Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTMV9DPP)

• DOT Name: Pleckstrin homology-like domain family A member 2 (PHLDA2)
• Synonyms: Beckwith-Wiedemann syndrome chromosomal region 1 candidate gene C protein; Imprinted in placenta and liver protein; Tumor-suppressing STF cDNA 3 protein; Tumor-suppressing subchromosomal transferable fragment candidate gene 3 protein; p17-Beckwith-Wiedemann region 1 C; p17-BWR1C
• Gene Name: PHLDA2
• Related Disease:
  Lung cancer
  Advanced cancer
  Alcohol dependence
  Apraxia
  Attention deficit hyperactivity disorder
  Autism spectrum disorder
  Autosomal dominant optic atrophy
  Autosomal dominant optic atrophy, classic form
  Brain cancer
  Complete hydatidiform mole
  Depression
  Diabetic retinopathy
  Fetal growth restriction
  Glioblastoma multiforme
  Leber hereditary optic neuropathy
  Lung adenocarcinoma
  Matthew-Wood syndrome
  Myopia
  Neuroblastoma
  Non-small-cell lung cancer
  Optic neuritis
  Osteosarcoma
  Post-traumatic stress disorder
  Refractive error
  Silver-Russell syndrome
  Bone osteosarcoma
  Neoplasm
  Retinopathy
  Parkinson disease
  Adrenal gland hyperfunction
  Bone benign neoplasm
  Brain neoplasm
  Childhood kidney Wilms tumor
  Glaucoma/ocular hypertension
  High blood pressure
  Wilms tumor
• UniProt ID: PHLA2_HUMAN
• Sequence:
  MKSPDEVLREGELEKRSDSLFQLWKKKRGVLTSDRLSLFPASPRARPKELRFHSILKVDC
  VERTGKYVYFTIVTTDHKEIDFRCAGESCWNAAIALALIDFQNRRALQDFRSRQERTAPA
  APAEDAVAAAAAAPSEPSEPSRPSPQPKPRTP
• Function: Plays a role in regulating placenta growth. May act via its PH domain that competes with other PH domain-containing proteins, thereby preventing their binding to membrane lipids.
• Tissue Specificity: Expressed in placenta and adult prostate gland. In placenta, it is present in all cells of the villous cytotrophoblast. The protein is absent in cells from hydatidiform moles. Hydatidiform mole is a gestation characterized by abnormal development of both fetus and trophoblast. The majority of hydatidiform moles are associated with an excess of paternal to maternal genomes and are likely to result from the abnormal expression of imprinted genes (at protein level). Expressed at low levels in adult liver and lung, and fetal liver. Expressed in adult brain and neuroblastoma, medullablastoma and glioblastoma cell lines.

Molecular Interaction Atlas (MIA) of This DOT

36 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Lung cancer	DISCM4YA	Definitive	Biomarker	[1]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[2]
Alcohol dependence	DIS4ZSCO	Strong	Biomarker	[3]
Apraxia	DISULX63	Strong	Genetic Variation	[4]
Attention deficit hyperactivity disorder	DISL8MX9	Strong	Biomarker	[5]
Autism spectrum disorder	DISXK8NV	Strong	Biomarker	[6]
Autosomal dominant optic atrophy	DISOCR1N	Strong	Genetic Variation	[7]
Autosomal dominant optic atrophy, classic form	DISXUAV9	Strong	Genetic Variation	[7]
Brain cancer	DISBKFB7	Strong	Altered Expression	[8]
Complete hydatidiform mole	DIS5QPI0	Strong	Biomarker	[9]
Depression	DIS3XJ69	Strong	Altered Expression	[10]
Diabetic retinopathy	DISHGUJM	Strong	Biomarker	[11]
Fetal growth restriction	DIS5WEJ5	Strong	Biomarker	[12]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[13]
Leber hereditary optic neuropathy	DIS7Y2EE	Strong	Biomarker	[14]
Lung adenocarcinoma	DISD51WR	Strong	Biomarker	[15]
Matthew-Wood syndrome	DISA7HR7	Strong	Biomarker	[2]
Myopia	DISK5S60	Strong	Biomarker	[16]
Neuroblastoma	DISVZBI4	Strong	Biomarker	[13]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[17]
Optic neuritis	DISDYCHC	Strong	Biomarker	[18]
Osteosarcoma	DISLQ7E2	Strong	Altered Expression	[19]
Post-traumatic stress disorder	DISHL1EY	Strong	Biomarker	[20]
Refractive error	DISWNEQ1	Strong	Biomarker	[21]
Silver-Russell syndrome	DISSVJ1D	Strong	Biomarker	[22]
Bone osteosarcoma	DIST1004	moderate	Altered Expression	[19]
Neoplasm	DISZKGEW	moderate	Biomarker	[23]
Retinopathy	DISB4B0F	moderate	Biomarker	[24]
Parkinson disease	DISQVHKL	Disputed	Biomarker	[25]
Adrenal gland hyperfunction	DISPP4ZK	Limited	Altered Expression	[26]
Bone benign neoplasm	DISEK84G	Limited	Altered Expression	[23]
Brain neoplasm	DISY3EKS	Limited	Altered Expression	[8]
Childhood kidney Wilms tumor	DIS0NMK3	Limited	Altered Expression	[27]
Glaucoma/ocular hypertension	DISLBXBY	Limited	Biomarker	[28]
High blood pressure	DISY2OHH	Limited	Biomarker	[29]
Wilms tumor	DISB6T16	Limited	Altered Expression	[27]

