Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT9XCFOC)

DOT Name	Heme transporter FLVCR1 (FLVCR1)
Synonyms	Feline leukemia virus subgroup C receptor-related protein 1; Feline leukemia virus subgroup C receptor; hFLVCR
Gene Name	FLVCR1
Related Disease	FLVCR1-related retinopathy with or without ataxia ( ) leukaemia ( ) Leukemia ( ) Posterior column ataxia-retinitis pigmentosa syndrome ( ) Thyroid gland papillary carcinoma ( ) Type-1/2 diabetes ( ) Adenoma ( ) Alzheimer disease ( ) Amyloidosis ( ) Analgesia ( ) Anxiety ( ) Anxiety disorder ( ) Atopic dermatitis ( ) Atrial fibrillation ( ) Benign prostatic hyperplasia ( ) Carcinoma ( ) Depression ( ) Graves disease ( ) Hepatitis C virus infection ( ) Hepatocellular carcinoma ( ) Hereditary sensory and autonomic neuropathy ( ) Huntington disease ( ) Irritable bowel syndrome ( ) Metastatic prostate carcinoma ( ) Neoplasm ( ) Non-small-cell lung cancer ( ) Pancreatic cancer ( ) Retinitis pigmentosa ( ) Stroke ( ) Bacterial infection ( ) High blood pressure ( ) Influenza ( ) Movement disorder ( ) Polycystic ovarian syndrome ( ) Advanced cancer ( ) Amyotrophic lateral sclerosis ( ) Asthma ( ) Autoimmune disease ( ) Breast cancer ( ) Breast carcinoma ( ) Chronic kidney disease ( ) Hyperglycemia ( ) Methicillin-resistant staphylococci infection ( ) Non-insulin dependent diabetes ( ) Obesity ( ) Parkinson disease ( ) Sensory ataxia ( ) Type-1 diabetes ( )
UniProt ID	FLVC1_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
Pfam ID	PF07690
Sequence	MARPDDEEGAAVAPGHPLAKGYLPLPRGAPVGKESVELQNGPKAGTFPVNGAPRDSLAAA SGVLGGPQTPLAPEEETQARLLPAGAGAETPGAESSPLPLTALSPRRFVVLLIFSLYSLV NAFQWIQYSIISNVFEGFYGVTLLHIDWLSMVYMLAYVPLIFPATWLLDTRGLRLTALLG SGLNCLGAWIKCGSVQQHLFWVTMLGQCLCSVAQVFILGLPSRIASVWFGPKEVSTACAT AVLGNQLGTAVGFLLPPVLVPNTQNDTNLLACNISTMFYGTSAVATLLFILTAIAFKEKP RYPPSQAQAALQDSPPEEYSYKKSIRNLFKNIPFVLLLITYGIMTGAFYSVSTLLNQMIL TYYEGEEVNAGRIGLTLVVAGMVGSILCGLWLDYTKTYKQTTLIVYILSFIGMVIFTFTL DLRYIIIVFVTGGVLGFFMTGYLPLGFEFAVEITYPESEGTSSGLLNASAQIFGILFTLA QGKLTSDYGPKAGNIFLCVWMFIGIILTALIKSDLRRHNINIGITNVDVKAIPADSPTDQ EPKTVMLSKQSESAI
Function	[Isoform 1]: Heme b transporter that mediates heme efflux from the cytoplasm to the extracellular compartment. Heme export depends on the presence of HPX and is required to maintain intracellular free heme balance, protecting cells from heme toxicity. Heme export provides protection from heme or ferrous iron toxicities in liver, brain, sensory neurons and during erythropoiesis, a process in which heme synthesis intensifies. Possibly export coproporphyrin and protoporphyrin IX, which are both intermediate products in the heme biosynthetic pathway. Does not export bilirubin. The molecular mechanism of heme transport, whether electrogenic, electroneutral or coupled to other ions, remains to be elucidated; [Isoform 1]: (Microbial infection) Confers susceptibility to feline leukemia virus subgroup C (FeLV-C) infection in vitro; [Isoform 2]: Heme b transporter that promotes heme efflux from the mitochondrion to the cytoplasm. Essential for erythroid differentiation.
Tissue Specificity	Found all hematopoietic tissues including peripheral blood lymphocytes. Some expression is found in pancreas and kidney.
