RGD Reference Report - Missense mutation in the alternative splice region of the PAX6 gene in eye anomalies. - Rat Genome Database

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Missense mutation in the alternative splice region of the PAX6 gene in eye anomalies.

Authors: Azuma, N  Yamaguchi, Y  Handa, H  Hayakawa, M  Kanai, A  Yamada, M 
Citation: Azuma N, etal., Am J Hum Genet. 1999 Sep;65(3):656-63.
RGD ID: 1601210
Pubmed: PMID:10441571   (View Abstract at PubMed)
PMCID: PMC1377971   (View Article at PubMed Central)
DOI: DOI:10.1086/302529   (Journal Full-text)

The PAX6 gene is involved in ocular morphogenesis, and PAX6 mutations have been detected in various types of ocular anomalies, including aniridia, Peters anomaly, corneal dystrophy, congenital cataract, and foveal hypoplasia. The gene encodes a transcriptional regulator that recognizes target genes through its paired-type DNA-binding domain. The paired domain is composed of two distinct DNA-binding subdomains, the N-terminal subdomain (NTS) and the C-terminal subdomain (CTS), which bind respective consensus DNA sequences. The human PAX6 gene produces two alternative splice isoforms that have the distinct structure of the paired domain. The insertion, into the NTS, of 14 additional amino acids encoded by exon 5a abolishes the DNA-binding activity of the NTS and unmasks the DNA-binding ability of the CTS. Thus, exon 5a appears to function as a molecular switch that specifies target genes. We ascertained a novel missense mutation in four pedigrees with Peters anomaly, congenital cataract, Axenfeldt anomaly, and/or foveal hypoplasia, which, to our knowledge, is the first mutation identified in the splice-variant region. A T-->A transition at the 20th nucleotide position of exon 5a results in a Val-->Asp (GTC-->GAC) substitution at the 7th codon of the alternative splice region. Functional analyses demonstrated that the V54D mutation slightly increased NTS binding and decreased CTS transactivation activity to almost half.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Eye Abnormalities  IAGP 1601210 RGD 
Eye Abnormalities  ISOPAX6 (Homo sapiens)1601210; 1601210 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Pax6  (paired box 6)

Genes (Mus musculus)
Pax6  (paired box 6)

Genes (Homo sapiens)
PAX6  (paired box 6)


Additional Information