Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT2LP7LJ)

• DOT Name: SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1 (SMARCB1)
• Synonyms: BRG1-associated factor 47; BAF47; Integrase interactor 1 protein; SNF5 homolog; hSNF5
• Gene Name: SMARCB1
• Related Disease:
  Adenocarcinoma
  Coffin-Siris syndrome
  Colorectal carcinoma
  Meningioma
  Neuroblastoma
  Rhabdoid tumor predisposition syndrome 1
  Adult glioblastoma
  Advanced cancer
  B-cell neoplasm
  Brain neoplasm
  Chordoma
  Choroid plexus carcinoma
  Hydrocephalus
  Intellectual disability, autosomal dominant 15
  Intracranial meningioma
  Malignant neoplasm
  Malignant peripheral nerve sheath tumor
  Primitive neuroectodermal tumor
  Renal cell carcinoma
  Schwannoma
  Schwannomatosis 1
  Soft tissue neoplasm
  Squamous cell carcinoma
  Endometrial carcinoma
  Glioblastoma multiforme
  Malignant soft tissue neoplasm
  Sarcoma
  Soft tissue sarcoma
  Stomach cancer
  Familial multiple meningioma
  Familial rhabdoid tumor
  Schwannomatosis
  Hereditary neoplastic syndrome
  Benign neoplasm
  Central nervous system cancer
  Central nervous system neoplasm
  Childhood acute lymphoblastic leukemia
  Clear cell renal carcinoma
  Complex neurodevelopmental disorder
  Melanoma
  Synovial sarcoma
• UniProt ID: SNF5_HUMAN
• PDB ID: 5AJ1; 5GJK; 5L7A; 5L7B; 6AX5; 6KAG; 6KZ7; 6LTH; 6LTJ; 6LZP; 6UCH; 7VDV; 7Y8R
• Pfam ID: PF21459 ; PF04855
• Sequence:
  MMMMALSKTFGQKPVKFQLEDDGEFYMIGSEVGNYLRMFRGSLYKRYPSLWRRLATVEER
  KKIVASSHGKKTKPNTKDHGYTTLATSVTLLKASEVEEILDGNDEKYKAVSISTEPPTYL
  REQKAKRNSQWVPTLPNSSHHLDAVPCSTTINRNRMGRDKKRTFPLCFDDHDPAVIHENA
  SQPEVLVPIRLDMEIDGQKLRDAFTWNMNEKLMTPEMFSEILCDDLDLNPLTFVPAIASA
  IRQQIESYPTDSILEDQSDQRVIIKLNIHVGNISLVDQFEWDMSEKENSPEKFALKLCSE
  LGLGGEFVTTIAYSIRGQLSWHQKTYAFSENPLPTVEIAIRNTGDADQWCPLLETLTDAE
  MEKKIRDQDRNTRRMRRLANTAPAW
• Function: Core component of the BAF (hSWI/SNF) complex. This ATP-dependent chromatin-remodeling complex plays important roles in cell proliferation and differentiation, in cellular antiviral activities and inhibition of tumor formation. The BAF complex is able to create a stable, altered form of chromatin that constrains fewer negative supercoils than normal. This change in supercoiling would be due to the conversion of up to one-half of the nucleosomes on polynucleosomal arrays into asymmetric structures, termed altosomes, each composed of 2 histones octamers. Stimulates in vitro the remodeling activity of SMARCA4/BRG1/BAF190A. Involved in activation of CSF1 promoter. Belongs to the neural progenitors-specific chromatin remodeling complex (npBAF complex) and the neuron-specific chromatin remodeling complex (nBAF complex). During neural development a switch from a stem/progenitor to a postmitotic chromatin remodeling mechanism occurs as neurons exit the cell cycle and become committed to their adult state. The transition from proliferating neural stem/progenitor cells to postmitotic neurons requires a switch in subunit composition of the npBAF and nBAF complexes. As neural progenitors exit mitosis and differentiate into neurons, npBAF complexes which contain ACTL6A/BAF53A and PHF10/BAF45A, are exchanged for homologous alternative ACTL6B/BAF53B and DPF1/BAF45B or DPF3/BAF45C subunits in neuron-specific complexes (nBAF). The npBAF complex is essential for the self-renewal/proliferative capacity of the multipotent neural stem cells. The nBAF complex along with CREST plays a role regulating the activity of genes essential for dendrite growth. Plays a key role in cell-cycle control and causes cell cycle arrest in G0/G1.
• KEGG Pathway:
  ATP-dependent chromatin remodeling (hsa03082)
  Viral life cycle - HIV-1 (hsa03250)
  Thermogenesis (hsa04714)
  Hepatocellular carcinoma (hsa05225)
• Reactome Pathway:
  RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known (R-HSA-8939243)
  RMTs methylate histone arginines (R-HSA-3214858)

