KCNJ18

potassium inwardly rectifying channel subfamily J member 18, the group of Potassium inwardly rectifying channel subfamily J

Basic information

Region (hg38): 17:21692523-21704612

Links

ENSG00000260458 ∙ NCBI:100134444 ∙ OMIM:613236 ∙ HGNC:39080 ∙ Uniprot:B7U540 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• thyrotoxic periodic paralysis, susceptibility to, 2 (Strong), mode of inheritance: AD
• thyrotoxic periodic paralysis, susceptibility to, 2 (Limited), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Thyrotoxic periodic paralysis, susceptibility to, 2	AD	Endocrine	Treatment of underlying hyperthyroidism is an effective treatment	Endocrine	16608889; 20074522; 21665951

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the KCNJ18 gene.

• Thyrotoxic_periodic_paralysis,_susceptibility_to,_2 (6 variants)
• not_provided (3 variants)
• KCNJ18-related_disorder (2 variants)
• not_specified (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the KCNJ18 gene is commonly pathogenic or not. These statistics are base on transcript: NM_001194958.2. 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	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	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

GnomAD

Source: gnomAD

dbNSFP

Source: dbNSFP

• 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

• gene_indispensability_pred: N
• gene_indispensability_score: 0.114

Gene ontology

• Biological process: regulation of ion transmembrane transport;potassium ion import across plasma membrane
• Cellular component: plasma membrane;integral component of membrane
• Molecular function: inward rectifier potassium channel activity