KCNQ4

KCNQ4
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	2OVC, 4GOW
Identifiers
Aliases	KCNQ4 , DFNA2, DFNA2A, KV7.4, potassium voltage-gated channel subfamily Q member 4
External IDs	OMIM: 603537 MGI: 1926803 HomoloGene: 78107 GeneCards: KCNQ4
Gene location (Human)
Chr.	Chromosome 1 (human)
End	40,840,452 bp
Gene location (Mouse)
Chr.	Chromosome 4 (mouse)
End	120,605,809 bp
RNA expression pattern
	Top expressed in
	retinal pigment epithelium; ; right coronary artery; ; gastric mucosa; ; parotid gland; ; popliteal artery; ; thoracic aorta; ; ascending aorta; ; left coronary artery; ; gastrocnemius muscle; ; left uterine tube;
	Top expressed in
	digastric muscle; ; extraocular muscle; ; knee joint; ; retinal pigment epithelium; ; temporal muscle; ; vastus lateralis muscle; ; sternocleidomastoid muscle; ; thoracic diaphragm; ; ascending aorta; ; triceps brachii muscle;
	More reference expression data
	More reference expression data
Gene ontology
Molecular function	potassium channel activity ; voltage-gated ion channel activity ; ion channel activity ; protein binding ; voltage-gated potassium channel activity ; delayed rectifier potassium channel activity ; calmodulin binding ;
Cellular component	integral component of membrane ; membrane ; voltage-gated potassium channel complex ; plasma membrane ; basal plasma membrane ;
Biological process	regulation of ion transmembrane transport ; ion transport ; sensory perception of sound ; potassium ion transport ; transmembrane transport ; potassium ion transmembrane transport ; inner ear morphogenesis ;
	Sources:Amigo / QuickGO
Orthologs
	9132
	60613
	ENSG00000117013
	ENSMUSG00000028631
	P56696
	Q9JK97
	NM_004700 ; NM_172163
	NM_001081142
	NP_004691 ; NP_751895
	NP_001074611
	Wikidata
View/Edit Human	View/Edit Mouse

Last updated October 20, 2022

Potassium voltage-gated channel subfamily KQT member 4, also known as voltage-gated potassium channel subunit K_v7.4, is a protein that in humans is encoded by the KCNQ4 gene.^[5]^[6]^[7]

Function

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 encoded protein can form a homomultimeric potassium channel or possibly a heteromultimeric channel in association with the protein encoded by the KCNQ3 gene.^[7]

Clinical significance

The current generated by this channel is inhibited by muscarinic acetylcholine receptor M1 and activated by retigabine, a novel anti-convulsant drug. 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.^[7]

Ligands

ML213: KCNQ2/Q4 channel opener.^[8]

Related Research Articles

K_v7.1 (KvLQT1) is a potassium channel protein whose primary subunit in humans is encoded by the KCNQ1 gene. K_v7.1 is a voltage and lipid-gated potassium channel present in the cell membranes of cardiac tissue and in inner ear neurons among other tissues. In the cardiac cells, K_v7.1 mediates the I_Ks (or slow delayed rectifying K⁺) current that contributes to the repolarization of the cell, terminating the cardiac action potential and thereby the heart's contraction. It is a member of the KCNQ family of potassium channels.

Nonsyndromic deafness is hearing loss that is not associated with other signs and symptoms. In contrast, syndromic deafness involves hearing loss that occurs with abnormalities in other parts of the body. Genetic changes are related to the following types of nonsyndromic deafness.

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K_v7.3 (KvLQT3) is a potassium channel protein coded for by the gene KCNQ3.

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Gap junction beta-6 protein (GJB6), also known as connexin 30 (Cx30) — is a protein that in humans is encoded by the GJB6 gene. Connexin 30 (Cx30) is one of several gap junction proteins expressed in the inner ear. Mutations in gap junction genes have been found to lead to both syndromic and nonsyndromic deafness. Mutations in this gene are associated with Clouston syndrome.

<span class="mw-page-title-main">Polycystin 2</span>

Polycystin-2 is a protein that in humans is encoded by the PKD2 gene.

Wolframin is a protein that in humans is encoded by the WFS1 gene.

Cochlin is a protein that in humans is encoded by the COCH gene. It is an extracellular matrix (ECM) protein highly abundant in the cochlea and vestibule of the inner ear, constituting the major non-collagen component of the ECM of the inner ear. The protein is highly conserved in human, mouse, and chicken, showing 94% and 79% amino acid identity of human to mouse and chicken sequences, respectively.

Gap junction beta-3 protein (GJB3), also known as connexin 31 (Cx31) — is a protein that in humans is encoded by the GJB3 gene.

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Alpha-tectorin is a protein that in humans is encoded by the TECTA gene.

Eyes absent homolog 4 is a protein that in humans is encoded by the EYA4 gene.

Transmembrane channel-like protein 1 is a protein that in humans is encoded by the TMC1 gene. TMC1 contains six transmembrane domains with both the C and N termini on the endoplasmic side of the membrane, as well as a large loop between domains 4 and 5. This topology is similar to that of transient receptor potential channels (TRPs), a family of proteins involved in the perception of senses such as temperature, taste, pressure, and vision. TMC1 has been located in the post-natal mouse cochlea, and knockouts for TMC1 and TMC2 result in both auditory and vestibular deficits indicating TMC1 is a molecular part of auditory transduction.

Myosin-XV is a protein that in humans is encoded by the MYO15A gene.

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References

1 2 3 GRCh38: Ensembl release 89: ENSG00000117013 - Ensembl, May 2017
1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000028631 - Ensembl, May 2017
↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑ Kubisch C, Schroeder BC, Friedrich T, Lutjohann B, El-Amraoui A, Marlin S, Petit C, Jentsch TJ (Mar 1999). "KCNQ4, a novel potassium channel expressed in sensory outer hair cells, is mutated in dominant deafness". Cell. 96 (3): 437–46. doi: 10.1016/S0092-8674(00)80556-5 . PMID 10025409.
↑ Gutman GA, Chandy KG, Grissmer S, Lazdunski M, McKinnon D, Pardo LA, Robertson GA, Rudy B, Sanguinetti MC, Stuhmer W, Wang X (Dec 2005). "International Union of Pharmacology. LIII. Nomenclature and molecular relationships of voltage-gated potassium channels". Pharmacol Rev. 57 (4): 473–508. doi:10.1124/pr.57.4.10. PMID 16382104. S2CID 219195192.
1 2 3 "Entrez Gene: KCNQ4 potassium voltage-gated channel, KQT-like subfamily, member 4".
↑ Yu H, Wu M, Townsend SD, et al. (2011). "Discovery, Synthesis, and Structure Activity Relationship of a Series of N-Aryl- bicyclo[2.2.1]heptane-2-carboxamides: Characterization of ML213 as a Novel KCNQ2 and KCNQ4 Potassium Channel Opener". ACS Chem Neurosci. 2 (10): 572–577. doi:10.1021/cn200065b. PMC 3223964 . PMID 22125664.

External links

GeneReviews/NCBI/NIH/UW entry on Deafness and Hereditary Hearing Loss Overview
KCNQ4+protein,+human at the US National Library of Medicine Medical Subject Headings (MeSH)
GeneReviews/NCBI/NIH/UW entry on DFNA2 Nonsyndromic Hearing Loss

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[refGRCh38Ensembl-1] 1 2 3 GRCh38: Ensembl release 89: ENSG00000117013 - Ensembl, May 2017

[refGRCm38Ensembl-2] 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000028631 - Ensembl, May 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[pmid10025409-5] Kubisch C, Schroeder BC, Friedrich T, Lutjohann B, El-Amraoui A, Marlin S, Petit C, Jentsch TJ (Mar 1999). "KCNQ4, a novel potassium channel expressed in sensory outer hair cells, is mutated in dominant deafness". Cell. 96 (3): 437–46. doi: 10.1016/S0092-8674(00)80556-5 . PMID 10025409.

[pmid16382104-6] Gutman GA, Chandy KG, Grissmer S, Lazdunski M, McKinnon D, Pardo LA, Robertson GA, Rudy B, Sanguinetti MC, Stuhmer W, Wang X (Dec 2005). "International Union of Pharmacology. LIII. Nomenclature and molecular relationships of voltage-gated potassium channels". Pharmacol Rev. 57 (4): 473–508. doi:10.1124/pr.57.4.10. PMID 16382104. S2CID 219195192.

[entrez-7] 1 2 3 "Entrez Gene: KCNQ4 potassium voltage-gated channel, KQT-like subfamily, member 4".

[pmid22125664-8] Yu H, Wu M, Townsend SD, et al. (2011). "Discovery, Synthesis, and Structure Activity Relationship of a Series of N-Aryl- bicyclo[2.2.1]heptane-2-carboxamides: Characterization of ML213 as a Novel KCNQ2 and KCNQ4 Potassium Channel Opener". ACS Chem Neurosci. 2 (10): 572–577. doi:10.1021/cn200065b. PMC 3223964 . PMID 22125664.

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