Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTD9C4IF)

• DOT Name: G-protein coupled receptor-associated protein LMBRD2 (LMBRD2)
• Synonyms: LMBR1 domain-containing protein 2
• Gene Name: LMBRD2
• Related Disease:
  Developmental delay with variable neurologic and brain abnormalities
  Neurodevelopmental disorder with microcephaly and dysmorphic facies
  Complex neurodevelopmental disorder
• UniProt ID: LMBD2_HUMAN
• Pfam ID: PF04791
• Sequence:
  MSGAALGLEIVFVFFLALFLLHRYGDFKKQHRLVIIGTLLAWYLCFLIVFILPLDVSTTI
  YNRCKHAAANSSPPENSNITGLYATANPVPSQHPCFKPWSYIPDGIMPIFWRVVYWTSQF
  LTWILLPFMQSYARSGGFSITGKIKTALIENAIYYGTYLLIFGAFLIYVAVNPHLHLEWN
  QLQTIGIAAANTWGLFLLVLLLGYGLVEIPRSYWNGAKRGYLLMKTYFKAAKLMTEKADA
  EENLEDAMEEVRKVNESIKYNHPLRKCVDTILKKCPTEYQEKMGRNMDDYEDFDEKHSIY
  PSEKSLVKLHKQVIYSVQRHRRTQVQWQILLEQAFYLEDVAKNETSATHQFVHTFQSPEP
  ENRFIQYFYNPTFEWYWECLLRPWFYKILAVVLSIFSVIVVWSECTFFSTTPVLSLFAVF
  IQLAEKTYNYIYIEIACFLSIFFLSICVYSTVFRIRVFNYYYLASHHQTDAYSLLFSGML
  FCRLTPPLCLNFLGLTHMDSSISHKNTQPTAYTSIMGSMKVLSFIADGFYIYYPMLVVIL
  CIATYFSLGTRCLNLLGFQQFMGDDDMTSDLVNEGKELIRKEKRKRQRQEEGENRRREWK
  ERYGHNREDSTRNRNIHTDPKESNFSDVNTNRSAFKYTRANNRTERDRIELLQDAEPLDF
  NAETFTDDPLESESGRYQPGGRYLSMSRSDIFNDV
• Function: Recruited to ligand-activated beta-2 adrenergic receptor/ADRB2, it negatively regulates the adrenergic receptor signaling pathway. May also regulate other G-protein coupled receptors including type-1 angiotensin II receptor/AGTR1 (Probable).

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Developmental delay with variable neurologic and brain abnormalities	DIS7CYZ5	Strong	Autosomal dominant	[1]
Neurodevelopmental disorder with microcephaly and dysmorphic facies	DISHCZQ5	Moderate	Autosomal dominant	[2]
Complex neurodevelopmental disorder	DISB9AFI	No Known	Autosomal dominant	[3]

7 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 G-protein coupled receptor-associated protein LMBRD2 (LMBRD2).	[4]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of G-protein coupled receptor-associated protein LMBRD2 (LMBRD2).	[5]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of G-protein coupled receptor-associated protein LMBRD2 (LMBRD2).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of G-protein coupled receptor-associated protein LMBRD2 (LMBRD2).	[7]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of G-protein coupled receptor-associated protein LMBRD2 (LMBRD2).	[8]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of G-protein coupled receptor-associated protein LMBRD2 (LMBRD2).	[10]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of G-protein coupled receptor-associated protein LMBRD2 (LMBRD2).	[11]

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 decreases the methylation of G-protein coupled receptor-associated protein LMBRD2 (LMBRD2).	[9]

References

• [1] A clinical utility study of exome sequencing versus conventional genetic testing in pediatric neurology. Genet Med. 2017 Sep;19(9):1055-1063. doi: 10.1038/gim.2017.1. Epub 2017 Mar 23.
• [2] De novo missense variants in LMBRD2 are associated with developmental and motor delays, brain structure abnormalities and dysmorphic features. J Med Genet. 2021 Oct;58(10):712-716. doi: 10.1136/jmedgenet-2020-107137. Epub 2020 Aug 20.
• [3] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [4] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [5] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [6] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [7] New insights into BaP-induced toxicity: role of major metabolites in transcriptomics and contribution to hepatocarcinogenesis. Arch Toxicol. 2016 Jun;90(6):1449-58.
• [8] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [9] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [10] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [11] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.