Details of Drug Off-Target (DOT)

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

• DOT Name: Glypican-6 (GPC6)
• Gene Name: GPC6
• Related Disease:
  Intervertebral disc degeneration
  Neurotic disorder
  Advanced cancer
  Alzheimer disease
  Attention deficit hyperactivity disorder
  Autosomal recessive omodysplasia
  Bone development disease
  Breast cancer
  Breast carcinoma
  Cardiovascular disease
  Colorectal carcinoma
  Congenital deformities of limbs
  Epithelial ovarian cancer
  Keipert syndrome
  Metastatic malignant neoplasm
  Metastatic melanoma
  Neoplasm
  Omodysplasia
  Osteoporosis
  Retinoblastoma
  Simpson-Golabi-Behmel syndrome
  Simpson-Golabi-Behmel syndrome type 1
  Melanoma
  Schizophrenia
• UniProt ID: GPC6_HUMAN
• Pfam ID: PF01153
• Sequence:
  MPSWIGAVILPLLGLLLSLPAGADVKARSCGEVRQAYGAKGFSLADIPYQEIAGEHLRIC
  PQEYTCCTTEMEDKLSQQSKLEFENLVEETSHFVRTTFVSRHKKFDEFFRELLENAEKSL
  NDMFVRTYGMLYMQNSEVFQDLFTELKRYYTGGNVNLEEMLNDFWARLLERMFQLINPQY
  HFSEDYLECVSKYTDQLKPFGDVPRKLKIQVTRAFIAARTFVQGLTVGREVANRVSKVSP
  TPGCIRALMKMLYCPYCRGLPTVRPCNNYCLNVMKGCLANQADLDTEWNLFIDAMLLVAE
  RLEGPFNIESVMDPIDVKISEAIMNMQENSMQVSAKVFQGCGQPKPAPALRSARSAPENF
  NTRFRPYNPEERPTTAAGTSLDRLVTDIKEKLKLSKKVWSALPYTICKDESVTAGTSNEE
  ECWNGHSKARYLPEIMNDGLTNQINNPEVDVDITRPDTFIRQQIMALRVMTNKLKNAYNG
  NDVNFQDTSDESSGSGSGSGCMDDVCPTEFEFVTTEAPAVDPDRREVDSSAAQRGHSLLS
  WSLTCIVLALQRLCR
• Function: Cell surface proteoglycan that bears heparan sulfate. Putative cell surface coreceptor for growth factors, extracellular matrix proteins, proteases and anti-proteases. Enhances migration and invasion of cancer cells through WNT5A signaling.
• Tissue Specificity: Widely expressed. High expression in fetal kidney and lung and lower expressions in fetal liver and brain. In adult tissues, very abundant in ovary, high levels also observed in liver, kidney, small intestine and colon. Not detected in peripheral blood leukocytes. Detected in breast cancer cells (at protein level).
• Reactome Pathway:
  HS-GAG biosynthesis (R-HSA-2022928)
  HS-GAG degradation (R-HSA-2024096)
  Defective B4GALT7 causes EDS, progeroid type (R-HSA-3560783)
  Defective B3GAT3 causes JDSSDHD (R-HSA-3560801)
  Defective EXT2 causes exostoses 2 (R-HSA-3656237)
  Defective EXT1 causes exostoses 1, TRPS2 and CHDS (R-HSA-3656253)
  Defective B3GALT6 causes EDSP2 and SEMDJL1 (R-HSA-4420332)
  Attachment and Entry (R-HSA-9694614)
  Retinoid metabolism and transport (R-HSA-975634)
  A tetrasaccharide linker sequence is required for GAG synthesis (R-HSA-1971475)

Molecular Interaction Atlas (MIA) of This DOT

24 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Intervertebral disc degeneration	DISG3AIM	Definitive	Genetic Variation	[1]
Neurotic disorder	DIS1YCE9	Definitive	Genetic Variation	[2]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[3]
Alzheimer disease	DISF8S70	Strong	Genetic Variation	[4]
Attention deficit hyperactivity disorder	DISL8MX9	Strong	Genetic Variation	[5]
Autosomal recessive omodysplasia	DIS2E6PV	Strong	Autosomal recessive	[6]
Bone development disease	DISVKAZS	Strong	Biomarker	[7]
Breast cancer	DIS7DPX1	Strong	Biomarker	[8]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[8]
Cardiovascular disease	DIS2IQDX	Strong	Biomarker	[9]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[3]
Congenital deformities of limbs	DISP4N1Q	Strong	Biomarker	[6]
Epithelial ovarian cancer	DIS56MH2	Strong	Genetic Variation	[10]
Keipert syndrome	DISJ7D7I	Strong	Biomarker	[7]
Metastatic malignant neoplasm	DIS86UK6	Strong	Biomarker	[11]
Metastatic melanoma	DISSL43L	Strong	Altered Expression	[11]
Neoplasm	DISZKGEW	Strong	Altered Expression	[11]
Omodysplasia	DISREAME	Strong	Genetic Variation	[12]
Osteoporosis	DISF2JE0	Strong	Biomarker	[13]
Retinoblastoma	DISVPNPB	Strong	Genetic Variation	[14]
Simpson-Golabi-Behmel syndrome	DIS9H9TY	Strong	Genetic Variation	[12]
Simpson-Golabi-Behmel syndrome type 1	DISYV73N	Strong	Genetic Variation	[12]
Melanoma	DIS1RRCY	Limited	Biomarker	[11]
Schizophrenia	DISSRV2N	Limited	Genetic Variation	[15]

24 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 Glypican-6 (GPC6).	[16]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Glypican-6 (GPC6).	[17]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Glypican-6 (GPC6).	[18]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Glypican-6 (GPC6).	[19]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Glypican-6 (GPC6).	[20]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Glypican-6 (GPC6).	[21]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Glypican-6 (GPC6).	[23]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Glypican-6 (GPC6).	[24]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Glypican-6 (GPC6).	[25]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Glypican-6 (GPC6).	[25]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Glypican-6 (GPC6).	[26]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Glypican-6 (GPC6).	[27]
Panobinostat	DM58WKG	Approved	Panobinostat decreases the expression of Glypican-6 (GPC6).	[28]
Dexamethasone	DMMWZET	Approved	Dexamethasone decreases the expression of Glypican-6 (GPC6).	[29]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol increases the expression of Glypican-6 (GPC6).	[30]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Glypican-6 (GPC6).	[31]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Glypican-6 (GPC6).	[28]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Glypican-6 (GPC6).	[32]
Belinostat	DM6OC53	Phase 2	Belinostat decreases the expression of Glypican-6 (GPC6).	[28]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Glypican-6 (GPC6).	[17]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Glypican-6 (GPC6).	[33]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Glypican-6 (GPC6).	[34]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Glypican-6 (GPC6).	[35]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Glypican-6 (GPC6).	[36]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Glypican-6 (GPC6).	[22]

References

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