A transition mutation (G to A) in the splice donor site of intron 10 resulted in an aberrant transcript lacking exon 10. Furthermore, codons 436 through 455 in the Mad homology 2 domain, were shifted out of frame. Analysis of protein levels showed reductions greater than 50% in heterozygous ES cells as well as in primary embryonic fibroblasts, indicating a dominant negative property. No truncated protein was detected in primary embryonic fibroblasts.