Glycogen storage disease type 1b (GSD-1b) is caused by deficiencies in the
glucose-6-phosphate transporter (G6PT), which works together with glucose-6
-phosphatase to maintain glucose homeostasis. In humans, there are two alte
rnatively spliced transcripts, G6PT and variant G6PT (vG6PT), differing by
the inclusion of a 66-bp exon-7 sequence in vG6PT. We have previously shown
that the G6PT protein functions as a microsomal glucose-6-phosphate (G6P)
transporter, which is anchored to the endoplasmic reticulum by ten transmem
brane helices. Here, we demonstrate that vG6PT is also active in microsomal
G6P transport. The additional 22 amino acids in vG6PT is predicted to cons
titute a part of the luminal loop 4. Our data indicate that this loop plays
no vital role in microsomal: G6P transport. Further, we show that G6PT mRN
A is expressed in all organs and tissues examined, but that the vG6PT trans
cript is expressed exclusively in the brain, heart, and skeletal muscle. Th
ese results raise the possibility that mutations in exon-7 of the G6PT gene
, which would not perturb glucose homeostasis, might have other deleterious
effects.