depressive disorder
  Melanoma
  Nasopharyngeal carcinoma
  Neoplasm
  Non-alcoholic fatty liver disease
  Non-small-cell lung cancer
  Osteosarcoma
  Ovarian cancer
  Ovarian neoplasm
  Plasma cell myeloma
  Prostate cancer
  Prostate carcinoma
  Stomach cancer
  T-cell acute lymphoblastic leukaemia
  Triple negative breast cancer
  Dystonia
  Head-neck squamous cell carcinoma
  Lung adenocarcinoma
  Transitional cell carcinoma
  Carcinoma
  Colorectal carcinoma
  Glioma
  Parkinson disease
• UniProt ID: TIM8A_HUMAN
• Pfam ID: PF02953
• Sequence:
  MDSSSSSSAAGLGAVDPQLQHFIEVETQKQRFQQLVHQMTELCWEKCMDKPGPKLDSRAE
  ACFVNCVERFIDTSQFILNRLEQTQKSKPVFSESLSD
• Function: Mitochondrial intermembrane chaperone that participates in the import and insertion of some multi-pass transmembrane proteins into the mitochondrial inner membrane. Also required for the transfer of beta-barrel precursors from the TOM complex to the sorting and assembly machinery (SAM complex) of the outer membrane. Acts as a chaperone-like protein that protects the hydrophobic precursors from aggregation and guide them through the mitochondrial intermembrane space. The TIMM8-TIMM13 complex mediates the import of proteins such as TIMM23, SLC25A12/ARALAR1 and SLC25A13/ARALAR2, while the predominant TIMM9-TIMM10 70 kDa complex mediates the import of much more proteins. Probably necessary for normal neurologic development.
• Tissue Specificity: Highly expressed in fetal and adult brain, followed by fetal lung, liver and kidney. Also expressed in heart, placenta, lung, liver, kidney, pancreas, skeletal muscle and heart.
• Reactome Pathway: Mitochondrial protein import (R-HSA-1268020)

Molecular Interaction Atlas (MIA) of This DOT

49 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Deafness dystonia syndrome	DIS0480U	Definitive	X-linked	[1]
Metastatic malignant neoplasm	DIS86UK6	Definitive	Biomarker	[2]
Non-insulin dependent diabetes	DISK1O5Z	Definitive	Biomarker	[3]
Pancreatic cancer	DISJC981	Definitive	Biomarker	[4]
Acute lymphocytic leukaemia	DISPX75S	Strong	Biomarker	[5]
Acute myelogenous leukaemia	DISCSPTN	Strong	Genetic Variation	[6]
Adenocarcinoma	DIS3IHTY	Strong	Biomarker	[7]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[8]
Bone osteosarcoma	DIST1004	Strong	Biomarker	[9]
Breast cancer	DIS7DPX1	Strong	Biomarker	[10]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[10]
Carcinoma of esophagus	DISS6G4D	Strong	Biomarker	[2]
Cardiac failure	DISDC067	Strong	Genetic Variation	[11]
Cervical cancer	DISFSHPF	Strong	Biomarker	[12]
Cervical carcinoma	DIST4S00	Strong	Biomarker	[12]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[13]
Congestive heart failure	DIS32MEA	Strong	Genetic Variation	[11]
Deafness	DISKCLH4	Strong	Genetic Variation	[14]
Endometrial carcinoma	DISXR5CY	Strong	Genetic Variation	[15]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[16]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Biomarker	[17]
Fanconi anemia complementation group A	DIS8PZLI	Strong	Biomarker	[18]
Fanconi's anemia	DISGW6Q8	Strong	Biomarker	[18]
Gastric cancer	DISXGOUK	Strong	Biomarker	[19]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[20]
Hyperglycemia	DIS0BZB5	Strong	Biomarker	[21]
Major depressive disorder	DIS4CL3X	Strong	Biomarker	[22]
Melanoma	DIS1RRCY	Strong	Biomarker	[23]
Nasopharyngeal carcinoma	DISAOTQ0	Strong	Biomarker	[24]
Neoplasm	DISZKGEW	Strong	Biomarker	[25]
Non-alcoholic fatty liver disease	DISDG1NL	Strong	Biomarker	[3]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[26]
Osteosarcoma	DISLQ7E2	Strong	Biomarker	[9]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[16]
Ovarian neoplasm	DISEAFTY	Strong	Biomarker	[16]
Plasma cell myeloma	DIS0DFZ0	Strong	Biomarker	[27]
Prostate cancer	DISF190Y	Strong	Biomarker	[28]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[28]
Stomach cancer	DISKIJSX	Strong	Biomarker	[19]
T-cell acute lymphoblastic leukaemia	DIS17AI2	Strong	Genetic Variation	[29]
Triple negative breast cancer	DISAMG6N	Strong	Biomarker	[30]
Dystonia	DISJLFGW	moderate	Biomarker	[31]
Head-neck squamous cell carcinoma	DISF7P24	moderate	Biomarker	[32]
Lung adenocarcinoma	DISD51WR	moderate	Biomarker	[33]
Transitional cell carcinoma	DISWVVDR	moderate	Biomarker	[34]
Carcinoma	DISH9F1N	Limited	Altered Expression	[35]
Colorectal carcinoma	DIS5PYL0	Limited	Biomarker	[36]
Glioma	DIS5RPEH	Limited	Biomarker	[37]
Parkinson disease	DISQVHKL	Limited	Altered Expression	[38]

