Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTLZAS0P)

DOT Name Hemicentin-1 (HMCN1)
Synonyms Fibulin-6; FIBL-6
Gene Name HMCN1
Related Disease
Hyperglycemia ( )
Nephropathy ( )
Advanced cancer ( )
Cholelithiasis ( )
Diabetic kidney disease ( )
Epithelial ovarian cancer ( )
Myocardial infarction ( )
Ovarian cancer ( )
Ovarian neoplasm ( )
Sjogren syndrome ( )
Age related macular degeneration 1 ( )
UniProt ID
HMCN1_HUMAN
Pfam ID
PF12662 ; PF07645 ; PF07474 ; PF07679 ; PF13927 ; PF00090
Sequence
MISWEVVHTVFLFALLYSSLAQDASPQSEIRAEEIPEGASTLAFVFDVTGSMYDDLVQVI
EGASKILETSLKRPKRPLFNFALVPFHDPEIGPVTITTDPKKFQYELRELYVQGGGDCPE
MSIGAIKIALEISLPGSFIYVFTDARSKDYRLTHEVLQLIQQKQSQVVFVLTGDCDDRTH
IGYKVYEEIASTSSGQVFHLDKKQVNEVLKWVEEAVQASKVHLLSTDHLEQAVNTWRIPF
DPSLKEVTVSLSGPSPMIEIRNPLGKLIKKGFGLHELLNIHNSAKVVNVKEPEAGMWTVK
TSSSGRHSVRITGLSTIDFRAGFSRKPTLDFKKTVSRPVQGIPTYVLLNTSGISTPARID
LLELLSISGSSLKTIPVKYYPHRKPYGIWNISDFVPPNEAFFLKVTGYDKDDYLFQRVSS
VSFSSIVPDAPKVTMPEKTPGYYLQPGQIPCSVDSLLPFTLSFVRNGVTLGVDQYLKESA
SVNLDIAKVTLSDEGFYECIAVSSAGTGRAQTFFDVSEPPPVIQVPNNVTVTPGERAVLT
CLIISAVDYNLTWQRNDRDVRLAEPARIRTLANLSLELKSVKFNDAGEYHCMVSSEGGSS
AASVFLTVQEPPKVTVMPKNQSFTGGSEVSIMCSATGYPKPKIAWTVNDMFIVGSHRYRM
TSDGTLFIKNAAPKDAGIYGCLASNSAGTDKQNSTLRYIEAPKLMVVQSELLVALGDITV
MECKTSGIPPPQVKWFKGDLELRPSTFLIIDPLLGLLKIQETQDLDAGDYTCVAINEAGR
ATGKITLDVGSPPVFIQEPADVSMEIGSNVTLPCYVQGYPEPTIKWRRLDNMPIFSRPFS
VSSISQLRTGALFILNLWASDKGTYICEAENQFGKIQSETTVTVTGLVAPLIGISPSVAN
VIEGQQLTLPCTLLAGNPIPERRWIKNSAMLLQNPYITVRSDGSLHIERVQLQDGGEYTC
VASNVAGTNNKTTSVVVHVLPTIQHGQQILSTIEGIPVTLPCKASGNPKPSVIWSKKGEL
ISTSSAKFSAGADGSLYVVSPGGEESGEYVCTATNTAGYAKRKVQLTVYVRPRVFGDQRG
LSQDKPVEISVLAGEEVTLPCEVKSLPPPIITWAKETQLISPFSPRHTFLPSGSMKITET
RTSDSGMYLCVATNIAGNVTQAVKLNVHVPPKIQRGPKHLKVQVGQRVDIPCNAQGTPLP
VITWSKGGSTMLVDGEHHVSNPDGTLSIDQATPSDAGIYTCVATNIAGTDETEITLHVQE
PPTVEDLEPPYNTTFQERVANQRIEFPCPAKGTPKPTIKWLHNGRELTGREPGISILEDG
TLLVIASVTPYDNGEYICVAVNEAGTTERKYNLKVHVPPVIKDKEQVTNVSVLLNQLTNL
FCEVEGTPSPIIMWYKDNVQVTESSTIQTVNNGKILKLFRATPEDAGRYSCKAINIAGTS
QKYFNIDVLVPPTIIGTNFPNEVSVVLNRDVALECQVKGTPFPDIHWFKDGKPLFLGDPN
VELLDRGQVLHLKNARRNDKGRYQCTVSNAAGKQAKDIKLTIYIPPSIKGGNVTTDISVL
INSLIKLECETRGLPMPAITWYKDGQPIMSSSQALYIDKGQYLHIPRAQVSDSATYTCHV
ANVAGTAEKSFHVDVYVPPMIEGNLATPLNKQVVIAHSLTLECKAAGNPSPILTWLKDGV
PVKANDNIRIEAGGKKLEIMSAQEIDRGQYICVATSVAGEKEIKYEVDVLVPPAIEGGDE
TSYFIVMVNNLLELDCHVTGSPPPTIMWLKDGQLIDERDGFKILLNGRKLVIAQAQVSNT
GLYRCMAANTAGDHKKEFEVTVHVPPTIKSSGLSERVVVKYKPVALQCIANGIPNPSITW
LKDDQPVNTAQGNLKIQSSGRVLQIAKTLLEDAGRYTCVATNAAGETQQHIQLHVHEPPS
LEDAGKMLNETVLVSNPVQLECKAAGNPVPVITWYKDNRLLSGSTSMTFLNRGQIIDIES
AQISDAGIYKCVAINSAGATELFYSLQVHVAPSISGSNNMVAVVVNNPVRLECEARGIPA