Reactome Pathway	(Name not found ) Heme biosynthesis (R-HSA-189451 )

Molecular Interaction Atlas (MIA) of This DOT

48 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
FLVCR1-related retinopathy with or without ataxia	DISX5QI5	Definitive	Autosomal recessive	[1]
leukaemia	DISS7D1V	Definitive	Genetic Variation	[2]
Leukemia	DISNAKFL	Definitive	Genetic Variation	[2]
Posterior column ataxia-retinitis pigmentosa syndrome	DIS8OWR2	Definitive	Autosomal recessive	[3]
Thyroid gland papillary carcinoma	DIS48YMM	Definitive	Biomarker	[4]
Type-1/2 diabetes	DISIUHAP	Definitive	Biomarker	[5]
Adenoma	DIS78ZEV	Strong	Biomarker	[6]
Alzheimer disease	DISF8S70	Strong	Biomarker	[7]
Amyloidosis	DISHTAI2	Strong	Biomarker	[7]
Analgesia	DISK3TVI	Strong	Biomarker	[8]
Anxiety	DISIJDBA	Strong	Biomarker	[9]
Anxiety disorder	DISBI2BT	Strong	Biomarker	[9]
Atopic dermatitis	DISTCP41	Strong	Biomarker	[10]
Atrial fibrillation	DIS15W6U	Strong	Altered Expression	[11]
Benign prostatic hyperplasia	DISI3CW2	Strong	Biomarker	[12]
Carcinoma	DISH9F1N	Strong	Biomarker	[6]
Depression	DIS3XJ69	Strong	Biomarker	[13]
Graves disease	DISU4KOQ	Strong	Biomarker	[14]
Hepatitis C virus infection	DISQ0M8R	Strong	Altered Expression	[15]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[16]
Hereditary sensory and autonomic neuropathy	DIS2VOAM	Strong	Genetic Variation	[17]
Huntington disease	DISQPLA4	Strong	Biomarker	[18]
Irritable bowel syndrome	DIS27206	Strong	Biomarker	[9]
Metastatic prostate carcinoma	DISVBEZ9	Strong	Biomarker	[19]
Neoplasm	DISZKGEW	Strong	Biomarker	[20]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Genetic Variation	[21]
Pancreatic cancer	DISJC981	Strong	Genetic Variation	[22]
Retinitis pigmentosa	DISCGPY8	Strong	Genetic Variation	[23]
Stroke	DISX6UHX	Strong	Biomarker	[24]
Bacterial infection	DIS5QJ9S	moderate	Biomarker	[25]
High blood pressure	DISY2OHH	moderate	Biomarker	[26]
Influenza	DIS3PNU3	moderate	Biomarker	[27]
Movement disorder	DISOJJ2D	moderate	Genetic Variation	[3]
Polycystic ovarian syndrome	DISZ2BNG	moderate	Biomarker	[28]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[29]
Amyotrophic lateral sclerosis	DISF7HVM	Limited	Biomarker	[30]
Asthma	DISW9QNS	Limited	Biomarker	[31]
Autoimmune disease	DISORMTM	Limited	Biomarker	[32]
Breast cancer	DIS7DPX1	Limited	Biomarker	[33]
Breast carcinoma	DIS2UE88	Limited	Biomarker	[33]
Chronic kidney disease	DISW82R7	Limited	Biomarker	[34]
Hyperglycemia	DIS0BZB5	Limited	Altered Expression	[35]
Methicillin-resistant staphylococci infection	DIS6DRDZ	Limited	Biomarker	[36]
Non-insulin dependent diabetes	DISK1O5Z	Limited	Genetic Variation	[37]
Obesity	DIS47Y1K	Limited	Altered Expression	[35]
Parkinson disease	DISQVHKL	Limited	Biomarker	[38]
Sensory ataxia	DISSMCYQ	Limited	Genetic Variation	[39]
Type-1 diabetes	DIS7HLUB	Limited	Biomarker	[32]
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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

7 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 Heme transporter FLVCR1 (FLVCR1).	[40]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Heme transporter FLVCR1 (FLVCR1).	[41]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Heme transporter FLVCR1 (FLVCR1).	[42]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Heme transporter FLVCR1 (FLVCR1).	[43]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Heme transporter FLVCR1 (FLVCR1).	[44]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Heme transporter FLVCR1 (FLVCR1).	[45]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Heme transporter FLVCR1 (FLVCR1).	[47]
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⏷ Show the Full List of 7 Drug(s)

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Heme transporter FLVCR1 (FLVCR1).	[46]
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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	Posterior column ataxia with retinitis pigmentosa coexisting with sensory-autonomic neuropathy and leukemia due to the homozygous p.Pro221Ser FLVCR1 mutation.Am J Med Genet B Neuropsychiatr Genet. 2017 Oct;174(7):732-739. doi: 10.1002/ajmg.b.32570. Epub 2017 Aug 2.
