Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTAKS5WS)

• DOT Name: Ectodysplasin-A (EDA)
• Synonyms: Ectodermal dysplasia protein; EDA protein
• Gene Name: EDA
• Related Disease:
  Bone osteosarcoma
  Cone-rod dystrophy 2
  Glomerulosclerosis
  Nephropathy
  Osteosarcoma
  Peeling skin syndrome 1
  Potocki-Shaffer syndrome
  Systemic sclerosis
  Tooth agenesis, selective, X-linked, 1
  X-linked hypohidrotic ectodermal dysplasia
  Acute myocardial infarction
  Allergic rhinitis
  Analgesia
  Arrhythmia
  Arteriosclerosis
  Atherosclerosis
  Bacterial infection
  Breast cancer
  Breast carcinoma
  Chronic kidney disease
  Depression
  Diabetic kidney disease
  Ectodermal dysplasia and immune deficiency
  Ehlers-Danlos syndrome
  Familial long QT syndrome
  Fatty liver disease
  Hyperlipidemia
  Hypotrichosis
  Immunodeficiency
  Incontinentia pigmenti
  Myelofibrosis
  Neoplasm
  Non-alcoholic fatty liver disease
  Primary myelofibrosis
  Psoriasis
  Renal fibrosis
  Sjogren syndrome
  Trichohepatoenteric syndrome
  Alopecia
  Anhidrosis
  Stroke
  Tooth agenesis
  Attention deficit hyperactivity disorder
  Craniofrontonasal syndrome
  Melanoma
  Proliferative vitreoretinopathy
  Psychotic disorder
  Schizophrenia
  Type-1/2 diabetes
• UniProt ID: EDA_HUMAN
• PDB ID: 1RJ7; 1RJ8; 7X9G
• Pfam ID: PF00229
• Sequence:
  MGYPEVERRELLPAAAPRERGSQGCGCGGAPARAGEGNSCLLFLGFFGLSLALHLLTLCC
  YLELRSELRRERGAESRLGGSGTPGTSGTLSSLGGLDPDSPITSHLGQPSPKQQPLEPGE
  AALHSDSQDGHQMALLNFFFPDEKPYSEEESRRVRRNKRSKSNEGADGPVKNKKKGKKAG
  PPGPNGPPGPPGPPGPQGPPGIPGIPGIPGTTVMGPPGPPGPPGPQGPPGLQGPSGAADK
  AGTRENQPAVVHLQGQGSAIQVKNDLSGGVLNDWSRITMNPKVFKLHPRSGELEVLVDGT
  YFIYSQVEVYYINFTDFASYEVVVDEKPFLQCTRSIETGKTNYNTCYTAGVCLLKARQKI
  AVKMVHADISINMSKHTTFFGAIRLGEAPAS
• Function: Cytokine which is involved in epithelial-mesenchymal signaling during morphogenesis of ectodermal organs. Functions as a ligand activating the DEATH-domain containing receptors EDAR and EDA2R. May also play a role in cell adhesion; [Isoform 1]: Binds only to the receptor EDAR, while isoform 3 binds exclusively to the receptor EDA2R; [Isoform 3]: Binds only to the receptor EDA2R.
• Tissue Specificity: Not abundant; expressed in specific cell types of ectodermal (but not mesodermal) origin of keratinocytes, hair follicles, sweat glands. Also in adult heart, liver, muscle, pancreas, prostate, fetal liver, uterus, small intestine and umbilical chord.
• KEGG Pathway:
  Cytokine-cytokine receptor interaction (hsa04060)
  NF-kappa B sig.ling pathway (hsa04064)

