Disease relevance of CTNNA3

• Using phage display, we identified Na(+)/H(+) exchanger regulatory factor (NHERF)-2 as a novel binding partner for the cadherin-associated protein, beta-catenin [1].

Psychiatry related information on CTNNA3

• Genetic variation in CTNNA3 encoding alpha-3 catenin and Alzheimer's disease [2].

High impact information on CTNNA3

• Here we report the molecular cloning of the cadherin-associated tyrosine phosphatase and identify it as PTP1B [3].
• This makes VR22 an attractive candidate gene because beta catenin interacts with presenilin 1, which has many mutations that elevate Abeta42 and cause early onset familial AD [4].
• Fine mapping of the alpha-T catenin gene to a quantitative trait locus on chromosome 10 in late-onset Alzheimer's disease pedigrees [4].
• Bounding of the association region using multiple SNPs showed VR22 to be the only confirmed gene within the region of association [4].
• This association clearly contributed to the linkage at approximately 80 cM because the lod scores decreased when linkage analysis was performed conditional upon the VR22 association [4].

Biological context of CTNNA3

• The CTNNA3 gene was mapped to chromosome band 10q21 by both fluorescence in situ hybridization and polymerase-chain-reaction-based hybrid mapping [5].
• Mutation screening of all 18 exons of the CTNNA3 gene in this family has, however, not detected any DCM-linked CTNNA3 mutations [5].
• Similarly, we found no evidence for association between CTNNA3 and AD in a sample of subjects showing linkage to chromosome 10, nor were these SNPs associated with Abeta deposition in brain [6].
• As shown here we demonstrate that the CTNNA3 gene is subject to imprinting with preferential expression of the maternal allele in first trimester placental tissues [7].
• Differential downregulation of alphaT-catenin expression in placenta: trophoblast cell type-dependent imprinting of the CTNNA3 gene [7].

Anatomical context of CTNNA3

• Interestingly, these two clusters, near CTNNA3 and KCNMA1 and each containing five genes with down-regulated expression in androgenetic placentas, coincided with the regions with maximal maternal allele sharing seen in the pre-eclamptic sisters [8].
• Alpha T-catenin is a novel member of the alpha-catenin family, which shows most abundant expression in cardiomyocytes and in peritubular myoid cells of the testis, pointing to a specific function for alpha T-catenin in particular muscle tissues [5].
• Like other alpha-catenins, alpha T-catenin provides an indispensable link between the cadherin-based cell-cell adhesion complex and the cytoskeleton, to mediate cell-cell adhesion [5].
• OBJECTIVES: To determine the value of loss of the expression of E-cadherin and cadherin-associated molecules as useful markers for both prognosis and bladder recurrence in patients with upper urinary tract cancer [9].

Regulatory relationships of CTNNA3

• GATA-4 and MEF2C transcription factors control the tissue-specific expression of the alphaT-catenin gene CTNNA3 [10].

Other interactions of CTNNA3

• Assessment of the CTNNA3 gene encoding human alpha T-catenin regarding its involvement in dilated cardiomyopathy [5].
• The trophoblast cell type-dependent imprinting of CTNNA3 is identical to p57KIP2 imprinting with respect to trophoblast cell type (villus) and parental origin of the expressed allele (maternal) [7].
• Insulin degrading enzyme and alpha-3 catenin polymorphisms in Italian patients with Alzheimer disease [11].

Analytical, diagnostic and therapeutic context of CTNNA3

• As this suggests that the CTNNA3 gene is subject to imprinting, we performed allele-specific RT-PCR on early placenta tissues using informative heterozygous samples [7].

References