Soluble or nitric oxide (NO) stimulated guanglyl cyclases are obligate heme-containing heterodimers (alpha/ beta). We report the full-length cDNA of the human ortholog of the rat beta(2)-subunit from human kidney. A database search yielded matches of the 3' non-coding sequence with previously unassigned expressed sequence tags from kidney and stomach signet ring cell carcinoma. PCR comparison of cDNA from stomach signet ring cell carcinoma and normal stomach tissue demonstrated beta(2) subunit expression in cancer but not in normal tissue. On the cDNA level a frameshift deletion of one nucleotide was present in the novel human sequence which was confirmed on the genomic DNA level, In four closely related nonhuman primate species the frameshift deletion was absent while analysis of genomic DNA from different ethnic backgrounds revealed the uniform presence of the frameshift deletion in the human population.