KCNJ18 (potassium inwardly rectifying channel subfamily J member 18)

Gene

• Entrez ID: 100134444
• Gene name: Potassium inwardly rectifying channel subfamily J member 18
• Gene symbol: KCNJ18
• Synonyms (NCBI Gene): KIR2.6, TTPP2
• Chromosome: 17
• Chromosome location: 17p11.2
• Summary: This gene encodes a member of the inwardly rectifying potassium channel family. Transcription of this locus is regulated by thyroid hormone, and the encoded protein plays a role in resting membrane potential maintenance. Mutations in this locus have been

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs527236151	C>T	Pathogenic	Coding sequence variant, missense variant
rs527236152	C>T	Pathogenic	Coding sequence variant, missense variant
rs527236153	C>-	Risk-factor, pathogenic	Frameshift variant, coding sequence variant
rs527236154	G>A	Pathogenic	Coding sequence variant, missense variant
rs527236155	G>A,C	Pathogenic	Coding sequence variant, missense variant
rs527236156	C>T	Pathogenic	Stop gained, coding sequence variant
rs527236157	C>T	Pathogenic	Stop gained, coding sequence variant
rs527236158	C>T	Risk-factor, pathogenic	Coding sequence variant, missense variant
rs527236159	A>G	Risk-factor, pathogenic	Coding sequence variant, missense variant
rs672601244	G>A	Risk-factor	Coding sequence variant, missense variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT1081481	hsa-miR-1229	CLIP-seq
MIRT1081482	hsa-miR-129-5p	CLIP-seq
MIRT1081483	hsa-miR-132	CLIP-seq
MIRT1081484	hsa-miR-212	CLIP-seq
MIRT1081485	hsa-miR-30a	CLIP-seq
MIRT1081486	hsa-miR-30b	CLIP-seq
MIRT1081487	hsa-miR-30c	CLIP-seq
MIRT1081488	hsa-miR-30d	CLIP-seq
MIRT1081489	hsa-miR-30e	CLIP-seq
MIRT2020184	hsa-miR-1204	CLIP-seq
MIRT2020185	hsa-miR-361-3p	CLIP-seq
MIRT2020186	hsa-miR-4459	CLIP-seq
MIRT2020187	hsa-miR-4655-3p	CLIP-seq
MIRT2020188	hsa-miR-665	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0005242	Function	Inward rectifier potassium channel activity	IBA
GO:0005242	Function	Inward rectifier potassium channel activity	IDA	20074522
GO:0005242	Function	Inward rectifier potassium channel activity	IEA
GO:0005242	Function	Inward rectifier potassium channel activity	IMP	21665951
GO:0005515	Function	Protein binding	IPI	32296183, 32541000
GO:0005783	Component	Endoplasmic reticulum	IDA	21209095
GO:0005783	Component	Endoplasmic reticulum	IEA
GO:0005886	Component	Plasma membrane	IBA
GO:0005886	Component	Plasma membrane	IDA	20074522, 21665951
GO:0005886	Component	Plasma membrane	IEA
GO:0006811	Process	Monoatomic ion transport	IEA
GO:0006813	Process	Potassium ion transport	IEA
GO:0016020	Component	Membrane	IEA
GO:0034220	Process	Monoatomic ion transmembrane transport	IEA
GO:0034702	Component	Monoatomic ion channel complex	IEA
GO:0034765	Process	Regulation of monoatomic ion transmembrane transport	IBA
GO:1990573	Process	Potassium ion import across plasma membrane	IBA

Other IDs

• MIM: 613236
• HGNC: 39080
• e!Ensembl: ENSG00000260458

Protein

• UniProt ID: B7U540
• Protein name: Inward rectifier potassium channel 18 (Inward rectifier K(+) channel Kir2.6) (Potassium channel, inwardly rectifying subfamily J member 18)
• Protein function: Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow into the cell rather than out of it. Their voltage dependence is regulated by the concentration of extracellular potassium; as external potass
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF08466	IRK_N	2 → 46	Inward rectifier potassium channel N-terminal	Family
  PF01007	IRK	47 → 187	Inward rectifier potassium channel transmembrane domain	Domain
  PF17655	IRK_C	194 → 367	Inward rectifier potassium channel C-terminal domain	Domain

• Tissue specificity: TISSUE SPECIFICITY: Specifically expressed in skeletal muscle. {ECO:0000269|PubMed:20074522}.
• Sequence:

