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Gene Review

AHI1  -  Abelson helper integration site 1

Homo sapiens

Synonyms: AHI-1, Abelson helper integration site 1 protein homolog, FLJ20069, JBTS3, Jouberin, ...
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Disease relevance of AHI1

  • Clinically, the patient exhibiting the AHI1 mutation was the most severely affected child with a profound encephalopathy, major hypotonia, ataxia, Leber congenital amaurosis, and normal IVth ventricle at the MRI [1].
  • Subjects with AHI1 mutations may be at risk of developing both retinal dystrophy and progressive kidney disease [2].
  • In two cases of childhood T-ALL, both carrying a t(6;7)(q23;q32 through 36), split FISH signals were produced by adjacent PAC, mapping the breakpoints to within an approximately 150 Kb region containing the genes c-MYB and AHI1 [3].
  • The ORF1 sequence was amplified and fused to the malE gene of Escherichia coli and antisera were raised against the resulting fusion protein [4].
  • The major oncogenic determinants for human adenovirus type 9 (Ad9) and high-risk human papillomaviruses (HPV) are the E4-ORF1 and E6 proteins, respectively [5].

High impact information on AHI1

  • Mutagenesis studies showed that the location of the termination codon of ORF-1 protein plays a crucial role in directing translation of ORF-2 from the upstream initiation codons in vivo [6].
  • However, progress has been made in recent years with the mapping of three genetic loci and the identification of mutations in two genes, AHI1 and NPHP1 [7].
  • AHI1 gene mutations cause specific forms of Joubert syndrome-related disorders [8].
  • One (ORF1) of the two unknown ORFs locates immediately upstream of pufB, while the other (ORF2) locates between pufB and pufA [9].
  • Partial sequence (2,018 nt) of the most 5' ORF (ORF-1) reveals a 3C-like serine protease motif [10].

Chemical compound and disease context of AHI1

  • The balhimycin biosynthetic gene cluster of the glycopeptide producer Amycolatopsis balhimycina includes a gene (orf1) with unknown function. orf1 shows high similarity to the mbtH gene from Mycobacterium tuberculosis [11].
  • Herbaspirillum seropedicae strains mutated in the nifX or orf1 genes showed 90% or 50% reduction in nitrogenase activity under low levels of iron or molybdenum respectively [12].

Biological context of AHI1

  • Recently, mutations in AHI1 on chromosome 6q23.3 were found in JBTS patients without NPHP [13].
  • METHODS: We screened a cohort of 117 JS subjects for AHI1 mutations by a combination of haplotype analysis and sequencing of the gene, and for the homozygous NPHP1 deletion by sequencing and marker analysis [2].
  • ORF-1 was shown to be necessary and sufficient for transactivating viral gene expression directed by the SFV-1 LTR [14].
  • Northern blots, Southern blots, and primer extension analyses indicated that ORF-1 and dbp comprised a two-gene operon located on the 49-kb linear plasmid [15].
  • The comparison of the two strains identified a localized area of divergent nucleic and amino acid sequence that was previously reported in the region encoding the nonstructural gene(s) (ORF1) [16].

Anatomical context of AHI1

  • We find that JBTS1 and -3 primarily show features restricted to the central nervous system, with JBTS1 showing largely pure cerebellar and midbrain-hindbrain junction involvement, and JBTS3 displaying cerebellar, midbrain-hindbrain junction, and cerebral cortical features, most notably polymicrogyria [17].
  • Its involvement in human leukemogenesis is demonstrated by gross perturbations in its expression in human leukemia cells, particularly in cutaneous T-cell lymphoma cell lines where increases in AHI-1 transcripts of 40-fold are seen [18].
  • T cells infected with strain 484-77 of group C express four viral U-like small RNAs (HSUR1-4) and a 1.2-kb mRNA which encodes open reading frames ORF-1 and ORF-2 [19].
  • ORF1 of the ubiquitous 2.3 kb linear plasmid of maize mitochondria encodes a 39 kDa protein detected with polyclonal antibodies raised to a beta-galactosidase:ORF1 fusion protein [20].
  • The DNA sequence containing ORF-1 was transiently expressed in COS-1 cells, and the viral protein produced in these cells was found to react with anti-MDV serotype-1 Antigen B-specific monoclonal antibodies [21].

