Affinage

AHI1

Jouberin · UniProt Q8N157

Length
1196 aa
Mass
137.1 kDa
Annotated
2026-04-28
100 papers in source corpus 22 papers cited in narrative 21 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

AHI1 (Jouberin) is a WD40-repeat and SH3-domain scaffolding protein that functions at the basal body/transition zone of primary cilia and in the neuronal cytoplasm, where it coordinates vesicular trafficking, receptor stability, and signaling pathways essential for brain, retinal, and renal development. At the ciliary base, AHI1 stabilizes Rab8a to promote ciliogenesis and outer-segment protein trafficking, interacts with NPHP1, and is recruited by Cby1; loss of AHI1 impairs cilia formation, causes rhodopsin mislocalization, and triggers photoreceptor degeneration (PMID:19625297, PMID:20081859, PMID:25103236). In neurons, AHI1 forms a complex with HAP1 to sustain TrkB receptor levels and neurotrophin signaling, stabilizes the glucocorticoid receptor in the cytoplasm, and represses the circadian regulator RORα to control BMAL1/Rev-Erbα–dependent dopamine and serotonin biosynthesis (PMID:18636121, PMID:20956301, PMID:33782379, PMID:29449373). Loss-of-function mutations in AHI1—particularly those disrupting its N-terminal WD40 repeats—cause Joubert syndrome with cerebellar vermis hypoplasia, retinal dystrophy, and renal disease, while in macrophages AHI1 recruits the deubiquitinase OTUD1 to stabilize Tyk2 and maintain basal type-I interferon signaling (PMID:15322546, PMID:35821088, PMID:25616960).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 2004 High

    Identification of AHI1 as the causative gene for Joubert syndrome established that a WD40/SH3-domain protein is required for cerebellar and cortical development, and that its highest expression maps to neurons whose axons form the decussating tracts disrupted in the disease.

    Evidence Positional cloning, mutation screening in JBTS families, expression profiling in embryonic brain

    PMID:15322546 PMID:15467982

    Open questions at the time
    • No subcellular localization or interacting partners identified at this stage
    • Mechanism linking AHI1 loss to axonal decussation defect unknown
  2. 2008 High

    Discovery of the AHI1–HAP1 complex and its role in stabilizing TrkB receptor levels and internalization provided the first molecular pathway—neurotrophin receptor trafficking—through which AHI1 loss causes cerebellar defects.

    Evidence Reciprocal co-immunoprecipitation, Hap1-KO mouse, Ahi1 knockdown in neuronal culture with TrkB level/signaling readouts

    PMID:18636121

    Open questions at the time
    • Whether HAP1-independent functions of AHI1 contribute to cerebellar phenotype
    • Subcellular site of the AHI1–HAP1–TrkB complex not resolved
  3. 2008 High

    Identification of an AHI1–BCR-ABL–JAK2 interaction complex in CML stem/progenitor cells revealed a non-ciliary, oncogenic scaffolding role for AHI1 in modulating tyrosine kinase signaling and drug resistance.

    Evidence Co-immunoprecipitation, gain/loss-of-function in hematopoietic cells, in vivo leukemia model, phosphorylation assays

    PMID:18936234

    Open questions at the time
    • Structural basis of AHI1 interaction with BCR-ABL and JAK2 unknown
    • Whether this role is relevant outside CML
  4. 2009 High

    Localization of AHI1 to the mother centriole/basal body and demonstration that its loss destabilizes Rab8a and impairs ciliogenesis established AHI1 as a transition-zone scaffold linking vesicular trafficking to primary cilium formation.

    Evidence shRNA knockdown, Ahi1-KO mouse, immunofluorescence, ciliogenesis and endocytic trafficking assays

    PMID:19625297

    Open questions at the time
    • Direct binding to Rab8a not shown—could be indirect stabilization
    • How AHI1 is itself recruited to the basal body was unknown
  5. 2010 High

    Ahi1-null mice failing to form photoreceptor outer segments despite normal connecting cilia, with dose-sensitive genetic interaction with Nphp1, demonstrated that AHI1 acts downstream of cilium assembly in outer-segment disc morphogenesis and protein trafficking.

    Evidence Ahi1-KO mouse, Nphp1 epistasis, opsin mislocalization and Rab8a reduction in photoreceptors, apoptosis assays

    PMID:20081859 PMID:20592197

    Open questions at the time
    • Precise cargo(s) trafficked by AHI1-dependent Rab8a pathway in photoreceptors not fully defined
    • Structural basis of AHI1–NPHP1 interaction unknown
  6. 2010 High

    Conditional neuronal Ahi1 knockout showed that endocytic TrkB degradation—not just reduced expression—underlies depressive-like behavior, which could be rescued by TrkB overexpression in the amygdala, pinpointing AHI1's role in receptor recycling in mature neurons.

