Details of Drug Off-Target (DOT)

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

• DOT Name: FYVE, RhoGEF and PH domain-containing protein 4 (FGD4)
• Synonyms: Actin filament-binding protein frabin; FGD1-related F-actin-binding protein; Zinc finger FYVE domain-containing protein 6
• Gene Name: FGD4
• Related Disease:
  Charcot marie tooth disease
  Benign prostatic hyperplasia
  Breast cancer
  Breast carcinoma
  Charcot-Marie-Tooth disease type 4H
  Demyelinating polyneuropathy
  Hereditary motor and sensory neuropathy
  High blood pressure
  Myelodysplastic syndrome
  Neoplasm
  Peripheral neuropathy
  Prostate cancer
  Prostate carcinoma
  Tooth disorder
  Nasopharyngeal carcinoma
  Peripheral sensory neuropathies
  Charcot-Marie-Tooth disease type 4
  Charcot-Marie-Tooth disease type 3
• UniProt ID: FGD4_HUMAN
• Pfam ID: PF01363 ; PF00169 ; PF00621
• Sequence:
  MEEIKPASASCVSKEKPSKVSDLISRFEGGSSLSNYSDLKKESAVNLNAPRTPGRHGLTT
  TPQQKLLSQHLPQRQGNDTDKTQGAQTCVANGVMAAQNQMECEEEKAATLSSDTSIQASE
  PLLDTHIVNGERDETATAPASPTTDSCDGNASDSSYRTPGIGPVLPLEERGAETETKVQE
  RENGESPLELEQLDQHHEMKETNEQKLHKIANELLLTERAYVNRLDLLDQVFYCKLLEEA
  NRGSFPAEMVNKIFSNISSINAFHSKFLLPELEKRMQEWETTPRIGDILQKLAPFLKMYG
  EYVKGFDNAMELVKNMTERIPQFKSVVEEIQKQKICGSLTLQHHMLEPVQRIPRYEMLLK
  DYLRKLPPDSLDWNDAKKSLEIISTAASHSNSAIRKMENLKKLLEIYEMLGEEEDIVNPS
  NELIKEGQILKLAARNTSAQERYLFLFNNMLLYCVPKFSLVGSKFTVRTRVGIDGMKIVE
  TQNEEYPHTFQVSGKERTLELQASSAQDKEEWIKALQETIDAFHQRHETFRNAIAKDNDI
  HSEVSTAELGKRAPRWIRDNEVTMCMKCKEPFNALTRRRHHCRACGYVVCWKCSDYKAQL
  EYDGGKLSKVCKDCYQIISGFTDSEEKKRKGILEIESAEVSGNSVVCSFLQYMEKSKPWQ
  KAWCVIPKQDPLVLYMYGAPQDVRAQATIPLLGYVVDEMPRSADLPHSFKLTQSKSVHSF
  AADSEELKQKWLKVILLAVTGETPGGPNEHPATLDDHPEPKKKSEC
• Function: Activates CDC42, a member of the Ras-like family of Rho- and Rac proteins, by exchanging bound GDP for free GTP. Plays a role in regulating the actin cytoskeleton and cell shape. Activates MAPK8.
• Tissue Specificity: Expressed in different tissues, including brain, cerebellum, peripheral nerve, skeletal muscle, heart, uterus, placenta and testis.
• Reactome Pathway:
  G alpha (12/13) signalling events (R-HSA-416482)
  CDC42 GTPase cycle (R-HSA-9013148)
  NRAGE signals death through JNK (R-HSA-193648)

Molecular Interaction Atlas (MIA) of This DOT

18 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Charcot marie tooth disease	DIS3BT2L	Definitive	Autosomal recessive	[1]
Benign prostatic hyperplasia	DISI3CW2	Strong	Altered Expression	[2]
Breast cancer	DIS7DPX1	Strong	Biomarker	[3]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[3]
Charcot-Marie-Tooth disease type 4H	DISKNV1E	Strong	Autosomal recessive	[4]
Demyelinating polyneuropathy	DIS7IO4W	Strong	Genetic Variation	[5]
Hereditary motor and sensory neuropathy	DISR0X2K	Strong	Altered Expression	[2]
High blood pressure	DISY2OHH	Strong	Genetic Variation	[6]
Myelodysplastic syndrome	DISYHNUI	Strong	Biomarker	[7]
Neoplasm	DISZKGEW	Strong	Biomarker	[8]
Peripheral neuropathy	DIS7KN5G	Strong	Genetic Variation	[3]
Prostate cancer	DISF190Y	Strong	Altered Expression	[2]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[2]
Tooth disorder	DISBXWAX	Strong	Genetic Variation	[9]
Nasopharyngeal carcinoma	DISAOTQ0	moderate	Biomarker	[10]
Peripheral sensory neuropathies	DISYWI6M	moderate	Genetic Variation	[11]
Charcot-Marie-Tooth disease type 4	DISM8IZN	Disputed	Genetic Variation	[12]
Charcot-Marie-Tooth disease type 3	DIS6DQK1	Limited	Biomarker	[13]

3 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 FYVE, RhoGEF and PH domain-containing protein 4 (FGD4).	[14]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of FYVE, RhoGEF and PH domain-containing protein 4 (FGD4).	[20]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of FYVE, RhoGEF and PH domain-containing protein 4 (FGD4).	[30]

21 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 FYVE, RhoGEF and PH domain-containing protein 4 (FGD4).	[15]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of FYVE, RhoGEF and PH domain-containing protein 4 (FGD4).	[16]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of FYVE, RhoGEF and PH domain-containing protein 4 (FGD4).	[17]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of FYVE, RhoGEF and PH domain-containing protein 4 (FGD4).	[18]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of FYVE, RhoGEF and PH domain-containing protein 4 (FGD4).	[19]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of FYVE, RhoGEF and PH domain-containing protein 4 (FGD4).	[21]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of FYVE, RhoGEF and PH domain-containing protein 4 (FGD4).	[21]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of FYVE, RhoGEF and PH domain-containing protein 4 (FGD4).	[22]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of FYVE, RhoGEF and PH domain-containing protein 4 (FGD4).	[23]
Cannabidiol	DM0659E	Approved	Cannabidiol increases the expression of FYVE, RhoGEF and PH domain-containing protein 4 (FGD4).	[24]
Melphalan	DMOLNHF	Approved	Melphalan decreases the expression of FYVE, RhoGEF and PH domain-containing protein 4 (FGD4).	[25]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of FYVE, RhoGEF and PH domain-containing protein 4 (FGD4).	[26]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of FYVE, RhoGEF and PH domain-containing protein 4 (FGD4).	[27]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of FYVE, RhoGEF and PH domain-containing protein 4 (FGD4).	[28]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of FYVE, RhoGEF and PH domain-containing protein 4 (FGD4).	[29]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of FYVE, RhoGEF and PH domain-containing protein 4 (FGD4).	[31]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of FYVE, RhoGEF and PH domain-containing protein 4 (FGD4).	[32]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of FYVE, RhoGEF and PH domain-containing protein 4 (FGD4).	[33]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of FYVE, RhoGEF and PH domain-containing protein 4 (FGD4).	[34]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of FYVE, RhoGEF and PH domain-containing protein 4 (FGD4).	[35]
crotylaldehyde	DMTWRQI	Investigative	crotylaldehyde increases the expression of FYVE, RhoGEF and PH domain-containing protein 4 (FGD4).	[36]

References

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