Molecular Interaction Atlas (MIA) of This DOT

49 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Bone osteosarcoma	DIST1004	Definitive	Biomarker	[1]
Cone-rod dystrophy 2	DISX2RWY	Definitive	Biomarker	[2]
Glomerulosclerosis	DISJF20Z	Definitive	Biomarker	[3]
Nephropathy	DISXWP4P	Definitive	Biomarker	[3]
Osteosarcoma	DISLQ7E2	Definitive	Biomarker	[1]
Peeling skin syndrome 1	DIS35574	Definitive	Altered Expression	[4]
Potocki-Shaffer syndrome	DISKGU59	Definitive	Altered Expression	[4]
Systemic sclerosis	DISF44L6	Definitive	Altered Expression	[4]
Tooth agenesis, selective, X-linked, 1	DISRZTNF	Definitive	X-linked	[5]
X-linked hypohidrotic ectodermal dysplasia	DISST0XM	Definitive	X-linked	[6]
Acute myocardial infarction	DISE3HTG	Strong	Biomarker	[7]
Allergic rhinitis	DIS3U9HN	Strong	Biomarker	[8]
Analgesia	DISK3TVI	Strong	Genetic Variation	[9]
Arrhythmia	DISFF2NI	Strong	Altered Expression	[10]
Arteriosclerosis	DISK5QGC	Strong	Biomarker	[11]
Atherosclerosis	DISMN9J3	Strong	Biomarker	[11]
Bacterial infection	DIS5QJ9S	Strong	Biomarker	[12]
Breast cancer	DIS7DPX1	Strong	Posttranslational Modification	[13]
Breast carcinoma	DIS2UE88	Strong	Posttranslational Modification	[13]
Chronic kidney disease	DISW82R7	Strong	Biomarker	[14]
Depression	DIS3XJ69	Strong	Biomarker	[15]
Diabetic kidney disease	DISJMWEY	Strong	Biomarker	[16]
Ectodermal dysplasia and immune deficiency	DISLMZXR	Strong	Genetic Variation	[17]
Ehlers-Danlos syndrome	DISSVBRR	Strong	Biomarker	[18]
Familial long QT syndrome	DISRNNCY	Strong	Biomarker	[19]
Fatty liver disease	DIS485QZ	Strong	Altered Expression	[20]
Hyperlipidemia	DIS61J3S	Strong	Biomarker	[21]
Hypotrichosis	DISSW933	Strong	Genetic Variation	[22]
Immunodeficiency	DIS093I0	Strong	Genetic Variation	[23]
Incontinentia pigmenti	DIS0ALLE	Strong	Biomarker	[24]
Myelofibrosis	DISIMP21	Strong	Biomarker	[25]
Neoplasm	DISZKGEW	Strong	Biomarker	[26]
Non-alcoholic fatty liver disease	DISDG1NL	Strong	Biomarker	[20]
Primary myelofibrosis	DIS6L0CN	Strong	Biomarker	[25]
Psoriasis	DIS59VMN	Strong	Altered Expression	[27]
Renal fibrosis	DISMHI3I	Strong	Biomarker	[28]
Sjogren syndrome	DISUBX7H	Strong	Biomarker	[29]
Trichohepatoenteric syndrome	DISL3ODF	Strong	Genetic Variation	[30]
Alopecia	DIS37HU4	moderate	Biomarker	[31]
Anhidrosis	DISYLSTC	moderate	Genetic Variation	[32]
Stroke	DISX6UHX	moderate	Biomarker	[33]
Tooth agenesis	DIS1PWC7	Supportive	Autosomal dominant	[34]
Attention deficit hyperactivity disorder	DISL8MX9	Limited	Biomarker	[10]
Craniofrontonasal syndrome	DISSO9WK	Limited	Biomarker	[35]
Melanoma	DIS1RRCY	Limited	Biomarker	[36]
Proliferative vitreoretinopathy	DISZTEK1	Limited	Altered Expression	[37]
Psychotic disorder	DIS4UQOT	Limited	Biomarker	[38]
Schizophrenia	DISSRV2N	Limited	Biomarker	[38]
Type-1/2 diabetes	DISIUHAP	Limited	Biomarker	[39]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Ectodysplasin-A (EDA).	[40]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Ectodysplasin-A (EDA).	[46]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Ectodysplasin-A (EDA).	[50]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Ectodysplasin-A (EDA).	[41]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Ectodysplasin-A (EDA).	[42]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Ectodysplasin-A (EDA).	[43]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Ectodysplasin-A (EDA).	[44]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Ectodysplasin-A (EDA).	[45]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Ectodysplasin-A (EDA).	[47]
PF-3758309	DM36PKZ	Phase 1	PF-3758309 increases the expression of Ectodysplasin-A (EDA).	[48]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Ectodysplasin-A (EDA).	[49]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Ectodysplasin-A (EDA).	[51]

References

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