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Gene Review

PAX6  -  paired box 6

Homo sapiens

Synonyms: AN, AN2, Aniridia type II protein, D11S812E, FVH1, ...
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Disease relevance of PAX6

  • All observed mutations support the notion that haploinsufficiency in PAX6 results in aniridia and associated eye anomalies [1].
  • The expression of PAX6, PTEN, vascular endothelial growth factor, and epidermal growth factor receptor in gliomas: relationship to tumor grade and survival [2].
  • PAX6 mutations have been detected in various ocular anomalies, including aniridia, Peters anomaly, corneal dystrophy, congenital cataracts, and foveal hypoplasia [3].
  • Mutation of the PAX6 gene in patients with autosomal dominant keratitis [4].
  • EN1, EN2, and PAX6 genes were also expressed in normal cerebellar tissue, and their expression in medulloblastoma is consistent with the hypothesis that this tumor originates in the external granular layer of the developing cerebellum [5].

Psychiatry related information on PAX6


High impact information on PAX6


Chemical compound and disease context of PAX6


Biological context of PAX6


Anatomical context of PAX6

  • In the early fetal period (9 developmental weeks) PAX6 expression increased in the spinal cord [6].
  • PAX6 expression was detected in both layers of the optic cup, optic stalk and prospective corneal epithelium [6].
  • The PAX6 gene is involved in ocular morphogenesis and is expressed in the developing central nervous system and numerous ocular tissues during development [3].
  • Mutations of the PAX6 gene detected in patients with a variety of optic-nerve malformations [3].
  • These results are consistent with deficient auditory interhemispheric transfer in patients with a PAX6 mutation, which may be attributable to structural and/or functional abnormalities of the anterior commisure and corpus callosum, although the exact contribution of these two formations to our findings remains unclear [16].

Associations of PAX6 with chemical compounds

  • One patient (P2) had a PAX6 protein with de novo in-frame deletion of alanine, arginine, and proline at codon positions 37, 38, and 39 [1].
  • PAX6 functions as a transcription factor and has two DNA binding domains (a paired domain and a homeodomain) which are joined by a linker, and a transactivation domain enriched in proline, serine and threonine (PST) at the C-terminus [17].
  • PAX6 has two DNA binding domains, a glycine-rich region that links the two DNA binding domains, and a transactivation domain [18].
  • Twenty-eight percent of identified PAX6 mutations are C-T changes at CpG dinucleotides, 20% are splicing errors, and more than 30% are deletion or insertion events [19].
  • Heterozygous PAX6 mutation may cause glucose intolerance [12].

Physical interactions of PAX6

  • Effect of CTCF-binding motif on regulation of PAX6 transcription [20].
  • Kap13 binds to Pax6 via a nuclear localization sequence (NLS), which is located within a segment of 80 amino acid residues that includes the homeodomain [21].
  • Direct sequencing of PAX6 and the DNA-binding domain of FOXC1 failed to detect a mutation [22].
  • However, Pax6 binds cooperatively with SOX2 to the DC5 sequence, resulting in formation of a high-mobility form of ternary complex in vitro, which correlates with the enhancer activation in vivo [23].

Regulatory relationships of PAX6

  • We show here that the pancreatic transcription factor PAX6 preferentially binds to and more effectively trans activates the variant than the wild-type UCP2 promoter allele in the beta-cell line INS1-E [24].
  • Data from immunoprecipitation and transient transfection assays demonstrated that SEF and Sp1 interacted in vitro and may act together in vivo to regulate PAX6 expression [25].

Other interactions of PAX6

  • Recursive partitioning analysis showed a favorable outcome for patients with high expression values of PTEN and PAX6 compared with low expression values of one or both genes (P < 0.0001) [2].
  • Population-based risk estimates of Wilms tumor in sporadic aniridia. A comprehensive mutation screening procedure of PAX6 identifies 80% of mutations in aniridia [26].
  • Mutations in the PITX2, FOXC1, and PAX6 genes have been associated with Rieger syndrome [27].
  • Position effects with cytogenetic rearrangements well outside the coding region have been implicated for four of the genes discussed: POU3F4, SOX9, PAX6, and GL13 [28].
  • Four of the detected mutations affected PAX6-mediated transcriptional repression of the PAX2 promoter in a reporter assay [3].

