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Paired box gene 6 (aniridia, keratitis)
PDB rendering based on 2cue.
Available structures: 2cue, 6pax
Symbol(s) PAX6; AN; AN2; D11S812E; MGC17209; MGDA; WAGR
External IDs OMIM: 607108 MGI: 97490 Homologene: 1212
RNA expression pattern

More reference expression data

Human Mouse
Entrez 5080 18508
Ensembl ENSG00000007372 ENSMUSG00000027168
Uniprot P26367 Q3UTV5
Refseq NM_000280 (mRNA)
NP_000271 (protein)
NM_013627 (mRNA)
NP_038655 (protein)
Location Chr 11: 31.77 - 31.8 Mb Chr 2: 105.47 - 105.5 Mb
Pubmed search [1] [2]

Paired box gene 6 (aniridia, keratitis), also known as PAX6, is a human gene.

PAX6 is the most researched of the Pax genes and appears throughout the literature as a "master control" gene for the development of eyes and sensory organs, certain neural and epidermal tissues as well as other homologous structures, usually derived from ectodermal tissues. This transcription factor is most famous for its use in the interspecifically induced expression of ectopic eyes and is of medical importance because heterozygous mutants produce a wide spectrum of ocular defects such as Aniridia in humans.

PAX6 protein is highly conserved across species, and for instance mouse PAX6 can trigger eye development in Drosophila melanogaster.

Genomic organisation of the PAX6 locus varies considerably between species, including the number and distribution of exons, cis-regulatory elements, and transcription start sites. The first work on genomic organisation was performed in quail, although the picture of the mouse locus is the most complete to date. This consists of 2 confirmed promoters (P0 and P1), 16 exons, and at least 6 enhancers. The 16 confirmed exons are numbered 0 through 13 with the additions of exon α located between exons 4 and 5, and the alternatively spliced exon 5a. Each promoter is associated with its own proximal exon (exon 0 for P0, exon 1 for P1) resulting in transcripts which are alternatively spliced in the 5’ un-translated region.

The vertebrate PAX6 locus encodes at least three different protein isoforms, these being the canonical PAX6, PAX6(5a), and PAX6(ΔPD). The canonical PAX6 protein contains an N-terminal paired domain, connected by a linker region to a paired-type homeodomain, and a prolein/serine/threonine (P/S/T)-rich C-terminal domain. The paired domain and paired-type homeodomain each have DNA binding activities, while the P/S/T-rich domain possesses a transactivation function. PAX6(5a) is a product of the alternatively spliced exon 5a resulting in a 14 residue insertion in the paired domain which alters the specificity of this DNA binding activity. The nucleotide sequence corresponding to the linker region encodes a set of three alternative translation start codons from which the third PAX6 isoform originates. Collectively known as the PAX6(ΔPD) or pairedless isoforms, these three gene products all lack a paired domain. The pairedless proteins possess molecular weights of 43, 33, or 32kDa, depending on the particular start codon used. PAX6 transactivation function is attributed to the variable length C-terminal P/S/T-rich domain which stretches to 153 residues in human and mouse proteins.

Of the four Drosophila Pax6 orthologues, it is thought that the eyeless (ey) and twin of eyeless (toy) gene products share functional homology with the vertebrate canonical Pax6 isoform, while the eyegone (eyg) and twin of eyegone (toe) gene products share functional homology with the vertebrate Pax6(5a) isoform. Eyeless and eyegone were named for their respective mutant phenotypes.

