Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTMORU7G)

• DOT Name: Geminin coiled-coil domain-containing protein 1 (GMNC)
• Gene Name: GMNC
• Related Disease:
  Alzheimer disease
  Congenital hydrocephalus
  Isolated neonatal sclerosing cholangitis
  Male infertility
• UniProt ID: GEMC1_HUMAN
• PDB ID: 5C9N
• Sequence:
  MNTILPCQDQYFVGGQSYNCPYSTTTSESSVDVSTETWVSFWAAGLLDNRELQQAPQAQE
  SFSDSNFPLPDLCSWEEAQLSSQLYRNKQLQDTLVQKEEELARLHEENNHLRQYLNSALV
  KCLEEKAKKLLSSDEFSKAYGKFRKGKRKSKEQRYSPAEIPHPKNAKRNLSSEFANCEEQ
  AGPPVDPWVLQTLGLKDLDTIDDTSSANYSALASHPRRVASTFSQFPDDAVDYKNIPRED
  MPIDYRGDRTTPLHSTATHGEDFHILSQLSNPPVGLKTLPYYTAHVSPNKTEMAFSTSLS
  PHCNVKTHSFHQGQAFVRRDEEGGWKFTWVPKQS
• Function: Regulator of DNA replication. Promotes initiation of chromosomal DNA replication by mediating TOPBP1- and CDK2-dependent recruitment of CDC45L onto replication origins.

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Alzheimer disease	DISF8S70	Strong	Genetic Variation	[1]
Congenital hydrocephalus	DIS7O6UL	Strong	Biomarker	[2]
Isolated neonatal sclerosing cholangitis	DIS6G5UY	Strong	Biomarker	[2]
Male infertility	DISY3YZZ	Strong	Biomarker	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Malathion	DMXZ84M	Approved	Malathion increases the expression of Geminin coiled-coil domain-containing protein 1 (GMNC).	[4]

1 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 affects the methylation of Geminin coiled-coil domain-containing protein 1 (GMNC).	[5]

References

• [1] GWAS of cerebrospinal fluid tau levels identifies risk variants for Alzheimer's disease.Neuron. 2013 Apr 24;78(2):256-68. doi: 10.1016/j.neuron.2013.02.026. Epub 2013 Apr 4.
• [2] GemC1 is a critical switch for neural stem cell generation in the postnatal brain.Glia. 2019 Dec;67(12):2360-2373. doi: 10.1002/glia.23690. Epub 2019 Jul 22.
• [3] Defects in efferent duct multiciliogenesis underlie male infertility in GEMC1-, MCIDAS- or CCNO-deficient mice.Development. 2019 Apr 23;146(8):dev162628. doi: 10.1242/dev.162628.
• [4] Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
• [5] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.