KCNJ8

potassium inwardly rectifying channel subfamily J member 8, the group of Potassium inwardly rectifying channel subfamily J

Basic information

Region (hg38): 12:21764955-21775600

Links

ENSG00000121361 ∙ NCBI:3764 ∙ OMIM:600935 ∙ HGNC:6269 ∙ Uniprot:Q15842 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Brugada syndrome (Limited), mode of inheritance: Unknown
• hypertrichotic osteochondrodysplasia Cantu type (Supportive), mode of inheritance: AD
• hypertrichotic osteochondrodysplasia Cantu type (Strong), mode of inheritance: AD
• Brugada syndrome 1 (Disputed Evidence), mode of inheritance: AD

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the KCNJ8 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the KCNJ8 gene is commonly pathogenic or not.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			2	69	4	75
missense		1	85	2	1	89
nonsense			1			1
start loss			1			1
frameshift			1			1
inframe indel			6			6
splice donor/acceptor (+/-2bp)						0
splice region				1		1
non coding				5	7	12
Total	0	1	96	76	12

Variants in KCNJ8

This is a list of pathogenic ClinVar variants found in the KCNJ8 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
12-21765468-A-T			Benign (Jul 11, 2018)
12-21765732-C-T		not specified • Brugada syndrome • Cardiovascular phenotype	Likely benign (Aug 18, 2022)
12-21765733-G-A		Cardiovascular phenotype • Hypertrophic cardiomyopathy • Brugada syndrome • KCNJ8-related disorder	Benign/Likely benign (Jan 22, 2024)
12-21765735-T-C		Cardiovascular phenotype	Likely benign (Aug 19, 2019)
12-21765741-T-C		Brugada syndrome	Likely benign (Sep 29, 2020)
12-21765756-A-T		Cardiovascular phenotype	Likely benign (Jun 22, 2021)
12-21765761-T-C		Brugada syndrome	Uncertain significance (May 02, 2022)
12-21765762-A-C		Brugada syndrome	Uncertain significance (Oct 04, 2023)
12-21765766-T-G		Brugada syndrome • Cardiovascular phenotype	Uncertain significance (Mar 13, 2024)
12-21765780-C-T		Brugada syndrome	Uncertain significance (Oct 08, 2018)
12-21765784-A-G		Cardiovascular phenotype	Uncertain significance (Sep 06, 2023)
12-21765786-G-A		Cardiovascular phenotype	Likely benign (Jul 03, 2023)
12-21765788-A-AAGAATTGTTCCTTCGGAT		Cardiovascular phenotype	Uncertain significance (Jul 26, 2016)
12-21765790-G-A		Cardiovascular phenotype	Uncertain significance (Jun 21, 2024)
12-21765793-T-C		Brugada syndrome	Uncertain significance (Jan 02, 2023)
12-21765795-G-A		Cardiovascular phenotype	Likely benign (May 11, 2023)
12-21765802-C-A		Brugada syndrome	Uncertain significance (Aug 12, 2022)
12-21765802-C-T		Brugada syndrome • Cardiovascular phenotype	Uncertain significance (Dec 08, 2023)
12-21765801-T-TCGGATAGAATTGTTCCTC		Brugada syndrome	Uncertain significance (Mar 09, 2022)
12-21765804-G-C		Hypertrophic cardiomyopathy	Likely benign (Feb 05, 2019)
12-21765806-T-C		Brugada syndrome	Uncertain significance (Nov 08, 2022)
12-21765816-C-G		Brugada syndrome • Cardiac arrhythmia • Cardiovascular phenotype	Uncertain significance (May 06, 2022)
12-21765822-C-T		Brugada syndrome	Uncertain significance (Aug 18, 2022)
12-21765824-T-C		Cardiovascular phenotype	Uncertain significance (May 27, 2022)
12-21765832-T-C		Brugada syndrome • Cardiovascular phenotype	Uncertain significance (Nov 27, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
KCNJ8	protein_coding	protein_coding	ENST00000240662	2	10627

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.380	0.618	125740	0	8	125748	0.0000318

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.45	92	244	0.377	0.0000138	2804
Missense in Polyphen		28	128.85	0.21731		1576
Synonymous	0.965	78	89.6	0.870	0.00000482	860
Loss of Function	2.64	3	13.5	0.223	0.00000111	129