3	Mutations in the Heme Exporter FLVCR1 Cause Sensory Neurodegeneration with Loss of Pain Perception. PLoS Genet. 2016 Dec 6;12(12):e1006461. doi: 10.1371/journal.pgen.1006461. eCollection 2016 Dec.
4	Serum-based metabolic alterations in patients with papillary thyroid carcinoma unveiled by non-targeted 1H-NMR metabolomics approach.Iran J Basic Med Sci. 2018 Nov;21(11):1140-1147. doi: 10.22038/IJBMS.2018.30375.7323.
5	Risk factors for postoperative stroke in adults patients with moyamoya disease: a systematic review with meta-analysis.BMC Neurol. 2019 May 15;19(1):98. doi: 10.1186/s12883-019-1327-1.
6	miRNA expression in colon polyps provides evidence for a multihit model of colon cancer.PLoS One. 2011;6(6):e20465. doi: 10.1371/journal.pone.0020465. Epub 2011 Jun 9.
7	In silico-guided identification of potential inhibitors against (2)m aggregation in dialysis-related amyloidosis.J Biomol Struct Dyn. 2020 Aug;38(13):3927-3941. doi: 10.1080/07391102.2019.1668852. Epub 2019 Sep 27.
8	Evaluation of ultrasound-guided transversalis fascia plane block for postoperative analgesia in cesarean section: A prospective, randomized, controlled clinical trial.J Clin Anesth. 2020 Feb;59:56-60. doi: 10.1016/j.jclinane.2019.06.025. Epub 2019 Jun 27.
9	Anxiety and depression in irritable bowel syndrome: Exploring the interaction with other symptoms and pathophysiology using multivariate analyses.Neurogastroenterol Motil. 2019 Aug;31(8):e13619. doi: 10.1111/nmo.13619. Epub 2019 May 5.
10	Insight into the redox status of inflammatory skin equivalents as determined by EPR spectroscopy.Chem Biol Interact. 2019 Sep 1;310:108752. doi: 10.1016/j.cbi.2019.108752. Epub 2019 Jul 19.
11	Predictors for Intracranial Hemorrhage Following Intravenous Thrombolysis in Posterior Circulation Stroke.Transl Stroke Res. 2018 Dec;9(6):582-588. doi: 10.1007/s12975-018-0608-0. Epub 2018 Jan 15.
12	Current state of biomarkers for the diagnosis and assessment of treatment efficacy of prostate cancer.Discov Med. 2019 Jun;27(150):235-243.
13	Cancer treatment effects on cognition and depression: The moderating role of physical activity.Breast. 2019 Apr;44:73-80. doi: 10.1016/j.breast.2019.01.004. Epub 2019 Jan 16.
14	Genome-wide association analysis of autoantibody positivity in type 1 diabetes cases.PLoS Genet. 2011 Aug;7(8):e1002216. doi: 10.1371/journal.pgen.1002216. Epub 2011 Aug 4.
15	Hepatitis C virus core protein triggers abnormal porphyrin metabolism in human hepatocellular carcinoma cells.PLoS One. 2018 Jun 1;13(6):e0198345. doi: 10.1371/journal.pone.0198345. eCollection 2018.
16	Effect of protocatechuic acid-layered double hydroxide nanoparticles on diethylnitrosamine/phenobarbital-induced hepatocellular carcinoma in mice.PLoS One. 2019 May 29;14(5):e0217009. doi: 10.1371/journal.pone.0217009. eCollection 2019.
17	Heme and sensory neuropathy: insights from novel mutations in the heme exporter feline leukemia virus subgroup C receptor 1.Pain. 2019 Dec;160(12):2766-2775. doi: 10.1097/j.pain.0000000000001675.
18	NMR Spectroscopy-based Metabolomics of Drosophila Model of Huntington's Disease Suggests Altered Cell Energetics.J Proteome Res. 2017 Oct 6;16(10):3863-3872. doi: 10.1021/acs.jproteome.7b00491. Epub 2017 Sep 26.
19	Assessment of a fragment of e-cadherin as a serum biomarker with predictive value for prostate cancer.Br J Cancer. 2005 Jun 6;92(11):2018-23. doi: 10.1038/sj.bjc.6602599.
20	Oncogenic Role of Secreted Engrailed Homeobox 2 (EN2) in Prostate Cancer.J Clin Med. 2019 Sep 6;8(9):1400. doi: 10.3390/jcm8091400.
21	Highly potent mRNA based cancer vaccines represent an attractive platform for combination therapies supporting an improved therapeutic effect.J Gene Med. 2012 Jun;14(6):428-39. doi: 10.1002/jgm.2605.
22	Methylation status of p14ARF and p16INK4a as detected in pancreatic secretions.Br J Cancer. 2003 Jan 27;88(2):217-22. doi: 10.1038/sj.bjc.6600734.
