Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT8K2YWY)

• DOT Name: Jouberin (AHI1)
• Synonyms: Abelson helper integration site 1 protein homolog; AHI-1
• Gene Name: AHI1
• Related Disease:
  Joubert syndrome 17
  Joubert syndrome 3
  Advanced cancer
  Alzheimer disease
  Anxiety
  B-cell neoplasm
  Blindness
  Cerebellar disorder
  Colorectal carcinoma
  Gastroenteritis
  Glioblastoma multiforme
  Hepatitis
  Hepatitis A virus infection
  Hepatitis E virus infection
  Hepatocellular carcinoma
  Inherited retinal dystrophy
  Joubert syndrome 1
  leukaemia
  Leukemia
  Lymphoma
  Multiple sclerosis
  Neoplasm
  Nephropathy
  Nephrotic syndrome
  Obesity
  Polydactyly
  Primary cutaneous T-cell lymphoma
  Retinal degeneration
  Retinopathy
  Rheumatoid arthritis
  Schizophrenia
  Sezary syndrome
  Adult lymphoma
  Classic Hodgkin lymphoma
  Human T-lymphotropic virus 1 infectious disease
  Intellectual disability
  Pediatric lymphoma
  Joubert syndrome
  Joubert syndrome with ocular defect
  Acute myelogenous leukaemia
  Autism
  Ciliopathy
  Depression
  Nephronophthisis
  Retinitis pigmentosa
  Systemic lupus erythematosus
• UniProt ID: AHI1_HUMAN
• PDB ID: 4ESR
• Pfam ID: PF00018 ; PF00400
• Sequence:
  MPTAESEAKVKTKVRFEELLKTHSDLMREKKKLKKKLVRSEENISPDTIRSNLHYMKETT
  SDDPDTIRSNLPHIKETTSDDVSAANTNNLKKSTRVTKNKLRNTQLATENPNGDASVEED
  KQGKPNKKVIKTVPQLTTQDLKPETPENKVDSTHQKTHTKPQPGVDHQKSEKANEGREET
  DLEEDEELMQAYQCHVTEEMAKEIKRKIRKKLKEQLTYFPSDTLFHDDKLSSEKRKKKKE
  VPVFSKAETSTLTISGDTVEGEQKKESSVRSVSSDSHQDDEISSMEQSTEDSMQDDTKPK
  PKKTKKKTKAVADNNEDVDGDGVHEITSRDSPVYPKCLLDDDLVLGVYIHRTDRLKSDFM
  ISHPMVKIHVVDEHTGQYVKKDDSGRPVSSYYEKENVDYILPIMTQPYDFKQLKSRLPEW
  EEQIVFNENFPYLLRGSDESPKVILFFEILDFLSVDEIKNNSEVQNQECGFRKIAWAFLK
  LLGANGNANINSKLRLQLYYPPTKPRSPLSVVEAFEWWSKCPRNHYPSTLYVTVRGLKVP
  DCIKPSYRSMMALQEEKGKPVHCERHHESSSVDTEPGLEESKEVIKWKRLPGQACRIPNK
  HLFSLNAGERGCFCLDFSHNGRILAAACASRDGYPIILYEIPSGRFMRELCGHLNIIYDL
  SWSKDDHYILTSSSDGTARIWKNEINNTNTFRVLPHPSFVYTAKFHPAVRELVVTGCYDS
  MIRIWKVEMREDSAILVRQFDVHKSFINSLCFDTEGHHMYSGDCTGVIVVWNTYVKINDL
  EHSVHHWTINKEIKETEFKGIPISYLEIHPNGKRLLIHTKDSTLRIMDLRILVARKFVGA
  ANYREKIHSTLTPCGTFLFAGSEDGIVYVWNPETGEQVAMYSDLPFKSPIRDISYHPFEN
  MVAFCAFGQNEPILLYIYDFHVAQQEAEMFKRYNGTFPLPGIHQSQDALCTCPKLPHQGS
  FQIDEFVHTESSSTKMQLVKQRLETVTEVIRSCAAKVNKNLSFTSPPAVSSQQSKLKQSN
  MLTAQEILHQFGFTQTGIISIERKPCNHQVDTAPTVVALYDYTANRSDELTIHRGDIIRV
  FFKDNEDWWYGSIGKGQEGYFPANHVASETLYQELPPEIKERSPPLSPEEKTKIEKSPAP
  QKQSINKNKSQDFRLGSESMTHSEMRKEQSHEDQGHIMDTRMRKNKQAGRKVTLIE
• Function: Involved in vesicle trafficking and required for ciliogenesis, formation of primary non-motile cilium, and recruitment of RAB8A to the basal body of primary cilium. Component of the tectonic-like complex, a complex localized at the transition zone of primary cilia and acting as a barrier that prevents diffusion of transmembrane proteins between the cilia and plasma membranes. Involved in neuronal differentiation. As a positive modulator of classical Wnt signaling, may play a crucial role in ciliary signaling during cerebellum embryonic development.
• Tissue Specificity: Highly expressed in the most primitive normal hematopoietic cells. Expressed in brain, particularly in neurons that give rise to the crossing axons of the corticospinal tract and superior cerebellar peduncles. Expressed in kidney (renal collecting duct cells) (at protein level).
• Reactome Pathway: Anchoring of the basal body to the plasma membrane (R-HSA-5620912)

