Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTOUZN9G)

• DOT Name: Lipopolysaccharide-responsive and beige-like anchor protein (LRBA)
• Synonyms: Beige-like protein; CDC4-like protein
• Gene Name: LRBA
• Related Disease:
  Combined immunodeficiency due to LRBA deficiency
  Leishmaniasis
  Arthritis
  Asthma
  Autoimmune lymphoproliferative syndrome due to CTLA4 haploinsuffiency
  Autoimmune lymphoproliferative syndrome type 1
  Cervical Intraepithelial neoplasia
  Chronic granulomatous disease
  Common variable immunodeficiency
  Immunodeficiency
  Inflammatory bowel disease
  Juvenile idiopathic arthritis
  Mycobacterium infection
  Pelvic inflammatory disease
  Acute myelogenous leukaemia
  Autoimmune disease
  Hypoglycemia
  Immune system disorder
  Advanced cancer
  Gastric adenocarcinoma
  Gastric cancer
  Hyperglycemia
  Intestinal disorder
  Melanoma
  Neoplasm
  Periodontitis
  Stomach cancer
  Type-1 diabetes
• UniProt ID: LRBA_HUMAN
• PDB ID: 1T77
• Pfam ID: PF02138 ; PF06469 ; PF15787 ; PF13385 ; PF20426 ; PF20425 ; PF14844
• Sequence:
  MASEDNRVPSPPPTGDDGGGGGREETPTEGGALSLKPGLPIRGIRMKFAVLTGLVEVGEV
  SNRDIVETVFNLLVGGQFDLEMNFIIQEGESINCMVDLLEKCDITCQAEVWSMFTAILKK
  SIRNLQVCTEVGLVEKVLGKIEKVDNMIADLLVDMLGVLASYNLTVRELKLFFSKLQGDK
  GRWPPHAGKLLSVLKHMPQKYGPDAFFNFPGKSAAAIALPPIAKWPYQNGFTFHTWLRMD
  PVNNINVDKDKPYLYCFRTSKGLGYSAHFVGGCLIVTSIKSKGKGFQHCVKFDFKPQKWY
  MVTIVHIYNRWKNSELRCYVNGELASYGEITWFVNTSDTFDKCFLGSSETADANRVFCGQ
  MTAVYLFSEALNAAQIFAIYQLGLGYKGTFKFKAESDLFLAEHHKLLLYDGKLSSAIAFT
  YNPRATDAQLCLESSPKDNPSIFVHSPHALMLQDVKAVLTHSIQSAMHSIGGVQVLFPLF
  AQLDYRQYLSDEIDLTICSTLLAFIMELLKNSIAMQEQMLACKGFLVIGYSLEKSSKSHV
  SRAVLELCLAFSKYLSNLQNGMPLLKQLCDHVLLNPAIWIHTPAKVQLMLYTYLSTEFIG
  TVNIYNTIRRVGTVLLIMHTLKYYYWAVNPQDRSGITPKGLDGPRPNQKEMLSLRAFLLM
  FIKQLVMKDSGVKEDELQAILNYLLTMHEDDNLMDVLQLLVALMSEHPNSMIPAFDQRNG
  LRVIYKLLASKSEGIRVQALKAMGYFLKHLAPKRKAEVMLGHGLFSLLAERLMLQTNLIT
  MTTYNVLFEILIEQIGTQVIHKQHPDPDSSVKIQNPQILKVIATLLRNSPQCPESMEVRR
  AFLSDMIKLFNNSRENRRSLLQCSVWQEWMLSLCYFNPKNSDEQKITEMVYAIFRILLYH
  AVKYEWGGWRVWVDTLSITHSKVTFEIHKENLANIFREQQGKVDEEIGLCSSTSVQAASG
  IRRDINVSVGSQQPDTKDSPVCPHFTTNGNENSSIEKTSSLESASNIELQTTNTSYEEMK
  AEQENQELPDEGTLEETLTNETRNADDLEVSSDIIEAVAISSNSFITTGKDSMTVSEVTA