PSLTWLKDGSPVSSFSNGLQVLSGGRILALTSAQISDTGRYTCVAVNAAGEKQRDIDLRV
YVPPNIMGEEQNVSVLISQAVELLCQSDAIPPPTLTWLKDGHPLLKKPGLSISENRSVLK
IEDAQVQDTGRYTCEATNVAGKTEKNYNVNIWVPPNIGGSDELTQLTVIEGNLISLLCES
SGIPPPNLIWKKKGSPVLTDSMGRVRILSGGRQLQISIAEKSDAALYSCVASNVAGTAKK
EYNLQVYIRPTITNSGSHPTEIIVTRGKSISLECEVQGIPPPTVTWMKDGHPLIKAKGVE
ILDEGHILQLKNIHVSDTGRYVCVAVNVAGMTDKKYDLSVHAPPSIIGNHRSPENISVVE
KNSVSLTCEASGIPLPSITWFKDGWPVSLSNSVRILSGGRMLRLMQTTMEDAGQYTCVVR
NAAGEERKIFGLSVLVPPHIVGENTLEDVKVKEKQSVTLTCEVTGNPVPEITWHKDGQPL
QEDEAHHIISGGRFLQITNVQVPHTGRYTCLASSPAGHKSRSFSLNVFVSPTIAGVGSDG
NPEDVTVILNSPTSLVCEAYSYPPATITWFKDGTPLESNRNIRILPGGRTLQILNAQEDN
AGRYSCVATNEAGEMIKHYEVKVYIPPIINKGDLWGPGLSPKEVKIKVNNTLTLECEAYA
IPSASLSWYKDGQPLKSDDHVNIAANGHTLQIKEAQISDTGRYTCVASNIAGEDELDFDV
NIQVPPSFQKLWEIGNMLDTGRNGEAKDVIINNPISLYCETNAAPPPTLTWYKDGHPLTS
SDKVLILPGGRVLQIPRAKVEDAGRYTCVAVNEAGEDSLQYDVRVLVPPIIKGANSDLPE
EVTVLVNKSALIECLSSGSPAPRNSWQKDGQPLLEDDHHKFLSNGRILQILNTQITDIGR
YVCVAENTAGSAKKYFNLNVHVPPSVIGPKSENLTVVVNNFISLTCEVSGFPPPDLSWLK
NEQPIKLNTNTLIVPGGRTLQIIRAKVSDGGEYTCIAINQAGESKKKFSLTVYVPPSIKD
HDSESLSVVNVREGTSVSLECESNAVPPPVITWYKNGRMITESTHVEILADGQMLHIKKA
EVSDTGQYVCRAINVAGRDDKNFHLNVYVPPSIEGPEREVIVETISNPVTLTCDATGIPP
PTIAWLKNHKRIENSDSLEVRILSGGSKLQIARSQHSDSGNYTCIASNMEGKAQKYYFLS
IQVPPSVAGAEIPSDVSVLLGENVELVCNANGIPTPLIQWLKDGKPIASGETERIRVSAN
GSTLNIYGALTSDTGKYTCVATNPAGEEDRIFNLNVYVTPTIRGNKDEAEKLMTLVDTSI
NIECRATGTPPPQINWLKNGLPLPLSSHIRLLAAGQVIRIVRAQVSDVAVYTCVASNRAG
VDNKHYNLQVFAPPNMDNSMGTEEITVLKGSSTSMACITDGTPAPSMAWLRDGQPLGLDA
HLTVSTHGMVLQLLKAETEDSGKYTCIASNEAGEVSKHFILKVLEPPHINGSEEHEEISV
IVNNPLELTCIASGIPAPKMTWMKDGRPLPQTDQVQTLGGGEVLRISTAQVEDTGRYTCL
ASSPAGDDDKEYLVRVHVPPNIAGTDEPRDITVLRNRQVTLECKSDAVPPPVITWLRNGE
RLQATPRVRILSGGRYLQINNADLGDTANYTCVASNIAGKTTREFILTVNVPPNIKGGPQ
SLVILLNKSTVLECIAEGVPTPRITWRKDGAVLAGNHARYSILENGFLHIQSAHVTDTGR
YLCMATNAAGTDRRRIDLQVHVPPSIAPGPTNMTVIVNVQTTLACEATGIPKPSINWRKN
GHLLNVDQNQNSYRLLSSGSLVIISPSVDDTATYECTVTNGAGDDKRTVDLTVQVPPSIA
DEPTDFLVTKHAPAVITCTASGVPFPSIHWTKNGIRLLPRGDGYRILSSGAIEILATQLN
HAGRYTCVARNAAGSAHRHVTLHVHEPPVIQPQPSELHVILNNPILLPCEATGTPSPFIT
WQKEGINVNTSGRNHAVLPSGGLQISRAVREDAGTYMCVAQNPAGTALGKIKLNVQVPPV
ISPHLKEYVIAVDKPITLSCEADGLPPPDITWHKDGRAIVESIRQRVLSSGSLQIAFVQP
GDAGHYTCMAANVAGSSSTSTKLTVHVPPRIRSTEGHYTVNENSQAILPCVADGIPTPAI
NWKKDNVLLANLLGKYTAEPYGELILENVVLEDSGFYTCVANNAAGEDTHTVSLTVHVLP
TFTELPGDVSLNKGEQLRLSCKATGIPLPKLTWTFNNNIIPAHFDSVNGHSELVIERVSK
EDSGTYVCTAENSVGFVKAIGFVYVKEPPVFKGDYPSNWIEPLGGNAILNCEVKGDPTPT
IQWNRKGVDIEISHRIRQLGNGSLAIYGTVNEDAGDYTCVATNEAGVVERSMSLTLQSPP
IITLEPVETVINAGGKIILNCQATGEPQPTITWSRQGHSISWDDRVNVLSNNSLYIADAQ
KEDTSEFECVARNLMGSVLVRVPVIVQVHGGFSQWSAWRACSVTCGKGIQKRSRLCNQPL
PANGGKPCQGSDLEMRNCQNKPCPVDGSWSEWSLWEECTRSCGRGNQTRTRTCNNPSVQH