This DOT Affected the Drug Response of 3 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Pleckstrin homology-like domain family A member 2 (PHLDA2) increases the response to substance of Cisplatin.	[63]
Gefitinib	DM15F0X	Approved	Pleckstrin homology-like domain family A member 2 (PHLDA2) affects the response to substance of Gefitinib.	[17]
Epirubicin	DMPDW6T	Approved	Pleckstrin homology-like domain family A member 2 (PHLDA2) increases the response to substance of Epirubicin.	[63]

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 Pleckstrin homology-like domain family A member 2 (PHLDA2).	[30]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Pleckstrin homology-like domain family A member 2 (PHLDA2).	[56]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Pleckstrin homology-like domain family A member 2 (PHLDA2).	[57]

35 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 Pleckstrin homology-like domain family A member 2 (PHLDA2).	[31]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Pleckstrin homology-like domain family A member 2 (PHLDA2).	[32]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Pleckstrin homology-like domain family A member 2 (PHLDA2).	[33]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Pleckstrin homology-like domain family A member 2 (PHLDA2).	[34]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Pleckstrin homology-like domain family A member 2 (PHLDA2).	[35]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Pleckstrin homology-like domain family A member 2 (PHLDA2).	[36]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Pleckstrin homology-like domain family A member 2 (PHLDA2).	[37]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Pleckstrin homology-like domain family A member 2 (PHLDA2).	[38]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Pleckstrin homology-like domain family A member 2 (PHLDA2).	[39]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Pleckstrin homology-like domain family A member 2 (PHLDA2).	[40]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Pleckstrin homology-like domain family A member 2 (PHLDA2).	[41]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Pleckstrin homology-like domain family A member 2 (PHLDA2).	[42]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of Pleckstrin homology-like domain family A member 2 (PHLDA2).	[43]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Pleckstrin homology-like domain family A member 2 (PHLDA2).	[44]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Pleckstrin homology-like domain family A member 2 (PHLDA2).	[40]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Pleckstrin homology-like domain family A member 2 (PHLDA2).	[41]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of Pleckstrin homology-like domain family A member 2 (PHLDA2).	[45]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Pleckstrin homology-like domain family A member 2 (PHLDA2).	[46]
Troglitazone	DM3VFPD	Approved	Troglitazone increases the expression of Pleckstrin homology-like domain family A member 2 (PHLDA2).	[47]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone decreases the expression of Pleckstrin homology-like domain family A member 2 (PHLDA2).	[48]
Azathioprine	DMMZSXQ	Approved	Azathioprine increases the expression of Pleckstrin homology-like domain family A member 2 (PHLDA2).	[49]
Irinotecan	DMP6SC2	Approved	Irinotecan increases the expression of Pleckstrin homology-like domain family A member 2 (PHLDA2).	[50]
Piroxicam	DMTK234	Approved	Piroxicam decreases the expression of Pleckstrin homology-like domain family A member 2 (PHLDA2).	[51]
Cyclophosphamide	DM4O2Z7	Approved	Cyclophosphamide increases the expression of Pleckstrin homology-like domain family A member 2 (PHLDA2).	[52]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Pleckstrin homology-like domain family A member 2 (PHLDA2).	[53]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Pleckstrin homology-like domain family A member 2 (PHLDA2).	[41]
Rigosertib	DMOSTXF	Phase 3	Rigosertib increases the expression of Pleckstrin homology-like domain family A member 2 (PHLDA2).	[54]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Pleckstrin homology-like domain family A member 2 (PHLDA2).	[55]
Belinostat	DM6OC53	Phase 2	Belinostat increases the expression of Pleckstrin homology-like domain family A member 2 (PHLDA2).	[41]
PMID27336223-Compound-5	DM6E50A	Patented	PMID27336223-Compound-5 decreases the expression of Pleckstrin homology-like domain family A member 2 (PHLDA2).	[48]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Pleckstrin homology-like domain family A member 2 (PHLDA2).	[58]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Pleckstrin homology-like domain family A member 2 (PHLDA2).	[59]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Pleckstrin homology-like domain family A member 2 (PHLDA2).	[60]
Nickel chloride	DMI12Y8	Investigative	Nickel chloride increases the expression of Pleckstrin homology-like domain family A member 2 (PHLDA2).	[61]
cinnamaldehyde	DMZDUXG	Investigative	cinnamaldehyde increases the expression of Pleckstrin homology-like domain family A member 2 (PHLDA2).	[62]

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