  SISSPSEEDASEMPEFLDKSIVEEEEDDDYVELKVEGSPTEEANLPTELQDNSLSPAASE
  AGEKLDMFGNDDKLIFQEGKPVTEKQTDTETQDSKDSGIQTMTASGSSAMSPETTVSQIA
  VESDLGQMLEEGKKATNLTRETKLINDCHGSVSEASSEQKIAKLDVSNVATDTERLELKA
  SPNVEAPQPHRHVLEISRQHEQPGQGIAPDAVNGQRRDSRSTVFRIPEFNWSQMHQRLLT
  DLLFSIETDIQMWRSHSTKTVMDFVNSSDNVIFVHNTIHLISQVMDNMVMACGGILPLLS
  AATSATHELENIEPTQGLSIEASVTFLQRLISLVDVLIFASSLGFTEIEAEKSMSSGGIL
  RQCLRLVCAVAVRNCLECQQHSQLKTRGDKALKPMHSLIPLGKSAAKSPVDIVTGGISPV
  RDLDRLLQDMDINRLRAVVFRDIEDSKQAQFLALAVVYFISVLMVSKYRDILEPQNERHS
  QSCTETGSENENVSLSEITPAAFSTLTTASVEESESTSSARRRDSGIGEETATGLGSHVE
  VTPHTAPPGVSAGPDAISEVLSTLSLEVNKSPETKNDRGNDLDTKATPSVSVSKNVNVKD
  ILRSLVNIPADGVTVDPALLPPACLGALGDLSVEQPVQFRSFDRSVIVAAKKSAVSPSTF
  NTSIPTNAVSVVSSVDSAQASDMGGESPGSRSSNAKLPSVPTVDSVSQDPVSNMSITERL
  EHALEKAAPLLREIFVDFAPFLSRTLLGSHGQELLIEGTSLVCMKSSSSVVELVMLLCSQ
  EWQNSIQKNAGLAFIELVNEGRLLSQTMKDHLVRVANEAEFILSRQRAEDIHRHAEFESL
  CAQYSADKREDEKMCDHLIRAAKYRDHVTATQLIQKIINILTDKHGAWGNSAVSRPLEFW
  RLDYWEDDLRRRRRFVRNPLGSTHPEATLKTAVEHVCIFKLRENSKATDEDILAKGKQSI
  RSQALGNQNSENEILLEGDDDTLSSVDEKDLENLAGPVSLSTPAQLVAPSVVVKGTLSVT
  SSELYFEVDEEDPNFKKIDPKILAYTEGLHGKWLFTEIRSIFSRRYLLQNTALEIFMANR
  VAVMFNFPDPATVKKVVNYLPRVGVGTSFGLPQTRRISLASPRQLFKASNMTQRWQHREI
  SNFEYLMFLNTIAGRSYNDLNQYPVFPWVITNYESEELDLTLPTNFRDLSKPIGALNPKR
  AAFFAERYESWEDDQVPKFHYGTHYSTASFVLAWLLRIEPFTTYFLNLQGGKFDHADRTF
  SSISRAWRNSQRDTSDIKELIPEFYYLPEMFVNFNNYNLGVMDDGTVVSDVELPPWAKTS
  EEFVHINRLALESEFVSCQLHQWIDLIFGYKQQGPEAVRALNVFYYLTYEGAVNLNSITD
  PVLREAVEAQIRSFGQTPSQLLIEPHPPRGSAMQVSPLMFTDKAQQDVIMVLKFPSNSPV
  THVAANTQPGLATPAVITVTANRLFAVNKWHNLPAHQGAVQDQPYQLPVEIDPLIASNTG
  MHRRQITDLLDQSIQVHSQCFVITSDNRYILVCGFWDKSFRVYSTDTGRLIQVVFGHWDV
  VTCLARSESYIGGNCYILSGSRDATLLLWYWNGKCSGIGDNPGSETAAPRAILTGHDYEV
  TCAAVCAELGLVLSGSQEGPCLIHSMNGDLLRTLEGPENCLKPKLIQASREGHCVIFYEN
  GLFCTFSVNGKLQATMETDDNIRAIQLSRDGQYLLTGGDRGVVVVRQVSDLKQLFAYPGC
  DAGIRAMALSYDQRCIISGMASGSIVLFYNDFNRWHHEYQTRY
• Function: Involved in coupling signal transduction and vesicle trafficking to enable polarized secretion and/or membrane deposition of immune effector molecules. Involved in phagophore growth during mitophagy by regulating ATG9A trafficking to mitochondria.
• Tissue Specificity: Ubiquitous.

