Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTNQLL21)

• DOT Name: Dedicator of cytokinesis protein 8 (DOCK8)
• Gene Name: DOCK8
• Related Disease:
  Combined immunodeficiency due to DOCK8 deficiency
  Cutaneous melanoma
  Allergic asthma
  Alzheimer disease
  Alzheimer disease 3
  Asthma
  Autoimmune disease
  Bacterial infection
  Breast cancer
  Breast carcinoma
  Ear infection
  Hepatocellular carcinoma
  Immunodeficiency
  Intellectual disability
  Lung cancer
  Lung carcinoma
  Lung squamous cell carcinoma
  Multiple sclerosis
  Nervous system inflammation
  Neuroblastoma
  Neurodevelopmental disorder
  Pelvic inflammatory disease
  Severe combined immunodeficiency
  Skin and skin-structure infection
  Skin cancer
  Skin disease
  Systemic lupus erythematosus
  Type-1 diabetes
  Wiskott-Aldrich syndrome
  Food allergy
  Immune system disorder
  Autosomal dominant non-syndromic intellectual disability
  Acute lymphocytic leukaemia
  B-cell lymphoma
  Lymphoid leukemia
  Advanced cancer
  Chronic mucocutaneous candidiasis
  Complex neurodevelopmental disorder
  Cytomegalovirus retinitis
  Human papillomavirus infection
  Inborn error of immunity
• UniProt ID: DOCK8_HUMAN
• Pfam ID: PF06920 ; PF20422 ; PF20421 ; PF14429 ; PF11878
• Sequence:
  MATLPSAERRAFALKINRYSSAEIRKQFTLPPNLGQYHRQSISTSGFPSLQLPQFYDPVE
  PVDFEGLLMTHLNSLDVQLAQELGDFTDDDLDVVFTPKECRTLQPSLPEEGVELDPHVRD
  CVQTYIREWLIVNRKNQGSPEICGFKKTGSRKDFHKTLPKQTFESETLECSEPAAQAGPR
  HLNVLCDVSGKGPVTACDFDLRSLQPDKRLENLLQQVSAEDFEKQNEEARRTNRQAELFA
  LYPSVDEEDAVEIRPVPECPKEHLGNRILVKLLTLKFEIEIEPLFASIALYDVKERKKIS
  ENFHCDLNSDQFKGFLRAHTPSVAASSQARSAVFSVTYPSSDIYLVVKIEKVLQQGEIGD
  CAEPYTVIKESDGGKSKEKIEKLKLQAESFCQRLGKYRMPFAWAPISLSSFFNVSTLERE
  VTDVDSVVGRSSVGERRTLAQSRRLSERALSLEENGVGSNFKTSTLSVSSFFKQEGDRLS
  DEDLFKFLADYKRSSSLQRRVKSIPGLLRLEISTAPEIINCCLTPEMLPVKPFPENRTRP
  HKEILEFPTREVYVPHTVYRNLLYVYPQRLNFVNKLASARNITIKIQFMCGEDASNAMPV
  IFGKSSGPEFLQEVYTAVTYHNKSPDFYEEVKIKLPAKLTVNHHLLFTFYHISCQQKQGA
  SVETLLGYSWLPILLNERLQTGSYCLPVALEKLPPNYSMHSAEKVPLQNPPIKWAEGHKG
  VFNIEVQAVSSVHTQDNHLEKFFTLCHSLESQVTFPIRVLDQKISEMALEHELKLSIICL
  NSSRLEPLVLFLHLVLDKLFQLSVQPMVIAGQTANFSQFAFESVVAIANSLHNSKDLSKD
  QHGRNCLLASYVHYVFRLPEVQRDVPKSGAPTALLDPRSYHTYGRTSAAAVSSKLLQARV
