Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTX7402E)

• DOT Name: Gem-associated protein 4 (GEMIN4)
• Synonyms: Gemin-4; Component of gems 4; p97
• Gene Name: GEMIN4
• Related Disease:
  Malaria
  Adult lymphoma
  Adult T-cell leukemia/lymphoma
  Alcohol dependence
  Bladder cancer
  Carcinoma of esophagus
  Carcinoma of liver and intrahepatic biliary tract
  Cataract
  Clear cell renal carcinoma
  Depression
  Esophageal cancer
  Esophageal squamous cell carcinoma
  Frontotemporal dementia
  Hepatocellular carcinoma
  Inclusion body myopathy with Paget disease of bone and frontotemporal dementia
  Liver cancer
  Lung adenocarcinoma
  Lymphoma
  Mantle cell lymphoma
  Neoplasm of esophagus
  Neurodevelopmental disorder with microcephaly, cataracts, and renal abnormalities
  Pediatric lymphoma
  Pick disease
  Plasma cell myeloma
  Pneumonitis
  Renal cell carcinoma
  Squamous cell carcinoma
  Tuberculosis
  Urinary bladder cancer
  Urinary bladder neoplasm
  Amyotrophic lateral sclerosis
  Breast cancer
  Breast carcinoma
  Cervical carcinoma
  Dementia
  Herpes simplex infection
  Influenza
  Prostate cancer
  Prostate carcinoma
  Ankylosing spondylitis
  Bone Paget disease
  Carcinoma
  Cervical cancer
  Cutaneous squamous cell carcinoma
  Lung cancer
  Lung carcinoma
  Melanoma
  Myopathy
  Nervous system disease
• UniProt ID: GEMI4_HUMAN
• Sequence:
  MDLGPLNICEEMTILHGGFLLAEQLFHPKALAELTKSDWERVGRPIVEALREISSAAAHS
  QPFAWKKKALIIIWAKVLQPHPVTPSDTETRWQEDLFFSVGNMIPTINHTILFELLKSLE
  ASGLFIQLLMALPTTICHAELERFLEHVTVDTSAEDVAFFLDVWWEVMKHKGHPQDPLLS
  QFSAMAHKYLPALDEFPHPPKRLRSDPDACPTMPLLAMLLRGLTQIQSRILGPGRKCCAL
  ANLADMLTVFALTEDDPQEVSATVYLDKLATVISVWNSDTQNPYHQQALAEKVKEAERDV
  SLTSLAKLPSETIFVGCEFLHHLLREWGEELQAVLRSSQGTSYDSYRLCDSLTSFSQNAT
  LYLNRTSLSKEDRQVVSELAECVRDFLRKTSTVLKNRALEDITASIAMAVIQQKMDRHME
  VCYIFASEKKWAFSDEWVACLGSNRALFRQPDLVLRLLETVIDVSTADRAIPESQIRQVI
  HLILECYADLSLPGKNKVLAGILRSWGRKGLSEKLLAYVEGFQEDLNTTFNQLTQSASEQ
  GLAKAVASVARLVIVHPEVTVKKMCSLAVVNLGTHKFLAQILTAFPALRFVEEQGPNSSA
  TFMVSCLKETVWMKFSTPKEEKQFLELLNCLMSPVKPQGIPVAALLEPDEVLKEFVLPFL
  RLDVEEVDLSLRIFIQTLEANACREEYWLQTCSPFPLLFSLCQLLDRFSKYWQLPKEKRC
  LSLDRKDLAIHILELLCEIVSANAETFSPDVWIKSLSWLHRKLEQLDWTVGLRLKSFFEG
  HFKCEVPATLFEICKLSEDEWTSQAHPGYGAGTGLLAWMECCCVSSGISERMLSLLVVDV
  GNPEEVRLFSKGFLVALVQVMPWCSPQEWQRLHQLTRRLLEKQLLHVPYSLEYIQFVPLL
  NLKPFAQELQLSVLFLRTFQFLCSHSCRDWLPLEGWNHVVKLLCGSLTRLLDSVRAIQAA
  GPWVQGPEQDLTQEALFVYTQVFCHALHIMAMLHPEVCEPLYVLALETLTCYETLSKTNP
  SVSSLLQRAHEQRFLKSIAEGIGPEERRQTLLQKMSSF
• Function: The SMN complex catalyzes the assembly of small nuclear ribonucleoproteins (snRNPs), the building blocks of the spliceosome, and thereby plays an important role in the splicing of cellular pre-mRNAs. Most spliceosomal snRNPs contain a common set of Sm proteins SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF and SNRPG that assemble in a heptameric protein ring on the Sm site of the small nuclear RNA to form the core snRNP (Sm core). In the cytosol, the Sm proteins SNRPD1, SNRPD2, SNRPE, SNRPF and SNRPG are trapped in an inactive 6S pICln-Sm complex by the chaperone CLNS1A that controls the assembly of the core snRNP. To assemble core snRNPs, the SMN complex accepts the trapped 5Sm proteins from CLNS1A forming an intermediate. Binding of snRNA inside 5Sm triggers eviction of the SMN complex, thereby allowing binding of SNRPD3 and SNRPB to complete assembly of the core snRNP.
• Reactome Pathway:
  SARS-CoV-2 modulates host translation machinery (R-HSA-9754678)
  snRNP Assembly (R-HSA-191859)