GGRPCEGNAVEIIMCNIRPCPVHGAWSAWQPWGTCSESCGKGTQTRARLCNNPPPAFGGS
YCDGAETQMQVCNERNCPIHGKWATWASWSACSVSCGGGARQRTRGCSDPVPQYGGRKCE
GSDVQSDFCNSDPCPTHGNWSPWSGWGTCSRTCNGGQMRRYRTCDNPPPSNGGRACGGPD
SQIQRCNTDMCPVDGSWGSWHSWSQCSASCGGGEKTRKRLCDHPVPVKGGRPCPGDTTQV
TRCNVQACPGGPQRARGSVIGNINDVEFGIAFLNATITDSPNSDTRIIRAKITNVPRSLG
SAMRKIVSILNPIYWTTAKEIGEAVNGFTLTNAVFKRETQVEFATGEILQMSHIARGLDS
DGSLLLDIVVSGYVLQLQSPAEVTVKDYTEDYIQTGPGQLYAYSTRLFTIDGISIPYTWN
HTVFYDQAQGRMPFLVETLHASSVESDYNQIEETLGFKIHASISKGDRSNQCPSGFTLDS
VGPFCADEDECAAGNPCSHSCHNAMGTYYCSCPKGLTIAADGRTCQDIDECALGRHTCHA
GQDCDNTIGSYRCVVRCGSGFRRTSDGLSCQDINECQESSPCHQRCFNAIGSFHCGCEPG
YQLKGRKCMDVNECRQNVCRPDQHCKNTRGGYKCIDLCPNGMTKAENGTCIDIDECKDGT
HQCRYNQICENTRGSYRCVCPRGYRSQGVGRPCMDINECEQVPKPCAHQCSNTPGSFKCI
CPPGQHLLGDGKSCAGLERLPNYGTQYSSYNLARFSPVRNNYQPQQHYRQYSHLYSSYSE
YRNSRTSLSRTRRTIRKTCPEGSEASHDTCVDIDECENTDACQHECKNTFGSYQCICPPG
YQLTHNGKTCQDIDECLEQNVHCGPNRMCFNMRGSYQCIDTPCPPNYQRDPVSGFCLKNC
PPNDLECALSPYALEYKLVSLPFGIATNQDLIRLVAYTQDGVMHPRTTFLMVDEEQTVPF
ALRDENLKGVVYTTRPLREAETYRMRVRASSYSANGTIEYQTTFIVYIAVSAYPY
Function
Involved in transforming growth factor beta-mediated rearrangement of the podocyte cytoskeleton which includes reduction of F-actin fibers and broadening, flattening and elongation of podocytes. Plays a role in basement membrane organization. May promote cleavage furrow maturation during cytokinesis in preimplantation embryos. May play a role in the architecture of adhesive and flexible epithelial cell junctions. May play a role during myocardial remodeling by imparting an effect on cardiac fibroblast migration.
Tissue Specificity
Expressed in hair follicles and in the dermis (at protein level).; [Isoform 1]: Expressed in skin fibroblasts and retinal pigment epithelium (RPE) cells.; [Isoform 2]: Expressed in skin fibroblasts and retinal pigment epithelium (RPE) cells.

Molecular Interaction Atlas (MIA) of This DOT

11 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Hyperglycemia DIS0BZB5 Definitive Biomarker [1]
Nephropathy DISXWP4P Definitive Biomarker [1]
Advanced cancer DISAT1Z9 Strong Biomarker [2]
Cholelithiasis DISERLZB Strong Genetic Variation [3]
Diabetic kidney disease DISJMWEY Strong Genetic Variation [4]
Epithelial ovarian cancer DIS56MH2 Strong Biomarker [2]
Myocardial infarction DIS655KI Strong Altered Expression [5]
Ovarian cancer DISZJHAP Strong Biomarker [2]
Ovarian neoplasm DISEAFTY Strong Biomarker [2]
Sjogren syndrome DISUBX7H Strong Altered Expression [6]
Age related macular degeneration 1 DISJSM4U Limited Autosomal dominant [7]
