Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTF5ZRYJ)

• DOT Name: Protein FAM161A (FAM161A)
• Gene Name: FAM161A
• Related Disease:
  Retinitis pigmentosa 28
  Ciliopathy
  Retinopathy
  Retinitis pigmentosa
  Blindness
  Inherited retinal dystrophy
• UniProt ID: F161A_HUMAN
• Pfam ID: PF10595
• Sequence:
  MATSHRVAKLVASSLQTPVNPITGARVAQYEREDPLKALAAAEAILEDEEEEKVAQPAGA
  SADLNTSFSGVDEHAPISYEDFVNFPDIHHSNEEYFKKVEELKAAHIETMAKLEKMYQDK
  LHLKEVQPVVIREDSLSDSSRSVSEKNSYHPVSLMTSFSEPDLGQSSSLYVSSSEEELPN
  LEKEYPRKNRMMTYAKELINNMWTDFCVEDYIRCKDTGFHAAEKRRKKRKEWVPTITVPE
  PFQMMIREQKKKEESMKSKSDIEMVHKALKKQEEDPEYKKKFRANPVPASVFLPLYHDLV
  KQKEERRRSLKEKSKEALLASQKPFKFIAREEQKRAAREKQLRDFLKYKKKTNRFKARPI
  PRSTYGSTTNDKLKEEELYRNLRTQLRAQEHLQNSSPLPCRSACGCRNPRCPEQAVKLKC
  KHKVRCPTPDFEDLPERYQKHLSEHKSPKLLTVCKPFDLHASPHASIKREKILADIEADE
  ENLKETRWPYLSPRRKSPVRCAGVNPVPCNCNPPVPTVSSRGREQAVRKSEKERMREYQR
  ELEEREEKLKKRPLLFERVAQKNARMAAEKHYSNTLKALGISDEFVSKKGQSGKVLEYFN
  NQETKSVTEDKESFNEEEKIEERENGEENYFIDTNSQDSYKEKDEANEESEEEKSVEESH
• Function: Involved in ciliogenesis.
• Tissue Specificity: Isoform 1 and isoform 3 are widely expressed with highest levels in retina and testis, with isoform 1 being the most abundant in all tissues tested.

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Retinitis pigmentosa 28	DISKYC2N	Definitive	Autosomal recessive	[1]
Ciliopathy	DIS10G4I	Strong	Biomarker	[2]
Retinopathy	DISB4B0F	Strong	Biomarker	[3]
Retinitis pigmentosa	DISCGPY8	Supportive	Autosomal dominant	[4]
Blindness	DISTIM10	Limited	Genetic Variation	[5]
Inherited retinal dystrophy	DISGGL77	Limited	CausalMutation	[6]

12 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 Protein FAM161A (FAM161A).	[7]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Protein FAM161A (FAM161A).	[8]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Protein FAM161A (FAM161A).	[9]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Protein FAM161A (FAM161A).	[10]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Protein FAM161A (FAM161A).	[11]
Quercetin	DM3NC4M	Approved	Quercetin affects the expression of Protein FAM161A (FAM161A).	[8]
Marinol	DM70IK5	Approved	Marinol increases the expression of Protein FAM161A (FAM161A).	[12]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of Protein FAM161A (FAM161A).	[13]
APR-246	DMNFADH	Phase 2	APR-246 affects the expression of Protein FAM161A (FAM161A).	[14]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Protein FAM161A (FAM161A).	[16]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Protein FAM161A (FAM161A).	[17]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate decreases the expression of Protein FAM161A (FAM161A).	[18]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Protein FAM161A (FAM161A).	[15]

References

• [1] Homozygosity mapping reveals null mutations in FAM161A as a cause of autosomal-recessive retinitis pigmentosa. Am J Hum Genet. 2010 Sep 10;87(3):382-91. doi: 10.1016/j.ajhg.2010.07.022. Epub 2010 Aug 12.
• [2] FAM161A, associated with retinitis pigmentosa, is a component of the cilia-basal body complex and interacts with proteins involved in ciliopathies.Hum Mol Genet. 2012 Dec 1;21(23):5174-84. doi: 10.1093/hmg/dds368. Epub 2012 Sep 1.
• [3] Interactome analysis reveals that FAM161A, deficient in recessive retinitis pigmentosa, is a component of the Golgi-centrosomal network.Hum Mol Genet. 2015 Jun 15;24(12):3359-71. doi: 10.1093/hmg/ddv085. Epub 2015 Mar 5.
• [4] 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.
• [5] Molecular genetics of FAM161A in North American patients with early-onset retinitis pigmentosa.PLoS One. 2014 Mar 20;9(3):e92479. doi: 10.1371/journal.pone.0092479. eCollection 2014.
• [6] Molecular genetic analysis using targeted NGS analysis of 677 individuals with retinal dystrophy.Sci Rep. 2019 Feb 4;9(1):1219. doi: 10.1038/s41598-018-38007-2.
• [7] 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.
• [8] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [9] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [10] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [11] Epidermal growth factor receptor signalling in human breast cancer cells operates parallel to estrogen receptor alpha signalling and results in tamoxifen insensitive proliferation. BMC Cancer. 2014 Apr 23;14:283.
• [12] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [13] A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.
• [14] Mutant p53 reactivation by PRIMA-1MET induces multiple signaling pathways converging on apoptosis. Oncogene. 2010 Mar 4;29(9):1329-38. doi: 10.1038/onc.2009.425. Epub 2009 Nov 30.
• [15] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
• [16] Bisphenol A Exposure Changes the Transcriptomic and Proteomic Dynamics of Human Retinoblastoma Y79 Cells. Genes (Basel). 2021 Feb 11;12(2):264. doi: 10.3390/genes12020264.
• [17] Sulforaphane-induced apoptosis in human leukemia HL-60 cells through extrinsic and intrinsic signal pathways and altering associated genes expression assayed by cDNA microarray. Environ Toxicol. 2017 Jan;32(1):311-328.
• [18] Transcriptome dynamics of alternative splicing events revealed early phase of apoptosis induced by methylparaben in H1299 human lung carcinoma cells. Arch Toxicol. 2020 Jan;94(1):127-140. doi: 10.1007/s00204-019-02629-w. Epub 2019 Nov 20.