Mesangial cells play an important role in maintaining a structure and function of the glomerulus and in the pathogenesis of glomerular diseases. To identify a specific gene expressed in human mesangial cells, we used a rapid large-scale DNA sequencing and computerized data processing to compare the transcripts in cultured human mesangial cells with various different cells and organs. Using this novel approach, we discovered a new mesangium-predominant gene termed "megsin." We obtained a full-length cDNA clone of megsin, which coded for a novel 380-amino acid protein. Amino acid homology search revealed that megsin belonged to the serpin (serine protease inhibitor) superfamily. The amino acid sequences in the reactive loop site of megsin showed characteristic features of functional serpins. Northern blot and reverse-transcribed PCR analyses of various tissues and cells demonstrated that megsin was predominantly expressed in human mesangial cells. In situ hybridization studies showed the megsin expression in the mesangium of normal glomeruli, while it increased in the expanded mesangium of glomeruli from patients with IgA nephropathy with the degree of mesangial proliferation. Here we report a new human mesangium-predominant gene that may function as an inhibitory serpin in normal and abnormal biological processes of glomerulus.