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

Summary

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

Genomic context

Location:: 1p34.2

Exon count:: 15

Annotation release	Status	Assembly	Chr	Location
109.20200228	current	GRCh38.p13 (GCF_000001405.39)	1	NC_000001.11 (40783787..40840457)
105	previous assembly	GRCh37.p13 (GCF_000001405.25)	1	NC_000001.10 (41249684..41306124)

Chromosome 1 - NC_000001.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

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 (PIP2) Affinity and Signaling Sensitivities in Smooth Muscle Cells.
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.
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.
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 Ca2+-directed interactions between calmodulin and the proximal C terminus of KCNQ4 K+ channels.
Results indicate that the KCNQ4 variant p.(Pro291Leu) causes early onset, progressive hearing loss in homozygous individuals and late onset, progressive mild to moderate hearing loss when inherited in a heterozygous state. It suggests that the same variant may affect the severity of the phenotype as well as the age of onset in mono-allelic or bi-allelic forms.
Title: Bi-allelic Pro291Leu variant in KCNQ4 leads to early onset non-syndromic hearing loss.
Results show that rs4660468 T allele of KCNQ4 involves with a higher risk of noise-induced hearing loss (NIHL) and it could be one biomarker of susceptibility for Chinese noise exposed workers. Furthermore, genetic variations of KCNQ4 and noise exposure jointly contribute to the NIHL risks by gene-environment interactions.
Title: Genetic variation in KCNQ4 gene is associated with susceptibility to noise-induced hearing loss in a Chinese population.
KCNQ4 gene polymorphisms associated with susceptibility to noise-induced hearing loss.
Title: [The genetic aspects of occupational hearing impairment].
mutations in KCNQ4 gene are unlikely to be a major causative factor of ADNSHL in our studied patients from West Bengal, India, pointing to other genes might be responsible for ADNSHL in our studied patients
Title: Absence of KCNQ4 mutation in Bengali families with ADNSHL originated from West Bengal, India.
The fundamental processes that dictate Kv7.4 activity.
Title: Synergistic interplay of Gβγ and phosphatidylinositol 4,5-bisphosphate dictates Kv7.4 channel activity.
A novel KCNQ4 mutation, c.887 G > A (p.G296D), was identified in all five affected members in a Chinese family with autosomal dominant non-syndromic deafness 2. This mutation leads to a glycine-to-aspartic acid substitution at position 296 in the pore region of the KCNQ4 channel.
Title: A novel pore-region mutation, c.887G > A (p.G296D) in KCNQ4, causing hearing loss in a Chinese family with autosomal dominant non-syndromic deafness 2.

Submit: New GeneRIF Correction See all GeneRIFs (52)

Phenotypes

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

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Autosomal dominant nonsyndromic deafness 2A MedGen: C2677637 OMIM: 600101 GeneReviews: DFNA2 Nonsyndromic Hearing Loss, Hereditary Hearing Loss and Deafness Overview	Compare labs

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

SHGC-146764 (e-PCR)
- UniSTS:175417

SHGC-149399 (e-PCR)
- UniSTS:176981

SHGC-146823 (e-PCR)
- UniSTS:175454

SHGC-74653 (e-PCR)
- UniSTS:49005

Homology

Homologs of the KCNQ4 gene: The KCNQ4 gene is conserved in chimpanzee, dog, cow, mouse, rat, chicken, and frog.
Orthologs from Annotation Pipeline: 218 organisms have orthologs with human gene KCNQ4
Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
calmodulin binding	IBA Inferred from Biological aspect of Ancestor more info	PubMed
delayed rectifier potassium channel activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed
potassium channel activity	TAS Traceable Author Statement more info	PubMed
protein binding	IPI Inferred from Physical Interaction more info	PubMed
voltage-gated potassium channel activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed

Process	Evidence Code	Pubs
inner ear morphogenesis	IEA Inferred from Electronic Annotation more info
potassium ion transmembrane transport	IBA Inferred from Biological aspect of Ancestor more info	PubMed
potassium ion transport	TAS Traceable Author Statement more info	PubMed
regulation of ion transmembrane transport	IEA Inferred from Electronic Annotation more info
sensory perception of sound	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
basal plasma membrane	IEA Inferred from Electronic Annotation more info
integral component of membrane	IBA Inferred from Biological aspect of Ancestor more info	PubMed
plasma membrane	TAS Traceable Author Statement more info
voltage-gated potassium channel complex	IBA Inferred from Biological aspect of Ancestor more info	PubMed

General protein information

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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)

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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

NG_008139.3 RefSeqGene

Range

5001..61666

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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
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