Molecular Interaction Atlas (MIA) of This DOT

49 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Malaria	DISQ9Y50	Definitive	Biomarker	[1]
Adult lymphoma	DISK8IZR	Strong	Altered Expression	[2]
Adult T-cell leukemia/lymphoma	DIS882XU	Strong	Biomarker	[3]
Alcohol dependence	DIS4ZSCO	Strong	Biomarker	[4]
Bladder cancer	DISUHNM0	Strong	Genetic Variation	[5]
Carcinoma of esophagus	DISS6G4D	Strong	Genetic Variation	[6]
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	Strong	Biomarker	[7]
Cataract	DISUD7SL	Strong	Genetic Variation	[8]
Clear cell renal carcinoma	DISBXRFJ	Strong	Genetic Variation	[9]
Depression	DIS3XJ69	Strong	Genetic Variation	[10]
Esophageal cancer	DISGB2VN	Strong	Genetic Variation	[6]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Genetic Variation	[11]
Frontotemporal dementia	DISKYHXL	Strong	Genetic Variation	[12]
Hepatocellular carcinoma	DIS0J828	Strong	Genetic Variation	[13]
Inclusion body myopathy with Paget disease of bone and frontotemporal dementia	DISK4S94	Strong	Genetic Variation	[14]
Liver cancer	DISDE4BI	Strong	Biomarker	[7]
Lung adenocarcinoma	DISD51WR	Strong	Biomarker	[15]
Lymphoma	DISN6V4S	Strong	Altered Expression	[2]
Mantle cell lymphoma	DISFREOV	Strong	Biomarker	[16]
Neoplasm of esophagus	DISOLKAQ	Strong	Genetic Variation	[6]
Neurodevelopmental disorder with microcephaly, cataracts, and renal abnormalities	DIS1BXKX	Strong	Autosomal recessive	[17]
Pediatric lymphoma	DIS51BK2	Strong	Altered Expression	[2]
Pick disease	DISP6X50	Strong	Genetic Variation	[12]
Plasma cell myeloma	DIS0DFZ0	Strong	Biomarker	[18]
Pneumonitis	DIS88E0K	Strong	Genetic Variation	[19]
Renal cell carcinoma	DISQZ2X8	Strong	Genetic Variation	[9]
Squamous cell carcinoma	DISQVIFL	Strong	Posttranslational Modification	[20]
Tuberculosis	DIS2YIMD	Strong	Genetic Variation	[21]
Urinary bladder cancer	DISDV4T7	Strong	Genetic Variation	[5]
Urinary bladder neoplasm	DIS7HACE	Strong	Genetic Variation	[5]
Amyotrophic lateral sclerosis	DISF7HVM	moderate	Genetic Variation	[22]
Breast cancer	DIS7DPX1	moderate	Genetic Variation	[23]
Breast carcinoma	DIS2UE88	moderate	Genetic Variation	[23]
Cervical carcinoma	DIST4S00	moderate	Biomarker	[15]
Dementia	DISXL1WY	moderate	Biomarker	[24]
Herpes simplex infection	DISL1SAV	moderate	Altered Expression	[25]
Influenza	DIS3PNU3	moderate	Altered Expression	[25]
Prostate cancer	DISF190Y	moderate	Genetic Variation	[26]
Prostate carcinoma	DISMJPLE	moderate	Genetic Variation	[26]
Ankylosing spondylitis	DISRC6IR	Limited	Genetic Variation	[27]
Bone Paget disease	DISIPS4V	Limited	Genetic Variation	[28]
Carcinoma	DISH9F1N	Limited	Biomarker	[29]
Cervical cancer	DISFSHPF	Limited	Biomarker	[30]
Cutaneous squamous cell carcinoma	DIS3LXUG	Limited	Altered Expression	[31]
Lung cancer	DISCM4YA	Limited	Genetic Variation	[32]
Lung carcinoma	DISTR26C	Limited	Genetic Variation	[32]
Melanoma	DIS1RRCY	Limited	Biomarker	[33]
Myopathy	DISOWG27	Limited	Genetic Variation	[12]
Nervous system disease	DISJ7GGT	Limited	Genetic Variation	[34]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Gem-associated protein 4 (GEMIN4).	[35]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Gem-associated protein 4 (GEMIN4).	[46]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Gem-associated protein 4 (GEMIN4).	[36]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Gem-associated protein 4 (GEMIN4).	[37]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Gem-associated protein 4 (GEMIN4).	[38]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Gem-associated protein 4 (GEMIN4).	[39]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Gem-associated protein 4 (GEMIN4).	[40]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Gem-associated protein 4 (GEMIN4).	[41]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Gem-associated protein 4 (GEMIN4).	[41]
Demecolcine	DMCZQGK	Approved	Demecolcine decreases the expression of Gem-associated protein 4 (GEMIN4).	[42]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Gem-associated protein 4 (GEMIN4).	[43]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Gem-associated protein 4 (GEMIN4).	[44]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Gem-associated protein 4 (GEMIN4).	[45]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Gem-associated protein 4 (GEMIN4).	[47]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Gem-associated protein 4 (GEMIN4).	[48]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Gem-associated protein 4 (GEMIN4).	[49]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Gem-associated protein 4 (GEMIN4).	[50]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Gem-associated protein 4 (GEMIN4).	[51]
chloropicrin	DMSGBQA	Investigative	chloropicrin decreases the expression of Gem-associated protein 4 (GEMIN4).	[52]
Nickel chloride	DMI12Y8	Investigative	Nickel chloride decreases the expression of Gem-associated protein 4 (GEMIN4).	[53]

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