Molecular Interaction Atlas (MIA) of This DOT

28 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Combined immunodeficiency due to LRBA deficiency	DISRVZOT	Definitive	Autosomal recessive	[1]
Leishmaniasis	DISABTW7	Definitive	Biomarker	[2]
Arthritis	DIST1YEL	Strong	Biomarker	[3]
Asthma	DISW9QNS	Strong	Biomarker	[4]
Autoimmune lymphoproliferative syndrome due to CTLA4 haploinsuffiency	DISDAF1Y	Strong	Biomarker	[5]
Autoimmune lymphoproliferative syndrome type 1	DISAFGRA	Strong	Biomarker	[6]
Cervical Intraepithelial neoplasia	DISXP757	Strong	Biomarker	[7]
Chronic granulomatous disease	DIS9ZR24	Strong	Biomarker	[8]
Common variable immunodeficiency	DISHE7JQ	Strong	Biomarker	[4]
Immunodeficiency	DIS093I0	Strong	Biomarker	[9]
Inflammatory bowel disease	DISGN23E	Strong	Biomarker	[10]
Juvenile idiopathic arthritis	DISQZGBV	Strong	Biomarker	[3]
Mycobacterium infection	DISNSMUD	Strong	Biomarker	[8]
Pelvic inflammatory disease	DISWQR4J	Strong	Biomarker	[11]
Acute myelogenous leukaemia	DISCSPTN	moderate	Genetic Variation	[12]
Autoimmune disease	DISORMTM	moderate	Biomarker	[2]
Hypoglycemia	DISRCKR7	moderate	Biomarker	[13]
Immune system disorder	DISAEGPH	moderate	Biomarker	[14]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[15]
Gastric adenocarcinoma	DISWWLTC	Limited	Genetic Variation	[15]
Gastric cancer	DISXGOUK	Limited	Biomarker	[15]
Hyperglycemia	DIS0BZB5	Limited	Biomarker	[16]
Intestinal disorder	DISGPMUQ	Limited	Biomarker	[17]
Melanoma	DIS1RRCY	Limited	Biomarker	[15]
Neoplasm	DISZKGEW	Limited	Biomarker	[18]
Periodontitis	DISI9JOI	Limited	Biomarker	[19]
Stomach cancer	DISKIJSX	Limited	Biomarker	[15]
Type-1 diabetes	DIS7HLUB	Limited	Genetic Variation	[20]

4 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 Lipopolysaccharide-responsive and beige-like anchor protein (LRBA).	[21]
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of Lipopolysaccharide-responsive and beige-like anchor protein (LRBA).	[29]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Lipopolysaccharide-responsive and beige-like anchor protein (LRBA).	[34]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Lipopolysaccharide-responsive and beige-like anchor protein (LRBA).	[34]

16 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 Lipopolysaccharide-responsive and beige-like anchor protein (LRBA).	[22]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Lipopolysaccharide-responsive and beige-like anchor protein (LRBA).	[23]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Lipopolysaccharide-responsive and beige-like anchor protein (LRBA).	[24]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Lipopolysaccharide-responsive and beige-like anchor protein (LRBA).	[25]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Lipopolysaccharide-responsive and beige-like anchor protein (LRBA).	[26]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Lipopolysaccharide-responsive and beige-like anchor protein (LRBA).	[27]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Lipopolysaccharide-responsive and beige-like anchor protein (LRBA).	[28]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of Lipopolysaccharide-responsive and beige-like anchor protein (LRBA).	[30]
Bicalutamide	DMZMSPF	Approved	Bicalutamide increases the expression of Lipopolysaccharide-responsive and beige-like anchor protein (LRBA).	[31]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene affects the expression of Lipopolysaccharide-responsive and beige-like anchor protein (LRBA).	[23]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Lipopolysaccharide-responsive and beige-like anchor protein (LRBA).	[32]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Lipopolysaccharide-responsive and beige-like anchor protein (LRBA).	[33]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Lipopolysaccharide-responsive and beige-like anchor protein (LRBA).	[35]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Lipopolysaccharide-responsive and beige-like anchor protein (LRBA).	[36]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Lipopolysaccharide-responsive and beige-like anchor protein (LRBA).	[37]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A increases the expression of Lipopolysaccharide-responsive and beige-like anchor protein (LRBA).	[38]

References

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