Molecular Interaction Atlas (MIA) of This DOT

41 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adenocarcinoma	DIS3IHTY	Definitive	Altered Expression	[1]
Coffin-Siris syndrome	DIS8L03H	Definitive	Autosomal dominant	[2]
Colorectal carcinoma	DIS5PYL0	Definitive	Biomarker	[1]
Meningioma	DISPT4TG	Definitive	Genetic Variation	[3]
Neuroblastoma	DISVZBI4	Definitive	Posttranslational Modification	[4]
Rhabdoid tumor predisposition syndrome 1	DISDIJXV	Definitive	Autosomal dominant	[2]
Adult glioblastoma	DISVP4LU	Strong	Biomarker	[5]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[6]
B-cell neoplasm	DISVY326	Strong	Biomarker	[7]
Brain neoplasm	DISY3EKS	Strong	Biomarker	[8]
Chordoma	DISCHJE7	Strong	Biomarker	[9]
Choroid plexus carcinoma	DISQ04MQ	Strong	Biomarker	[10]
Hydrocephalus	DISIZUF7	Strong	Genetic Variation	[11]
Intellectual disability, autosomal dominant 15	DISMX8E6	Strong	Autosomal dominant	[12]
Intracranial meningioma	DISD09EF	Strong	Genetic Variation	[13]
Malignant neoplasm	DISS6SNG	Strong	Biomarker	[14]
Malignant peripheral nerve sheath tumor	DIS0JTN6	Strong	Biomarker	[15]
Primitive neuroectodermal tumor	DISFHXHA	Strong	Altered Expression	[16]
Renal cell carcinoma	DISQZ2X8	Strong	Biomarker	[17]
Schwannoma	DISTTVLA	Strong	Genetic Variation	[18]
Schwannomatosis 1	DISFDUF2	Strong	Autosomal dominant	[19]
Soft tissue neoplasm	DISP2OHE	Strong	Biomarker	[20]
Squamous cell carcinoma	DISQVIFL	Strong	Biomarker	[21]
Endometrial carcinoma	DISXR5CY	moderate	Biomarker	[22]
Glioblastoma multiforme	DISK8246	moderate	Biomarker	[5]
Malignant soft tissue neoplasm	DISTC6NO	moderate	Biomarker	[23]
Sarcoma	DISZDG3U	moderate	Biomarker	[23]
Soft tissue sarcoma	DISSN8XB	moderate	Biomarker	[24]
Stomach cancer	DISKIJSX	moderate	Biomarker	[25]
Familial multiple meningioma	DIS7ZS52	Supportive	Autosomal dominant	[26]
Familial rhabdoid tumor	DISC6GHQ	Supportive	Autosomal dominant	[27]
Schwannomatosis	DISDWAM1	Supportive	Autosomal dominant	[28]
Hereditary neoplastic syndrome	DISGXLG5	Disputed	CausalMutation	[29]
Benign neoplasm	DISDUXAD	Limited	Genetic Variation	[30]
Central nervous system cancer	DISNVYSW	Limited	Biomarker	[31]
Central nervous system neoplasm	DISFC18W	Limited	Altered Expression	[32]
Childhood acute lymphoblastic leukemia	DISJ5D6U	Limited	Biomarker	[33]
Clear cell renal carcinoma	DISBXRFJ	Limited	Altered Expression	[34]
Complex neurodevelopmental disorder	DISB9AFI	Limited	Autosomal dominant	[19]
Melanoma	DIS1RRCY	Limited	Altered Expression	[35]
Synovial sarcoma	DISEZJS7	Limited	Altered Expression	[36]

12 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 SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1 (SMARCB1).	[37]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1 (SMARCB1).	[38]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1 (SMARCB1).	[39]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1 (SMARCB1).	[40]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1 (SMARCB1).	[41]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1 (SMARCB1).	[42]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1 (SMARCB1).	[43]
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the expression of SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1 (SMARCB1).	[44]
Cannabidiol	DM0659E	Approved	Cannabidiol decreases the expression of SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1 (SMARCB1).	[45]
Clozapine	DMFC71L	Approved	Clozapine decreases the expression of SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1 (SMARCB1).	[45]
Benzatropine	DMF7EXL	Approved	Benzatropine decreases the expression of SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1 (SMARCB1).	[45]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1 (SMARCB1).	[49]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1 (SMARCB1).	[46]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1 (SMARCB1).	[47]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1 (SMARCB1).	[48]

References

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