Associations of AHI1 with chemical compounds

  • We designed and synthesized AHI4 that has an axial hydroxyl group instead of geminal methyl groups at C-6' of AHI1, previously reported as a lead compound for the development of non-azole inhibitors of ABA 8'-hydroxylase [22].
  • ORF-2 has no start methionine and is in the -1 frame compared with ORF-1 [10].
  • The N-terminal amino acid sequences and monomer sizes of components A and B correspond to those of ORF1 and ORF3 respectively (ORF = open reading frame) of a recently published sequence of a clone which complements mutants unable to degrade epoxypropane [23].
  • The predicted amino acid sequence of component A (ORF1) has been analysed and shown to contain a potential ADP binding site near the N-terminus and putative cofactor binding domain near the C-terminus, with sequence similarity to the biotinyl and lipoyl binding domains of biotin-dependent carboxylases and 2-oxoacid dehydrogenases respectively [23].
  • Four genes, a homolog of pabB, and three genes conserved between methanogenic Archaea and Bacteria possessing H(4)MPT-linked functions, orfY, orf1, and afpA were shown to be involved in formaldehyde oxidation/detoxification, as judged by specific mutant phenotypes [24].

Other interactions of AHI1

  • A significant difference was found between apnoea-hypopnoea indices (AHI) recorded in PSG1, PSG2 and PSGtot (mean+/-SD, AHI1 33+/-27, AHI2 45+/-28, AHItot 40+/-25 events x h(-1), respectively; p<0.01) [25].
  • Genotype-phenotype studies indicate that, unlike CORS2, JBTS3 appears not to be associated with renal dysfunction [26].

Analytical, diagnostic and therapeutic context of AHI1

  • Sequence analysis of the clones identified two open reading frames (ORFs), one of which (ORF1) coded for a predicted 39 kDa gene product [4].
  • Sequence analysis performed from internal ORF1 and ORF2 PCR products displayed strong homogeneity between the HEV isolates, determining a regional cluster [27].
  • Orf1 was truncated by molecular cloning and the corresponding 228-aa-long polypeptide did not exhibit any significant homology with other cognate proteins [28].
  • Site-directed mutagenesis confirmed that this product was derived from ORF 1 and that frameshifting was not involved [29].
  • Three of the peptides (EH174 from ORF-1, EH286 from ORF-2 and EH362 from ORF-3) showed antigenic activity and possible application for the development of anti-HEV test kits (the peptide-based ELISA) [30].


