Vesicular transport to and from the lysosome and late endosome is defective in 
patients with Chediak-Higashi syndrome (CHS) and in mutant beige (bg) mice. CHS 
and bg cells have giant, perinuclear vesicles with characteristics of late 
endosomes and lysosomes that arise from dysregulated homotypic fusion. CHS and 
bg lysosomes also exhibit compartmental missorting of proteins, such as 
elastase, glucuronidase and cathepsin G. Lyst, a candidate gene for bg, was 
identified by direct complementary DNA selection from a yeast artificial 
chromosome (YAC) clone containing a 650-kilobase segment of the bg-critical 
region on mouse chromosome 13. Lyst is disrupted by a 5-kilobase deletion in bg 
mice, and Lyst messenger RNA is markedly reduced in bg homozygotes. The 
homologous human gene, LYST, is highly conserved with mouse Lyst, and contains a 
frame-shift mutation at nucleotides 117-118 of the coding domain in a CHS 
patient. Thus bg mice and human CHS patients have homologous disorders 
associated with Lyst mutations. Lyst encodes a protein with a carboxy-terminal 
prenylation motif and multiple potential phosphorylation sites. Lyst protein is 
predicted to form extended helical domains, and has a region of sequence similar 
to stathmin, a coiled-coil phosphoprotein thought to act as a relay integrating 
cellular signal response coupling.