KCNE4

protein-coding

potassium voltage-gated channel subfamily E regulatory subunit 4, the group of Potassium voltage-gated channel regulatory subunits

Gene summary

Voltage-gated potassium (Kv) channels represent the most complex class of voltage-gated ion channels from both functional and structural standpoints. Their diverse functions include regulating neurotransmitter release, heart rate, insulin secretion, neuronal excitability, epithelial electrolyte transport, smooth muscle contraction, and cell volume. This gene encodes a member of the potassium channel, voltage-gated, isk-related subfamily. This member is a type I membrane protein, and a beta subunit that assembles with a potassium channel alpha-subunit to modulate the gating kinetics and enhance stability of the multimeric complex. This gene is prominently expressed in the embryo and in adult uterus. [provided by RefSeq, Jul 2008]

MANE transcript

NM_080671.4

Inheritance

—

ClinVar variants

U:20

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.3

Max pathogenic AF

—

Genomic locus

chr2:223,052,190-223,198,399

External References & Databases

Ensembl (ENSG00000152049)

Transcript & Mutation Effects

hg38 • Region Span ~146.2 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to KCNE4 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 20

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_080671.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous						0
missense			20 clinvar			20
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	20	0	0	20

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 2 of 2 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_080671.4	RefSeq	NP_542402.4	1	MANE Select
ENST00000281830.4	Ensembl	ENSP00000281830.5	1	MANE Select

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Antiarrhythmic Pathway, Pharmacodynamics
Phase 2 - plateau phase
Phase 3 - rapid repolarisation
Cardiac conduction
Muscle contraction

Biological Process

regulation of ventricular cardiac muscle cell membrane repolarization
ventricular cardiac muscle cell action potential
membrane repolarization during action potential
regulation of heart rate by cardiac conduction
potassium ion export across plasma membrane

Molecular Function

delayed rectifier potassium channel activity
protein binding
potassium channel regulator activity
ion channel binding
voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization

Cellular Component

voltage-gated potassium channel complex
apical plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000604125
Coding exons: 1
Length: 146586
Individuals with no LoFs: 125641
Homozygous LoFs: 0
Heterozygous LoFs: 3
Defined: 125644
p: 0.0000119

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.338	104	114	0.911	0.00000765	1106
Missense (PolyPhen)		31	39.882	0.7773		451
Synonymous	0.192	57	58.9	0.968	0.00000487	347
Loss of Function	1.18	1	3.33	0.300	1.42e-7	44

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000064	0.000062	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.0000088	0.0000088	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Ancillary protein that assembles as a beta subunit with a voltage-gated potassium channel complex of pore-forming alpha subunits. Modulates the gating kinetics and enhances stability of the channel complex. May associate with KCNQ1/KVLTQ1 and inhibit potassium current.;

Recessive Scores

pRec: 0.115

Intolerance Scores

RVIS EVS: -0.03
RVIS percentile EVS: 51.4

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Indispensability pred.: N
Indispensability score: 0.301

Gene Damage Prediction

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