KCNK18

Highest pathogenic variant AF is 0.000119564465

Gene type

protein_coding

Transcript type

protein_coding

Transcript

ENST00000334549

Coding exons

3

Length

12811

Individuals with no LoFs

124965

Homozygous LoFs

12

Heterozygous LoFs

771

Defined

125748

p

0.00312

Function

FUNCTION: Outward rectifying potassium channel. Produces rapidly activating outward rectifier K(+) currents. May function as background potassium channel that sets the resting membrane potential. Channel activity is directly activated by calcium signal. Activated by the G(q)-protein coupled receptor pathway. The calcium signal robustly activates the channel via calcineurin, whereas the anchoring of 14-3-3/YWHAH interferes with the return of the current to the resting state after activation. Inhibited also by arachidonic acid and other naturally occurring unsaturated free fatty acids. Channel activity is also enhanced by volatile anesthetics, such as isoflurane. Appears to be the primary target of hydroxy-alpha-sanshool, an ingredient of Schezuan pepper. May be involved in the somatosensory function with special respect to pain sensation (By similarity). {ECO:0000250, ECO:0000269|PubMed:12754259, ECO:0000269|PubMed:15562060}.;

Disease

DISEASE: Migraine with or without aura 13 (MGR13) [MIM:613656]: A form of migraine transmitted in an autosomal dominant pattern. Migraine is a disabling symptom complex of periodic headaches, usually temporal and unilateral. Headaches are often accompanied by irritability, nausea, vomiting and photophobia, preceded by constriction of the cranial arteries. The two major subtypes are common migraine (migraine without aura) and classic migraine (migraine with aura). Classic migraine is characterized by recurrent attacks of reversible neurological symptoms (aura) that precede or accompany the headache. Aura may include a combination of sensory disturbances, such as blurred vision, hallucinations, vertigo, numbness and difficulty in concentrating and speaking. {ECO:0000269|PubMed:20871611}. Note=The disease is caused by mutations affecting the gene represented in this entry. Susceptibility to migraine has been shown to be conferred by a frameshift mutation that segregates with the disorder in a large multigenerational family. Migraine was associated with sensitivity to lights, sounds, and smells, as well as nausea and occasional vomiting. Triggers included fatigue, alcohol and bright lights. Mutations in KCNK18 are a rare cause of migraine.;