    Evidence Cre-loxP conditional KO, behavioral tests, Western blot, viral TrkB rescue, antidepressant treatment

    PMID:20956301

    Open questions at the time
    • Whether AHI1 directly prevents TrkB ubiquitination or lysosomal sorting not tested
    • Relevance to human neuropsychiatric phenotypes of JBTS not directly tested
  7. 2013 High

    Structure-function analysis of the Joubert-associated V443D mutation showed that it destabilizes AHI1, disrupts its basal body localization, and reduces binding to both NPHP1 and HAP1, unifying ciliary and neuronal trafficking defects under a single molecular lesion.

    Evidence Mutant construct transfection, co-immunoprecipitation, quantitative protein stability analysis, patient fibroblast ciliogenesis assays

    PMID:23532844

    Open questions at the time
    • Crystal structure of AHI1 WD40 domain not available to explain V443D effect
    • Whether all JBTS mutations act through the same mechanism unclear
  8. 2014 High

    Super-resolution imaging showed Cby1 recruits AHI1 to a ring-shaped domain at the distal centriole, answering the open question of how AHI1 reaches the transition zone and placing it downstream of OFD1-Cby1 in the centriolar maturation hierarchy.

    Evidence 3D-SIM and STED microscopy, Cby1-KO mouse, ciliogenesis assays

    PMID:25103236

    Open questions at the time
    • Whether Cby1-AHI1 interaction is direct or mediated by other TZ components
    • How AHI1 ring organization relates to its Rab8a-stabilizing function at the TZ
  9. 2015 Medium

    Demonstration that C-terminal SH3-domain truncations are non-pathogenic while WD40-disrupting mutations cause JBTS established the WD40 repeat region as the essential functional domain for AHI1's developmental role.

    Evidence Exome sequencing of homozygous truncation carriers, zebrafish morpholino targeting N-terminal vs C-terminal regions

    PMID:25616960

    Open questions at the time
    • Role of the SH3 domain in non-ciliary contexts (e.g., BCR-ABL binding) not assessed
    • Morpholino approaches have inherent off-target limitations
  10. 2017 Medium

    Zebrafish ahi1 mutants showed cone degeneration and rhodopsin mislocalization with intact connecting cilia and normal Cc2d2a/Cep290 localization, confirming AHI1 functions downstream of transition zone assembly in outer segment disc morphogenesis across vertebrates.

    Evidence TALEN-generated zebrafish mutants, electron microscopy, immunohistochemistry, optokinetic response

    PMID:28118669

    Open questions at the time
    • Molecular cargo sorted by AHI1 in cone vs rod photoreceptors not identified
    • Whether AHI1 interacts with IFT components not tested
  11. 2018 Medium

    AHI1's repression of RORα was shown to control BMAL1/Rev-Erbα levels and thereby dopamine (TH) biosynthesis in the midbrain, providing a circadian-clock-linked mechanism for the depressive phenotype of Ahi1-KO mice reversible by Rev-Erbα inhibition.

    Evidence Ahi1-KO mouse, Bmal1 epistasis, co-immunoprecipitation, stereotaxic SR8278 injection, behavioral assays

    PMID:29449373

    Open questions at the time
    • Direct biochemical mechanism of AHI1-mediated RORα repression not defined
    • Whether this pathway operates in human neurons not tested
  12. 2021 High

    Discovery that AHI1 stabilizes the glucocorticoid receptor in the cytoplasm and is required for stress-induced GR nuclear translocation provided a non-ciliary, cytoplasmic scaffolding function relevant to stress response and antidepressant sensitivity.

    Evidence Co-immunoprecipitation, Ahi1-KO mouse, nuclear/cytoplasmic fractionation, behavioral tests with antidepressant treatment

    PMID:33782379

    Open questions at the time
    • Whether AHI1 prevents GR ubiquitination directly or recruits a DUB is unknown
    • Relationship between GR stabilization and circadian clock regulation by AHI1 not integrated
  13. 2022 High

    Identification of the AHI1–OTUD1–Tyk2 axis in macrophages revealed that AHI1 recruits a deubiquitinase to maintain basal interferon-I signaling, extending AHI1's scaffolding function to innate immunity and explaining immunodeficiency in depression.

