Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT12HBL0)

• DOT Name: Interphotoreceptor matrix proteoglycan 1 (IMPG1)
• Synonyms: Interphotoreceptor matrix proteoglycan of 150 kDa; IPM-150; Sialoprotein associated with cones and rods
• Gene Name: IMPG1
• Related Disease:
  Inherited retinal dystrophy
  Vitelliform macular dystrophy 4
  Age-related macular degeneration
  Hereditary macular dystrophy
  Leber congenital amaurosis
  North Carolina macular dystrophy
  Retinopathy
  Stargardt disease 3
  Vitelliform macular dystrophy
  Retinitis pigmentosa
  Adult-onset foveomacular vitelliform dystrophy
• UniProt ID: IMPG1_HUMAN
• Pfam ID: PF01390
• Sequence:
  MYLETRRAIFVFWIFLQVQGTKDISINIYHSETKDIDNPPRNETTESTEKMYKMSTMRRI
  FDLAKHRTKRSAFFPTGVKVCPQESMKQILDSLQAYYRLRVCQEAVWEAYRIFLDRIPDT
  GEYQDWVSICQQETFCLFDIGKNFSNSQEHLDLLQQRIKQRSFPDRKDEISAEKTLGEPG
  ETIVISTDVANVSLGPFPLTPDDTLLNEILDNTLNDTKMPTTERETEFAVLEEQRVELSV
  SLVNQKFKAELADSQSPYYQELAGKSQLQMQKIFKKLPGFKKIHVLGFRPKKEKDGSSST
  EMQLTAIFKRHSAEAKSPASDLLSFDSNKIESEEVYHGTMEEDKQPEIYLTATDLKRLIS
  KALEEEQSLDVGTIQFTDEIAGSLPAFGPDTQSELPTSFAVITEDATLSPELPPVEPQLE
  TVDGAEHGLPDTSWSPPAMASTSLSEAPPFFMASSIFSLTDQGTTDTMATDQTMLVPGLT
  IPTSDYSAISQLALGISHPPASSDDSRSSAGGEDMVRHLDEMDLSDTPAPSEVPELSEYV
  SVPDHFLEDTTPVSALQYITTSSMTIAPKGRELVVFFSLRVANMAFSNDLFNKSSLEYRA
  LEQQFTQLLVPYLRSNLTGFKQLEILNFRNGSVIVNSKMKFAKSVPYNLTKAVHGVLEDF
  RSAAAQQLHLEIDSYSLNIEPADQADPCKFLACGEFAQCVKNERTEEAECRCKPGYDSQG
  SLDGLEPGLCGPGTKECEVLQGKGAPCRLPDHSENQAYKTSVKKFQNQQNNKVISKRNSE
  LLTVEYEEFNHQDWEGN
• Function: Chondroitin sulfate-, heparin- and hyaluronan-binding protein. May serve to form a basic macromolecular scaffold comprising the insoluble interphotoreceptor matrix.
• Tissue Specificity: Expressed in the retina (at protein level) . In the retina, specifically expressed by cone and rod photoreceptor cells . Localizes to cone and rod photoreceptor cells surrounding the interphotoreceptor matrix of the retina .

Molecular Interaction Atlas (MIA) of This DOT

11 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Inherited retinal dystrophy	DISGGL77	Definitive	Autosomal dominant	[1]
Vitelliform macular dystrophy 4	DISA5CNX	Definitive	Autosomal recessive	[1]
Age-related macular degeneration	DIS0XS2C	Strong	Genetic Variation	[2]
Hereditary macular dystrophy	DISEYSYY	Strong	Genetic Variation	[2]
Leber congenital amaurosis	DISMGH8F	Strong	Biomarker	[3]
North Carolina macular dystrophy	DISMPOAO	Strong	Genetic Variation	[4]
Retinopathy	DISB4B0F	Strong	Biomarker	[3]
Stargardt disease 3	DIS7SKAQ	Strong	Genetic Variation	[4]
Vitelliform macular dystrophy	DISEFYYN	Strong	Genetic Variation	[5]
Retinitis pigmentosa	DISCGPY8	Moderate	Autosomal recessive	[6]
Adult-onset foveomacular vitelliform dystrophy	DISPYJN2	Supportive	Autosomal dominant	[2]

4 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 Interphotoreceptor matrix proteoglycan 1 (IMPG1).	[7]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Interphotoreceptor matrix proteoglycan 1 (IMPG1).	[8]
Belinostat	DM6OC53	Phase 2	Belinostat increases the expression of Interphotoreceptor matrix proteoglycan 1 (IMPG1).	[8]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Interphotoreceptor matrix proteoglycan 1 (IMPG1).	[8]

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 decreases the methylation of Interphotoreceptor matrix proteoglycan 1 (IMPG1).	[9]

References

• [1] 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.
• [2] Mutations in IMPG1 cause vitelliform macular dystrophies. Am J Hum Genet. 2013 Sep 5;93(3):571-8. doi: 10.1016/j.ajhg.2013.07.018. Epub 2013 Aug 29.
• [3] Organization of the human IMPG2 gene and its evaluation as a candidate gene in age-related macular degeneration and other retinal degenerative disorders. Invest Ophthalmol Vis Sci. 2001 Dec;42(13):3123-9.
• [4] Assessment of the interphotoreceptor matrix proteoglycan-1 (IMPG1) gene localised to 6q13-q15 in autosomal dominant Stargardt-like disease (ADSTGD), progressive bifocal chorioretinal atrophy (PBCRA), and North Carolina macular dystrophy (MCDR1).J Med Genet. 1998 Aug;35(8):641-5. doi: 10.1136/jmg.35.8.641.
• [5] Gene discovery and prevalence in inherited retinal dystrophies.C R Biol. 2014 Mar;337(3):160-6. doi: 10.1016/j.crvi.2013.12.001. Epub 2014 Mar 4.
• [6] Pathogenic variants in IMPG1 cause autosomal dominant and autosomal recessive retinitis pigmentosa. J Med Genet. 2021 Aug;58(8):570-578. doi: 10.1136/jmedgenet-2020-107150. Epub 2020 Aug 17.
• [7] 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.
• [8] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [9] 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.