KCNJ3

potassium inwardly rectifying channel subfamily J member 3, the group of Potassium inwardly rectifying channel subfamily J

Basic information

Region (hg38): 2:154697854-154858354

Links

ENSG00000162989 ∙ NCBI:3760 ∙ OMIM:601534 ∙ HGNC:6264 ∙ Uniprot:P48549 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Leber congenital amaurosis 16	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Ophthalmologic	21763485; 25475713; 25921210

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the KCNJ3 gene.

• Inborn genetic diseases (2 variants)
• not provided (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the KCNJ3 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					1	1
missense			2			2
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	2	0	1

Variants in KCNJ3

This is a list of pathogenic ClinVar variants found in the KCNJ3 region.

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

Position	Type	Phenotype	Significance	ClinVar
2-154698959-A-G		not specified	Uncertain significance (Jan 23, 2024)
2-154699025-C-T		not specified	Uncertain significance (Jan 24, 2024)
2-154699097-A-G		not specified	Uncertain significance (Sep 22, 2023)
2-154709735-C-T		not specified	Uncertain significance (Sep 20, 2023)
2-154709738-T-A		not specified	Uncertain significance (Dec 20, 2023)
2-154854757-C-T		not specified	Uncertain significance (Oct 21, 2021)
2-154855268-C-A		not specified	Uncertain significance (Oct 27, 2023)
2-154855301-T-C			Benign (Mar 29, 2018)
2-154855309-C-A		not specified	Uncertain significance (Apr 22, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
KCNJ3	protein_coding	protein_coding	ENST00000295101	3	160053

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.991	0.00892	125709	0	2	125711	0.00000795

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	4.06	97	293	0.332	0.0000166	3301
Missense in Polyphen		29	145.45	0.19938		1563
Synonymous	1.10	100	115	0.869	0.00000715	991
Loss of Function	3.78	1	18.6	0.0539	0.00000110	190

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	0.0000672	0.0000462
European (Non-Finnish)	0.00000884	0.00000879
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
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. This receptor plays a crucial role in regulating the heartbeat.
• Pathway: Oxytocin signaling pathway - Homo sapiens (human);Retrograde endocannabinoid signaling - Homo sapiens (human);Serotonergic synapse - Homo sapiens (human);Dopaminergic synapse - Homo sapiens (human);Glutamatergic synapse - Homo sapiens (human);Circadian entrainment - Homo sapiens (human);Estrogen signaling pathway - Homo sapiens (human);Cholinergic synapse - Homo sapiens (human);Morphine addiction - 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;G Protein Signaling Pathways;Calcium Regulation in the Cardiac Cell;Neuronal System;Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits;Activation of GABAB receptors;GABA B receptor activation;GABA receptor activation;Neurotransmitter receptors and postsynaptic signal transmission;Transmission across Chemical Synapses;Activation of G protein gated Potassium channels;G protein gated Potassium channels;Inwardly rectifying K+ channels;Potassium Channels (Consensus)

Recessive Scores

• pRec: 0.186

Intolerance Scores

• rvis_EVS: 0.01
• rvis_percentile_EVS: 54.95

Haploinsufficiency Scores

• pHI: 0.244
• hipred: Y
• hipred_score: 0.800
• ghis: 0.418

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.455

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Kcnj3
• Phenotype: homeostasis/metabolism phenotype; skeleton phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); 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); reproductive system phenotype

Gene ontology

• Biological process: potassium ion transport;regulation of ion transmembrane transport;response to electrical stimulus;regulation of heart rate by cardiac conduction;membrane repolarization during atrial cardiac muscle cell action potential;membrane repolarization during ventricular cardiac muscle cell action potential;ventricular cardiac muscle cell membrane repolarization;potassium ion import across plasma membrane
• Cellular component: plasma membrane;voltage-gated potassium channel complex;external side of plasma membrane;T-tubule;parallel fiber to Purkinje cell synapse;integral component of presynaptic membrane
• Molecular function: inward rectifier potassium channel activity;protein binding;G-protein activated inward rectifier potassium channel activity;voltage-gated potassium channel activity involved in atrial cardiac muscle cell action potential repolarization;voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization