Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTKJ44EV)

• DOT Name: Interferon regulatory factor 6 (IRF6)
• Synonyms: IRF-6
• Gene Name: IRF6
• Related Disease:
  Autosomal dominant popliteal pterygium syndrome
  Coronary atherosclerosis
  Myocardial infarction
  Van der Woude syndrome 1
  Advanced cancer
  Alzheimer disease
  Arteriosclerosis
  Atherosclerosis
  Bartsocas-Papas syndrome 1
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Cardiovascular disease
  Cervical cancer
  Cervical carcinoma
  Cleft lip and alveolus
  Colorectal carcinoma
  Congenital deformities of limbs
  Crohn disease
  Dementia
  Depression
  Facial cleft
  Fatty liver disease
  Gastric cancer
  Head-neck squamous cell carcinoma
  Lung cancer
  Lung carcinoma
  Metabolic disorder
  Multiple sclerosis
  Neoplasm
  Pancreatic cancer
  Prostate cancer
  Prostate carcinoma
  Squamous cell carcinoma
  Stomach cancer
  Systemic lupus erythematosus
  Autoimmune disease
  Stroke
  Tooth agenesis
  Van der Woude syndrome
  Coronary heart disease
  Inflammatory bowel disease
  Melanoma
  Nasopharyngeal carcinoma
  Obesity
  Orofacial cleft 6, susceptibility to
  Tuberculosis
• UniProt ID: IRF6_HUMAN
• Pfam ID: PF00605 ; PF10401
• Sequence:
  MALHPRRVRLKPWLVAQVDSGLYPGLIWLHRDSKRFQIPWKHATRHSPQQEEENTIFKAW
  AVETGKYQEGVDDPDPAKWKAQLRCALNKSREFNLMYDGTKEVPMNPVKIYQVCDIPQPQ
  GSIINPGSTGSAPWDEKDNDVDEEDEEDELDQSQHHVPIQDTFPFLNINGSPMAPASVGN
  CSVGNCSPEAVWPKTEPLEMEVPQAPIQPFYSSPELWISSLPMTDLDIKFQYRGKEYGQT
  MTVSNPQGCRLFYGDLGPMPDQEELFGPVSLEQVKFPGPEHITNEKQKLFTSKLLDVMDR
  GLILEVSGHAIYAIRLCQCKVYWSGPCAPSLVAPNLIERQKKVKLFCLETFLSDLIAHQK
  GQIEKQPPFEIYLCFGEEWPDGKPLERKLILVQVIPVVARMIYEMFSGDFTRSFDSGSVR
  LQISTPDIKDNIVAQLKQLYRILQTQESWQPMQPTPSMQLPPALPPQ
• Function: Probable DNA-binding transcriptional activator. Key determinant of the keratinocyte proliferation-differentiation switch involved in appropriate epidermal development. Plays a role in regulating mammary epithelial cell proliferation. May regulate WDR65 transcription.
• Tissue Specificity: Expressed in normal mammary epithelial cells. Expression is reduced or absent in breast carcinomas.
• Reactome Pathway:
  Interferon alpha/beta signaling (R-HSA-909733)
  Interferon gamma signaling (R-HSA-877300)