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⏷ Show the Full List of 11 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
This DOT Affected the Drug Response of 5 Drug(s)
Drug Name Drug ID Highest Status Interaction REF
Doxorubicin DMVP5YE Approved Hemicentin-1 (HMCN1) increases the response to substance of Doxorubicin. [22]
Cisplatin DMRHGI9 Approved Hemicentin-1 (HMCN1) increases the response to substance of Cisplatin. [22]
Methotrexate DM2TEOL Approved Hemicentin-1 (HMCN1) increases the response to substance of Methotrexate. [22]
Paclitaxel DMLB81S Approved Hemicentin-1 (HMCN1) increases the response to substance of Paclitaxel. [22]
Topotecan DMP6G8T Approved Hemicentin-1 (HMCN1) increases the response to substance of Topotecan. [22]
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14 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 Hemicentin-1 (HMCN1). [8]
Acetaminophen DMUIE76 Approved Acetaminophen increases the expression of Hemicentin-1 (HMCN1). [9]
Calcitriol DM8ZVJ7 Approved Calcitriol increases the expression of Hemicentin-1 (HMCN1). [10]
Triclosan DMZUR4N Approved Triclosan decreases the expression of Hemicentin-1 (HMCN1). [11]
Zoledronate DMIXC7G Approved Zoledronate decreases the expression of Hemicentin-1 (HMCN1). [12]
Progesterone DMUY35B Approved Progesterone decreases the expression of Hemicentin-1 (HMCN1). [13]
Dexamethasone DMMWZET Approved Dexamethasone decreases the expression of Hemicentin-1 (HMCN1). [14]
Ethanol DMDRQZU Approved Ethanol increases the expression of Hemicentin-1 (HMCN1). [15]
Dasatinib DMJV2EK Approved Dasatinib increases the expression of Hemicentin-1 (HMCN1). [16]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the expression of Hemicentin-1 (HMCN1). [17]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 decreases the expression of Hemicentin-1 (HMCN1). [18]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the expression of Hemicentin-1 (HMCN1). [19]
Trichostatin A DM9C8NX Investigative Trichostatin A increases the expression of Hemicentin-1 (HMCN1). [20]
3R14S-OCHRATOXIN A DM2KEW6 Investigative 3R14S-OCHRATOXIN A increases the expression of Hemicentin-1 (HMCN1). [21]
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⏷ Show the Full List of 14 Drug(s)

References

1 Hemicentin 1 influences podocyte dynamic changes in glomerular diseases.Am J Physiol Renal Physiol. 2018 Jun 1;314(6):F1154-F1165. doi: 10.1152/ajprenal.00198.2017. Epub 2018 Feb 28.
2 SRPX and HMCN1 regulate cancerassociated fibroblasts to promote the invasiveness of ovarian carcinoma.Oncol Rep. 2019 Dec;42(6):2706-2715. doi: 10.3892/or.2019.7379. Epub 2019 Oct 17.