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  2. AHI1 mutations cause both retinal dystrophy and renal cystic disease in Joubert syndrome. Parisi, M.A., Doherty, D., Eckert, M.L., Shaw, D.W., Ozyurek, H., Aysun, S., Giray, O., Al Swaid, A., Al Shahwan, S., Dohayan, N., Bakhsh, E., Indridason, O.S., Dobyns, W.B., Bennett, C.L., Chance, P.F., Glass, I.A. J. Med. Genet. (2006) [Pubmed]
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  7. Genetic basis of Joubert syndrome and related disorders of cerebellar development. Louie, C.M., Gleeson, J.G. Hum. Mol. Genet. (2005) [Pubmed]
  8. AHI1 gene mutations cause specific forms of Joubert syndrome-related disorders. Valente, E.M., Brancati, F., Silhavy, J.L., Castori, M., Marsh, S.E., Barrano, G., Bertini, E., Boltshauser, E., Zaki, M.S., Abdel-Aleem, A., Abdel-Salam, G.M., Bellacchio, E., Battini, R., Cruse, R.P., Dobyns, W.B., Krishnamoorthy, K.S., Lagier-Tourenne, C., Magee, A., Pascual-Castroviejo, I., Salpietro, C.D., Sarco, D., Dallapiccola, B., Gleeson, J.G. Ann. Neurol. (2006) [Pubmed]
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  11. The small MbtH-like protein encoded by an internal gene of the balhimycin biosynthetic gene cluster is not required for glycopeptide production. Stegmann, E., Rausch, C., Stockert, S., Burkert, D., Wohlleben, W. FEMS Microbiol. Lett. (2006) [Pubmed]
  12. Nitrogenase activity of Herbaspirillum seropedicae grown under low iron levels requires the products of nifXorf1 genes. Klassen, G., de Oliveira Pedrosa, F., de Souza, E.M., Yates, M.G., Rigo, L.U. FEMS Microbiol. Lett. (2003) [Pubmed]
  13. Identification of the first AHI1 gene mutations in nephronophthisis-associated Joubert syndrome. Utsch, B., Sayer, J.A., Attanasio, M., Pereira, R.R., Eccles, M., Hennies, H.C., Otto, E.A., Hildebrandt, F. Pediatr. Nephrol. (2006) [Pubmed]
  14. Identification of the simian foamy virus transcriptional transactivator gene (taf). Mergia, A., Shaw, K.E., Pratt-Lowe, E., Barry, P.A., Luciw, P.A. J. Virol. (1991) [Pubmed]
  15. Decorin-binding protein of Borrelia burgdorferi is encoded within a two-gene operon and is protective in the murine model of Lyme borreliosis. Hagman, K.E., Lahdenne, P., Popova, T.G., Porcella, S.F., Akins, D.R., Radolf, J.D., Norgard, M.V. Infect. Immun. (1998) [Pubmed]
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  18. Evidence for an oncogenic role of AHI-1 in Sezary syndrome, a leukemic variant of human cutaneous T-cell lymphomas. Ringrose, A., Zhou, Y., Pang, E., Zhou, L., Lin, A.E., Sheng, G., Li, X.J., Weng, A., Su, M.W., Pittelkow, M.R., Jiang, X. Leukemia (2006) [Pubmed]
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  20. Expression of ORF1 of the linear 2.3 kb plasmid of maize mitochondria: product localization and similarities to the 130 kDa protein encoded by the S2 episome. Leon, P., O'Brien-Vedder, C., Walbot, V. Curr. Genet. (1992) [Pubmed]
  21. Open reading frames in a 4556 nucleotide sequence within MDV-1 BamHI-D DNA fragment: evidence for splicing of mRNA from a new viral glycoprotein gene. Becker, Y., Asher, Y., Tabor, E., Davidson, I., Malkinson, M. Virus Genes (1994) [Pubmed]
  22. A new non-azole inhibitor of ABA 8'-hydroxylase: Effect of the hydroxyl group substituted for geminal methyl groups in the six-membered ring. Araki, Y., Miyawaki, A., Miyashita, T., Mizutani, M., Hirai, N., Todoroki, Y. Bioorg. Med. Chem. Lett. (2006) [Pubmed]
  23. Purification and characterization of two components of epoxypropane isomerase/carboxylase from Xanthobacter Py2. Chion, C.K., Leak, D.J. Biochem. J. (1996) [Pubmed]
  24. Analysis of gene islands involved in methanopterin-linked C1 transfer reactions reveals new functions and provides evolutionary insights. Kalyuzhnaya, M.G., Korotkova, N., Crowther, G., Marx, C.J., Lidstrom, M.E., Chistoserdova, L. J. Bacteriol. (2005) [Pubmed]
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  26. Homozygosity mapping of a third Joubert syndrome locus to 6q23. Lagier-Tourenne, C., Boltshauser, E., Breivik, N., Gribaa, M., Bétard, C., Barbot, C., Koenig, M. J. Med. Genet. (2004) [Pubmed]
  27. Identification of a novel hepatitis E virus in Nigeria. Buisson, Y., Grandadam, M., Nicand, E., Cheval, P., van Cuyck-Gandre, H., Innis, B., Rehel, P., Coursaget, P., Teyssou, R., Tsarev, S. J. Gen. Virol. (2000) [Pubmed]
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  30. Synthesis and application of hepatitis E virus peptides to diagnosis. Qi, Z., Cui, D., Pan, W., Yu, C., Song, Y., Cui, H., Arima, T. J. Virol. Methods (1995) [Pubmed]
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