The CHKB gene encodes for a key protein in phospholipid biosynthesis. The choline kinase and ethanolamine kinase proteins, which are coded by the CHKB gene, catalyze the phosphorylation of choline/ethanolamine in vitro to phosphocholine/phosphoethanolamine. The catalysis is controlled by ATP in the presence of magnesium and ADP, and commits choline to the enzymatic pathway for biosynthesis of phosphatidylcholine. This is the first step in the biosynthesis of phosphocholine/phosphoethanolamine in all animal cells, and is done by the Kennedy pathway. The highly purified choline kinases from mammalian sources and their recombinant gene products have been shown to have ethanolamine kinase activity as well, indicating that both activities reside on the same protein. However, it has been shown that the protein has higher activity with ethanolamine and may not significantly contribute to in vivo phosphatidylcholine biosynthesis. The choline kinase-like protein encoded by CHKB belongs to the choline/ethanolamine kinase family; however, its exact function is not known. At least two transcript variants encoding two different isoforms have been found for this gene, and one of the transcripts is bicistronic.
Clinical significance
Mutations in CHKB have been found to result in mitochondrial deficiencies and associated disorders. Knockdown of the gene has been known to result in decreased choline kinase and phosphatidylcholine activity. This impairment in activity may lead to a modified composition of the phospholipid composition in the mitochondrial membrane resulting in major disorders in the function and structure of the mitochondria. Major disorders include as Megaconial Congenital Muscular Dystrophy, and Narcolepsy.
CHKB mutations have been majorly associated with Megaconial Congenital Muscular Dystrophy. Megaconial Congenital Muscular Dystrophy is an autosomal recessivecongenital muscular dystrophy characterized by muscle biopsy results displaying an enlarged mitochondria which are common in the periphery of the fibers but scarce around the center. Common clinical manifestations of MDCMC include:
Symptoms such as neurogenicatrophy, enlarged mitochondria in the periphery of the fibers, and complex I deficiency were shown in a Spanish patient with a homozygousmutation of c.810T>A. Another patient with a homozygous mutation in the CHKB gene exhibited rhythmic jerkings of arms, which were characterized as muscle spasms. Finally, a patient with a homozygous c.810T>A showed signs of Gower's sign, hypotonia, and proximal muscle weakness.
Narcolepsy
is a neurological disabling sleep disorder, characterized by excessive daytime sleepiness, sleep fragmentation, symptoms of abnormal rapid-eye-movement sleep, cataplexy, hypnagogic hallucinations, and sleep paralysis. Cataplexy is a sudden loss of muscle tone triggered by emotions, which is the most valuable clinical feature used to diagnose narcolepsy. Human narcolepsy is primarily a sporadically occurring disorder but familial clustering has been observed.
