Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTRWDV3P)

• DOT Name: AT-rich interactive domain-containing protein 1A (ARID1A)
• Synonyms: ARID domain-containing protein 1A; B120; BRG1-associated factor 250; BAF250; BRG1-associated factor 250a; BAF250A; Osa homolog 1; hOSA1; SWI-like protein; SWI/SNF complex protein p270; SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin subfamily F member 1; hELD
• Gene Name: ARID1A
• Related Disease:
  B-cell lymphoma
  Clear cell renal carcinoma
  Coffin-Siris syndrome
  Coffin-Siris syndrome 1
  Epithelial ovarian cancer
  Follicular lymphoma
  Ovarian cancer
  Ovarian neoplasm
  Advanced cancer
  Breast neoplasm
  Cervical carcinoma
  Cholangiocarcinoma
  Colorectal neoplasm
  Familial multiple trichoepithelioma
  Gastric neoplasm
  Hepatocellular carcinoma
  Hereditary diffuse gastric adenocarcinoma
  Intellectual disability
  Intellectual disability, autosomal dominant 14
  Intrahepatic cholangiocarcinoma
  Mucinous adenocarcinoma
  Neuroblastoma
  Primary cutaneous T-cell lymphoma
  Prostate cancer
  Prostate neoplasm
  Squamous cell carcinoma
  Stomach cancer
  T-cell lymphoma
  Transitional cell carcinoma
  Urinary bladder cancer
  Urinary bladder neoplasm
  Wilms tumor
  Atypical endometrial hyperplasia
  Burkitt lymphoma
  Isolated congenital microcephaly
  Clear cell adenocarcinoma
  Colorectal carcinoma
  Endometrium neoplasm
  Epstein barr virus infection
  Esophageal adenocarcinoma
  Gastric cancer
  Obesity
  Pancreatic ductal carcinoma
  Sezary syndrome
• UniProt ID: ARI1A_HUMAN
• PDB ID: 1RYU; 6LTH; 6LTJ
• Pfam ID: PF01388 ; PF12031
• Sequence:
  MAAQVAPAAASSLGNPPPPPPSELKKAEQQQREEAGGEAAAAAAAERGEMKAAAGQESEG
  PAVGPPQPLGKELQDGAESNGGGGGGGAGSGGGPGAEPDLKNSNGNAGPRPALNNNLTEP
  PGGGGGGSSDGVGAPPHSAAAALPPPAYGFGQPYGRSPSAVAAAAAAVFHQQHGGQQSPG
  LAALQSGGGGGLEPYAGPQQNSHDHGFPNHQYNSYYPNRSAYPPPAPAYALSSPRGGTPG
  SGAAAAAGSKPPPSSSASASSSSSSFAQQRFGAMGGGGPSAAGGGTPQPTATPTLNQLLT
  SPSSARGYQGYPGGDYSGGPQDGGAGKGPADMASQCWGAAAAAAAAAAASGGAQQRSHHA
  PMSPGSSGGGGQPLARTPQPSSPMDQMGKMRPQPYGGTNPYSQQQGPPSGPQQGHGYPGQ
  PYGSQTPQRYPMTMQGRAQSAMGGLSYTQQIPPYGQQGPSGYGQQGQTPYYNQQSPHPQQ
  QQPPYSQQPPSQTPHAQPSYQQQPQSQPPQLQSSQPPYSQQPSQPPHQQSPAPYPSQQST
  TQQHPQSQPPYSQPQAQSPYQQQQPQQPAPSTLSQQAAYPQPQSQQSQQTAYSQQRFPPP
  QELSQDSFGSQASSAPSMTSSKGGQEDMNLSLQSRPSSLPDLSGSIDDLPMGTEGALSPG
  VSTSGISSSQGEQSNPAQSPFSPHTSPHLPGIRGPSPSPVGSPASVAQSRSGPLSPAAVP
  GNQMPPRPPSGQSDSIMHPSMNQSSIAQDRGYMQRNPQMPQYSSPQPGSALSPRQPSGGQ
  IHTGMGSYQQNSMGSYGPQGGQYGPQGGYPRQPNYNALPNANYPSAGMAGGINPMGAGGQ
  MHGQPGIPPYGTLPPGRMSHASMGNRPYGPNMANMPPQVGSGMCPPPGGMNRKTQETAVA
  MHVAANSIQNRPPGYPNMNQGGMMGTGPPYGQGINSMAGMINPQGPPYSMGGTMANNSAG
  MAASPEMMGLGDVKLTPATKMNNKADGTPKTESKSKKSSSSTTTNEKITKLYELGGEPER
  KMWVDRYLAFTEEKAMGMTNLPAVGRKPLDLYRLYVSVKEIGGLTQVNKNKKWRELATNL
  NVGTSSSAASSLKKQYIQCLYAFECKIERGEDPPPDIFAAADSKKSQPKIQPPSPAGSGS
  MQGPQTPQSTSSSMAEGGDLKPPTPASTPHSQIPPLPGMSRSNSVGIQDAFNDGSDSTFQ
  KRNSMTPNPGYQPSMNTSDMMGRMSYEPNKDPYGSMRKAPGSDPFMSSGQGPNGGMGDPY
  SRAAGPGLGNVAMGPRQHYPYGGPYDRVRTEPGIGPEGNMSTGAPQPNLMPSNPDSGMYS
  PSRYPPQQQQQQQQRHDSYGNQFSTQGTPSGSPFPSQQTTMYQQQQQNYKRPMDGTYGPP
  AKRHEGEMYSVPYSTGQGQPQQQQLPPAQPQPASQQQAAQPSPQQDVYNQYGNAYPATAT
  AATERRPAGGPQNQFPFQFGRDRVSAPPGTNAQQNMPPQMMGGPIQASAEVAQQGTMWQG
  RNDMTYNYANRQSTGSAPQGPAYHGVNRTDEMLHTDQRANHEGSWPSHGTRQPPYGPSAP
  VPPMTRPPPSNYQPPPSMQNHIPQVSSPAPLPRPMENRTSPSKSPFLHSGMKMQKAGPPV
  PASHIAPAPVQPPMIRRDITFPPGSVEATQPVLKQRRRLTMKDIGTPEAWRVMMSLKSGL
  LAESTWALDTINILLYDDNSIMTFNLSQLPGLLELLVEYFRRCLIEIFGILKEYEVGDPG
  QRTLLDPGRFSKVSSPAPMEGGEEEEELLGPKLEEEEEEEVVENDEEIAFSGKDKPASEN
  SEEKLISKFDKLPVKIVQKNDPFVVDCSDKLGRVQEFDSGLLHWRIGGGDTTEHIQTHFE
  SKTELLPSRPHAPCPPAPRKHVTTAEGTPGTTDQEGPPPDGPPEKRITATMDDMLSTRSS
  TLTEDGAKSSEAIKESSKFPFGISPAQSHRNIKILEDEPHSKDETPLCTLLDWQDSLAKR
  CVCVSNTIRSLSFVPGNDFEMSKHPGLLLILGKLILLHHKHPERKQAPLTYEKEEEQDQG
  VSCNKVEWWWDCLEMLRENTLVTLANISGQLDLSPYPESICLPVLDGLLHWAVCPSAEAQ
  DPFSTLGPNAVLSPQRLVLETLSKLSIQDNNVDLILATPPFSRLEKLYSTMVRFLSDRKN
  PVCREMAVVLLANLAQGDSLAARAIAVQKGSIGNLLGFLEDSLAATQFQQSQASLLHMQN
  PPFEPTSVDMMRRAARALLALAKVDENHSEFTLYESRLLDISVSPLMNSLVSQVICDVLF
  LIGQS
• Function: Involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology). Component of SWI/SNF chromatin remodeling complexes that carry out key enzymatic activities, changing chromatin structure by altering DNA-histone contacts within a nucleosome in an ATP-dependent manner. Binds DNA non-specifically. 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.
• Tissue Specificity: Highly expressed in spleen, thymus, prostate, testis, ovary, small intestine, colon, and PBL, and at a much lower level in heart, brain, placenta, lung, liver, skeletal muscle, kidney, and pancreas.
• KEGG Pathway:
  ATP-dependent chromatin remodeling (hsa03082)
  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

