Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTFPSJ0T)

• DOT Name: Interphotoreceptor matrix proteoglycan 2 (IMPG2)
• Synonyms: Interphotoreceptor matrix proteoglycan of 200 kDa; IPM 200; Sialoprotein associated with cones and rods proteoglycan; Spacrcan
• Gene Name: IMPG2
• Related Disease:
  Inherited retinal dystrophy
  Retinitis pigmentosa 56
  Vitelliform macular dystrophy 5
  Eye disorder
  Leber congenital amaurosis
  Vitelliform macular dystrophy
  Age-related macular degeneration
  Adult-onset foveomacular vitelliform dystrophy
  Retinitis pigmentosa
  Crohn disease
  Inflammatory bowel disease
• UniProt ID: IMPG2_HUMAN
• Pfam ID: PF01390
• Sequence:
  MIMFPLFGKISLGILIFVLIEGDFPSLTAQTYLSIEEIQEPKSAVSFLLPEESTDLSLAT
  KKKQPLDRRETERQWLIRRRRSILFPNGVKICPDESVAEAVANHVKYFKVRVCQEAVWEA
  FRTFWDRLPGREEYHYWMNLCEDGVTSIFEMGTNFSESVEHRSLIMKKLTYAKETVSSSE
  LSSPVPVGDTSTLGDTTLSVPHPEVDAYEGASESSLERPEESISNEIENVIEEATKPAGE
  QIAEFSIHLLGKQYREELQDSSSFHHQHLEEEFISEVENAFTGLPGYKEIRVLEFRSPKE
  NDSGVDVYYAVTFNGEAISNTTWDLISLHSNKVENHGLVELDDKPTVVYTISNFRDYIAE
  TLQQNFLLGNSSLNPDPDSLQLINVRGVLRHQTEDLVWNTQSSSLQATPSSILDNTFQAA
  WPSADESITSSIPPLDFSSGPPSATGRELWSESPLGDLVSTHKLAFPSKMGLSSSPEVLE
  VSSLTLHSVTPAVLQTGLPVASEERTSGSHLVEDGLANVEESEDFLSIDSLPSSSFTQPV
  PKETIPSMEDSDVSLTSSPYLTSSIPFGLDSLTSKVKDQLKVSPFLPDASMEKELIFDGG
  LGSGSGQKVDLITWPWSETSSEKSAEPLSKPWLEDDDSLLPAEIEDKKLVLVDKMDSTDQ
  ISKHSKYEHDDRSTHFPEEEPLSGPAVPIFADTAAESASLTLPKHISEVPGVDDYSVTKA
  PLILTSVAISASTDKSDQADAILREDMEQITESSNYEWFDSEVSMVKPDMQTLWTILPES
  ERVWTRTSSLEKLSRDILASTPQSADRLWLSVTQSTKLPPTTISTLLEDEVIMGVQDISL
  ELDRIGTDYYQPEQVQEQNGKVGSYVEMSTSVHSTEMVSVAWPTEGGDDLSYTQTSGALV
  VFFSLRVTNMMFSEDLFNKNSLEYKALEQRFLELLVPYLQSNLTGFQNLEILNFRNGSIV
  VNSRMKFANSVPPNVNNAVYMILEDFCTTAYNTMNLAIDKYSLDVESGDEANPCKFQACN
  EFSECLVNPWSGEAKCRCFPGYLSVEERPCQSLCDLQPDFCLNDGKCDIMPGHGAICRCR
  VGENWWYRGKHCEEFVSEPVIIGITIASVVGLLVIFSAIIYFFIRTLQAHHDRSERESPF
  SGSSRQPDSLSSIENAVKYNPVYESHRAGCEKYEGPYPQHPFYSSASGDVIGGLSREEIR
  QMYESSELSREEIQERMRVLELYANDPEFAAFVREQQVEEV
• Function: Chondroitin sulfate- and hyaluronan-binding proteoglycan involved in the organization of interphotoreceptor matrix; may participate in the maturation and maintenance of the light-sensitive photoreceptor outer segment. Binds heparin.
• Tissue Specificity: Expressed in the retina (at protein level) . Expressed by photoreceptors of the interphotoreceptor matrix (IPM) surrounding both rods and cones (at protein level) . IPM occupies the subretinal space between the apices of the retinal pigment epithelium and the neural retina . Expressed in the pineal gland (at protein level) .

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 recessive	[1]
Retinitis pigmentosa 56	DIS2XQC7	Definitive	Autosomal recessive	[2]
Vitelliform macular dystrophy 5	DISEFWLD	Definitive	Autosomal dominant	[3]
Eye disorder	DISB52BH	Strong	CausalMutation	[4]
Leber congenital amaurosis	DISMGH8F	Strong	Altered Expression	[5]
Vitelliform macular dystrophy	DISEFYYN	Strong	Genetic Variation	[6]
Age-related macular degeneration	DIS0XS2C	moderate	Biomarker	[5]
Adult-onset foveomacular vitelliform dystrophy	DISPYJN2	Supportive	Autosomal dominant	[6]
Retinitis pigmentosa	DISCGPY8	Supportive	Autosomal dominant	[7]
Crohn disease	DIS2C5Q8	Limited	Genetic Variation	[8]
Inflammatory bowel disease	DISGN23E	Limited	Genetic Variation	[8]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Interphotoreceptor matrix proteoglycan 2 (IMPG2).	[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] IMPG2-associated retinitis pigmentosa displays relatively early macular involvement. Invest Ophthalmol Vis Sci. 2014 May 29;55(6):3939-53. doi: 10.1167/iovs.14-14129.
• [3] ADULT-ONSET VITELLIFORM MACULAR DYSTROPHY SECONDARY TO A NOVEL IMPG2 GENE VARIANT. Retin Cases Brief Rep. 2021 Jul 1;15(4):356-358. doi: 10.1097/ICB.0000000000000824.
• [4] Mutations in IMPG2, encoding interphotoreceptor matrix proteoglycan 2, cause autosomal-recessive retinitis pigmentosa. Am J Hum Genet. 2010 Aug 13;87(2):199-208. doi: 10.1016/j.ajhg.2010.07.004. Epub 2010 Jul 30.
• [5] 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.
• [6] Frequency and clinical pattern of vitelliform macular dystrophy caused by mutations of interphotoreceptor matrix IMPG1 and IMPG2 genes. Ophthalmology. 2014 Dec;121(12):2406-14. doi: 10.1016/j.ophtha.2014.06.028. Epub 2014 Jul 29.
• [7] Nonsyndromic Retinitis Pigmentosa Overview. 2000 Aug 4 [updated 2023 Apr 6]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews(?) [Internet]. Seattle (WA): University of Washington, Seattle; 1993C2024.
• [8] Genome-wide association study implicates immune activation of multiple integrin genes in inflammatory bowel disease.Nat Genet. 2017 Feb;49(2):256-261. doi: 10.1038/ng.3760. Epub 2017 Jan 9.
• [9] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.