KCNA5

potassium voltage-gated channel subfamily A member 5, the group of Potassium voltage-gated channels

Basic information

Region (hg38): 12:5043878-5046788

Links

ENSG00000130037 ∙ NCBI:3741 ∙ OMIM:176267 ∙ HGNC:6224 ∙ Uniprot:P22460 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• atrial fibrillation, familial, 7 (Strong), mode of inheritance: AD
• familial atrial fibrillation (Supportive), mode of inheritance: AD
• atrial fibrillation, familial, 7 (Limited), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Atrial fibrillation, familial, 7	AD	Cardiovascular	Surveillance for and medical intervention to prevent morbidity related to atrial fibrillation may be beneficial	Cardiovascular	16772329; 17266934; 19343045; 20638934

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the KCNA5 gene.

• Atrial fibrillation, familial, 7 (389 variants)
• not provided (78 variants)
• Inborn genetic diseases (21 variants)
• not specified (13 variants)
• Pulmonary arterial hypertension (5 variants)
• KCNA5-related condition (2 variants)
• Cardiac arrhythmia (1 variants)
• Heart disease (1 variants)
• Third degree atrioventricular block (1 variants)
• Brugada syndrome 1 (1 variants)
• altered potassium channel function (1 variants)
• Pulmonary hypertension, primary, 1 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the KCNA5 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			6	95	8	109
missense			237	11	1	249
nonsense			3			3
start loss			1			1
frameshift			14			14
inframe indel			7			7
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding			10	3	3	16
Total	0	0	278	109	12

Variants in KCNA5

This is a list of pathogenic ClinVar variants found in the KCNA5 region.

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

Position	Type	Phenotype	Significance	ClinVar
12-5043885-GGGC-G			Likely benign (Sep 16, 2018)
12-5043889-G-GAA			Likely benign (Sep 22, 2018)
12-5043938-G-C		Atrial fibrillation, familial, 7	Uncertain significance (Jan 13, 2018)
12-5043981-C-T		Atrial fibrillation, familial, 7	Benign (Sep 06, 2018)
12-5044063-G-C		Atrial fibrillation, familial, 7	Uncertain significance (Jan 13, 2018)
12-5044096-G-T		Atrial fibrillation, familial, 7	Uncertain significance (Jan 13, 2018)
12-5044099-G-C		Atrial fibrillation, familial, 7	Uncertain significance (Jan 12, 2018)
12-5044148-A-G		Atrial fibrillation, familial, 7	Uncertain significance (Sep 06, 2022)
12-5044149-T-C		Atrial fibrillation, familial, 7	Uncertain significance (Dec 14, 2023)
12-5044157-G-T		Atrial fibrillation, familial, 7	Uncertain significance (Feb 24, 2023)
12-5044161-T-C		Atrial fibrillation, familial, 7	Uncertain significance (Jul 09, 2019)
12-5044167-C-G		Atrial fibrillation, familial, 7	Uncertain significance (Dec 12, 2021)
12-5044175-A-G		Atrial fibrillation, familial, 7	Uncertain significance (Aug 25, 2021)
12-5044176-A-ACGG		Atrial fibrillation, familial, 7	Uncertain significance (Nov 20, 2020)
12-5044178-GGC-G		Atrial fibrillation, familial, 7	Uncertain significance (Apr 09, 2021)
12-5044182-G-A		Atrial fibrillation, familial, 7	Uncertain significance (Dec 05, 2020)
12-5044183-T-C		Atrial fibrillation, familial, 7	Conflicting classifications of pathogenicity (Jan 04, 2024)
12-5044183-T-G		Atrial fibrillation, familial, 7	Likely benign (Sep 21, 2023)
12-5044188-T-G		Atrial fibrillation, familial, 7 • Inborn genetic diseases	Uncertain significance (Nov 30, 2022)
12-5044190-A-G		Atrial fibrillation, familial, 7	Uncertain significance (Feb 21, 2023)
12-5044191-C-T		Atrial fibrillation, familial, 7	Uncertain significance (Sep 06, 2023)
12-5044203-G-A		Atrial fibrillation, familial, 7	Uncertain significance (May 01, 2023)
12-5044208-G-A		Atrial fibrillation, familial, 7	Uncertain significance (Jul 02, 2020)
12-5044211-G-A		Atrial fibrillation, familial, 7	Uncertain significance (Mar 06, 2022)
12-5044214-C-T		Atrial fibrillation, familial, 7	Uncertain significance (Aug 03, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
KCNA5	protein_coding	protein_coding	ENST00000252321	1	2865