  MSSSNPDLAGTHSAADEEVKNIMSSKIADRNCSRMSYYCSGSSDAPSSPAAPRPASKKHF
  HEELALQMVVSTGMVRETVFKYAWFFFELLVKSMAQHVHNMDKRDSFRRTRFSDRFMDDI
  TTIVNVVTSEIAALLVKPQKENEQAEKMNISLAFFLYDLLSLMDRGFVFNLIRHYCSQLS
  AKLSNLPTLISMRLEFLRILCSHEHYLNLNLFFMNADTAPTSPCPSISSQNSSSCSSFQD
  QKIASMFDLTSEYRQQHFLTGLLFTELAAALDAEGEGISKVQRKAVSAIHSLLSSHDLDP
  RCVKPEVKVKIAALYLPLVGIILDALPQLCDFTVADTRRYRTSGSDEEQEGAGAINQNVA
  LAIAGNNFNLKTSGIVLSSLPYKQYNMLNADTTRNLMICFLWIMKNADQSLIRKWIADLP
  STQLNRILDLLFICVLCFEYKGKQSSDKVSTQVLQKSRDVKARLEEALLRGEGARGEMMR
  RRAPGNDRFPGLNENLRWKKEQTHWRQANEKLDKTKAELDQEALISGNLATEAHLIILDM
  QENIIQASSALDCKDSLLGGVLRVLVNSLNCDQSTTYLTHCFATLRALIAKFGDLLFEEE
  VEQCFDLCHQVLHHCSSSMDVTRSQACATLYLLMRFSFGATSNFARVKMQVTMSLASLVG
  RAPDFNEEHLRRSLRTILAYSEEDTAMQMTPFPTQVEELLCNLNSILYDTVKMREFQEDP
  EMLMDLMYRIAKSYQASPDLRLTWLQNMAEKHTKKKCYTEAAMCLVHAAALVAEYLSMLE
  DHSYLPVGSVSFQNISSNVLEESVVSEDTLSPDEDGVCAGQYFTESGLVGLLEQAAELFS
  TGGLYETVNEVYKLVIPILEAHREFRKLTLTHSKLQRAFDSIVNKDHKRMFGTYFRVGFF
  GSKFGDLDEQEFVYKEPAITKLPEISHRLEAFYGQCFGAEFVEVIKDSTPVDKTKLDPNK
  AYIQITFVEPYFDEYEMKDRVTYFEKNFNLRRFMYTTPFTLEGRPRGELHEQYRRNTVLT
  TMHAFPYIKTRISVIQKEEFVLTPIEVAIEDMKKKTLQLAVAINQEPPDAKMLQMVLQGS
  VGATVNQGPLEVAQVFLAEIPADPKLYRHHNKLRLCFKEFIMRCGEAVEKNKRLITADQR
  EYQQELKKNYNKLKENLRPMIERKIPELYKPIFRVESQKRDSFHRSSFRKCETQLSQGS
• Function: Guanine nucleotide exchange factor (GEF) which specifically activates small GTPase CDC42 by exchanging bound GDP for free GTP. During immune responses, required for interstitial dendritic cell (DC) migration by locally activating CDC42 at the leading edge membrane of DC. Required for CD4(+) T-cell migration in response to chemokine stimulation by promoting CDC42 activation at T cell leading edge membrane. Is involved in NK cell cytotoxicity by controlling polarization of microtubule-organizing center (MTOC), and possibly regulating CCDC88B-mediated lytic granule transport to MTOC during cell killing.
• Tissue Specificity: Expressed in peripheral blood mononuclear cells (PBMCs).
• Reactome Pathway:
  RAC1 GTPase cycle (R-HSA-9013149)
  RHOJ GTPase cycle (R-HSA-9013409)
  Factors involved in megakaryocyte development and platelet production (R-HSA-983231)
  CDC42 GTPase cycle (R-HSA-9013148)

