We have identified a novel human gene on chromosome 10q24 located contiguously to the 3' end of the NFKB2/lyt-10 gene in a tail to tail arrangement. We describe here a cDNA of 4307 bp, isolated from an adult human brain cDNA library, which contains an open reading frame encoding a putative protein of 645 amino acids with a predicted molecular weight of 71 kDa. Database homology searches indicate that this is a novel gene coding for a putative protein containing two discrete domains with significant homology to the Sec7 and pleckstrin-homology (PH) domains, respectively. We named this gene PSD (plekstrin-Sec7 domains gene). Northern blot analysis of a panel of RNAs from normal human tissues using the PSD cDNA as probe revealed the presence of three different tissue-specific transcripts of approximately 4.3, 2.3, and 1.8 kb, the longest of which is expressed only in brain. Our data suggest that the PSD gene may code for a protein related to a recently identified protein family containing both the Sec7 and the PH domains thought to be involved in signaling transduction processes.