KCNQ3 potassium voltage-gated channel subfamily Q member 3 [Homo sapiens (human)] - Gene

Summary

Official Symbol: KCNQ3provided by HGNC
Official Full Name: potassium voltage-gated channel subfamily Q member 3provided by HGNC
Primary source: HGNC:HGNC:6297
See related: Ensembl:ENSG00000184156 MIM:602232; AllianceGenome:HGNC:6297
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: EBN2; BFNC2; KV7.3
Summary: This gene encodes a protein that functions in the regulation of neuronal excitability. The encoded protein forms an M-channel by associating with the products of the related KCNQ2 or KCNQ5 genes, which both encode integral membrane proteins. M-channel currents are inhibited by M1 muscarinic acetylcholine receptors and are activated by retigabine, a novel anti-convulsant drug. Defects in this gene are a cause of benign familial neonatal convulsions type 2 (BFNC2), also known as epilepsy, benign neonatal type 2 (EBN2). Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, May 2014]
Expression: Biased expression in brain (RPKM 5.1) and adrenal (RPKM 0.4) See more
Orthologs: mouse all
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Genomic context

Location:: 8q24.22

Exon count:: 17

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	8	NC_000008.11 (132120861..132481095, complement)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	8	NC_060932.1 (133243767..133604173, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	8	NC_000008.10 (133133108..133493342, complement)

Chromosome 8 - NC_000008.11 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?

SMAD4 and KCNQ3 alterations are associated with lymph node metastases in oesophageal adenocarcinoma.
Title: SMAD4 and KCNQ3 alterations are associated with lymph node metastases in oesophageal adenocarcinoma.
Phenotypic Spectrum in a Family Sharing a Heterozygous KCNQ3 Variant.
Title: Phenotypic Spectrum in a Family Sharing a Heterozygous KCNQ3 Variant.
The identification of two pathogenic variants in a family with mild and severe forms of developmental delay.
Title: The identification of two pathogenic variants in a family with mild and severe forms of developmental delay.
Heteromeric Assembly of Truncated Neuronal Kv7 Channels: Implications for Neurologic Disease and Pharmacotherapy.
Title: Heteromeric Assembly of Truncated Neuronal Kv7 Channels: Implications for Neurologic Disease and Pharmacotherapy.
a tight spatial and functional relationship between the DAT/GLT-1 transporters and the Kv7.2/7.3 potassium channel that immediately readjusts the membrane potential of the neuron, probably to limit the neurotransmitter-mediated neuronal depolarization
Title: Identification of potassium channel proteins Kv7.2/7.3 as common partners of the dopamine and glutamate transporters DAT and GLT-1.
Epilepsy-associated R230C mutation allows S4 movement but shifts the open/closed transition of the gate to very negative potentials.
Title: Epilepsy-associated mutations in the voltage sensor of KCNQ3 affect voltage dependence of channel opening.
Patients with recurrent de novo variants in KCNQ3 exhibited global developmental delay and autistic features.
Title: Autism and developmental disability caused by KCNQ3 gain-of-function variants.
PIP2 modulates KCNQ3 channel function by interacting synergistically with a minimum of four cytoplasmic domains
Title: Phosphatidylinositol 4,5-bisphosphate (PIP(2)) regulates KCNQ3 K(+) channels by interacting with four cytoplasmic channel domains.
Phylogenetic analysis, electrostatic potential mapping, in silico docking, electrophysiology, and radioligand binding assays reveal that the anticonvulsant binding pocket evolved to accommodate endogenous neurotransmitters including gamma-aminobutyric acid, which directly activates KCNQ5 and KCNQ3 via W265.
Title: Direct neurotransmitter activation of voltage-gated potassium channels.
An optimum cholesterol level in the plasma membrane is required for the proper functioning of Kv7.2/Kv7.3 channels.
Title: Regulation of Kv7.2/Kv7.3 channels by cholesterol: Relevance of an optimum plasma membrane cholesterol content.