Molecular Interaction Atlas (MIA) of This DOT

41 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Combined immunodeficiency due to DOCK8 deficiency	DISRXLGV	Definitive	Autosomal recessive	[1]
Cutaneous melanoma	DIS3MMH9	Definitive	Genetic Variation	[2]
Allergic asthma	DISHF0H3	Strong	Biomarker	[3]
Alzheimer disease	DISF8S70	Strong	Biomarker	[4]
Alzheimer disease 3	DISVT69G	Strong	Biomarker	[4]
Asthma	DISW9QNS	Strong	Biomarker	[3]
Autoimmune disease	DISORMTM	Strong	Biomarker	[5]
Bacterial infection	DIS5QJ9S	Strong	Altered Expression	[6]
Breast cancer	DIS7DPX1	Strong	Genetic Variation	[7]
Breast carcinoma	DIS2UE88	Strong	Genetic Variation	[7]
Ear infection	DIS8ZWQ4	Strong	Genetic Variation	[8]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[9]
Immunodeficiency	DIS093I0	Strong	Biomarker	[5]
Intellectual disability	DISMBNXP	Strong	Genetic Variation	[10]
Lung cancer	DISCM4YA	Strong	Altered Expression	[7]
Lung carcinoma	DISTR26C	Strong	Altered Expression	[7]
Lung squamous cell carcinoma	DISXPIBD	Strong	Biomarker	[11]
Multiple sclerosis	DISB2WZI	Strong	Altered Expression	[12]
Nervous system inflammation	DISB3X5A	Strong	Biomarker	[12]
Neuroblastoma	DISVZBI4	Strong	Biomarker	[13]
Neurodevelopmental disorder	DIS372XH	Strong	Genetic Variation	[14]
Pelvic inflammatory disease	DISWQR4J	Strong	Genetic Variation	[15]
Severe combined immunodeficiency	DIS6MF4Q	Strong	Biomarker	[16]
Skin and skin-structure infection	DIS3F9EY	Strong	Biomarker	[17]
Skin cancer	DISTM18U	Strong	Biomarker	[5]
Skin disease	DISDW8R6	Strong	Biomarker	[18]
Systemic lupus erythematosus	DISI1SZ7	Strong	Biomarker	[19]
Type-1 diabetes	DIS7HLUB	Strong	Biomarker	[20]
Wiskott-Aldrich syndrome	DISATMDB	Strong	Biomarker	[21]
Food allergy	DISMQ1BP	moderate	Altered Expression	[22]
Immune system disorder	DISAEGPH	moderate	Genetic Variation	[23]
Autosomal dominant non-syndromic intellectual disability	DISD6L06	Supportive	Autosomal dominant	[10]
Acute lymphocytic leukaemia	DISPX75S	Disputed	Genetic Variation	[24]
B-cell lymphoma	DISIH1YQ	Disputed	Genetic Variation	[24]
Lymphoid leukemia	DIS65TYQ	Disputed	Genetic Variation	[24]
Advanced cancer	DISAT1Z9	Limited	Genetic Variation	[25]
Chronic mucocutaneous candidiasis	DISPSGYF	Limited	Genetic Variation	[26]
Complex neurodevelopmental disorder	DISB9AFI	Limited	Autosomal dominant	[27]
Cytomegalovirus retinitis	DIS5JC9D	Limited	Genetic Variation	[28]
Human papillomavirus infection	DISX61LX	Limited	Biomarker	[29]
Inborn error of immunity	DISNGCMN	Limited	Biomarker	[15]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Nitazoxanide	DMOWLVG	Approved	Dedicator of cytokinesis protein 8 (DOCK8) affects the response to substance of Nitazoxanide.	[43]

1 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 Dedicator of cytokinesis protein 8 (DOCK8).	[30]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Dedicator of cytokinesis protein 8 (DOCK8).	[31]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Dedicator of cytokinesis protein 8 (DOCK8).	[32]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Dedicator of cytokinesis protein 8 (DOCK8).	[33]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Dedicator of cytokinesis protein 8 (DOCK8).	[34]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Dedicator of cytokinesis protein 8 (DOCK8).	[35]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Dedicator of cytokinesis protein 8 (DOCK8).	[35]
Demecolcine	DMCZQGK	Approved	Demecolcine decreases the expression of Dedicator of cytokinesis protein 8 (DOCK8).	[36]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Dedicator of cytokinesis protein 8 (DOCK8).	[37]
Fenfluramine	DM0762O	Phase 3	Fenfluramine increases the expression of Dedicator of cytokinesis protein 8 (DOCK8).	[38]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Dedicator of cytokinesis protein 8 (DOCK8).	[39]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Dedicator of cytokinesis protein 8 (DOCK8).	[40]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Dedicator of cytokinesis protein 8 (DOCK8).	[41]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Dedicator of cytokinesis protein 8 (DOCK8).	[34]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Dedicator of cytokinesis protein 8 (DOCK8).	[42]

References

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