Sign in to NCBI
Format

Send to:

Choose Destination

KCNQ4 potassium voltage-gated channel subfamily Q member 4 [ Homo sapiens (human) ]

Gene ID: 9132, updated on 8-Jul-2021

Summary

Go to the top of the page Help
Official Symbol
KCNQ4provided by HGNC
Official Full Name
potassium voltage-gated channel subfamily Q member 4provided by HGNC
Primary source
HGNC:HGNC:6298
See related
Ensembl:ENSG00000117013 MIM:603537
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
DFNA2; KV7.4; DFNA2A
Summary
The protein encoded by this gene forms a potassium channel that is thought to play a critical role in the regulation of neuronal excitability, particularly in sensory cells of the cochlea. The current generated by this channel is inhibited by M1 muscarinic acetylcholine receptors and activated by retigabine, a novel anti-convulsant drug. The encoded protein can form a homomultimeric potassium channel or possibly a heteromultimeric channel in association with the protein encoded by the KCNQ3 gene. Defects in this gene are a cause of nonsyndromic sensorineural deafness type 2 (DFNA2), an autosomal dominant form of progressive hearing loss. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
Expression
Ubiquitous expression in endometrium (RPKM 1.8), prostate (RPKM 1.3) and 24 other tissues See more
Orthologs
mouse all
NEW
Try the new Gene table
Try the new Transcript table

Genomic context

Go to the top of the page Help
See KCNQ4 in Genome Data Viewer
Location:
1p34.2
Exon count:
15
Annotation release Status Assembly Chr Location
109.20210514 current GRCh38.p13 (GCF_000001405.39) 1 NC_000001.11 (40783787..40840457)
105.20201022 previous assembly GRCh37.p13 (GCF_000001405.25) 1 NC_000001.10 (41249459..41306124)

Chromosome 1 - NC_000001.11Genomic Context describing neighboring genes Neighboring gene nuclear transcription factor Y subunit gamma Neighboring gene microRNA 30e Neighboring gene microRNA 30c-1 Neighboring gene RNA, 7SL, cytoplasmic 326, pseudogene Neighboring gene GATA motif-containing MPRA enhancers 242 and 247 Neighboring gene uncharacterized LOC105378676 Neighboring gene Cbp/p300 interacting transactivator with Glu/Asp rich carboxy-terminal domain 4

Genomic regions, transcripts, and products

Go to the top of the page Help

Go to nucleotide: Graphics FASTA GenBank

Expression

Go to the top of the page Help
  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

Go to the top of the pageHelp

Related articles in PubMed

  1. Structural Basis for the Modulation of Human KCNQ4 by Small-Molecule Drugs. Li T, et al. Mol Cell, 2021 Jan 7. PMID 33238160
  2. [Prediction of KCNQ4gene polymorphism varies with CNE or noise exposure duration on the Risk of NIHL-Cox model analysis based on cohort study]. Zhou WH, et al. Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi, 2020 Feb 20. PMID 32306673
  3. Molecular basis and restoration of function deficiencies of Kv7.4 variants associated with inherited hearing loss. Xia X, et al. Hear Res, 2020 Mar 15. PMID 31995783
  4. Rare KCNQ4 variants found in public databases underlie impaired channel activity that may contribute to hearing impairment. Jung J, et al. Exp Mol Med, 2019 Aug 21. PMID 31434872, Free PMC Article
  5. Bi-allelic Pro291Leu variant in KCNQ4 leads to early onset non-syndromic hearing loss. Ramzan M, et al. Gene, 2019 Jul 15. PMID 31028865, Free PMC Article

See all (73) citations in PubMed

See citations in PubMed for homologs of this gene provided by HomoloGene

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Molecular basis and restoration of function deficiencies of Kv7.4 variants associated with inherited hearing loss.
    Title: Molecular basis and restoration of function deficiencies of Kv7.4 variants associated with inherited hearing loss.
  2. Structural Basis for the Modulation of Human KCNQ4 by Small-Molecule Drugs.
    Title: Structural Basis for the Modulation of Human KCNQ4 by Small-Molecule Drugs.
  3. A comparative analysis of genetic hearing loss phenotypes in European/American and Japanese populations.
    Title: A comparative analysis of genetic hearing loss phenotypes in European/American and Japanese populations.
  4. In 3 families with hearing impairment, whole exome sequencing revealed 3 novel variants in KCNQ4, LHFPL5 and COCH genes. The KCNQ4 gene (DFNA2A) encodes a potassium channel (KV7.4) and the heterozygous variant identified (c.1647C>G, p.F549L) resulted in the substitution of Phe549 residing in the KV7.4 cytoplasmic region.
    Title: Novel Mutations in KCNQ4, LHFPL5 and COCH Genes in Iranian Families with Hearing Impairment.
  5. The mutant allele A of rs4660470 in KCNQ4 may be a risk factor for developing noise-induced hearing loss
    Title: [Prediction of KCNQ4gene polymorphism varies with CNE or noise exposure duration on the Risk of NIHL-Cox model analysis based on cohort study].
  6. KCNQ4 variants may contribute more to late-onset Non-Syndromic Hearing Loss (NSHL) than expected, and therefore, genetic screening for this gene is important for the prevention and treatment of NSHL.
    Title: Rare KCNQ4 variants found in public databases underlie impaired channel activity that may contribute to hearing impairment.
  7. Distinct functional domains were identified that confer differential sensitivities of Kv7.4 and Kv7.5 to stimulatory and inhibitory signaling.
    Title: Structural Determinants of Kv7.5 Potassium Channels That Confer Changes in Phosphatidylinositol 4,5-Bisphosphate (PIP<sub>2</sub>) Affinity and Signaling Sensitivities in Smooth Muscle Cells.
  8. The c.140T>C (p.Leu47Pro) mutation in KCNQ4 causes progressive nonsyndromic hearing loss.
    Title: A recurrent mutation in KCNQ4 in Korean families with nonsyndromic hearing loss and rescue of the channel activity by KCNQ activators.
  9. Mutation in KCNQ4 gene is associated with nonsyndromic hearing loss.
    Title: Whole-exome sequencing identifies two novel mutations in KCNQ4 in individuals with nonsyndromic hearing loss.
  10. findings suggest that in response to increased Ca(2+), CaM undergoes lobe switching that imposes a dramatic mutually induced conformational fit to both the proximal C terminus of KCNQ4 channels and CaM, likely underlying Ca(2+)-dependent regulation of KCNQ gating.
    Title: A mutually induced conformational fit underlies Ca<sup>2+</sup>-directed interactions between calmodulin and the proximal C terminus of KCNQ4 K<sup>+</sup> channels.
Submit: New GeneRIF Correction See all GeneRIFs (58)