Analytical, diagnostic and therapeutic context of PAX6


  1. Mutation in the PAX6 gene in twenty patients with aniridia. Chao, L.Y., Huff, V., Strong, L.C., Saunders, G.F. Hum. Mutat. (2000) [Pubmed]
  2. The expression of PAX6, PTEN, vascular endothelial growth factor, and epidermal growth factor receptor in gliomas: relationship to tumor grade and survival. Zhou, Y.H., Tan, F., Hess, K.R., Yung, W.K. Clin. Cancer Res. (2003) [Pubmed]
  3. Mutations of the PAX6 gene detected in patients with a variety of optic-nerve malformations. Azuma, N., Yamaguchi, Y., Handa, H., Tadokoro, K., Asaka, A., Kawase, E., Yamada, M. Am. J. Hum. Genet. (2003) [Pubmed]
  4. Mutation of the PAX6 gene in patients with autosomal dominant keratitis. Mirzayans, F., Pearce, W.G., MacDonald, I.M., Walter, M.A. Am. J. Hum. Genet. (1995) [Pubmed]
  5. Deregulated expression of PAX5 in medulloblastoma. Kozmik, Z., Sure, U., Rüedi, D., Busslinger, M., Aguzzi, A. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  6. Expression pattern of PAX3 and PAX6 genes during human embryogenesis. Terzić, J., Saraga-Babić, M. Int. J. Dev. Biol. (1999) [Pubmed]
  7. Cloning of breakpoints of a chromosome translocation identifies the AN2 locus. Gessler, M., Simola, K.O., Bruns, G.A. Science (1989) [Pubmed]
  8. PAX6 haploinsufficiency causes cerebral malformation and olfactory dysfunction in humans. Sisodiya, S.M., Free, S.L., Williamson, K.A., Mitchell, T.N., Willis, C., Stevens, J.M., Kendall, B.E., Shorvon, S.D., Hanson, I.M., Moore, A.T., van Heyningen, V. Nat. Genet. (2001) [Pubmed]
  9. Functional PAX-6 gene-linked polymorphic region: potential association with paranoid schizophrenia. Stöber, G., Syagailo, Y.V., Okladnova, O., Jungkunz, G., Knapp, M., Beckmann, H., Lesch, K.P. Biol. Psychiatry (1999) [Pubmed]
  10. PAX6 missense mutation in isolated foveal hypoplasia. Azuma, N., Nishina, S., Yanagisawa, H., Okuyama, T., Yamada, M. Nat. Genet. (1996) [Pubmed]
  11. Influence of PAX6 gene dosage on development: overexpression causes severe eye abnormalities. Schedl, A., Ross, A., Lee, M., Engelkamp, D., Rashbass, P., van Heyningen, V., Hastie, N.D. Cell (1996) [Pubmed]
  12. A case of novel de novo paired box gene 6 (PAX6) mutation with early-onset diabetes mellitus and aniridia. Nishi, M., Sasahara, M., Shono, T., Saika, S., Yamamoto, Y., Ohkawa, K., Furuta, H., Nakao, T., Sasaki, H., Nanjo, K. Diabet. Med. (2005) [Pubmed]
  13. Congenital bilateral severe microphthalmia with mental retardation and cerebral palsy: chromosome aberration, 46, XY, t (2;6)(q31;q24). Hirayama, T., Kobayashi, T., Fujino, O. Journal of Nippon Medical School = Nihon Ika Daigaku zasshi. (2005) [Pubmed]
  14. A novel PAX6 frameshift mutation in a kindred from Atlantic Canada with familial aniridia. Gupta, S.K., Orr, A., Bulman, D., De Becker, I., Guernsey, D.L., Neumann, P.E. Can. J. Ophthalmol. (1999) [Pubmed]
  15. Frequent chromosome aberrations revealed by molecular cytogenetic studies in patients with aniridia. Crolla, J.A., van Heyningen, V. Am. J. Hum. Genet. (2002) [Pubmed]
