Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTE7H0YV)

• DOT Name: Rod outer segment membrane protein 1 (ROM1)
• Synonyms: ROSP1; Tetraspanin-23; Tspan-23
• Gene Name: ROM1
• Related Disease:
  Non-insulin dependent diabetes
  Retinopathy
  Advanced cancer
  Age-related macular degeneration
  Alzheimer disease
  Analgesia
  Aural atresia, congenital
  Bacterial arthritis
  Campomelic dysplasia
  Charcot marie tooth disease
  Chronic obstructive pulmonary disease
  Craniometaphyseal dysplasia, autosomal dominant
  Deafness
  Hereditary macular dystrophy
  Infective arthritis
  Insomnia
  Late-onset Parkinson disease
  Lung cancer
  Lung carcinoma
  Malignant soft tissue neoplasm
  Osteoarthritis
  Pelvic inflammatory disease
  Sarcoma
  Breast cancer
  Breast carcinoma
  Hypertension, pregnancy-induced
  Prostate cancer
  Prostate carcinoma
  Retinitis pigmentosa
  Intellectual disability
  Retinitis punctata albescens
  Congenital alveolar dysplasia
  Retinitis pigmentosa 7
  Vitelliform macular dystrophy
• UniProt ID: ROM1_HUMAN
• PDB ID: 7ZW1
• Pfam ID: PF00335
• Sequence:
  MAPVLPLVLPLQPRIRLAQGLWLLSWLLALAGGVILLCSGHLLVQLRHLGTFLAPSCQFP
  VLPQAALAAGAVALGTGLVGVGASRASLNAALYPPWRGVLGPLLVAGTAGGGGLLVVGLG
  LALALPGSLDEALEEGLVTALAHYKDTEVPGHCQAKRLVDELQLRYHCCGRHGYKDWFGV
  QWVSSRYLDPGDRDVADRIQSNVEGLYLTDGVPFSCCNPHSPRPCLQNRLSDSYAHPLFD
  PRQPNQNLWAQGCHEVLLEHLQDLAGTLGSMLAVTFLLQALVLLGLRYLQTALEGLGGVI
  DAGGETQGYLFPSGLKDMLKTAWLQGGVACRPAPEEAPPGEAPPKEDLSEA
• Function: Plays a role in rod outer segment (ROS) morphogenesis. May play a role with PRPH2 in the maintenance of the structure of ROS curved disks. Plays a role in the organization of the ROS and maintenance of ROS disk diameter. Involved in the maintenance of the retina outer nuclear layer.
• Tissue Specificity: Retina photoreceptors (at protein level) . In rim region of ROS disks .

