Details of Drug Off-Target (DOT)

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

• DOT Name: MAM and LDL-receptor class A domain-containing protein 1 (MALRD1)
• Gene Name: MALRD1
• Related Disease:
  Alopecia areata
  Diabetic macular edema
  Diabetic retinopathy
  Vitamin D deficiency
  X-linked reticulate pigmentary disorder
  Lung carcinoma
• UniProt ID: MALR1_HUMAN
• Pfam ID: PF00008 ; PF00057 ; PF00629
• Sequence:
  MLFFLDRMLAFPMNETFCCLWIACVFNSTLAQQGTESFQCDNGVSLPPDSICDFTDQCGD
  SSDERHCLNYERCDFEDGLCHMTQDQSLQPSWTKRSGMIGLSPPFYDHNGDVSAHFLSLV
  SRVDSISSSLRSRVFLPTNDQHDCQITFYYFSCQVSGKLMVGLQTACGGPIQHLWQNTAA
  LPNQWERNVIKIQSSQRFQVVFEGQMASTYEQDEVIAIDDISFSSGCLPANDGILLCQEA
  LNAERELCHPDTDLCRFDATDEELRLCQACGFEFDMCEWTSEASAGQISWMRTKAREIPA
  FESTPQQDQGGDDEGYYVWVGAKHGFTLNHLDSRAYLNSSVCHCLGKSCHLQFYYAMESS
  VLRVRLYNNKEEEIFWTYNISTHSQWVKADVLIPEDLKTFKIIFEGTLLSQRSFIALDHL
  WVYACGQTQSRKLCSADEFPCTSGQCIAKESVCDSRQDCSDESDEDPATCSKHLTCDFES
  GFCGWEPFLTEDSHWKLMKGLNNGEHHFPAADHTANINHGSFIYLEAQRSPGVAKLGSPV
  LTKLLTASTPCQVQFWYHLSQHSNLSVFTRTSLDGNLQKQGKIIRFSESQWSHAKIDLIA
  EAGESTLPFQLILEATVLSSNATVALDDISVSQECEISYKSLPRTSTQSKFSKCDFEANS
  CDWFEAISGDHFDWIRSSQSELSADFEHQAPPRDHSLNASQGHFMFILKKSSSLWQVAKL
  QSPTFSQTGPGCILSFWFYNYGLSVGAAELQLHMENSHDSTVIWRVLYNQGKQWLEATIQ
  LGRLSQPFHLSLDKVSLGIYDGVSAIDDIRFENCTLPLPAESCEGLDHFWCRHTRACIEK
  LRLCDLVDDCGDRTDEVNCAPELQCNFETGICNWEQDAKDDFDWTRSQGPTPTLNTGPMK
  DNTLGTAKGHYLYIESSEPQAFQDSAALLSPILNATDTKGCTFRFYYHMFGKRIYRLAIY
  QRIWSDSRGQLLWQIFGNQGNRWIRKHLNISSRQPFQILVEASVGDGFTGDIAIDDLSFM
  DCTLYPGNLPADLPTPPETSVPVTLPPHNCTDNEFICRSDGHCIEKMQKCDFKYDCPDKS
  DEASCVMEVCSFEKRSLCKWYQPIPVHLLQDSNTFRWGLGNGISIHHGEENHRPSVDHTQ
  NTTDGWYLYADSSNGKFGDTADILTPIISLTGPKCTLVFWTHMNGATVGSLQVLIKKDNV
  TSKLWAQTGQQGAQWKRAEVFLGIRSHTQIVFRAKRGISYIGDVAVDDISFQDCSPLLSP
  ERKCTDHEFMCANKHCIAKDKLCDFVNDCADNSDETTFICRTSSGRCDFEFDLCSWKQEK
  DEDFDWNLKASSIPAAGTEPAADHTLGNSSGHYIFIKSLFPQQPMRAARISSPVISKRSK
  NCKIIFHYHMYGNGIGALTLMQVSVTNQTKVLLNLTVEQGNFWRREELSLFGDEDFQLKF
  EGRVGKGQRGDIALDDIVLTENCLSLHDSVQEELAVPLPTGFCPLGYRECHNGKCYRLEQ
  SCNFVDNCGDNTDENECGSSCTFEKGWCGWQNSQADNFDWVLGVGSHQSLRPPKDHTLGN
  ENGHFMYLEATAVGLRGDKAHFRSTMWRESSAACTMSFWYFVSAKATGSIQILIKTEKGL
  SKVWQESKQNPGNHWQKADILLGKLRNFEVIFQGIRTRDLGGGAAIDDIEFKNCTTVGEI
  SELCPEITDFLCRDKKCIASHLLCDYKPDCSDRSDEAHCAHYTSTTGSCNFETSSGNWTT
  ACSLTQDSEDDLDWAIGSRIPAKALIPDSDHTPGSGQHFLYVNSSGSKEGSVARITTSKS
  FPASLGMCTVRFWFYMIDPRSMGILKVYTIEESGLNILVWSVIGNKRTGWTYGSVPLSSN
  SPFKVAFEADLDGNEDIFIALDDISFTPECVTGGPVPVQPSPCEADQFSCIYTLQCVPLS
  GKCDGHEDCIDGSDEMDCPLSPTPPLCSNMEFPCSTDECIPSLLLCDGVPDCHFNEDELI
  CSNKSCSNGALVCASSNSCIPAHQRCDGFADCMDFQLDESSCSECPLNYCRNGGTCVVEK
  NGPMCRCRQGWKGNRCHIKFNPPATDFTYAQNNTWTLLGIGLAFLMTHITVAVLCFLANR
  KVPIRKTEGSGNCAFVNPVYGNWSNPEKTESSVYSFSNPLYGTTSGSLETLSHHLK
• Function: Enhances production and/or transport of FGF19 and thus has a role in regulation of bile acid synthesis.
• Tissue Specificity: Strongly expressed in the small intestine.

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Alopecia areata	DIS0XXBJ	Strong	Genetic Variation	[1]
Diabetic macular edema	DIS162FN	Strong	Genetic Variation	[2]
Diabetic retinopathy	DISHGUJM	Strong	Genetic Variation	[2]
Vitamin D deficiency	DISAWKYI	Strong	Biomarker	[3]
X-linked reticulate pigmentary disorder	DIS0RB5A	Strong	Genetic Variation	[2]
Lung carcinoma	DISTR26C	Limited	Genetic Variation	[4]

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 affects the methylation of MAM and LDL-receptor class A domain-containing protein 1 (MALRD1).	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of MAM and LDL-receptor class A domain-containing protein 1 (MALRD1).	[6]

References

• [1] Genome-wide pooling approach identifies SPATA5 as a new susceptibility locus for alopecia areata.Eur J Hum Genet. 2012 Mar;20(3):326-32. doi: 10.1038/ejhg.2011.185. Epub 2011 Oct 26.
• [2] Genome-wide association studies for diabetic macular edema and proliferative diabetic retinopathy.BMC Med Genet. 2018 May 8;19(1):71. doi: 10.1186/s12881-018-0587-8.
• [3] Murine Pancreatic Acinar Cell Carcinoma Growth Kinetics Are Independent of Dietary Vitamin D Deficiency or Supplementation.Front Oncol. 2017 Jun 28;7:133. doi: 10.3389/fonc.2017.00133. eCollection 2017.
• [4] Genome-wide association study of familial lung cancer.Carcinogenesis. 2018 Sep 21;39(9):1135-1140. doi: 10.1093/carcin/bgy080.
• [5] Effect of aflatoxin B(1), benzo[a]pyrene, and methapyrilene on transcriptomic and epigenetic alterations in human liver HepaRG cells. Food Chem Toxicol. 2018 Nov;121:214-223. doi: 10.1016/j.fct.2018.08.034. Epub 2018 Aug 26.
• [6] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.