KCNK18

Chr 10AD

potassium two pore domain channel subfamily K member 18

K(+) channel that conducts outward and inward rectifying currents at depolarized and hyperpolarized membrane potentials, respectively. The outward rectifying currents are voltage-dependent, coupled to K(+) electrochemical gradient across the membrane, whereas the inward currents can be induced in response to activation of Ca(2+)-mobilizing receptors (PubMed:12754259, PubMed:15562060, PubMed:20871611, PubMed:22355750, PubMed:26919430, PubMed:30573346). Homo- and heterodimerizes to form functional channels with distinct regulatory and gating properties. In trigeminal ganglia sensory neurons, the heterodimers of KCNK18/TRESK and KCNK2/TREK-1 or KCNK10/TREK-2 inhibit neuronal firing and neurogenic inflammation by stabilizing the resting membrane potential at K(+) equilibrium potential as well as by regulating the threshold of action potentials and the spike frequency (By similarity). In thymocytes, conducts K(+) currents upon T cell receptor (TCR) signaling leading to sustained Ca(2+) influx and NF-kappa-B activation, FOXP3 transcription and positive selection of regulatory T cell (Treg) progenitor subsets (PubMed:34702947). Appears to mediate the analgesics effects of hydroxy-alpha-sanshool, a metabolite naturally present in Schezuan pepper and other Xanthoxylum plants (By similarity)

OMIMResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

{Migraine, with or without aura, susceptibility to, 13}MIM #613656
AD
UniProtMigraine with or without aura 13
0
Active trials
Pubs (1 yr)
P/LP submissions
P/LP missense
1.10
LOEUF
Multiple*
Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint?
1.10LOEUF
pLI 0.001
Z-score 1.33
OE 0.56 (0.311.10)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?
-0.27Z-score
OE missense 1.05 (0.941.18)
209 obs / 198.4 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?
LoF OE?0.56 (0.311.10)
00.351.4
Missense OE?1.05 (0.941.18)
00.61.4
Synonymous OE?1.18
01.21.6
LoF obs/exp: 6 / 10.7Missense obs/exp: 209 / 198.4Syn Z: -1.28

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

KCNK18 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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