Submit: New GeneRIF Correction See all GeneRIFs (54)

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
Seizures, benign familial neonatal, 2 MedGen: C1852581 OMIM: 121201 GeneReviews: KCNQ3-Related Disorders	Compare labs

EBI GWAS Catalog

Description
Genetics of coronary artery calcification among African Americans, a meta-analysis. EBI GWAS Catalog EBI GWAS CatalogPubMed

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-582 (e-PCR)
- UniSTS:167684

D8S295E (e-PCR)
- UniSTS:147490

D8S558 (e-PCR), detects polymorphism
- UniSTS:59953

D8S558 (e-PCR), detects polymorphism
- UniSTS:51258

RH47380 (e-PCR)
- UniSTS:5707

SHGC-150710 (e-PCR)
- UniSTS:173410

SHGC-147728 (e-PCR)
- UniSTS:175976

RH102545 (e-PCR)
- UniSTS:96879

RH47376 (e-PCR)
- UniSTS:10355

D8S295E (e-PCR)
- UniSTS:6533

D8S1835 (e-PCR), detects polymorphism
- UniSTS:51114

Kcnq3 (e-PCR), detects polymorphism
- UniSTS:259499

D8S1431E (e-PCR)
- UniSTS:151220

KCNQ3_350 (e-PCR)
- UniSTS:277435

SHGC-154560 (e-PCR)
- UniSTS:178138

STS-AA033801 (e-PCR)
- UniSTS:28640

WI-14883 (e-PCR)
- UniSTS:68066

G62778 (e-PCR)
- UniSTS:139755

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables calmodulin binding	IDA Inferred from Direct Assay 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
enables voltage-gated potassium channel activity	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in action potential initiation	IEA Inferred from Electronic Annotation more info
involved_in apoptosome assembly	IEA Inferred from Electronic Annotation more info
involved_in cellular response to calcium ion	IEA Inferred from Electronic Annotation more info
involved_in cellular response to xenobiotic stimulus	IEA Inferred from Electronic Annotation more info
involved_in chemical synaptic transmission	TAS Traceable Author Statement more info	PubMed
involved_in endocytosis	IEA Inferred from Electronic Annotation more info
involved_in excitatory chemical synaptic transmission	IEA Inferred from Electronic Annotation more info
involved_in exocytosis	IEA Inferred from Electronic Annotation more info
involved_in gene expression	IEA Inferred from Electronic Annotation more info
involved_in inhibitory chemical synaptic transmission	IEA Inferred from Electronic Annotation more info
involved_in membrane hyperpolarization	IEA Inferred from Electronic Annotation more info
involved_in mitochondrial depolarization	IEA Inferred from Electronic Annotation more info
involved_in nerve development	IEA Inferred from Electronic Annotation more info
involved_in neuron apoptotic process	IEA Inferred from Electronic Annotation more info
involved_in neuron remodeling	IEA Inferred from Electronic Annotation more info
involved_in neuronal action potential	IEA Inferred from Electronic Annotation more info
involved_in potassium ion transmembrane transport	IBA Inferred from Biological aspect of Ancestor more info
involved_in potassium ion transmembrane transport	IDA Inferred from Direct Assay more info	PubMed
involved_in protein import into nucleus	IEA Inferred from Electronic Annotation more info
involved_in protein targeting	IEA Inferred from Electronic Annotation more info
involved_in psychomotor behavior	IEA Inferred from Electronic Annotation more info
involved_in regulation of action potential firing threshold	IEA Inferred from Electronic Annotation more info
involved_in regulation of synaptic plasticity	IEA Inferred from Electronic Annotation more info
involved_in response to auditory stimulus	IEA Inferred from Electronic Annotation more info
involved_in response to organic cyclic compound	IEA Inferred from Electronic Annotation more info
involved_in sensory perception of sound	IEA Inferred from Electronic Annotation more info
involved_in substantia propria of cornea development	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
located_in axon initial segment	ISS Inferred from Sequence or Structural Similarity more info	PubMed
located_in cell surface	IEA Inferred from Electronic Annotation more info
located_in mitochondrion	IEA Inferred from Electronic Annotation more info
located_in node of Ranvier	ISS Inferred from Sequence or Structural Similarity more info	PubMed
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	ISS Inferred from Sequence or Structural Similarity more info	PubMed
located_in plasma membrane	TAS Traceable Author Statement more info
located_in synapse	IEA Inferred from Electronic Annotation more info
part_of voltage-gated potassium channel complex	IBA Inferred from Biological aspect of Ancestor more info
part_of voltage-gated potassium channel complex	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: potassium voltage-gated channel subfamily KQT member 3

