KCNK18

potassium two pore domain channel subfamily K member 18, the group of Potassium two pore domain channel subfamily K

Basic information

Region (hg38): 10:117197489-117210299

Links

ENSG00000186795

∙ NCBI:338567 ∙ OMIM:613655 ∙ HGNC:19439 ∙ Uniprot:Q7Z418 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

migraine, with or without aura, susceptibility to, 13 (Limited), mode of inheritance: AD
migraine, with or without aura, susceptibility to, 13 (Limited), mode of inheritance: Unknown
migraine, with or without aura, susceptibility to, 13 (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Migraine, with or without aura, susceptibility to, 13	AD	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Neurologic	20871611

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the KCNK18 gene.

not_specified (49 variants)
not_provided (37 variants)
KCNK18-related_disorder (9 variants)
Migraine,_with_or_without_aura,_susceptibility_to,_13 (5 variants)
KCNK18-related_neurodevelopmental_disorder (1 variants)
Parkinson_disease (1 variants)
Parkinsonian_disorder (1 variants)
Vascular_parkinsonism (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the KCNK18 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000181840.1. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous				13 clinvar	3 clinvar	16
missense	1 clinvar	1 clinvar	51 clinvar	6 clinvar	5 clinvar	64
nonsense	1 clinvar					1
start loss						0
frameshift			4 clinvar			4
splice donor/acceptor (+/-2bp)						0
Total	2	1	55	19	8

Highest pathogenic variant AF is 0.000119564

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
KCNK18	protein_coding	protein_coding	ENST00000334549	3	12811

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00136	0.875	124965	12	771	125748	0.00312

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.268	209	198	1.05	0.0000110	2523
Missense in Polyphen		54	52.731	1.0241		724
Synonymous	-1.28	101	85.9	1.18	0.00000539	759
Loss of Function	1.33	6	10.7	0.560	4.71e-7	138

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00115	0.00115
Ashkenazi Jewish	0.00	0.00
East Asian	0.00261	0.00261
Finnish	0.000277	0.000277
European (Non-Finnish)	0.00104	0.00100
Middle Eastern	0.00261	0.00261
South Asian	0.0191	0.0189
Other	0.00114	0.00114

dbNSFP

Source: dbNSFP

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.;
Pathway: Neuronal System;Phase 4 - resting membrane potential;Cardiac conduction;Muscle contraction;TWIK-related spinal cord K+ channel (TRESK);Tandem pore domain potassium channels;Potassium Channels (Consensus)

Recessive Scores

pRec: 0.108

Intolerance Scores

loftool: 0.617
rvis_EVS: 0.35
rvis_percentile_EVS: 74.58

Haploinsufficiency Scores

pHI: 0.209
hipred: N
hipred_score: 0.146
ghis

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: N
gene_indispensability_score: 0.114

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

Gene name: Kcnk18
Phenotype: reproductive system phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan);

Gene ontology

Biological process: potassium ion transport;stabilization of membrane potential;cellular response to pH;potassium ion transmembrane transport;potassium ion export across plasma membrane
Cellular component: plasma membrane;integral component of plasma membrane
Molecular function: potassium channel activity;calcium-activated potassium channel activity;outward rectifier potassium channel activity;potassium ion leak channel activity