Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTV0H6MJ)

• DOT Name: GAS2-like protein 2 (GAS2L2)
• Synonyms: GAS2-related protein on chromosome 17; Growth arrest-specific protein 2-like 2
• Gene Name: GAS2L2
• Related Disease:
  Primary ciliary dyskinesia 1
  Ciliary dyskinesia, primary, 41
  Primary ciliary dyskinesia
• UniProt ID: GA2L2_HUMAN
• Pfam ID: PF00307 ; PF02187
• Sequence:
  MSQPAGGRRKPRTLGPPVCSIRPFKSSEQYLEAMKEDLAEWLRDLYGLDIDAANFLQVLE
  TGLVLCQHANVVTDAALAFLAEAPAQAQKIPMPRVGVSCNGAAQPGTFQARDNVSNFIQW
  CRKEMGIQEVLMFETEDLVLRKNVKNVVLCLLELGRRAWRFGVAAPTLVQLEEEIEEEVR
  RELALPPPDPSPPAPPRRQPCHFRNLDQMVQSLVSHCTCPVQFSMVKVSEGKYRVGDSNT
  LIFIRILRNHVMVRVGGGWDTLGHYLDKHDPCRCTSLSHKPGSFLKPPAPPVQHEVRVQD
  GPSQTQPTMTISRSQSPPPPVDWKTYTSSDRRLRPPTPSSPRPRRERGAGTGASREMAPF
  LRCQERSLIPSWRQPTAGDSPPSPQSSSTQKGRDPQCTSSGKREERYPPELPRGRIPTSW
  VHEETDSWGTDAGNPTPQRLRAIEATTKGISARGPSPLPRSFGPAECLGLRLPLRDEAKG
  AFFQFREPESVRSPTPVQGLTKIPIRLPPARPPTPGRSFPGATSGSPRTELGRDPIPLRA
  VTVDLAGSTHGDCSVEVRQEDQQLDIQVMAEARESWDLGLQEQEGRYTPLPLGGNKEQAI
  YCSLEEEILGNMKLLEVRSACPQGTRSGVIPRSGVYIPRLAGQWPEPGGPYDKAIQELAQ
  GSPSLLKVDLEAWKAAPTGSPKPAVTPGPGSLKGKLGARQSGPRTKASLSAKGTHMRKVP
  PQGGQDCSASTVSASPEAPTPSPLDPNSDKAKACLSKGRRTLRKPKRVPSIYKLKLRPRI
  RPRRDHRPEKQPSRIPRPLAYVFLGPARQPPKDRLLRAVLGSKGGEASRVDGASVGEEEE
  EGKEEKEPAAPLESSPQPPEGLQPHWLNQAPLPPEEESWV
• Function: Involved in the cross-linking of microtubules and microfilaments. Regulates microtubule dynamics and stability by interacting with microtubule plus-end tracking proteins, such as MAPRE1, to regulate microtubule growth along actin stress fibers. Enhances ADORA2-mediated adenylyl cyclase activation by acting as a scaffold to recruit trimeric G-protein complexes to ADORA2A. Regulates ciliary orientation and performance in cells located in the airway.
• Tissue Specificity: Expressed in bronchial and nasal epithelial cells (at protein level) . Expressed in brain, kidney, lung, testis, fallopian tubes, and skeletal muscle . Expressed at low levels in stomach and colon .

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Primary ciliary dyskinesia 1	DISPGX6H	Strong	GermlineCausalMutation	[1]
Ciliary dyskinesia, primary, 41	DISO542K	Moderate	Autosomal recessive	[2]
Primary ciliary dyskinesia	DISOBC7V	Supportive	Autosomal dominant	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of GAS2-like protein 2 (GAS2L2).	[3]

References

• [1] A biallelic mutation links MYORG to autosomal-recessive primary familial brain calcification. Brain. 2019 Feb 1;142(2):e4. doi: 10.1093/brain/awy343.
• [2] 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.
• [3] Genome-wide transcriptional and functional analysis of human T lymphocytes treated with benzo[alpha]pyrene. Int J Mol Sci. 2018 Nov 17;19(11).