KCNK18 (potassium two pore domain channel subfamily K member 18)

Gene

• Entrez ID: 338567
• Gene name: Potassium two pore domain channel subfamily K member 18
• Gene symbol: KCNK18
• Synonyms (NCBI Gene): K2p18.1, MGR13, TRESK, TRESK-2, TRESK2, TRIK
• Chromosome: 10
• Chromosome location: 10q25.3
• Summary: Potassium channels play a role in many cellular processes including maintenance of the action potential, muscle contraction, hormone secretion, osmotic regulation, and ion flow. This gene encodes a member of the superfamily of potassium channel proteins c

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs541915908	->T	Benign, likely-pathogenic	Frameshift variant, coding sequence variant
rs869025175	CT>-	Risk-factor, likely-pathogenic	Coding sequence variant, frameshift variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT023160	hsa-miR-124-3p	Microarray	18668037

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0005267	Function	Potassium channel activity	IEA
GO:0005886	Component	Plasma membrane	IBA
GO:0005886	Component	Plasma membrane	IC	12754259
GO:0005886	Component	Plasma membrane	IDA	20006580
GO:0005886	Component	Plasma membrane	IEA
GO:0005886	Component	Plasma membrane	TAS
GO:0006811	Process	Monoatomic ion transport	IEA
GO:0006813	Process	Potassium ion transport	IDA	20006580
GO:0006813	Process	Potassium ion transport	IEA
GO:0006813	Process	Potassium ion transport	IEA
GO:0015269	Function	Calcium-activated potassium channel activity	IEA
GO:0015271	Function	Outward rectifier potassium channel activity	IBA
GO:0015271	Function	Outward rectifier potassium channel activity	IDA	12754259, 26919430
GO:0016020	Component	Membrane	IEA
GO:0022841	Function	Potassium ion leak channel activity	IBA
GO:0032829	Process	Regulation of CD4-positive, CD25-positive, alpha-beta regulatory T cell differentiation	IEA
GO:0032829	Process	Regulation of CD4-positive, CD25-positive, alpha-beta regulatory T cell differentiation	ISS
GO:0034220	Process	Monoatomic ion transmembrane transport	IEA
GO:0046872	Function	Metal ion binding	IEA
GO:0071467	Process	Cellular response to pH	IDA	12754259
GO:0071805	Process	Potassium ion transmembrane transport	IBA
GO:0071805	Process	Potassium ion transmembrane transport	IEA
GO:0097623	Process	Potassium ion export across plasma membrane	IDA	12754259

Other IDs

• MIM: 613655
• HGNC: 19439
• e!Ensembl: ENSG00000186795

Protein

• UniProt ID: Q7Z418
• Protein name: Potassium channel subfamily K member 18 (TWIK-related individual potassium channel) (TWIK-related spinal cord potassium channel)
• Protein function: 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 mem
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF07885	Ion_trans_2	88 → 157	Ion channel	Family
  PF07885	Ion_trans_2	286 → 364	Ion channel	Family

• Tissue specificity: TISSUE SPECIFICITY: Expressed in dorsal root ganglion and trigeminal ganglion neurons. Detected at low levels in spinal cord. Expressed in regulatory T cells (at protein level). {ECO:0000269|PubMed:12754259, ECO:0000269|PubMed:15562060, ECO:0000269|PubMed
• Sequence:

  MEVSGHPQARRCCPEALGKLFPGLCFLCFLVTYALVGAVVFSAIEDGQVLVAADDGEFEK
  FLEELCRILNCSETVVEDRKQDLQGHLQKVKPQWFNRTTHWSFLSSLFFCCTVFSTVGYG
  YIYPVTRLGKYLCMLYALFGIPLMFLVLTDTGDILATILSTSYNRFRKFPFFTRPLLSKW
  CPKSLFKKKPDPKPADEAVPQIIISAEELPGPKLGTCPSRPSCSMELFERSHALEKQNTL
  QLPPQAMERSNSCPELVLGRLSYSIISNLDEVGQQVERLDIPLPIIALIVFAYISCAAAI
  LPFWETQLDFENAFYFCFVTLTTIGFGDTVLEHPNFFLFFSIYIIVGMEIVFIAFKLVQN
  RLIDIYKNVMLFFAKGKFYHLVKK

• Sequence length: 384

Pathways

Reactome:

TWIK-related spinal cord K+ channel (TRESK)
Phase 4 - resting membrane potential

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
KCNK18-related neurodevelopmental disorder	Pathogenic	rs146194900	RCV002509910	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Migraine, with or without aura, susceptibility to, 13	Pathogenic	rs2493501187	RCV002465408	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
KCNK18-related disorder	Benign; Likely benign; Uncertain significance; Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MIGRAINE DISORDERS	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MIGRAINE WITH AURA, SUSCEPTIBILITY TO, 13	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Parkinson disease	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Parkinsonian disorder	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Vascular parkinsonism	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Relationship Type	References	Evidence Score
Autism Spectrum Disorder	Associate	37195340	★☆☆☆☆ Found in Text Mining only
Developmental Disabilities	Associate	37195340	★☆☆☆☆ Found in Text Mining only
Diabetic Neuropathies	Associate	36430572	★☆☆☆☆ Found in Text Mining only
Epilepsy	Associate	37195340	★☆☆☆☆ Found in Text Mining only
Intellectual Disability	Associate	37195340	★☆☆☆☆ Found in Text Mining only
Migraine Disorders	Associate	26747084, 30653930	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Migraine Familial Basilar	Associate	28699403	★☆☆☆☆ Found in Text Mining only
Migraine with Aura	Associate	26747084, 36044383	★☆☆☆☆ Found in Text Mining only
Migraine without Aura	Associate	37195340	★☆☆☆☆ Found in Text Mining only
Neoplasms	Associate	24116006	★☆☆☆☆ Found in Text Mining only
Nerve Degeneration	Associate	30653930	★☆☆☆☆ Found in Text Mining only
Pain	Associate	26914156, 35806193	★☆☆☆☆ Found in Text Mining only
Peripheral Nervous System Diseases	Associate	35806193	★☆☆☆☆ Found in Text Mining only
Seizures	Associate	37195340	★☆☆☆☆ Found in Text Mining only
Seizures Febrile	Associate	37195340	★☆☆☆☆ Found in Text Mining only
Small Fiber Neuropathy	Associate	36430572	★☆☆☆☆ Found in Text Mining only