Molecular Interaction Atlas (MIA) of This DOT

34 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Non-insulin dependent diabetes	DISK1O5Z	Definitive	Altered Expression	[1]
Retinopathy	DISB4B0F	Definitive	Altered Expression	[2]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[3]
Age-related macular degeneration	DIS0XS2C	Strong	Biomarker	[4]
Alzheimer disease	DISF8S70	Strong	Biomarker	[5]
Analgesia	DISK3TVI	Strong	Biomarker	[6]
Aural atresia, congenital	DISCP7UV	Strong	Biomarker	[5]
Bacterial arthritis	DIS8R241	Strong	Biomarker	[7]
Campomelic dysplasia	DISVTW53	Strong	Biomarker	[8]
Charcot marie tooth disease	DIS3BT2L	Strong	Biomarker	[9]
Chronic obstructive pulmonary disease	DISQCIRF	Strong	Biomarker	[10]
Craniometaphyseal dysplasia, autosomal dominant	DISU12OO	Strong	Biomarker	[8]
Deafness	DISKCLH4	Strong	Biomarker	[11]
Hereditary macular dystrophy	DISEYSYY	Strong	Biomarker	[4]
Infective arthritis	DIS8YJPR	Strong	Biomarker	[7]
Insomnia	DIS0AFR7	Strong	Biomarker	[12]
Late-onset Parkinson disease	DIS9IOUI	Strong	Biomarker	[13]
Lung cancer	DISCM4YA	Strong	Biomarker	[10]
Lung carcinoma	DISTR26C	Strong	Biomarker	[10]
Malignant soft tissue neoplasm	DISTC6NO	Strong	Biomarker	[14]
Osteoarthritis	DIS05URM	Strong	Biomarker	[15]
Pelvic inflammatory disease	DISWQR4J	Strong	Biomarker	[16]
Sarcoma	DISZDG3U	Strong	Biomarker	[14]
Breast cancer	DIS7DPX1	moderate	Biomarker	[3]
Breast carcinoma	DIS2UE88	moderate	Biomarker	[3]
Hypertension, pregnancy-induced	DISHNU25	moderate	Biomarker	[17]
Prostate cancer	DISF190Y	moderate	Altered Expression	[3]
Prostate carcinoma	DISMJPLE	moderate	Altered Expression	[3]
Retinitis pigmentosa	DISCGPY8	Supportive	Autosomal dominant	[18]
Intellectual disability	DISMBNXP	Disputed	Altered Expression	[19]
Retinitis punctata albescens	DISVJAI4	Disputed	Biomarker	[20]
Congenital alveolar dysplasia	DIS1IYUN	Limited	Genetic Variation	[21]
Retinitis pigmentosa 7	DISP0YU7	Limited	Unknown	[22]
Vitelliform macular dystrophy	DISEFYYN	Limited	Biomarker	[23]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Rod outer segment membrane protein 1 (ROM1).	[24]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Rod outer segment membrane protein 1 (ROM1).	[25]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Rod outer segment membrane protein 1 (ROM1).	[26]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Rod outer segment membrane protein 1 (ROM1).	[27]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Rod outer segment membrane protein 1 (ROM1).	[27]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Rod outer segment membrane protein 1 (ROM1).	[28]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Rod outer segment membrane protein 1 (ROM1).	[29]
Bicalutamide	DMZMSPF	Approved	Bicalutamide increases the expression of Rod outer segment membrane protein 1 (ROM1).	[30]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Rod outer segment membrane protein 1 (ROM1).	[31]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Rod outer segment membrane protein 1 (ROM1).	[32]

References

• [1] Correlation between reactive oxygen metabolites & atherosclerotic risk factors in patients with type 2 diabetes mellitus.Indian J Med Res. 2013 Apr;137(4):742-8.
• [2] Prph2 initiates outer segment morphogenesis but maturation requires Prph2/Rom1 oligomerization.Hum Mol Genet. 2019 Feb 1;28(3):459-475. doi: 10.1093/hmg/ddy359.
• [3] Pre-diagnostic derivatives of reactive oxygen metabolites and the occurrence of lung, colorectal, breast and prostate cancer: An individual participant data meta-analysis of two large population-based studies.Int J Cancer. 2019 Jul 1;145(1):49-57. doi: 10.1002/ijc.32073. Epub 2019 Jan 5.
• [4] ABCA4 and ROM1: implications for modification of the PRPH2-associated macular dystrophy phenotype.Invest Ophthalmol Vis Sci. 2010 Aug;51(8):4253-65. doi: 10.1167/iovs.09-4655. Epub 2010 Mar 24.
• [5] Core cerebrospinal fluid biomarker profile in cerebral amyloid angiopathy: A meta-analysis.Neurology. 2018 Feb 27;90(9):e754-e762. doi: 10.1212/WNL.0000000000005030. Epub 2018 Jan 31.
• [6] Additional benefit of local infiltration of analgesia to femoral nerve block in total knee arthroplasty: double-blind randomized control study.Knee Surg Sports Traumatol Arthrosc. 2019 Jul;27(7):2368-2374. doi: 10.1007/s00167-018-5322-7. Epub 2018 Dec 8.
• [7] Outcomes after Total Hip Arthroplasty Using a Cementless S-ROM Modular Stem for Patients with High Hip Dislocation Secondary to Hip Pyogenic Arthritis.Orthop Surg. 2019 Jun;11(3):460-466. doi: 10.1111/os.12485.
• [8] Upper extremity outcome measures for collagen VI-related myopathy and LAMA2-related muscular dystrophy.Neuromuscul Disord. 2017 Mar;27(3):278-285. doi: 10.1016/j.nmd.2016.11.017. Epub 2016 Dec 5.
• [9] Electromyographic and biomechanical analysis of step negotiation in Charcot Marie Tooth subjects whose level walk is not impaired.Gait Posture. 2018 May;62:497-504. doi: 10.1016/j.gaitpost.2018.04.014. Epub 2018 Apr 13.
• [10] Association of Perioperative Redox Balance on Long-Term Outcome in Patients Undergoing Lung Resection.Ann Thorac Cardiovasc Surg. 2018 Feb 20;24(1):13-18. doi: 10.5761/atcs.oa.17-00127. Epub 2017 Nov 10.
• [11] Decreased postural control in people with moderate hearing loss.Medicine (Baltimore). 2018 Apr;97(14):e0244. doi: 10.1097/MD.0000000000010244.
• [12] Analysis of patients' sleep disorder after total knee arthroplasty-A retrospective study.J Orthop Sci. 2019 Jan;24(1):116-120. doi: 10.1016/j.jos.2018.07.019. Epub 2018 Aug 23.
• [13] Rom1 converts Y141C-Prph2-associated pattern dystrophy to retinitis pigmentosa.Hum Mol Genet. 2017 Feb 1;26(3):509-518. doi: 10.1093/hmg/ddw408.
• [14] Does Patellar Tendon Repair With Gastrocnemius Flap Augmentation Effectively Restore Active Extension After Proximal Tibial Sarcoma Resection?.Clin Orthop Relat Res. 2019 Mar;477(3):584-593. doi: 10.1097/CORR.0000000000000564.
• [15] Distribution of segmental foot kinematics in patients with degenerative joint disease of the ankle.J Orthop Res. 2018 Jun;36(6):1739-1746. doi: 10.1002/jor.23807. Epub 2017 Dec 15.
• [16] Impact of innate immunity in a subset of children with autism spectrum disorders: a case control study.J Neuroinflammation. 2008 Nov 21;5:52. doi: 10.1186/1742-2094-5-52.
• [17] Placental hypoplasia and maternal organic vascular disorder in pregnant women with gestational hypertension and preeclampsia.J Matern Fetal Neonatal Med. 2021 Feb;34(3):353-359. doi: 10.1080/14767058.2019.1608175. Epub 2019 May 2.
• [18] 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.
• [19] A study of oxidative stress and the newer antiepileptic drugs in epilepsy associated with severe motor and intellectual disabilities.J Chin Med Assoc. 2017 Jan;80(1):19-28. doi: 10.1016/j.jcma.2016.10.005. Epub 2016 Nov 23.
• [20] Retinitis punctata albescens associated with the Arg135Trp mutation in the rhodopsin gene. Am J Ophthalmol. 1996 Jan;121(1):19-25. doi: 10.1016/s0002-9394(14)70530-6.
• [21] Dominant and digenic mutations in the peripherin/RDS and ROM1 genes in retinitis pigmentosa.Invest Ophthalmol Vis Sci. 1997 Sep;38(10):1972-82.
• [22] Late-onset pattern macular dystrophy mimicking ABCA4 and PRPH2 disease is caused by a homozygous frameshift mutation in ROM1. Cold Spring Harb Mol Case Stud. 2019 Jun 3;5(3):a003624. doi: 10.1101/mcs.a003624. Print 2019 Jun.
• [23] A recombination event excludes the ROM1 locus from the Best's vitelliform macular dystrophy region.Hum Genet. 1995 Feb;95(2):219-22. doi: 10.1007/BF00209406.
• [24] 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.
• [25] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [26] Differential regulation of native estrogen receptor-regulatory elements by estradiol, tamoxifen, and raloxifene. Mol Endocrinol. 2008 Feb;22(2):287-303. doi: 10.1210/me.2007-0340. Epub 2007 Oct 25.
• [27] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [28] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [29] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [30] Casodex treatment induces hypoxia-related gene expression in the LNCaP prostate cancer progression model. BMC Urol. 2005 Mar 24;5:5.
• [31] 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.
• [32] Bisphenol A and bisphenol S induce distinct transcriptional profiles in differentiating human primary preadipocytes. PLoS One. 2016 Sep 29;11(9):e0163318.