    Evidence Co-immunoprecipitation, siRNA knockdown, ubiquitination assays, patient PBMCs, depression mouse model, pharmacological rescue

    PMID:35821088

    Open questions at the time
    • Whether the AHI1–OTUD1 interaction is WD40-dependent not tested
    • Relevance of this axis to Joubert syndrome immunophenotype not explored

Open questions

Synthesis pass · forward-looking unresolved questions
  • A unifying structural model of how AHI1's WD40 platform simultaneously engages ciliary (NPHP1, Rab8a, Cby1), neuronal (HAP1, TrkB, GR), and immune (OTUD1, Tyk2) partners—and whether these represent mutually exclusive or co-occurring complexes—remains unresolved.
  • No crystal or cryo-EM structure of full-length AHI1 or its WD40 domain exists
  • Stoichiometry and competition among binding partners not characterized
  • Whether AHI1's DUB-recruitment function (OTUD1) extends to GR or TrkB stabilization is untested

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 6 GO:0098772 molecular function regulator activity 3
Localization
GO:0005929 cilium 5 GO:0005815 microtubule organizing center 3 GO:0005829 cytosol 2
Pathway
R-HSA-162582 Signal Transduction 5 R-HSA-1852241 Organelle biogenesis and maintenance 5 R-HSA-1266738 Developmental Biology 4 R-HSA-9909396 Circadian clock 2 R-HSA-168256 Immune System 1
Partners
BCR-ABL1CBY1HAP1JAK2NPHP1NR3C1OTUD1RAB8A
Complex memberships
AHI1-BCR-ABL-JAK2 signaling complexAHI1-HAP1 endocytic trafficking complexAHI1-NPHP1 transition zone complex

