Hexokinase: gene structure and mutations

Abstract

Hexokinase (HK) deficiency is a rare red cell enzyme deficiency associated with hereditary non-spherocytic haemolytic anaemia; to date, only 17 affected families have been reported. Human HK has four major isozymes, each of which is encoded by a separate gene. Recent studies have shown that both ubiquitously expressed type I HK (HK-I) and erythroid-specific HK-R are expressed in erythrocytes, and that these isozymes are encoded by the single HK-I gene. The human HK-I gene has 19 exons, the HK-I and HK-R transcripts being produced by using two distinct promoters. Thus, the first and second exons are specifically utilized for the erythroid-specific HK-R and ubiquitously expressed HK-I isozymes respectively. So far, only two HK variants have been analysed at the molecular level. Since the human HK-I crystal structure has recently been elucidated, the molecular analysis of the HK variants will be useful for discussing the structure-function relationship of the enzyme.