KCNE5

potassium voltage-gated channel subfamily E regulatory subunit 5, the group of Potassium voltage-gated channel regulatory subunits

Basic information

Region (hg38): X:109623699-109625172

Previous symbols: [ "KCNE1L" ]

Links

ENSG00000176076 ∙ NCBI:23630 ∙ OMIM:300328 ∙ HGNC:6241 ∙ Uniprot:Q9UJ90 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Brugada syndrome (Limited), mode of inheritance: Unknown
• Brugada syndrome (Disputed Evidence), mode of inheritance: AD

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the KCNE5 gene.

• Brugada syndrome (57 variants)
• Inborn genetic diseases (26 variants)
• not provided (8 variants)
• not specified (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the KCNE5 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				23		23
missense			38	1	1	40
nonsense			3			3
start loss						0
frameshift			1			1
inframe indel			1			1
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding				2		2
Total	0	0	43	26	1

Variants in KCNE5

This is a list of pathogenic ClinVar variants found in the KCNE5 region.

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

Position	Type	Phenotype	Significance	ClinVar
X-109624334-G-A			Likely benign (Feb 28, 2019)
X-109624598-C-T		not specified	Likely benign (Mar 03, 2022)
X-109624611-T-C		not specified	Uncertain significance (Mar 29, 2022)
X-109624618-G-C		not specified	Uncertain significance (Jul 15, 2023)
X-109624620-G-T		not specified	Uncertain significance (Aug 28, 2023)
X-109624624-G-A		Brugada syndrome	Uncertain significance (Apr 28, 2021)
X-109624625-C-G		Brugada syndrome	Likely benign (Jul 03, 2021)
X-109624634-G-C		Brugada syndrome	Likely benign (Jan 08, 2023)
X-109624647-C-T		Brugada syndrome	Uncertain significance (Sep 22, 2022)
X-109624650-C-A		Brugada syndrome	Uncertain significance (Aug 28, 2021)
X-109624663-G-A		Brugada syndrome • KCNE5-related disorder	Uncertain significance (Feb 21, 2024)
X-109624670-C-T		Brugada syndrome	Likely benign (Mar 01, 2022)
X-109624672-C-T		Brugada syndrome	Uncertain significance (Feb 02, 2022)
X-109624675-C-A		not specified	Uncertain significance (Jan 18, 2023)
X-109624675-C-T		Brugada syndrome • not specified	Conflicting classifications of pathogenicity (Jan 17, 2024)
X-109624682-G-A		Brugada syndrome • not specified	Likely benign (Sep 22, 2023)
X-109624683-GC-TT		Brugada syndrome	Uncertain significance (Dec 01, 2021)
X-109624685-G-T		Brugada syndrome	Uncertain significance (Mar 28, 2021)
X-109624687-C-T		Brugada syndrome • not specified	Conflicting classifications of pathogenicity (Jan 22, 2024)
X-109624688-G-A		Brugada syndrome • not specified	Benign/Likely benign (Jan 17, 2024)
X-109624691-G-A		not specified	Likely benign (Nov 20, 2022)
X-109624691-G-C		not specified	Likely benign (May 11, 2023)
X-109624692-G-T		Brugada syndrome	Uncertain significance (Jan 31, 2021)
X-109624694-C-G		Brugada syndrome • not specified	Likely benign (Jul 05, 2023)
X-109624696-G-A		Brugada syndrome • not specified	Likely benign (Jun 02, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
KCNE5	protein_coding	protein_coding	ENST00000372101	1	1465

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.119	0.622	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.407	60	69.5	0.863	0.00000639	876
Missense in Polyphen		10	17.284	0.57858		246
Synonymous	1.32	26	36.1	0.721	0.00000366	318
Loss of Function	0.396	1	1.53	0.654	1.33e-7	20

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: Potassium channel ancillary subunit that is essential for generation of some native K(+) currents by virtue of formation of heteromeric ion channel complex with voltage-gated potassium (Kv) channel pore-forming alpha subunits. Functions as an inhibitory beta-subunit of the repolarizing cardiac potassium ion channel KCNQ1. {ECO:0000269|PubMed:12324418}.
• Pathway: Antiarrhythmic Pathway, Pharmacodynamics;Phase 2 - plateau phase;Phase 3 - rapid repolarisation;Cardiac conduction;Muscle contraction (Consensus)

Recessive Scores

• pRec: 0.106

Haploinsufficiency Scores

• pHI: 0.237
• hipred: N
• hipred_score: 0.170
• ghis: 0.413

Essentials

• essential_gene_gene_trap: N

Mouse Genome Informatics

• Gene name: Kcne1l

Gene ontology

• Biological process: regulation of heart contraction;cardiac muscle contraction;regulation of membrane repolarization;regulation of ventricular cardiac muscle cell membrane repolarization;regulation of atrial cardiac muscle cell membrane repolarization;ventricular cardiac muscle cell action potential;membrane repolarization during action potential;atrial cardiac muscle cell action potential;regulation of heart rate by cardiac conduction;potassium ion export across plasma membrane;membrane repolarization during ventricular cardiac muscle cell action potential;regulation of potassium ion transmembrane transport;negative regulation of potassium ion transmembrane transport;positive regulation of potassium ion transmembrane transport;negative regulation of delayed rectifier potassium channel activity;negative regulation of potassium ion export across plasma membrane;regulation of cation channel activity
• Cellular component: plasma membrane;voltage-gated potassium channel complex
• Molecular function: voltage-gated potassium channel activity;delayed rectifier potassium channel activity;protein binding;potassium channel regulator activity;ion channel binding;voltage-gated potassium channel activity involved in cardiac muscle cell action potential repolarization;voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization