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Gene Review

Ahi1  -  Abelson helper integration site 1

Mus musculus

Synonyms: 1700015F03Rik, AHI-1, Abelson helper integration site 1 protein, Ahi-1, D10Bwg0629e, ...
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Disease relevance of Ahi1

  • The function of these proteins is unknown, but involvement in leukemogenesis has been suggested by the high frequency of Ahi-1 mutations seen in certain virus-induced murine leukemias [1].
  • Here we report the identification of a novel gene (Ahi-1) targeted by these provirus insertional mutations and the cloning of its cDNA [2].
  • Molecular cloning of cellular sequences adjacent to Moloney proviruses enabled us to identify a cellular region, designated Ahi-1, which was found occupied by the helper proviruses in 16% of Abelson pre-B-cell lymphomas [3].
  • Evidence for an oncogenic role of AHI-1 in Sezary syndrome, a leukemic variant of human cutaneous T-cell lymphomas [4].
  • 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 [4].

High impact information on Ahi1

  • AHI1 is most highly expressed in brain, particularly in neurons that give rise to the crossing axons of the corticospinal tract and superior cerebellar peduncles [5].
  • The gene is expressed strongly in embryonic hindbrain and forebrain, and our data suggest that AHI1 is required for both cerebellar and cortical development in humans [6].
  • Deregulated expression in Ph+ human leukemias of AHI-1, a gene activated by insertional mutagenesis in mouse models of leukemia [1].
  • Although 15 of 16 human lymphoid and myeloid leukemic cell lines showed aberrant control of AHI-1 expression, this was not seen in blasts obtained directly from patients with acute Philadelphia chromosome-negative (Ph(-)) leukemia (n = 15) [1].
  • Ahi-1/AHI-1 (Abelson helper integration site-1) encodes a family of protein isoforms containing one Src homology 3 (SH3) domain and multiple tryptophan-aspartic acid 40 (WD40)-repeat domains [1].

Biological context of Ahi1


Anatomical context of Ahi1


Regulatory relationships of Ahi1

  • To test whether provirus integration in the Ahi-1 region enhances the expression of Myb by a cis-acting mechanism, we have also examined Myb gene expression in A-MuLV-induced pre-B-lymphomas [8].
  • Since no significant alteration of c-myb expression was found in Abelson murine leukemia virus-induced pre-B-lymphomas harboring a provirus inserted within the Ahi-1 locus, this suggested that it harbors another gene whose dysregulation is involved in tumor formation [2].

Other interactions of Ahi1

  • The Ahi-1 locus was initially identified as a common helper provirus integration site in Abelson pre-B-cell lymphomas and shown to be closely linked to the c-myb proto-oncogene [2].
  • In addition, another previously identified provirus insertion site, Mis-2, was found to map within the 16th intron of the Ahi-1 gene [2].

Analytical, diagnostic and therapeutic context of Ahi1


  1. Deregulated expression in Ph+ human leukemias of AHI-1, a gene activated by insertional mutagenesis in mouse models of leukemia. Jiang, X., Zhao, Y., Chan, W.Y., Vercauteren, S., Pang, E., Kennedy, S., Nicolini, F., Eaves, A., Eaves, C. Blood (2004) [Pubmed]
  2. 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. Jiang, X., Hanna, Z., Kaouass, M., Girard, L., Jolicoeur, P. J. Virol. (2002) [Pubmed]
  3. Identification of a common helper provirus integration site in Abelson murine leukemia virus-induced lymphoma DNA. Poirier, Y., Kozak, C., Jolicoeur, P. J. Virol. (1988) [Pubmed]
  4. 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]
  5. Abnormal cerebellar development and axonal decussation due to mutations in AHI1 in Joubert syndrome. Ferland, R.J., Eyaid, W., Collura, R.V., Tully, L.D., Hill, R.S., Al-Nouri, D., Al-Rumayyan, A., Topcu, M., Gascon, G., Bodell, A., Shugart, Y.Y., Ruvolo, M., Walsh, C.A. Nat. Genet. (2004) [Pubmed]
  6. Mutations in the AHI1 gene, encoding jouberin, cause Joubert syndrome with cortical polymicrogyria. Dixon-Salazar, T., Silhavy, J.L., Marsh, S.E., Louie, C.M., Scott, L.C., Gururaj, A., Al-Gazali, L., Al-Tawari, A.A., Kayserili, H., Sztriha, L., Gleeson, J.G. Am. J. Hum. Genet. (2004) [Pubmed]
  7. Molecular Cloning of a Novel Gene ZAhi-1 and its Expression Analysis during Zebrafish Gametogenesis. Zhou, W., Song, P. Mol. Biol. Rep. (2006) [Pubmed]
  8. The Myb and Ahi-1 genes are physically very closely linked on mouse chromosome 10. Jiang, X., Villeneuve, L., Turmel, C., Kozak, C.A., Jolicoeur, P. Mamm. Genome (1994) [Pubmed]
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