3 A genome-wide association scan identifies the hepatic cholesterol transporter ABCG8 as a susceptibility factor for human gallstone disease.Nat Genet. 2007 Aug;39(8):995-9. doi: 10.1038/ng2101. Epub 2007 Jul 15.
4 Examination of association with candidate genes for diabetic nephropathy in a Mexican American population.Clin J Am Soc Nephrol. 2010 Jun;5(6):1072-8. doi: 10.2215/CJN.06550909. Epub 2010 Mar 18.
5 Fibulin-6 regulates pro-fibrotic TGF- responses in neonatal mouse ventricular cardiac fibroblasts.Sci Rep. 2017 Feb 17;7:42725. doi: 10.1038/srep42725.
6 Fibulin-6 expression and anoikis in human salivary gland epithelial cells: implications in Sjogren's syndrome.Int Immunol. 2009 Mar;21(3):303-11. doi: 10.1093/intimm/dxp001. Epub 2009 Feb 3.
7 The Gene Curation Coalition: A global effort to harmonize gene-disease evidence resources. Genet Med. 2022 Aug;24(8):1732-1742. doi: 10.1016/j.gim.2022.04.017. Epub 2022 May 4.
8 Stem cell transcriptome responses and corresponding biomarkers that indicate the transition from adaptive responses to cytotoxicity. Chem Res Toxicol. 2017 Apr 17;30(4):905-922.
9 Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
10 Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
11 Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
12 Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
13 Effects of progesterone treatment on expression of genes involved in uterine quiescence. Reprod Sci. 2011 Aug;18(8):781-97.
14 Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
15 Cardiac toxicity from ethanol exposure in human-induced pluripotent stem cell-derived cardiomyocytes. Toxicol Sci. 2019 May 1;169(1):280-292.
16 Dasatinib reverses cancer-associated fibroblasts (CAFs) from primary lung carcinomas to a phenotype comparable to that of normal fibroblasts. Mol Cancer. 2010 Jun 27;9:168.
17 Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
18 Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
19 Characterization of the Molecular Alterations Induced by the Prolonged Exposure of Normal Colon Mucosa and Colon Cancer Cells to Low-Dose Bisphenol A. Int J Mol Sci. 2022 Oct 1;23(19):11620. doi: 10.3390/ijms231911620.
20 From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
21 Persistence of epigenomic effects after recovery from repeated treatment with two nephrocarcinogens. Front Genet. 2018 Dec 3;9:558.
22 Microarray-based detection and expression analysis of extracellular matrix proteins in drug?resistant ovarian cancer cell lines. Oncol Rep. 2014 Nov;32(5):1981-90. doi: 10.3892/or.2014.3468. Epub 2014 Sep 9.