44 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
B-cell lymphoma	DISIH1YQ	Definitive	Genetic Variation	[1]
Clear cell renal carcinoma	DISBXRFJ	Definitive	Altered Expression	[2]
Coffin-Siris syndrome	DIS8L03H	Definitive	Autosomal dominant	[3]
Coffin-Siris syndrome 1	DIS95FRP	Definitive	Autosomal dominant	[4]
Epithelial ovarian cancer	DIS56MH2	Definitive	Altered Expression	[5]
Follicular lymphoma	DISVEUR6	Definitive	Genetic Variation	[1]
Ovarian cancer	DISZJHAP	Definitive	Altered Expression	[5]
Ovarian neoplasm	DISEAFTY	Definitive	Altered Expression	[5]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[6]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[7]
Cervical carcinoma	DIST4S00	Strong	Biomarker	[8]
Cholangiocarcinoma	DIS71F6X	Strong	Altered Expression	[9]
Colorectal neoplasm	DISR1UCN	Strong	Biomarker	[10]
Familial multiple trichoepithelioma	DISKZAUY	Strong	Genetic Variation	[11]
Gastric neoplasm	DISOKN4Y	Strong	Biomarker	[12]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[13]
Hereditary diffuse gastric adenocarcinoma	DISUIBYS	Strong	Biomarker	[12]
Intellectual disability	DISMBNXP	Strong	Genetic Variation	[14]
Intellectual disability, autosomal dominant 14	DISPYXMD	Strong	Autosomal dominant	[15]
Intrahepatic cholangiocarcinoma	DIS6GOC8	Strong	Biomarker	[16]
Mucinous adenocarcinoma	DISKNFE8	Strong	Biomarker	[17]
Neuroblastoma	DISVZBI4	Strong	Biomarker	[18]
Primary cutaneous T-cell lymphoma	DIS35WVW	Strong	Biomarker	[19]
Prostate cancer	DISF190Y	Strong	Biomarker	[20]
Prostate neoplasm	DISHDKGQ	Strong	Biomarker	[20]
Squamous cell carcinoma	DISQVIFL	Strong	Biomarker	[21]
Stomach cancer	DISKIJSX	Strong	Biomarker	[22]
T-cell lymphoma	DISSXRTQ	Strong	Biomarker	[23]
Transitional cell carcinoma	DISWVVDR	Strong	Biomarker	[24]
Urinary bladder cancer	DISDV4T7	Strong	Biomarker	[24]
Urinary bladder neoplasm	DIS7HACE	Strong	Biomarker	[24]
Wilms tumor	DISB6T16	Strong	Biomarker	[25]
Atypical endometrial hyperplasia	DIS2POYG	moderate	Genetic Variation	[26]
Burkitt lymphoma	DIS9D5XU	moderate	Biomarker	[27]
Isolated congenital microcephaly	DISUXHZ6	Disputed	Biomarker	[14]
Clear cell adenocarcinoma	DISYUGHZ	Limited	Altered Expression	[28]
Colorectal carcinoma	DIS5PYL0	Limited	Genetic Variation	[29]
Endometrium neoplasm	DIS6OS2L	Limited	Biomarker	[30]
Epstein barr virus infection	DISOO0WT	Limited	Genetic Variation	[31]
Esophageal adenocarcinoma	DISODWFP	Limited	Biomarker	[32]
Gastric cancer	DISXGOUK	Limited	Biomarker	[22]
Obesity	DIS47Y1K	Limited	Biomarker	[33]
Pancreatic ductal carcinoma	DIS26F9Q	Limited	Biomarker	[34]
Sezary syndrome	DISFMTC7	Limited	Genetic Variation	[35]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic trioxide	DM61TA4	Approved	AT-rich interactive domain-containing protein 1A (ARID1A) increases the response to substance of Arsenic trioxide.	[47]
Fulvestrant	DM0YZC6	Approved	AT-rich interactive domain-containing protein 1A (ARID1A) decreases the response to substance of Fulvestrant.	[48]
(+)-JQ1	DM1CZSJ	Phase 1	AT-rich interactive domain-containing protein 1A (ARID1A) increases the response to substance of (+)-JQ1.	[49]