  MTAASRANPYSIVSLEEDGLHLVTMSGANGFGNGKVHTRRRCRNRFVKKNGQCNIAFANM
  DEKSQRYLADMFTTCVDIRWRYMLLIFSLAFLASWLLFGVIFWVIAVAHGDLEPAEGHGR
  TPCVMQVHGFMAAFLFSIETQTTIGYGLRCVTEECLVAVFMVVAQSIVGCIIDSFMIGAI
  MAKMARPKKRAQTLLFSHNAVVALRDGKLCLMWRVGNLRKSHIVEAHVRAQLIKPRVTEE
  GEYIPLDQIDIDVGFDKGLDRIFLVSPITILHEIDEASPLFGISRQDLETDDFEIVVILE
  GMVEATAMTTQARSSYLANEILWGHRFEPVLFEEKNQYKIDYSHFHKTYEVPSTPRCSAK
  DLVENKFLLPSANSFCYENELAFLSRDEEDEADGDQDGRSRDGLSPQARHDFDRLQAGGG
  VLEQRPYRRGSEI

• Sequence length: 433

Pathways

KEGG:

Cholinergic synapse
Oxytocin signaling pathway

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)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
ASTHMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CHRONIC OBSTRUCTIVE PULMONARY DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
KCNJ18-related disorder	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
THYROTOXIC PERIODIC PARALYSIS	—	Disgenet, Orphanet Disgenet, Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Thyrotoxic periodic paralysis, susceptibility to, 2	risk factor; Uncertain significance	ClinVar CTD, ClinVar, GenCC CTD, ClinVar, GenCC	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Anemia Aplastic	Aplastic anemia	Pubtator	35435273	Stimulate	★☆☆☆☆ Found in Text Mining only
Carcinoma Squamous Cell	Squamous cell carcinoma	Pubtator	37694353	Associate	★☆☆☆☆ Found in Text Mining only
Familial Periodic Paralysis	Periodic Paralysis	BEFREE	25882930		★☆☆☆☆ Found in Text Mining only
Familial Periodic Paralysis	Periodic Paralysis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Graves Disease	Graves Disease	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hyperthyroidism	Hyperthyroidism	BEFREE	27178871		★☆☆☆☆ Found in Text Mining only
Hyperthyroidism	Hyperthyroidism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hypokalemic periodic paralysis	Hypokalemic Periodic Paralysis	BEFREE	25882930, 27178871		★☆☆☆☆ Found in Text Mining only
Hypokalemic periodic paralysis type 1	Hypokalemic Periodic Paralysis	GENOMICS_ENGLAND_DG	20074522		★☆☆☆☆ Found in Text Mining only
Hypokalemic periodic paralysis type 1	Hypokalemic Periodic Paralysis	BEFREE	27178871		★☆☆☆☆ Found in Text Mining only
Obesity	Obesity	HPO_DG			★☆☆☆☆ Found in Text Mining only
Pancreatic Neoplasms	Pancreatic neoplasm	Pubtator	33144687	Associate	★☆☆☆☆ Found in Text Mining only
Paralysis	Paralysis	Pubtator	20074522	Associate	★☆☆☆☆ Found in Text Mining only
Periodic hypokalemic paresis	Periodic hypokalemic paresis	HPO_DG			★☆☆☆☆ Found in Text Mining only
periodic paralysis (finding)	Periodic Paralysis	BEFREE	25882930		★☆☆☆☆ Found in Text Mining only
periodic paralysis (finding)	Periodic Paralysis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Quadriplegia	Quadriplegia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Second degree atrioventricular block	Atrioventricular block	HPO_DG			★☆☆☆☆ Found in Text Mining only
Thyrotoxic periodic paralysis	Thyrotoxic Periodic Paralysis	ORPHANET_DG	20074522		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Thyrotoxic periodic paralysis	Thyrotoxic Periodic Paralysis	Orphanet			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Thyrotoxic periodic paralysis	Thyrotoxic Periodic Paralysis	BEFREE	21665951, 25885757, 27008341, 28131627, 31361309		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Thyrotoxic periodic paralysis	Thyrotoxic Periodic Paralysis	CLINVAR_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Thyrotoxicosis with toxic single thyroid nodule	Thyrotoxicosis with toxic single thyroid nodule	HPO_DG			★☆☆☆☆ Found in Text Mining only
Toxic multinodular goiter	Toxic Goiter	HPO_DG			★☆☆☆☆ Found in Text Mining only
Ventricular Fibrillation	Ventricular Fibrillation	HPO_DG			★☆☆☆☆ Found in Text Mining only