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00109	0.956	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.0540	401	398	1.01	0.0000274	3936
Missense in Polyphen		167	187.7	0.88971		1883
Synonymous	-1.58	207	180	1.15	0.0000132	1342
Loss of Function	1.79	7	14.3	0.489	7.99e-7	147

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)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes. Forms tetrameric potassium-selective channels through which potassium ions pass in accordance with their electrochemical gradient. The channel alternates between opened and closed conformations in response to the voltage difference across the membrane. Can form functional homotetrameric channels and heterotetrameric channels that contain variable proportions of KCNA1, KCNA2, KCNA4, KCNA5, and possibly other family members as well; channel properties depend on the type of alpha subunits that are part of the channel (PubMed:12130714). Channel properties are modulated by cytoplasmic beta subunits that regulate the subcellular location of the alpha subunits and promote rapid inactivation (PubMed:12130714). Homotetrameric channels display rapid activation and slow inactivation (PubMed:8505626, PubMed:12130714). May play a role in regulating the secretion of insulin in normal pancreatic islets. Isoform 2 exhibits a voltage-dependent recovery from inactivation and an excessive cumulative inactivation (PubMed:11524461). {ECO:0000269|PubMed:11524461, ECO:0000269|PubMed:12130714, ECO:0000269|PubMed:8505626}.
• Disease: DISEASE: Atrial fibrillation, familial, 7 (ATFB7) [MIM:612240]: A familial form of atrial fibrillation, a common sustained cardiac rhythm disturbance. Atrial fibrillation is characterized by disorganized atrial electrical activity and ineffective atrial contraction promoting blood stasis in the atria and reduces ventricular filling. It can result in palpitations, syncope, thromboembolic stroke, and congestive heart failure. {ECO:0000269|PubMed:16772329}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: 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;Neuronal System;Voltage gated Potassium channels;Potassium Channels (Consensus)

Recessive Scores

• pRec: 0.206

Intolerance Scores

• loftool: 0.0940
• rvis_EVS: 0.8
• rvis_percentile_EVS: 87.59

Haploinsufficiency Scores

• pHI: 0.240
• hipred: Y
• hipred_score: 0.540
• ghis: 0.425

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.843

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Kcna5
• 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); hematopoietic system phenotype; immune system phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); muscle phenotype; cellular phenotype; homeostasis/metabolism phenotype

Gene ontology

• Biological process: response to hypoxia;potassium ion transport;Notch signaling pathway;response to mechanical stimulus;response to organic substance;regulation of vasoconstriction;regulation of membrane potential;response to hydrogen peroxide;regulation of potassium ion transport;regulation of insulin secretion;protein homooligomerization;negative regulation of cytosolic calcium ion concentration;potassium ion homeostasis;response to hyperoxia;membrane hyperpolarization;regulation of atrial cardiac muscle cell membrane repolarization;potassium ion transmembrane transport;atrial cardiac muscle cell action potential;membrane repolarization during bundle of His cell action potential;membrane repolarization during SA node cell action potential;regulation of heart rate by cardiac conduction;potassium ion export across plasma membrane;membrane repolarization during atrial cardiac muscle cell action potential;positive regulation of G1/S transition of mitotic cell cycle;positive regulation of myoblast proliferation
• Cellular component: endoplasmic reticulum;Golgi apparatus;plasma membrane;integral component of plasma membrane;caveola;voltage-gated potassium channel complex;cell surface;intercalated disc;integral component of membrane;Z disc;potassium channel complex;membrane raft;intracellular canaliculus;perinuclear region of cytoplasm
• Molecular function: signaling receptor binding;voltage-gated potassium channel activity;delayed rectifier potassium channel activity;protein binding;outward rectifier potassium channel activity;protein kinase binding;alpha-actinin binding;voltage-gated potassium channel activity involved in bundle of His cell action potential repolarization;voltage-gated potassium channel activity involved in atrial cardiac muscle cell action potential repolarization;voltage-gated potassium channel activity involved in SA node cell action potential repolarization;scaffold protein binding