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000528	0.0000527
Middle Eastern	0.00	0.00
South Asian	0.0000653	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: This potassium channel is controlled by G proteins. 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. Can be blocked by external barium (By similarity). {ECO:0000250|UniProtKB:Q63664, ECO:0000269|PubMed:28842488}.
• Disease: DISEASE: Sudden infant death syndrome (SIDS) [MIM:272120]: SIDS is the sudden death of an infant younger than 1 year that remains unexplained after a thorough case investigation, including performance of a complete autopsy, examination of the death scene, and review of clinical history. Pathophysiologic mechanisms for SIDS may include respiratory dysfunction, cardiac dysrhythmias, cardiorespiratory instability, and inborn errors of metabolism, but definitive pathogenic mechanisms precipitating an infant sudden death remain elusive. {ECO:0000269|PubMed:21836131}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.; DISEASE: Hypertrichotic osteochondrodysplasia (HTOCD) [MIM:239850]: A rare disorder characterized by congenital hypertrichosis, neonatal macrosomia, a distinct osteochondrodysplasia, and cardiomegaly. The hypertrichosis leads to thick scalp hair, which extends onto the forehead, and a general increase in body hair. In addition, macrocephaly and coarse facial features, including a broad nasal bridge, epicanthal folds, a wide mouth, and full lips, can be suggestive of a storage disorder. About half of affected individuals are macrosomic and edematous at birth, whereas in childhood they usually have a muscular appearance with little subcutaneous fat. Thickened calvarium, narrow thorax, wide ribs, flattened or ovoid vertebral bodies, coxa valga, osteopenia, enlarged medullary canals, and metaphyseal widening of long bones have been reported. Cardiac manifestations such as patent ductus arteriosus, ventricular hypertrophy, pulmonary hypertension, and pericardial effusions are present in approximately 80% of cases. Motor development is usually delayed due to hypotonia. Most patients have a mild speech delay, and a small percentage have learning difficulties or intellectual disability. {ECO:0000269|PubMed:24176758, ECO:0000269|PubMed:24700710, ECO:0000269|PubMed:28842488}. Note=The disease may be caused by mutations affecting distinct genetic loci, including the gene represented in this entry.
• Pathway: cGMP-PKG signaling pathway - Homo sapiens (human);Antiarrhythmic Pathway, Pharmacodynamics;Disopyramide Action Pathway;Procainamide (Antiarrhythmic) Action Pathway;Phenytoin (Antiarrhythmic) Action Pathway;Fosphenytoin (Antiarrhythmic) Action Pathway;Bopindolol Action Pathway;Timolol Action Pathway;Carteolol Action Pathway;Bevantolol Action Pathway;Practolol Action Pathway;Dobutamine Action Pathway;Isoprenaline Action Pathway;Arbutamine Action Pathway;Amiodarone Action Pathway;Levobunolol Action Pathway;Metipranolol Action Pathway;Mexiletine Action Pathway;Lidocaine (Antiarrhythmic) Action Pathway;Quinidine Action Pathway;Sotalol Action Pathway;Epinephrine Action Pathway;Betaxolol Action Pathway;Atenolol Action Pathway;Alprenolol Action Pathway;Acebutolol Action Pathway;Muscle/Heart Contraction;Diltiazem Action Pathway;Propranolol Action Pathway;Pindolol Action Pathway;Penbutolol Action Pathway;Oxprenolol Action Pathway;Metoprolol Action Pathway;Esmolol Action Pathway;Bisoprolol Action Pathway;Bupranolol Action Pathway;Nebivolol Action Pathway;Amlodipine Action Pathway;Verapamil Action Pathway;Nitrendipine Action Pathway;Nisoldipine Action Pathway;Nimodipine Action Pathway;Ibutilide Action Pathway;Tocainide Action Pathway;Flecainide Action Pathway;Isradipine Action Pathway;Nifedipine Action Pathway;Felodipine Action Pathway;Nadolol Action Pathway;Carvedilol Action Pathway;Labetalol Action Pathway;Sudden Infant Death Syndrome (SIDS) Susceptibility Pathways;Neuronal System;ATP sensitive Potassium channels;Inwardly rectifying K+ channels;Potassium Channels (Consensus)

Recessive Scores

• pRec: 0.210

Intolerance Scores

• loftool: 0.252
• rvis_EVS: 0.02
• rvis_percentile_EVS: 55.22

Haploinsufficiency Scores

• pHI: 0.606
• hipred: Y
• hipred_score: 0.818
• ghis: 0.496

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.698

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Kcnj8
• Phenotype: immune system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); homeostasis/metabolism phenotype; muscle phenotype

Gene ontology

• Biological process: kidney development;potassium ion transport;heart development;response to lipopolysaccharide;regulation of ion transmembrane transport;response to exogenous dsRNA;defense response to virus;membrane repolarization during ventricular cardiac muscle cell action potential;potassium ion import across plasma membrane
• Cellular component: mitochondrion;plasma membrane;voltage-gated potassium channel complex;inward rectifying potassium channel;myofibril;sarcolemma
• Molecular function: inward rectifier potassium channel activity;ATP binding;ATP-activated inward rectifier potassium channel activity;sulfonylurea receptor binding;voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization