Details of Drug Off-Target (DOT)

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

• DOT Name: Exophilin-5 (EXPH5)
• Synonyms: Synaptotagmin-like protein homolog lacking C2 domains b; SlaC2-b; Slp homolog lacking C2 domains b
• Gene Name: EXPH5
• Related Disease:
  Epidermolysis bullosa simplex
  Epidermolysis bullosa simplex 2F, with mottled pigmentation
  Epidermolysis bullosa simplex 4, localized or generalized intermediate, autosomal recessive
  Junctional epidermolysis bullosa
  Advanced cancer
  Epidermolysis bullosa
• UniProt ID: EXPH5_HUMAN
• Sequence:
  MTKVPPAFDFSFLNDEEARKILQVLERNEELQRAEKDRISKLQKTKRDIRWLQGVTGEWF
  EEIQRKKFCNETDVSQMLKQPLTYRLSKEMAKNDPIELPTSRSKNVTNQKKPTPFSSRMS
  FRSSFASLFSFRKSGKETSKLPSLGQKGCDGHAGPPMPVRGAAVQAKIYNSPLENHLVDS
  TFVPKPAVMREESGMPPPWDASLLENEFFQVLDDLDSKLAQEQSASSVNTRTPLNYGSRT
  QFGHFYSSGNRHGNITERHKKHYNETSNMSIYDILRPGTPREGFKTFSPRTSTIYDMYRT
  REPRVFKEDYVQKNTFGSTSLCFDSRQRSALPATGHFTARSLHFPATTQSKSGFIPPRHQ
  QSPKRTPLSSIIWNRSDSSRDRENQEEFLRAPSPMEIDPADKYVYPRGFQENKRYESYHS
  QNVYQRVSLNAPMENAMSPDTFENSENMPFYHQSNTFTRSFFSNTFGRSGEQRRFGQGPF
  WGQEKGHSFWSDFHRSRKSFSSSDRDFEMISMEANSVSAIHGHNVSSEHWESFSSGYGTD
  VSRGQEEPHPWQFDFQRSTLDSMVVSHGNETQLTPHFGTPNVCSMTGSSYHVKSSELVSQ
  QDSSPVEVHINKEASSFGIAQTLASSFKTSFSQISDDRRNPQSPNLQNPTVTLQKIFPNK
  PASHPMRSHTEVTVTSSNSVDSLPLAKSQPNILVTEVNNEKDLNESISEEDKQLSKMDQT
  NKAGEIPQPVSQTGISNSLPDFQNPLSQDSAKSNGFGFNASTIISSKKSPRVFSRKDTSK
  MYIPHTDKSNDIKQDKRFTENRKLGSTASLPFIQEHRTPPSFPRTDQGCHQELTVNNEDI
  SRIITNNHWSSALTDTQNAQYSKCKLTPGHKTSCDSLDLSSAALPDSSPSKNSSLDAPVV
  PSTTVFSRRSPSDKDPSLGEREEKDNAGKNQKNQFIVSHSENQERNDSPVPTHDEVVDVK
  CHSHSPFRNERGKGKIRHHISCIEKLSKTESISVPTSDHRSLIEANQSNSKVSELDTIYC
  TLPRKSSSFLIHGRQSGSKIMAASLRNGPPPFQIKNNVEDAMGNYMLNKFSPSSPESANE
  CSKVLSDSALEAPEATERMTNVKSSGSTSVRKGPLPFLINRAMSCPSGEPHASTGREGRK
  KPLTSGMDASELTPRAWERIISPVESDSSVRDCSLTKRQHQKENFQEYTEKEGKMAASRR
  SVFALSNEDPLPFCSDLSGKERGKTLHKVKTTSTFSVSGDEDNVKCLEVVSIYYTLPRKP
  SKKFCNLLQQYTQNTNLLIESPQVETETFPNALEKDKQNYSTREQSGTPSCENLKMSVNS
  DQTLTTENMTAFRLSNRGPLAPTLQEMASVEAAVSLPEEESKAREIFSDNLAKTPLGDSE
  NKKERGKKLQSETLHTSLMLQRKNVSEEKSENCQQSINSSNSGPSSLPALSEVNIGNSQT
  RRSSWECTGSGRAIPFTGSGKCPQKDHTSTAVGDGSSGSQPREGRGDIGTNCQKMTNKTL
  SHSESQVFALTPALHKLQLGEETQSDEPNLESLQSEPRELPQRSQEANMTESRKAEDEMQ
  KSAWDQPSLPEGNKNKTNLDDLVKGENRSSVKHRLAAMSKASRKFPAKDVSPRRHVATIF
  PQSGSRSGFDHLSLGTVECNPLFPEPTPKSAESIGESRLSENGKHVKKSENLLPITVLPN
  REPSTHVSNQKSNSISQRHQNEFKNVSESPSKHENSKDVTAAQNLVRESGAPSPITFTSL
  REAEFSDNQRRLSPPFPLEPAQKSRVSSPLASFLQQQRSASSLEWEPEPHLYRSKSLKSI
  NVHGDLLRKSHPPKVRERHFSESTSIDNALSRLTLGNEFSVNNGYSRRFRSFSELPSCDG
  NESWAYRSGTKTGPRSAISIYRPIDYGIFGKEQQLAFLENVKRSLTQGRLWKPSFLKNPG
  FLKDDLRNPPNPSESLSSNSPSSQVPEDGLSPSEPLNIYEDDPVDSDCDTDTTTDDEYYL
  DENDKESEL
• Function: May act as Rab effector protein and play a role in vesicle trafficking.
• Tissue Specificity: Expressed in keratinocytes.