Evidence

Reading pass · 21 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2004 AHI1 (Jouberin) is most highly expressed in neurons giving rise to the crossing axons of the corticospinal tract and superior cerebellar peduncles, and mutations in AHI1 cause abnormal axonal decussation and cerebellar vermis malformation in Joubert syndrome. Mutational analysis, expression profiling in brain tissue, human genetic linkage/positional cloning Nature genetics High 15322546
2004 AHI1 encodes an alternatively spliced signaling molecule (Jouberin) containing seven WD40 repeats, an SH3 domain, and numerous SH3-binding sites, and is required for both cerebellar and cortical development. Mutational analysis, protein domain annotation, expression analysis in embryonic hindbrain and forebrain American journal of human genetics High 15467982
2008 Mouse Ahi1 forms a stable protein complex with huntingtin-associated protein 1 (Hap1); Hap1 knockout reduces Ahi1 levels, and suppression of Ahi1 decreases Hap1 and TrkB receptor levels and internalization, leading to decreased TrkB signaling and defective cerebellar development with abnormal axonal decussation. Co-immunoprecipitation, knockdown in neuronal culture, Hap1-KO mouse model, Western blot, neurite outgrowth assay The Journal of clinical investigation High 18636121
2009 Ahi1 localizes to the mother centriole/basal body of the primary cilium; knockdown of Ahi1 impairs ciliogenesis, destabilizes Rab8a and prevents its proper localization to the basal body, and causes defects in endocytic vesicle trafficking from the plasma membrane to the Golgi and back. shRNAi knockdown, Ahi1-KO mouse, immunofluorescence/localization, ciliogenesis assay, endocytic trafficking assay Human molecular genetics High 19625297
2010 Ahi1-null mice fail to form photoreceptor outer segments, show abnormal distribution of opsin throughout photoreceptors, exhibit decreased expression of Rab8a in photoreceptors, and undergo rapid apoptotic photoreceptor death; outer segment protein trafficking is specifically defective while synaptic protein trafficking is normal; phenotype is dose-sensitively modified by Nphp1. Ahi1-KO mouse model, immunohistochemistry, Western blot, genetic epistasis with Nphp1, apoptosis assays Nature genetics High 20081859 20592197
2008 AHI-1 overexpression in hematopoietic cells confers growth advantages and induces leukemia in vivo; AHI-1 physically interacts with BCR-ABL and JAK2 to form an AHI-1–BCR-ABL–JAK2 interaction complex; modulation of AHI-1 expression regulates phosphorylation of BCR-ABL and JAK2-STAT5, mediating tyrosine kinase inhibitor response/resistance in CML stem/progenitor cells. Co-immunoprecipitation, RNAi knockdown, overexpression in murine and human cells, in vivo leukemia model, Western blot for phosphorylation The Journal of experimental medicine High 18936234
2010 Neuronal-specific Ahi1 deficiency in mice reduces TrkB protein levels in the brain; Ahi1 deficiency promotes degradation of endocytic TrkB and reduces TrkB signaling in neuronal cells, causing depressive phenotypes reversible by antidepressants or TrkB overexpression in the amygdala. Cre-loxP conditional knockout, behavioral tests, Western blot, TrkB overexpression rescue, antidepressant treatment Proceedings of the National Academy of Sciences of the United States of America High 20956301
2013 The Joubert syndrome-associated AHI1-V443D missense mutation causes aberrant localization of AHI1 at the basal bodies of primary cilia and at cell-cell junctions, decreases AHI1 protein stability by ~50%, reduces binding to NPHP1, and decreases binding to HAP1; primary cilia formation is reduced in fibroblasts from JBTS patients with AHI1 mutations. Transfection of mutant AHI1 constructs, co-immunoprecipitation, immunofluorescence, quantitative protein analysis, patient fibroblasts The Journal of biological chemistry High 23532844
2013 Full-length Ahi1 (but not N-terminal fragments) binds Hap1; this binding is regulated during neuronal differentiation by nerve growth factor, which induces dephosphorylation of Hap1A and decreases its association with Ahi1. Mass spectrometry of Ahi1 immunoprecipitates identifies Cend1/BM88 as an additional Ahi1 binding partner; loss of Ahi1 reduces Cend1 levels in the hypothalamus; overexpression of Cend1 rescues neurite extension defects in Ahi1-KO hypothalamic neurons. Co-immunoprecipitation, mass spectrometry, Ahi1-KO mouse, overexpression rescue, subcellular fractionation, Western blot The Journal of neuroscience High 23658157
2014 Cby1 is required for efficient recruitment of Ahi1 to a ring-shaped domain (~250 nm) at the distal end of the mature centriole (transition zone); Cby1 deletion reduces the amount of centriole-localized Ahi1 but not Ofd1, and Cby1-null cells have a ciliogenesis defect; Cby1 localization to the distal centriole depends on Ofd1. Super-resolution microscopy (3D-SIM and STED), Cby1-KO mouse, immunofluorescence, ciliogenesis assays Molecular biology of the cell High 25103236