Molecular Interaction Atlas (MIA) of This DOT

46 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Joubert syndrome 17	DIS9LHZ1	Definitive	Autosomal recessive	[1]
Joubert syndrome 3	DISE0CUW	Definitive	Autosomal recessive	[2]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[3]
Alzheimer disease	DISF8S70	Strong	Biomarker	[4]
Anxiety	DISIJDBA	Strong	Biomarker	[5]
B-cell neoplasm	DISVY326	Strong	Genetic Variation	[6]
Blindness	DISTIM10	Strong	Genetic Variation	[7]
Cerebellar disorder	DIS2O7WM	Strong	Biomarker	[8]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[9]
Gastroenteritis	DISXQCG5	Strong	Biomarker	[10]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[11]
Hepatitis	DISXXX35	Strong	Biomarker	[12]
Hepatitis A virus infection	DISUMFQV	Strong	Biomarker	[12]
Hepatitis E virus infection	DIS0TXIR	Strong	Biomarker	[13]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[14]
Inherited retinal dystrophy	DISGGL77	Strong	Genetic Variation	[15]
Joubert syndrome 1	DISC9Q82	Strong	GermlineCausalMutation	[16]
leukaemia	DISS7D1V	Strong	Biomarker	[17]
Leukemia	DISNAKFL	Strong	Biomarker	[18]
Lymphoma	DISN6V4S	Strong	Biomarker	[17]
Multiple sclerosis	DISB2WZI	Strong	Genetic Variation	[19]
Neoplasm	DISZKGEW	Strong	Biomarker	[20]
Nephropathy	DISXWP4P	Strong	Genetic Variation	[7]
Nephrotic syndrome	DISSPSC2	Strong	Genetic Variation	[21]
Obesity	DIS47Y1K	Strong	Biomarker	[22]
Polydactyly	DIS25BMZ	Strong	Biomarker	[23]
Primary cutaneous T-cell lymphoma	DIS35WVW	Strong	Altered Expression	[24]
Retinal degeneration	DISM1JHQ	Strong	Biomarker	[7]
Retinopathy	DISB4B0F	Strong	Biomarker	[7]
Rheumatoid arthritis	DISTSB4J	Strong	Altered Expression	[25]
Schizophrenia	DISSRV2N	Strong	Biomarker	[26]
Sezary syndrome	DISFMTC7	Strong	Altered Expression	[27]
Adult lymphoma	DISK8IZR	moderate	Biomarker	[17]
Classic Hodgkin lymphoma	DISV1LU6	moderate	Genetic Variation	[28]
Human T-lymphotropic virus 1 infectious disease	DISN5C4M	moderate	Genetic Variation	[29]
Intellectual disability	DISMBNXP	moderate	Biomarker	[30]
Pediatric lymphoma	DIS51BK2	moderate	Biomarker	[17]
Joubert syndrome	DIS7P5CO	Supportive	Autosomal recessive	[16]
Joubert syndrome with ocular defect	DISDJVUI	Supportive	Autosomal recessive	[31]
Acute myelogenous leukaemia	DISCSPTN	Limited	Genetic Variation	[32]
Autism	DISV4V1Z	Limited	Altered Expression	[8]
Ciliopathy	DIS10G4I	Limited	Genetic Variation	[33]
Depression	DIS3XJ69	Limited	Biomarker	[26]
Nephronophthisis	DISXU4HY	Limited	Altered Expression	[34]
Retinitis pigmentosa	DISCGPY8	Limited	Autosomal recessive	[35]
Systemic lupus erythematosus	DISI1SZ7	Limited	Genetic Variation	[36]

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 Jouberin (AHI1).	[37]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Jouberin (AHI1).	[42]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Jouberin (AHI1).	[45]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Jouberin (AHI1).	[47]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Jouberin (AHI1).	[38]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Jouberin (AHI1).	[39]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Jouberin (AHI1).	[40]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Jouberin (AHI1).	[41]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Jouberin (AHI1).	[43]
Cytarabine	DMZD5QR	Approved	Cytarabine increases the expression of Jouberin (AHI1).	[43]
Etoposide	DMNH3PG	Approved	Etoposide increases the expression of Jouberin (AHI1).	[43]
Omacetaxine mepesuccinate	DMPU2WX	Approved	Omacetaxine mepesuccinate increases the expression of Jouberin (AHI1).	[43]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Jouberin (AHI1).	[44]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Jouberin (AHI1).	[46]

References

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• [5] Effect of chronic unpredictable stress on mice with developmental under-expression of the Ahi1 gene: behavioral manifestations and neurobiological correlates.Transl Psychiatry. 2018 Jul 2;8(1):124. doi: 10.1038/s41398-018-0171-1.
• [6] Ahi-1, a novel gene encoding a modular protein with WD40-repeat and SH3 domains, is targeted by the Ahi-1 and Mis-2 provirus integrations.J Virol. 2002 Sep;76(18):9046-59. doi: 10.1128/jvi.76.18.9046-9059.2002.
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• [34] Genotype-phenotype correlation in 440 patients with NPHP-related ciliopathies.Kidney Int. 2011 Dec;80(11):1239-45. doi: 10.1038/ki.2011.284. Epub 2011 Aug 24.
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• [42] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
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