Phenotypes

Go to the top of the page Help

Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Variation

Go to the top of the page Help

See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Pathways from PubChem

Go to the top of the page

Interactions

Go to the top of the page Help
Products Interactant Other Gene Complex Source Pubs Description

General gene information

Go to the top of the page Help

Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables calmodulin binding IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
enables delayed rectifier potassium channel activity IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
enables potassium channel activity TAS
Traceable Author Statement
more info
 PubMed 
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables voltage-gated potassium channel activity IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
Process Evidence Code Pubs
involved_in inner ear morphogenesis IEA
Inferred from Electronic Annotation
more info
  
involved_in potassium ion transmembrane transport IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
involved_in potassium ion transport TAS
Traceable Author Statement
more info
 PubMed 
involved_in regulation of ion transmembrane transport IEA
Inferred from Electronic Annotation
more info
  
involved_in sensory perception of sound IEA
Inferred from Electronic Annotation
more info
  
Component Evidence Code Pubs
located_in basal plasma membrane IEA
Inferred from Electronic Annotation
more info
  
is_active_in integral component of membrane IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
located_in plasma membrane TAS
Traceable Author Statement
more info
  
part_of voltage-gated potassium channel complex IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 

General protein information

Go to the top of the page Help
Preferred Names
potassium voltage-gated channel subfamily KQT member 4
Names
potassium channel KQT-like 4
potassium channel subunit alpha KvLQT4
potassium channel, voltage gated KQT-like subfamily Q, member 4
potassium voltage-gated channel, KQT-like subfamily, member 4

NCBI Reference Sequences (RefSeq)

Go to the top of the page Help

NEW Try the new Transcript table

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_008139.3 RefSeqGene

    Range
    5001..61666
    Download
    GenBank, FASTA, Sequence Viewer (Graphics), LRG_1378

mRNA and Protein(s)

  1. NM_004700.4 → NP_004691.2  potassium voltage-gated channel subfamily KQT member 4 isoform a

    See identical proteins and their annotated locations for NP_004691.2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longer transcript and encodes the longer and predominant isoform (a).
    Source sequence(s)
    AC119677, AF105202, AK074957, CA411644, DA782056
    Consensus CDS
    CCDS456.1
    UniProtKB/Swiss-Prot
    P56696
    UniProtKB/TrEMBL
    B3KQH8
    Related
    ENSP00000262916.6, ENST00000347132.10
    Conserved Domains (4) summary
    pfam00520
    Location:126 → 330
    Ion_trans; Ion transport protein
    pfam03520
    Location:474 → 653
    KCNQ_channel; KCNQ voltage-gated potassium channel
    pfam06664
    Location:92 → 190
    MIG-14_Wnt-bd; Wnt-binding factor required for Wnt secretion
    pfam07885
    Location:246 → 320
    Ion_trans_2; Ion channel

  2. NM_172163.3 → NP_751895.1  potassium voltage-gated channel subfamily KQT member 4 isoform b

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) lacks an alternate in-frame exon in the central coding region, compared to variant 1, resulting in an isoform (b) that is shorter than isoform a. There are no publicly available transcripts supporting this variant; it is represented based on data in PMID:10025409.
    Source sequence(s)
    AC119677, AF105202, AK074957, CA411644, DA782056
    UniProtKB/Swiss-Prot
    P56696
    UniProtKB/TrEMBL
    B3KQH8
    Related
    ENSP00000423756.2, ENST00000509682.6
    Conserved Domains (4) summary
    pfam00520
    Location:126 → 330
    Ion_trans; Ion transport protein
    pfam03520
    Location:420 → 599
    KCNQ_channel; KCNQ voltage-gated potassium channel
    pfam06664
    Location:105 → 190
    MIG-14_Wnt-bd; Wnt-binding factor required for Wnt secretion
    pfam07885
    Location:246 → 320
    Ion_trans_2; Ion channel

RefSeqs of Annotated Genomes: Homo sapiens Updated Annotation Release 109.20210514

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p13 Primary Assembly

Genomic

  1. NC_000001.11 Reference GRCh38.p13 Primary Assembly

    Range
    40783787..40840457
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_017002792.1 → XP_016858281.1  potassium voltage-gated channel subfamily KQT member 4 isoform X1

    Related
    ENST00000506017.1
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
P56696.2 GenPept UniProtKB/Swiss-Prot:P56696

Gene LinkOut

The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

Chemical Information
Medical
Molecular Biology Databases
Research Materials
Tools
Miscellaneous
You are here: NCBI > Genes & Expression > Gene
Support Center