2022 AHI1 stabilizes basal type-I interferon signaling in macrophages by recruiting the deubiquitinase OTUD1 to deubiquitinate and stabilize Tyk2; AHI1 reduction (induced by arginine vasopressin in depression) downregulates Tyk2 and attenuates IFN-I signaling; the AHI1–OTUD1–Tyk2 axis mediates antiviral innate immune competence. Co-immunoprecipitation, siRNA knockdown, Western blot for ubiquitination/deubiquitination, patient PBMCs, depression mouse model, pharmacological rescue Cell research High 35821088
2021 AHI1 interacts with the glucocorticoid receptor (GR) in the cytoplasm, stabilizing GR; AHI1 deficiency promotes GR degradation in the cytoplasm and reduces stress-induced nuclear translocation of GR; Ahi1-KO mice display hyposensitivity to antidepressants under stress. Co-immunoprecipitation, Ahi1-KO mouse, Western blot, nuclear/cytoplasmic fractionation, behavioral tests, antidepressant treatment Translational psychiatry High 33782379
2022 Ahi1 regulates serotonin production through a GR/ERβ/TPH2 pathway: Ahi1 deficiency increases BMAL1 and Rev-Erbα, which repress TH and TPH2; AHI1 interacts with and represses RORα (a transcriptional regulator of circadian genes) to decrease BMAL1/Rev-Erbα expression; brain E2 levels decrease in male but not female Ahi1-KO mice, explaining sex-specific depression phenotypes. Western blot, gene knockdown, immunofluorescence, dual-luciferase reporter assay, rescue assay, Ahi1-KO mouse, E2 measurement Cell communication and signaling Medium 35643536
2018 Loss of AHI1 leads to upregulation of BMAL1 and Rev-Erbα in the midbrain; AHI1 interacts with and represses RORα to decrease BMAL1/Rev-Erbα, which in turn repress tyrosine hydroxylase (TH); Bmal1 deficiency reverses TH reduction caused by Ahi1 deficiency; microinfusion of Rev-Erbα inhibitor SR8278 into the ventral midbrain of Ahi1-KO mice increases TH expression in VTA and improves depressive symptoms. Ahi1-KO mouse, Western blot, Neuro-2a knockdown, co-immunoprecipitation, stereotaxic drug injection, behavioral assays The Journal of biological chemistry Medium 29449373
2009 AHI-1 overexpression in CTCL cells promotes transformation; stable knockdown of AHI-1 in CTCL cells identifies HCK (tyrosine kinase) and BIN1 (tumor suppressor) as downstream effectors; BIN1 physically interacts with MYC in CTCL cells; changes in HCK phosphorylation occur with AHI-1 modulation. Retroviral RNAi knockdown, microarray, quantitative RT-PCR, Co-immunoprecipitation, Western blot, inhibitor treatment Blood Medium 19211505
2008 Ahi1 protein accumulates in stigmoid bodies (cytoplasmic organelles in neurons) and is distributed in the cytoplasm, dendrites, and axons of neurons but is absent from glial cells; Ahi1 expression peaks during the first postnatal week in mouse brain and is present from embryonic day 10.5 through adulthood. Immunofluorescence, immunohistochemistry in human/mouse/zebrafish brain, developmental time course The Journal of comparative neurology Medium 18785627
2010 Brainstem Hap1-Ahi1 complex levels are upregulated by fasting, 2-deoxy-D-glucose treatment, and streptozotocin-induced insulin reduction; intra-brain insulin injection decreases Hap1-Ahi1 in the brainstem; knockdown of brainstem Hap1 decreases food intake and body weight, indicating the Hap1-Ahi1 complex acts as a sensor for insulin signals in feeding control. Western blot, intracranial insulin injection, STZ model, RNAi knockdown, behavioral (food intake) measurement FEBS letters Medium 21146532
2011 Ahi1 knockdown in zebrafish causes loss of cilia at Kupffer's vesicle and defects in cardiac left-right asymmetry; siRNA knockdown in renal epithelial cells demonstrates a role for Ahi1 in both ciliogenesis and cell-cell junction formation. Zebrafish morpholino knockdown, siRNA in renal epithelial cells, whole-mount in situ hybridization, ciliogenesis assay Cellular and molecular life sciences Medium 21959375
2017 Missense mutations in the WD40 domain of AHI1 cause non-syndromic retinitis pigmentosa; expression of mutant Jouberin in ciliated RPE cells shows significantly decreased enrichment at the ciliary base, without changes in the percentage of ciliated cells, cilium length, or intraflagellar transport. Exome sequencing, 3D structure homology modelling, patient fibroblast ciliogenesis assay, recombinant mutant protein expression in ciliated cells, immunofluorescence Journal of medical genetics Medium 28442542
2015 C-terminal AHI1 truncations (p.Arg1066* and p.Trp1088Leufs*16) that remove the SH3 domain do not cause Joubert syndrome in homozygous individuals; zebrafish morpholinos targeting near these C-terminal positions also do not produce ciliopathy, indicating the SH3 domain is dispensable for normal development, whereas N-terminal WD40-repeat-disrupting mutations are pathogenic. Whole-exome sequencing, homozygosity mapping, zebrafish morpholino knockdown (N-terminal vs C-terminal), clinical phenotyping Human molecular genetics Medium 25616960
2017 Zebrafish ahi1 mutants develop shorter cone outer segments, cone degeneration by 5 months, and rhodopsin mislocalization in rod photoreceptors; the connecting cilium forms normally and Cc2d2a and Cep290 localize properly in ahi1 mutants, indicating Ahi1 acts downstream of connecting cilium assembly in outer segment disc morphogenesis. TALEN-generated zebrafish mutants, histology, electron microscopy, immunohistochemistry, optokinetic response assay Investigative ophthalmology & visual science Medium 28118669