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Epidermolysis bullosa simplex	DIS2CZ6X	Strong	Biomarker	[1]
Epidermolysis bullosa simplex 2F, with mottled pigmentation	DIS7VDBV	Strong	Biomarker	[2]
Epidermolysis bullosa simplex 4, localized or generalized intermediate, autosomal recessive	DISZRA6Y	Strong	Autosomal recessive	[3]
Junctional epidermolysis bullosa	DISJRXWU	Disputed	Genetic Variation	[4]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[5]
Epidermolysis bullosa	DISVOTZQ	Limited	Genetic Variation	[4]

11 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 Exophilin-5 (EXPH5).	[6]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Exophilin-5 (EXPH5).	[7]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Exophilin-5 (EXPH5).	[8]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Exophilin-5 (EXPH5).	[9]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Exophilin-5 (EXPH5).	[10]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Exophilin-5 (EXPH5).	[11]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Exophilin-5 (EXPH5).	[12]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Exophilin-5 (EXPH5).	[11]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Exophilin-5 (EXPH5).	[15]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Exophilin-5 (EXPH5).	[16]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Exophilin-5 (EXPH5).	[17]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Fulvestrant	DM0YZC6	Approved	Fulvestrant decreases the methylation of Exophilin-5 (EXPH5).	[13]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Exophilin-5 (EXPH5).	[14]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Exophilin-5 (EXPH5).	[13]

References

• [1] A novel homozygous deletion in EXPH5 causes a skin fragility phenotype.Clin Exp Dermatol. 2016 Dec;41(8):915-918. doi: 10.1111/ced.12908. Epub 2016 Oct 11.
• [2] Association of Epidermolysis Bullosa Simplex With Mottled Pigmentation and EXPH5 Mutations.JAMA Dermatol. 2016 Oct 1;152(10):1137-1141. doi: 10.1001/jamadermatol.2016.2268.
• [3] 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.
• [4] Next generation sequencing identifies double homozygous mutations in two distinct genes (EXPH5 and COL17A1) in a patient with concomitant simplex and junctional epidermolysis bullosa.Hum Mutat. 2018 Oct;39(10):1349-1354. doi: 10.1002/humu.23592. Epub 2018 Aug 3.
• [5] Dissecting the mechanism of colorectal tumorigenesis based on RNA-sequencing data.Exp Mol Pathol. 2015 Apr;98(2):246-53. doi: 10.1016/j.yexmp.2015.01.004. Epub 2015 Jan 7.
• [6] 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.
• [7] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [8] 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.
• [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] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [11] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [12] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [13] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [14] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [15] 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.
• [16] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [17] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.