  16. Deficient auditory interhemispheric transfer in patients with PAX6 mutations. Bamiou, D.E., Musiek, F.E., Sisodiya, S.M., Free, S.L., Davies, R.A., Moore, A., van Heyningen, V., Luxon, L.M. Ann. Neurol. (2004) [Pubmed]
  17. Missense mutation at the C-terminus of PAX6 negatively modulates homeodomain function. Singh, S., Chao, L.Y., Mishra, R., Davies, J., Saunders, G.F. Hum. Mol. Genet. (2001) [Pubmed]
  18. Modulation of PAX6 homeodomain function by the paired domain. Singh, S., Stellrecht, C.M., Tang, H.K., Saunders, G.F. J. Biol. Chem. (2000) [Pubmed]
  19. PAX6 mutations reviewed. Prosser, J., van Heyningen, V. Hum. Mutat. (1998) [Pubmed]
  20. Effect of CTCF-binding motif on regulation of PAX6 transcription. Wu, D., Li, T., Lu, Z., Dai, W., Xu, M., Lu, L. Invest. Ophthalmol. Vis. Sci. (2006) [Pubmed]
  21. Paired-type homeodomain transcription factors are imported into the nucleus by karyopherin 13. Ploski, J.E., Shamsher, M.K., Radu, A. Mol. Cell. Biol. (2004) [Pubmed]
  22. A novel syndrome of congenital lid and punctal anomalies, corneal and chorioretinal dystrophy. Lee, T.K., Hébert, M., MacDonald, I.M. Ophthalmic Genet. (2003) [Pubmed]
  23. Pax6 and SOX2 form a co-DNA-binding partner complex that regulates initiation of lens development. Kamachi, Y., Uchikawa, M., Tanouchi, A., Sekido, R., Kondoh, H. Genes Dev. (2001) [Pubmed]
  24. A functional polymorphism in the promoter of UCP2 enhances obesity risk but reduces type 2 diabetes risk in obese middle-aged humans. Krempler, F., Esterbauer, H., Weitgasser, R., Ebenbichler, C., Patsch, J.R., Miller, K., Xie, M., Linnemayr, V., Oberkofler, H., Patsch, W. Diabetes (2002) [Pubmed]
  25. Activation of the human PAX6 gene through the exon 1 enhancer by transcription factors SEF and Sp1. Zheng, J.B., Zhou, Y.H., Maity, T., Liao, W.S., Saunders, G.F. Nucleic Acids Res. (2001) [Pubmed]
  26. Population-based risk estimates of Wilms tumor in sporadic aniridia. A comprehensive mutation screening procedure of PAX6 identifies 80% of mutations in aniridia. Grønskov, K., Olsen, J.H., Sand, A., Pedersen, W., Carlsen, N., Bak Jylling, A.M., Lyngbye, T., Brøndum-Nielsen, K., Rosenberg, T. Hum. Genet. (2001) [Pubmed]
  27. Novel identification of a four-base-pair deletion mutation in PITX2 in a Rieger syndrome family. Wang, Y., Zhao, H., Zhang, X., Feng, H. J. Dent. Res. (2003) [Pubmed]
  28. Transcription factors in disease. Engelkamp, D., van Heyningen, V. Curr. Opin. Genet. Dev. (1996) [Pubmed]
  29. PAX6 mutations in aniridia. Hanson, I.M., Seawright, A., Hardman, K., Hodgson, S., Zaletayev, D., Fekete, G., van Heyningen, V. Hum. Mol. Genet. (1993) [Pubmed]
  30. A novel PAX6 gene mutation in a Chinese family with aniridia. Song, S., Liu, Y., Guo, S., Zhang, L., Zhang, X., Wang, S., Lu, A., Li, L. Mol. Vis. (2005) [Pubmed]
  31. Quantitation of PAX6 and PAX6(5a) transcript levels in adult human lens, cornea, and monkey retina. Zhang, W., Cveklova, K., Oppermann, B., Kantorow, M., Cvekl, A. Mol. Vis. (2001) [Pubmed]
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