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2004 Abnormal cerebellar development and axonal decussation due to mutations in AHI1 in Joubert syndrome. Nature genetics 317 15322546
2001 Nucleic acid chaperone activity of the ORF1 protein from the mouse LINE-1 retrotransposon. Molecular and cellular biology 281 11134335
2000 Interactions of the PDZ-protein MAGI-1 with adenovirus E4-ORF1 and high-risk papillomavirus E6 oncoproteins. Oncogene 244 11077444
2005 Norovirus recombination in ORF1/ORF2 overlap. Emerging infectious diseases 238 16022784
2004 Mutations in the AHI1 gene, encoding jouberin, cause Joubert syndrome with cortical polymicrogyria. American journal of human genetics 231 15467982
2000 Multi-PDZ domain protein MUPP1 is a cellular target for both adenovirus E4-ORF1 and high-risk papillomavirus type 18 E6 oncoproteins. Journal of virology 213 11000240
1999 Hyperproduction of recombinant ferredoxins in escherichia coli by coexpression of the ORF1-ORF2-iscS-iscU-iscA-hscB-hs cA-fdx-ORF3 gene cluster. Journal of biochemistry 173 10393315
2010 AHI1 is required for photoreceptor outer segment development and is a modifier for retinal degeneration in nephronophthisis. Nature genetics 158 20081859
2005 LINE-1 retrotransposition requires the nucleic acid chaperone activity of the ORF1 protein. Journal of molecular biology 143 15826653
2013 Mapping the LINE1 ORF1 protein interactome reveals associated inhibitors of human retrotransposition. Nucleic acids research 140 23749060
1998 The product of the respiratory syncytial virus M2 gene ORF1 enhances readthrough of intergenic junctions during viral transcription. Journal of virology 140 9420254
1990 COX10 codes for a protein homologous to the ORF1 product of Paracoccus denitrificans and is required for the synthesis of yeast cytochrome oxidase. The Journal of biological chemistry 122 2167310
2010 Genetic screening of LCA in Belgium: predominance of CEP290 and identification of potential modifier alleles in AHI1 of CEP290-related phenotypes. Human mutation 116 20683928
2003 In vitro proteolytic processing of the MD145 norovirus ORF1 nonstructural polyprotein yields stable precursors and products similar to those detected in calicivirus-infected cells. Journal of virology 114 14512545
2014 Hepatitis E virus inhibits type I interferon induction by ORF1 products. Journal of virology 112 25100852
2002 High-affinity, non-sequence-specific RNA binding by the open reading frame 1 (ORF1) protein from long interspersed nuclear element 1 (LINE-1). The Journal of biological chemistry 105 12506113
2006 AHI1 gene mutations cause specific forms of Joubert syndrome-related disorders. Annals of neurology 104 16453322
2006 The ORF1 protein encoded by LINE-1: structure and function during L1 retrotransposition. Journal of biomedicine & biotechnology 103 16877816
2013 An ORF1-rearranged hepatitis E virus derived from a chronically infected patient efficiently replicates in cell culture. Journal of viral hepatitis 100 24750215
2002 Processing map and essential cleavage sites of the nonstructural polyprotein encoded by ORF1 of the feline calicivirus genome. Journal of virology 96 12072506
2005 AHI1 mutations cause both retinal dystrophy and renal cystic disease in Joubert syndrome. Journal of medical genetics 92 16155189
2008 LINE-1 ORF1 protein enhances Alu SINE retrotransposition. Gene 89 18534786
2009 Ahi1, whose human ortholog is mutated in Joubert syndrome, is required for Rab8a localization, ciliogenesis and vesicle trafficking. Human molecular genetics 83 19625297
2008 Huntingtin-associated protein 1 interacts with Ahi1 to regulate cerebellar and brainstem development in mice. The Journal of clinical investigation 78 18636121
2007 Human adenovirus Ad-36 induces adipogenesis via its E4 orf-1 gene. International journal of obesity (2005) 78 17984979
2003 Selective PDZ protein-dependent stimulation of phosphatidylinositol 3-kinase by the adenovirus E4-ORF1 oncoprotein. Oncogene 78 12569363
2001 Link of the unique oncogenic properties of adenovirus type 9 E4-ORF1 to a select interaction with the candidate tumor suppressor protein ZO-2. The EMBO journal 76 11598001
2008 Association of common variants in the Joubert syndrome gene (AHI1) with autism. Human molecular genetics 74 18782849
2000 Cloning, sequencing, and expression of the hepatitis E virus (HEV) nonstructural open reading frame 1 (ORF1). Journal of medical virology 74 10630959
2005 Identification of the first AHI1 gene mutations in nephronophthisis-associated Joubert syndrome. Pediatric nephrology (Berlin, Germany) 69 16240161
2006 Expression and processing of the Hepatitis E virus ORF1 nonstructural polyprotein. Virology journal 67 16725054
1997 Human herpesvirus 6 (HHV-6) ORF-1 transactivating gene exhibits malignant transforming activity and its protein binds to p53. Oncogene 67 9018122
1995 3C-like protease of rabbit hemorrhagic disease virus: identification of cleavage sites in the ORF1 polyprotein and analysis of cleavage specificity. Journal of virology 64 7474137
2000 Expression of the hepatitis E virus ORF1. Archives of virology 63 10963340
2006 AHI1, a pivotal neurodevelopmental gene, and C6orf217 are associated with susceptibility to schizophrenia. European journal of human genetics : EJHG 61 16773125