23	Phenotypic spectrum of autosomal recessive retinitis pigmentosa without posterior column ataxia caused by mutations in the FLVCR1 gene.Graefes Arch Clin Exp Ophthalmol. 2019 Mar;257(3):629-638. doi: 10.1007/s00417-018-04233-7. Epub 2019 Jan 17.
24	Inferolateral thalamic ischemia secondary to PCA P2 perforator occlusion mimics MCA stroke syndrome.Neurosurg Rev. 2020 Feb;43(1):339-342. doi: 10.1007/s10143-019-01211-3. Epub 2019 Nov 11.
25	TLR Stimulation Dynamically Regulates Heme and Iron Export Gene Expression in Macrophages.J Immunol Res. 2016;2016:4039038. doi: 10.1155/2016/4039038. Epub 2016 Feb 24.
26	Transcranial Doppler-determined change in posterior cerebral artery blood flow velocity does not reflect vertebral artery blood flow during exercise.Am J Physiol Heart Circ Physiol. 2017 Apr 1;312(4):H827-H831. doi: 10.1152/ajpheart.00676.2016. Epub 2017 Feb 10.
27	Re-evaluation of the evolution of influenza H1 viruses using direct PCA.Sci Rep. 2019 Dec 17;9(1):19287. doi: 10.1038/s41598-019-55254-z.
28	Metabolomics analysis of follicular fluid in women with ovarian endometriosis undergoing in vitro fertilization.Syst Biol Reprod Med. 2019 Feb;65(1):39-47. doi: 10.1080/19396368.2018.1478469. Epub 2018 May 28.
29	Novel 3-(2,6,9-trisubstituted-9H-purine)-8-chalcone derivatives as potent anti-gastric cancer agents: Design, synthesis and structural optimization.Eur J Med Chem. 2019 Jan 1;161:493-505. doi: 10.1016/j.ejmech.2018.10.058. Epub 2018 Oct 25.
30	A Possible Role for Platelet-Activating Factor Receptor in Amyotrophic Lateral Sclerosis Treatment.Front Neurol. 2018 Feb 6;9:39. doi: 10.3389/fneur.2018.00039. eCollection 2018.
31	Protocatechuic acid inhibits TGF-1-induced proliferation and migration of human airway smooth muscle cells.J Pharmacol Sci. 2019 Jan;139(1):9-14. doi: 10.1016/j.jphs.2018.10.011. Epub 2018 Nov 5.
32	ATPase4A Autoreactivity and Its Association With Autoimmune Phenotypes in the Type 1 Diabetes Genetics Consortium Study.Diabetes Care. 2015 Oct;38 Suppl 2(Suppl 2):S29-36. doi: 10.2337/dcs15-2006.
33	Propensity for different vascular distributions and cerebral edema of intraparenchymal brain metastases from different primary cancers.J Neurooncol. 2019 May;143(1):115-122. doi: 10.1007/s11060-019-03142-x. Epub 2019 Mar 5.
34	A risk prediction model for renal damage in a hypertensive Chinese Han population.Clin Exp Hypertens. 2019;41(6):552-557. doi: 10.1080/10641963.2018.1523913. Epub 2018 Oct 9.
35	Increased adipose tissue heme levels and exportation are associated with altered systemic glucose metabolism.Sci Rep. 2017 Jul 13;7(1):5305. doi: 10.1038/s41598-017-05597-2.
36	Spectrally resolved infrared microscopy and chemometric tools to reveal the interaction between blue light (470nm) and methicillin-resistant Staphylococcus aureus.J Photochem Photobiol B. 2017 Feb;167:150-157. doi: 10.1016/j.jphotobiol.2016.12.030. Epub 2016 Dec 23.
37	Gaussian graphical models identified food intake networks and risk of type 2 diabetes, CVD, and cancer in the EPIC-Potsdam study.Eur J Nutr. 2019 Jun;58(4):1673-1686. doi: 10.1007/s00394-018-1714-1. Epub 2018 May 14.
38	Advanced microarray analysis highlights modified neuro-immune signaling in nucleated blood cells from Parkinson's disease patients.J Neuroimmunol. 2008 Sep 15;201-202:227-36. doi: 10.1016/j.jneuroim.2008.06.019. Epub 2008 Aug 8.
39	Clinical and imaging characteristics of posterior column ataxia with retinitis pigmentosa with a specific FLVCR1 mutation.Ophthalmic Genet. 2018 Dec;39(6):735-740. doi: 10.1080/13816810.2018.1547913. Epub 2018 Nov 16.
40	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.
41	Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
42	Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
43	Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
44	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.
45	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.
46	Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
47	Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.