Molecular Interaction Atlas (MIA) of This DOT

47 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Autosomal dominant popliteal pterygium syndrome	DISJQLRA	Definitive	Autosomal dominant	[1]
Coronary atherosclerosis	DISKNDYU	Definitive	Genetic Variation	[2]
Myocardial infarction	DIS655KI	Definitive	Genetic Variation	[2]
Van der Woude syndrome 1	DIS8EHBM	Definitive	Autosomal dominant	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[3]
Alzheimer disease	DISF8S70	Strong	Biomarker	[4]
Arteriosclerosis	DISK5QGC	Strong	Biomarker	[5]
Atherosclerosis	DISMN9J3	Strong	Biomarker	[5]
Bartsocas-Papas syndrome 1	DIS12QS5	Strong	Genetic Variation	[6]
Breast cancer	DIS7DPX1	Strong	Genetic Variation	[7]
Breast carcinoma	DIS2UE88	Strong	Genetic Variation	[7]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[8]
Cardiovascular disease	DIS2IQDX	Strong	Biomarker	[9]
Cervical cancer	DISFSHPF	Strong	Posttranslational Modification	[10]
Cervical carcinoma	DIST4S00	Strong	Posttranslational Modification	[10]
Cleft lip and alveolus	DISD651B	Strong	SusceptibilityMutation	[11]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[12]
Congenital deformities of limbs	DISP4N1Q	Strong	Biomarker	[13]
Crohn disease	DIS2C5Q8	Strong	Genetic Variation	[14]
Dementia	DISXL1WY	Strong	Biomarker	[15]
Depression	DIS3XJ69	Strong	Biomarker	[16]
Facial cleft	DISXTTL9	Strong	Biomarker	[17]
Fatty liver disease	DIS485QZ	Strong	Biomarker	[18]
Gastric cancer	DISXGOUK	Strong	Altered Expression	[19]
Head-neck squamous cell carcinoma	DISF7P24	Strong	Biomarker	[20]
Lung cancer	DISCM4YA	Strong	Altered Expression	[21]
Lung carcinoma	DISTR26C	Strong	Altered Expression	[21]
Metabolic disorder	DIS71G5H	Strong	Biomarker	[18]
Multiple sclerosis	DISB2WZI	Strong	Biomarker	[22]
Neoplasm	DISZKGEW	Strong	Biomarker	[19]
Pancreatic cancer	DISJC981	Strong	Altered Expression	[23]
Prostate cancer	DISF190Y	Strong	Biomarker	[24]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[24]
Squamous cell carcinoma	DISQVIFL	Strong	Genetic Variation	[7]
Stomach cancer	DISKIJSX	Strong	Altered Expression	[19]
Systemic lupus erythematosus	DISI1SZ7	Strong	Genetic Variation	[25]
Autoimmune disease	DISORMTM	moderate	Biomarker	[26]
Stroke	DISX6UHX	moderate	Biomarker	[27]
Tooth agenesis	DIS1PWC7	Supportive	Autosomal dominant	[28]
Van der Woude syndrome	DISADZS1	Supportive	Autosomal dominant	[28]
Coronary heart disease	DIS5OIP1	Limited	Biomarker	[29]
Inflammatory bowel disease	DISGN23E	Limited	Genetic Variation	[14]
Melanoma	DIS1RRCY	Limited	Altered Expression	[30]
Nasopharyngeal carcinoma	DISAOTQ0	Limited	Altered Expression	[31]
Obesity	DIS47Y1K	Limited	Biomarker	[32]
Orofacial cleft 6, susceptibility to	DISXFTYQ	Limited	Unknown	[33]
Tuberculosis	DIS2YIMD	Limited	Altered Expression	[34]

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic trioxide	DM61TA4	Approved	Interferon regulatory factor 6 (IRF6) decreases the response to substance of Arsenic trioxide.	[49]
Methotrexate	DM2TEOL	Approved	Interferon regulatory factor 6 (IRF6) affects the response to substance of Methotrexate.	[50]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Interferon regulatory factor 6 (IRF6).	[35]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Interferon regulatory factor 6 (IRF6).	[43]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Interferon regulatory factor 6 (IRF6).	[36]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Interferon regulatory factor 6 (IRF6).	[37]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Interferon regulatory factor 6 (IRF6).	[38]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Interferon regulatory factor 6 (IRF6).	[39]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Interferon regulatory factor 6 (IRF6).	[36]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Interferon regulatory factor 6 (IRF6).	[40]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Interferon regulatory factor 6 (IRF6).	[41]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Interferon regulatory factor 6 (IRF6).	[42]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Interferon regulatory factor 6 (IRF6).	[44]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Interferon regulatory factor 6 (IRF6).	[45]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Interferon regulatory factor 6 (IRF6).	[46]
geraniol	DMS3CBD	Investigative	geraniol increases the expression of Interferon regulatory factor 6 (IRF6).	[47]
Nitrobenzanthrone	DMN6L70	Investigative	Nitrobenzanthrone decreases the expression of Interferon regulatory factor 6 (IRF6).	[48]

References

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