KCNJ18
protein-codingpotassium inwardly rectifying channel subfamily J member 18, the group of Potassium inwardly rectifying channel subfamily J
Gene 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 associated with thyrotoxic hypokalemic periodic paralysis. [provided by RefSeq, Jan 2013]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~12.1 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0013193
Submitter: PanelApp Australia
Inheritance Pattern: AD
Disease ID:MONDO:0013193
Submitter: Ambry Genetics
Inheritance Pattern: AD
Disease ID:MONDO:0013193
Submitter: Ambry Genetics
Clinical Genomic Database (CGD)
Manifestation: Endocrine
Intervention: Endocrine
Rationale: Treatment of underlying hyperthyroidism is an effective treatment
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to KCNJ18 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001194958.2. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 2 | 1 | 3 | |||
| missense | 7 | 1 | 8 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 8 | 3 | 1 | 12 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001181887.2 | 1 | MANE Select | |
| Ensembl | ENSP00000457807.2 | 1 | MANE Select | |
| RefSeq | XP_005276976.1 | 2 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- regulation of ion transmembrane transport
- potassium ion import across plasma membrane
Molecular Function
- inward rectifier potassium channel activity
Cellular Component
- plasma membrane
- integral component of membrane
dbNSFP Gene Annotations
Source:
- Function
- 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 potassium is raised, the voltage range of the channel opening shifts to more positive voltages. The inward rectification is mainly due to the blockage of outward current by internal magnesium. {ECO:0000269|PubMed:20074522, ECO:0000269|PubMed:27008341}.;
- Disease
- DISEASE: Thyrotoxic periodic paralysis 2 (TTPP2) [MIM:613239]: A sporadic muscular disorder characterized by episodic weakness and hypokalemia during a thyrotoxic state. It is clinically similar to hereditary hypokalemic periodic paralysis, except for the fact that hyperthyroidism is an absolute requirement for disease manifestation. The disease presents with recurrent episodes of acute muscular weakness of the four extremities that vary in severity from paresis to complete paralysis. Attacks are triggered by ingestion of a high carbohydrate load or strenuous physical activity followed by a period of rest. Thyrotoxic periodic paralysis can occur in association with any cause of hyperthyroidism, but is most commonly associated with Graves disease. {ECO:0000269|PubMed:20074522, ECO:0000269|PubMed:21665951, ECO:0000269|PubMed:25885757, ECO:0000269|PubMed:27178871}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.;
Essentials
- Indispensability pred.
- N
- Indispensability score
- 0.114