Further reading

  • Callaerts P, Halder G, Gehring WJ (1997). "PAX-6 in development and evolution.". Annu. Rev. Neurosci. 20: 483-532. doi:10.1146/annurev.neuro.20.1.483. PMID 9056723.
  • Prosser J, van Heyningen V (1998). "PAX6 mutations reviewed.". Hum. Mutat. 11 (2): 93-108. doi:<93::AID-HUMU1>3.0.CO;2-M 10.1002/(SICI)1098-1004(1998)11:2<93::AID-HUMU1>3.0.CO;2-M. PMID 9482572.
  • Hever AM, Williamson KA, van Heyningen V (2007). "Developmental malformations of the eye: the role of PAX6, SOX2 and OTX2.". Clin. Genet. 69 (6): 459-70. doi:10.1111/j.1399-0004.2006.00619.x. PMID 16712695.
  • Jordan T, Hanson I, Zaletayev D, et al. (1993). "The human PAX6 gene is mutated in two patients with aniridia.". Nat. Genet. 1 (5): 328-32. doi:10.1038/ng0892-328. PMID 1302030.
  • Glaser T, Walton DS, Maas RL (1994). "Genomic structure, evolutionary conservation and aniridia mutations in the human PAX6 gene.". Nat. Genet. 2 (3): 232-9. doi:10.1038/ng1192-232. PMID 1345175.
  • Ton CC, Hirvonen H, Miwa H, et al. (1992). "Positional cloning and characterization of a paired box- and homeobox-containing gene from the aniridia region.". Cell 67 (6): 1059-74. PMID 1684738.
  • O'Donnell FE, Pappas HR (1982). "Autosomal dominant foveal hypoplasia and presenile cataracts. A new syndrome.". Arch. Ophthalmol. 100 (2): 279-81. PMID 7065945.
  • Martha A, Strong LC, Ferrell RE, Saunders GF (1995). "Three novel aniridia mutations in the human PAX6 gene.". Hum. Mutat. 6 (1): 44-9. doi:10.1002/humu.1380060109. PMID 7550230.
  • Hanson I, Brown A, van Heyningen V (1995). "A new PAX6 mutation in familial aniridia.". J. Med. Genet. 32 (6): 488-9. PMID 7666404.
  • Mirzayans F, Pearce WG, MacDonald IM, Walter MA (1995). "Mutation of the PAX6 gene in patients with autosomal dominant keratitis.". Am. J. Hum. Genet. 57 (3): 539-48. PMID 7668281.
  • van Heyningen V, Little PF (1995). "Report of the fourth international workshop on human chromosome 11 mapping 1994.". Cytogenet. Cell Genet. 69 (3-4): 127-58. PMID 7698003.
  • Auffray C, Behar G, Bois F, et al. (1995). "[IMAGE: molecular integration of the analysis of the human genome and its expression]". C. R. Acad. Sci. III, Sci. Vie 318 (2): 263-72. PMID 7757816.
  • Martha A, Ferrell RE, Mintz-Hittner H, et al. (1994). "Paired box mutations in familial and sporadic aniridia predicts truncated aniridia proteins.". Am. J. Hum. Genet. 54 (5): 801-11. PMID 7909985.
  • Glaser T, Jepeal L, Edwards JG, et al. (1994). "PAX6 gene dosage effect in a family with congenital cataracts, aniridia, anophthalmia and central nervous system defects.". Nat. Genet. 7 (4): 463-71. doi:10.1038/ng0894-463. PMID 7951315.
  • Epstein JA, Glaser T, Cai J, et al. (1994). "Two independent and interactive DNA-binding subdomains of the Pax6 paired domain are regulated by alternative splicing.". Genes Dev. 8 (17): 2022-34. PMID 7958875.
  • Davis A, Cowell JK (1994). "Mutations in the PAX6 gene in patients with hereditary aniridia.". Hum. Mol. Genet. 2 (12): 2093-7. PMID 8111379.
  • Hanson IM, Fletcher JM, Jordan T, et al. (1994). "Mutations at the PAX6 locus are found in heterogeneous anterior segment malformations including Peters' anomaly.". Nat. Genet. 6 (2): 168-73. doi:10.1038/ng0294-168. PMID 8162071.
  • Hanson IM, Seawright A, Hardman K, et al. (1993). "PAX6 mutations in aniridia.". Hum. Mol. Genet. 2 (7): 915-20. PMID 8364574.
  • Azuma N, Nishina S, Yanagisawa H, et al. (1996). "PAX6 missense mutation in isolated foveal hypoplasia.". Nat. Genet. 13 (2): 141-2. doi:10.1038/ng0696-141. PMID 8640214.
This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "PAX6". A list of authors is available in Wikipedia.
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