19 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 Mitochondrial import inner membrane translocase subunit Tim8 A (TIMM8A).	[39]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Mitochondrial import inner membrane translocase subunit Tim8 A (TIMM8A).	[40]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Mitochondrial import inner membrane translocase subunit Tim8 A (TIMM8A).	[41]
Acetaminophen	DMUIE76	Approved	Acetaminophen affects the expression of Mitochondrial import inner membrane translocase subunit Tim8 A (TIMM8A).	[42]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Mitochondrial import inner membrane translocase subunit Tim8 A (TIMM8A).	[43]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Mitochondrial import inner membrane translocase subunit Tim8 A (TIMM8A).	[44]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Mitochondrial import inner membrane translocase subunit Tim8 A (TIMM8A).	[45]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Mitochondrial import inner membrane translocase subunit Tim8 A (TIMM8A).	[46]
Selenium	DM25CGV	Approved	Selenium decreases the expression of Mitochondrial import inner membrane translocase subunit Tim8 A (TIMM8A).	[47]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Mitochondrial import inner membrane translocase subunit Tim8 A (TIMM8A).	[48]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Mitochondrial import inner membrane translocase subunit Tim8 A (TIMM8A).	[47]
GSK2110183	DMZHB37	Phase 2	GSK2110183 decreases the expression of Mitochondrial import inner membrane translocase subunit Tim8 A (TIMM8A).	[49]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Mitochondrial import inner membrane translocase subunit Tim8 A (TIMM8A).	[51]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Mitochondrial import inner membrane translocase subunit Tim8 A (TIMM8A).	[53]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Mitochondrial import inner membrane translocase subunit Tim8 A (TIMM8A).	[54]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Mitochondrial import inner membrane translocase subunit Tim8 A (TIMM8A).	[55]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Mitochondrial import inner membrane translocase subunit Tim8 A (TIMM8A).	[56]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Mitochondrial import inner membrane translocase subunit Tim8 A (TIMM8A).	[57]
OXYQUINOLINE	DMZVS9Y	Investigative	OXYQUINOLINE decreases the expression of Mitochondrial import inner membrane translocase subunit Tim8 A (TIMM8A).	[46]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Mitochondrial import inner membrane translocase subunit Tim8 A (TIMM8A).	[50]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Mitochondrial import inner membrane translocase subunit Tim8 A (TIMM8A).	[52]

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