6 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 AT-rich interactive domain-containing protein 1A (ARID1A).	[36]
Quercetin	DM3NC4M	Approved	Quercetin decreases the phosphorylation of AT-rich interactive domain-containing protein 1A (ARID1A).	[39]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of AT-rich interactive domain-containing protein 1A (ARID1A).	[39]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of AT-rich interactive domain-containing protein 1A (ARID1A).	[42]
Coumarin	DM0N8ZM	Investigative	Coumarin affects the phosphorylation of AT-rich interactive domain-containing protein 1A (ARID1A).	[39]
Hexadecanoic acid	DMWUXDZ	Investigative	Hexadecanoic acid decreases the phosphorylation of AT-rich interactive domain-containing protein 1A (ARID1A).	[46]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of AT-rich interactive domain-containing protein 1A (ARID1A).	[37]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of AT-rich interactive domain-containing protein 1A (ARID1A).	[38]
Indomethacin	DMSC4A7	Approved	Indomethacin decreases the expression of AT-rich interactive domain-containing protein 1A (ARID1A).	[40]
Mivebresib	DMCPF90	Phase 1	Mivebresib decreases the expression of AT-rich interactive domain-containing protein 1A (ARID1A).	[41]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of AT-rich interactive domain-containing protein 1A (ARID1A).	[43]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of AT-rich interactive domain-containing protein 1A (ARID1A).	[44]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of AT-rich interactive domain-containing protein 1A (ARID1A).	[45]

References

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