PNKD

For the movement disorder also known as PNKD, see Paroxysmal Nonkinesigenic Dyskinesia.

PNKD is the abbreviation for a human neurological movement disorder paroxysmal nonkinesiogenic dyskinesia. Like many other human genetics disorders, PNKD also refers to the disease, the disease gene and the encoded protein. (PNKD) is a protein that in humans is encoded by the PNKD gene. Alternative splicing results in the transcription of three isoforms. The mouse ortholog is called brain protein 17 (Brp17).

Function

The function of PNKD proteins are unknown but the long and medium isoforms of PNKD contain a conserved β-lactamase domain which suggest it may function as an enzyme. The closest mammalian homolog to PNKD is HAGH, an enzyme involves in a two-step reaction to hydrolyze SLG and produce D-lactic acid and reduced GSH. However, the hydrolytic activity of PNKD is minimal.

The long form of PNKD is neuronal specific and encodes a synaptic protein that localizes dominantly to the pre-synaptic membrane. Post-synaptic area and vesicular structure also occasionally has PNKD long form. PNKD long form interacts with pre-synaptic protein RIM and inhibits synaptic exocytosis. PNKD with disease mutations is less effective in inhibition thus the synaptic release is increased. This would cause excessive neurotransmitter release in the brain and maybe the root cause for triggering epilepsy in PNKD patients.

Clinical significance

Point mutations in PNKD exon 1 cause an inherited neurological movement disorder in human, paroxysmal non-kinesigenic dyskinesia.