Names: potassium channel subunit alpha KvLQT3; potassium channel, voltage gated KQT-like subfamily Q, member 3; potassium channel, voltage-gated, subfamily Q, member 3; potassium voltage-gated channel, KQT-like subfamily, member 3; voltage-gated potassium channel subunit Kv7.3

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_008854.2 RefSeqGene

Range

4663..364897

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001204824.2 → NP_001191753.1 potassium voltage-gated channel subfamily KQT member 3 isoform 2

Status: REVIEWED

Description

Transcript Variant: This variant (2) contains an alternate 5' terminal exon and it thus differs in the 5' UTR and 5' coding region, compared to variant 1. The resulting isoform (2) has a distinct N-terminus and is shorter than isoform 1.

Source sequence(s)

AC131042, AF033347, AK296293, BX538233

Consensus CDS

CCDS56554.1

UniProtKB/TrEMBL

A0A1W2PQ71

Related

ENSP00000429799.1, ENST00000521134.6

Conserved Domains (4) summary

pfam00520
Location:19 → 243

Ion_trans; Ion transport protein

pfam03520
Location:332 → 536

KCNQ_channel; KCNQ voltage-gated potassium channel

pfam07885
Location:149 → 233

Ion_trans_2; Ion channel

pfam11956
Location:660 → 746

KCNQC3-Ank-G_bd; Ankyrin-G binding motif of KCNQ2-3
NM_004519.4 → NP_004510.1 potassium voltage-gated channel subfamily KQT member 3 isoform 1

See identical proteins and their annotated locations for NP_004510.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1). The 5' extent of this variant is inferred based on orthologous alignments.

Source sequence(s)

AC018540, AC131042, AF033347, AV728013, BX538233

Consensus CDS

CCDS34943.1

UniProtKB/Swiss-Prot

A2VCT8, B4DJY4, E7EQ89, O43525

Related

ENSP00000373648.3, ENST00000388996.10

Conserved Domains (4) summary

pfam00520
Location:139 → 363

Ion_trans; Ion transport protein

pfam03520
Location:452 → 656

KCNQ_channel; KCNQ voltage-gated potassium channel

pfam07885
Location:269 → 353

Ion_trans_2; Ion channel

pfam11956
Location:780 → 866

KCNQC3-Ank-G_bd; Ankyrin-G binding motif of KCNQ2-3

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000008.11 Reference GRCh38.p14 Primary Assembly

Range

132120861..132481095 complement

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_047421769.1 → XP_047277725.1 potassium voltage-gated channel subfamily KQT member 3 isoform X3

UniProtKB/TrEMBL

E7ET42

Related

ENSP00000428790.1, ENST00000519445.5
XM_011517026.3 → XP_011515328.1 potassium voltage-gated channel subfamily KQT member 3 isoform X2

UniProtKB/TrEMBL

A0A1W2PQ71

Conserved Domains (4) summary

pfam00520
Location:19 → 243

Ion_trans; Ion transport protein

pfam03520
Location:332 → 536

KCNQ_channel; KCNQ voltage-gated potassium channel

pfam07885
Location:149 → 233

Ion_trans_2; Ion channel

pfam11956
Location:660 → 746

KCNQC3-Ank-G_bd; Ankyrin-G binding motif of KCNQ2-3
XM_017013400.2 → XP_016868889.1 potassium voltage-gated channel subfamily KQT member 3 isoform X1

UniProtKB/TrEMBL

A0A1W2PQ71

Related

ENSP00000491940.1, ENST00000638588.1

Alternate T2T-CHM13v2.0

Genomic

NC_060932.1 Alternate T2T-CHM13v2.0

Range

133243767..133604173 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054360446.1 → XP_054216421.1 potassium voltage-gated channel subfamily KQT member 3 isoform X3

UniProtKB/TrEMBL

E7ET42
XM_054360445.1 → XP_054216420.1 potassium voltage-gated channel subfamily KQT member 3 isoform X2
XM_054360444.1 → XP_054216419.1 potassium voltage-gated channel subfamily KQT member 3 isoform X1