2015 The hepatitis E virus ORF1 'X-domain' residues form a putative macrodomain protein/Appr-1″-pase catalytic-site, critical for viral RNA replication. Gene 60 25870943
2008 AHI-1 interacts with BCR-ABL and modulates BCR-ABL transforming activity and imatinib response of CML stem/progenitor cells. The Journal of experimental medicine 60 18936234
2011 Evaluation of immune responses following infection of ponies with an EHV-1 ORF1/2 deletion mutant. Veterinary research 58 21314906
2009 The RNA polymerase dictates ORF1 requirement and timing of LINE and SINE retrotransposition. PLoS genetics 57 19390602
2016 Common variants at PVT1, ATG13-AMBRA1, AHI1 and CLEC16A are associated with selective IgA deficiency. Nature genetics 55 27723758
2010 Subcellular localization of the MNV-1 ORF1 proteins and their potential roles in the formation of the MNV-1 replication complex. Virology 55 20674956
2013 Molecular characterization of hepatitis E virus ORF1 gene supports a papain-like cysteine protease (PCP)-domain activity. Virus research 53 23978667
2011 Polymerization and nucleic acid-binding properties of human L1 ORF1 protein. Nucleic acids research 53 21937507
1997 The genome-linked protein of potato leafroll virus is located downstream of the putative protease domain of the ORF1 product. Virology 53 9268161
2014 Cby1 promotes Ahi1 recruitment to a ring-shaped domain at the centriole-cilium interface and facilitates proper cilium formation and function. Molecular biology of the cell 52 25103236
2005 Proteolytic processing of sapovirus ORF1 polyprotein. Journal of virology 50 15919882
2005 Immunogenicity of a recombinant pseudorabies virus expressing ORF1-ORF2 fusion protein of porcine circovirus type 2. Veterinary microbiology 49 16006077
2010 Retinal degeneration and failure of photoreceptor outer segment formation in mice with targeted deletion of the Joubert syndrome gene, Ahi1. The Journal of neuroscience : the official journal of the Society for Neuroscience 48 20592197
2014 C18 ORF1, a novel negative regulator of transforming growth factor-β signaling. The Journal of biological chemistry 47 24627487
2008 A single amino acid substitution in ORF1 dramatically decreases L1 retrotransposition and provides insight into nucleic acid chaperone activity. Nucleic acids research 46 18790804
2019 Recombinant Hepatitis E Viruses Harboring Tags in the ORF1 Protein. Journal of virology 44 31315997
2011 Lack of processing of the expressed ORF1 gene product of hepatitis E virus. Virology journal 44 21595991
2022 Depression compromises antiviral innate immunity via the AVP-AHI1-Tyk2 axis. Cell research 43 35821088
2018 Activities of Thrombin and Factor Xa Are Essential for Replication of Hepatitis E Virus and Are Possibly Implicated in ORF1 Polyprotein Processing. Journal of virology 43 29321328
2021 Phase separation of the LINE-1 ORF1 protein is mediated by the N-terminus and coiled-coil domain. Biophysical journal 42 33798566
2010 Neuronal Abelson helper integration site-1 (Ahi1) deficiency in mice alters TrkB signaling with a depressive phenotype. Proceedings of the National Academy of Sciences of the United States of America 42 20956301
2004 Deregulated expression in Ph+ human leukemias of AHI-1, a gene activated by insertional mutagenesis in mouse models of leukemia. Blood 42 14751929
2015 Genome sequence heterogeneity of Lake Sinai Virus found in honey bees and Orf1/RdRP-based polymorphisms in a single host. Virus research 40 25725149
2010 A large replication study and meta-analysis in European samples provides further support for association of AHI1 markers with schizophrenia. Human molecular genetics 40 20071346
2000 Use of a TT virus ORF1 recombinant protein to detect anti-TT virus antibodies in human sera. The Journal of general virology 40 11086126
2008 Species differences in the expression of Ahi1, a protein implicated in the neurodevelopmental disorder Joubert syndrome, with preferential accumulation to stigmoid bodies. The Journal of comparative neurology 36 18785627
2007 Support for involvement of the AHI1 locus in schizophrenia. European journal of human genetics : EJHG 36 17473831
2017 The Ciliopathy Gene ahi1 Is Required for Zebrafish Cone Photoreceptor Outer Segment Morphogenesis and Survival. Investigative ophthalmology & visual science 33 28118669
2014 The human adenovirus E4-ORF1 protein subverts discs large 1 to mediate membrane recruitment and dysregulation of phosphatidylinositol 3-kinase. PLoS pathogens 33 24788832
2019 Ciliary genes arl13b, ahi1 and cc2d2a differentially modify expression of visual acuity phenotypes but do not enhance retinal degeneration due to mutation of cep290 in zebrafish. PloS one 32 30970040
2007 DNA analysis of AHI1, NPHP1 and CYCLIN D1 in Joubert syndrome patients from the Netherlands. European journal of medical genetics 32 18054307
1999 High-frequency retrotransposition of a marked I factor in Drosophila melanogaster correlates with a dynamic expression pattern of the ORF1 protein in the cytoplasm of oocytes. Genetics 32 9927467
2013 Long interspersed nuclear element ORF-1 protein promotes proliferation and resistance to chemotherapy in hepatocellular carcinoma. World journal of gastroenterology 31 23466962
2009 Identification of tyrosine kinase, HCK, and tumor suppressor, BIN1, as potential mediators of AHI-1 oncogene in primary and transformed CTCL cells. Blood 31 19211505
