The specific cause of the GSD-1a stems from nonsense mutations, insertions/deletions with or without a shift in the reading frame, or splice site mutations that occur at the genetic level. The missense mutations affect the two large luminal loops and transmembrane helices of glucose 6-phosphatase-α, abolishing or greatly reducing activity of the enzyme. The specific cause of GSD-1b stems from "severe" mutations such as splice site mutations, frame-shifting mutations, and substitutions of a highly conserved residue that completely destroyed G6PT activity. These mutations lead to the prevalence of GSD-1 by preventing the transport of glucose-6-phosphate (G6P) into the luminal portion of the ER and also inhibiting the conversion of G6P into glucose to be used by the cell.