Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT24ABVC)

• DOT Name: DOMON domain-containing protein FRRS1L (FRRS1L)
• Synonyms: Brain protein CG-6; Ferric-chelate reductase 1-like protein
• Gene Name: FRRS1L
• Related Disease:
  Epilepsy
  Attention deficit hyperactivity disorder
  Choreatic disease
  Cognitive impairment
  Developmental and epileptic encephalopathy, 37
  Nervous system disease
  Autosomal recessive non-syndromic intellectual disability
• UniProt ID: FRS1L_HUMAN
• Pfam ID: PF03351
• Sequence:
  MARPPRQHPGVWASLLLLLLTGPAACAASPADDGAGPGGRGPRGRARGDTGADEAVPRHD
  SSYGTFAGEFYDLRYLSEEGYPFPTAPPVDPFAKIKVDDCGKTKGCFRYGKPGCNAETCD
  YFLSYRMIGADVEFELSADTDGWVAVGFSSDKKMGGDDVMACVHDDNGRVRIQHFYNVGQ
  WAKEIQRNPARDEEGVFENNRVTCRFKRPVNVPRDETIVDLHLSWYYLFAWGPAIQGSIT
  RHDIDSPPASERVVSIYKYEDIFMPSAAYQTFSSPFCLLLIVALTFYLLMGTP
• Function: Important modulator of glutamate signaling pathway.
• Tissue Specificity: Expressed in adult and fetal brain. Very weak expression in medulla, spinal cord and in adult ovary.

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Epilepsy	DISBB28L	Definitive	Genetic Variation	[1]
Attention deficit hyperactivity disorder	DISL8MX9	Strong	Biomarker	[2]
Choreatic disease	DISH8K3M	Strong	CausalMutation	[3]
Cognitive impairment	DISH2ERD	Strong	Genetic Variation	[2]
Developmental and epileptic encephalopathy, 37	DISY66K2	Strong	Autosomal recessive	[3]
Nervous system disease	DISJ7GGT	Strong	Biomarker	[3]
Autosomal recessive non-syndromic intellectual disability	DISJWRZZ	Supportive	Autosomal recessive	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of DOMON domain-containing protein FRRS1L (FRRS1L).	[5]
Panobinostat	DM58WKG	Approved	Panobinostat decreases the expression of DOMON domain-containing protein FRRS1L (FRRS1L).	[6]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of DOMON domain-containing protein FRRS1L (FRRS1L).	[6]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of DOMON domain-containing protein FRRS1L (FRRS1L).	[7]

References

• [1] Ferric Chelate Reductase 1 Like Protein (FRRS1L) Associates with Dynein Vesicles and Regulates Glutamatergic Synaptic Transmission.Front Mol Neurosci. 2017 Dec 8;10:402. doi: 10.3389/fnmol.2017.00402. eCollection 2017.
• [2] Loss of Frrs1l disrupts synaptic AMPA receptor function, and results in neurodevelopmental, motor, cognitive and electrographical abnormalities.Dis Model Mech. 2019 Feb 22;12(2):dmm036806. doi: 10.1242/dmm.036806.
• [3] Loss-of-Function Mutations in FRRS1L Lead to an Epileptic-Dyskinetic Encephalopathy. Am J Hum Genet. 2016 Jun 2;98(6):1249-1255. doi: 10.1016/j.ajhg.2016.04.008. Epub 2016 May 26.
• [4] AMPA-receptor specific biogenesis complexes control synaptic transmission and intellectual ability. Nat Commun. 2017 Jul 4;8:15910. doi: 10.1038/ncomms15910.
• [5] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [6] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [7] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.