2007 A new crucial protein interaction element that targets the adenovirus E4-ORF1 oncoprotein to membrane vesicles. Journal of virology 31 17314165
2013 The Joubert syndrome-associated missense mutation (V443D) in the Abelson-helper integration site 1 (AHI1) protein alters its localization and protein-protein interactions. The Journal of biological chemistry 30 23532844
2010 Fine mapping of AHI1 as a schizophrenia susceptibility gene: from association to evolutionary evidence. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 30 20371615
1997 Mutant adenovirus type 9 E4 ORF1 genes define three protein regions required for transformation of CREF cells. Journal of virology 30 9151828
2018 The deletion of the ORF1 and ORF71 genes reduces virulence of the neuropathogenic EHV-1 strain Ab4 without compromising host immunity in horses. PloS one 29 30440016
1997 A carboxy-terminal region required by the adenovirus type 9 E4 ORF1 oncoprotein for transformation mediates direct binding to cellular polypeptides. Journal of virology 29 9311876
1994 Two open reading frames (ORF1 and ORF2) within the 2.0-kilobase latency-associated transcript of herpes simplex virus type 1 are not essential for reactivation from latency. Journal of virology 29 7966597
2017 Mutational analysis of hepatitis E virus ORF1 "Y-domain": Effects on RNA replication and virion infectivity. World journal of gastroenterology 28 28216965
2006 Evidence for an oncogenic role of AHI-1 in Sezary syndrome, a leukemic variant of human cutaneous T-cell lymphomas. Leukemia 28 16838023
2022 Ahi1 regulates serotonin production by the GR/ERβ/TPH2 pathway involving sexual differences in depressive behaviors. Cell communication and signaling : CCS 27 35643536
2015 Non-manifesting AHI1 truncations indicate localized loss-of-function tolerance in a severe Mendelian disease gene. Human molecular genetics 26 25616960
2013 Loss of Ahi1 affects early development by impairing BM88/Cend1-mediated neuronal differentiation. The Journal of neuroscience : the official journal of the Society for Neuroscience 26 23658157
2007 Actinorhodin biosynthesis: structural requirements for post-PKS tailoring intermediates revealed by functional analysis of ActVI-ORF1 reductase. Biochemistry 26 17579485
2012 Identification of the promoter in the intergenic region between orf1 and cry8Ea1 controlled by sigma H factor. Applied and environmental microbiology 25 22504821
2013 Neural mechanisms underlying stress resilience in Ahi1 knockout mice: relevance to neuropsychiatric disorders. Molecular psychiatry 24 24042478
2011 Modelling a ciliopathy: Ahi1 knockdown in model systems reveals an essential role in brain, retinal, and renal development. Cellular and molecular life sciences : CMLS 24 21959375
2015 Crystal Structure of Xanthomonas AvrRxo1-ORF1, a Type III Effector with a Polynucleotide Kinase Domain, and Its Interactor AvrRxo1-ORF2. Structure (London, England : 1993) 23 26344722
2021 Ahi1 regulates the nuclear translocation of glucocorticoid receptor to modulate stress response. Translational psychiatry 22 33782379
2012 The role of AHI1 and CDKN1C in cutaneous T-cell lymphoma progression. Experimental dermatology 22 23171462
2010 Brainstem Hap1-Ahi1 is involved in insulin-mediated feeding control. FEBS letters 22 21146532
2022 Two mutations in the ORF1 of genotype 1 hepatitis E virus enhance virus replication and may associate with fulminant hepatic failure. Proceedings of the National Academy of Sciences of the United States of America 21 35969750
2019 Skeletal muscle LINE-1 ORF1 mRNA is higher in older humans but decreases with endurance exercise and is negatively associated with higher physical activity. Journal of applied physiology (Bethesda, Md. : 1985) 21 31369326
2018 Tyrosine hydroxylase down-regulation after loss of Abelson helper integration site 1 (AHI1) promotes depression via the circadian clock pathway in mice. The Journal of biological chemistry 21 29449373
2018 LINE-1 ORF1 Protein Is Up-regulated by Reactive Oxygen Species and Associated with Bladder Urothelial Carcinoma Progression. Cancer genomics & proteomics 21 29496693
2018 The Amino-Terminal Region of Hepatitis E Virus ORF1 Containing a Methyltransferase (Met) and a Papain-Like Cysteine Protease (PCP) Domain Counteracts Type I Interferon Response. Viruses 21 30567349
2016 Hepatitis E virus ORF1 encoded macro domain protein interacts with light chain subunit of human ferritin and inhibits its secretion. Molecular and cellular biochemistry 21 27170377
2014 Expression of the murine norovirus (MNV) ORF1 polyprotein is sufficient to induce apoptosis in a virus-free cell model. PloS one 20 24599381
2014 Hijacking Dlg1 for oncogenic phosphatidylinositol 3-kinase activation in human epithelial cells is a conserved mechanism of human adenovirus E4-ORF1 proteins. Journal of virology 20 25253337
2010 Impact of the AHI1 gene on the vulnerability to schizophrenia: a case-control association study. PloS one 20 20805890
2002 Pathological changes of renal epithelial cells in mice transgenic for the TT virus ORF1 gene. The Journal of general virology 20 11752710
2017 Missense mutations in the WD40 domain of AHI1 cause non-syndromic retinitis pigmentosa. Journal of medical genetics 19 28442542