Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTKFE4HP)

• DOT Name: Leucine-rich repeat, immunoglobulin-like domain and transmembrane domain-containing protein 3 (LRIT3)
• Gene Name: LRIT3
• Related Disease:
  Congenital stationary night blindness 1F
  Congenital stationary night blindness
• UniProt ID: LRIT3_HUMAN
• Pfam ID: PF13927 ; PF13855
• Sequence:
  MHLFACLCIVLSFLEGVGCLCPSQCTCDYHGRNDGSGSRLVLCNDMDMNELPTNLPVDTV
  KLRIEKTVIRRISAEAFYYLVELQYLWVTYNSVASIDPSSFYNLKQLHELRLDGNSLAAF
  PWASLLDMPLLRTLDLHNNKITSVPNEALRYLKNLAYLDLSSNRLTTLPPDFLESWTHLV
  STPSGVLDLSPSRIILGLQDNPWFCDCHISKMIELSKVVDPAIVLLDPLMTCSEPERLTG
  ILFQRAELEHCLKPSVMTSATKIMSALGSNVLLRCDATGFPTPQITWTRSDSSPVNYTVI
  QESPEEGVRWSIMSLTGISSKDAGDYKCKAKNLAGMSEAVVTVTVLGITTTPIPPDTSER
  TGDHPEWDVQPGSGRSTSVSSASSYLWSSSFSPTSSFSASTLSPPSTASFSLSPFSSSTV
  SSTTTLSTSISASTTMANKRSFQLHQGGKRNLKVAKNGSKLPPASTSKKEELALLDQTML
  TETNAAIENLRVVSETKESVTLTWNMINTTHNSAVTVLYSKYGGKDLLLLNADSSKNQVT
  IDGLEPGGQYMACVCPKGVPPQKDQCITFSTERVEGDDSQWSLLLVVTSTACVVILPLIC
  FLLYKVCKLQCKSEPFWEDDLAKETYIQFETLFPRSQSVGELWTRSHRDDSEKLLLCSRS
  SVESQVTFKSEGSRPEYYC
• Function: Plays a role in the synapse formation and synaptic transmission between cone photoreceptor cells and retinal bipolar cells. Required for normal transmission of a light-evoked stimulus from the cone photoreceptor cells to the ON-bipolar cells and ON-ganglion cells in the inner retina. Required in retinal ON-bipolar cells for normal localization of the cation channel TRPM1 at dendrite tips. Seems to play a specific role in synaptic contacts made by ON-bipolar cells with cone photoreceptor pedicles. May also have a role in cone synapse formation. Might facilitate FGFR1 exit from the endoplasmic reticulum to the Golgi. Could be a regulator of the FGFRs.
• Tissue Specificity: Detected in the outer plexiform layer (OPL) of the retina where it localizes to ON-bipolar cells (at protein level).

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Congenital stationary night blindness 1F	DISLSR7P	Strong	Autosomal recessive	[1]
Congenital stationary night blindness	DISX0CWK	Supportive	Autosomal dominant	[1]

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 increases the methylation of Leucine-rich repeat, immunoglobulin-like domain and transmembrane domain-containing protein 3 (LRIT3).	[2]

References

• [1] Whole-exome sequencing identifies LRIT3 mutations as a cause of autosomal-recessive complete congenital stationary night blindness. Am J Hum Genet. 2013 Jan 10;92(1):67-75. doi: 10.1016/j.ajhg.2012.10.023. Epub 2012 Dec 13.
• [2] 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.