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KCND3 potassium voltage-gated channel subfamily D member 3 [ Homo sapiens (human) ]

Gene ID: 3752, updated on 11-Apr-2024

Summary

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Official Symbol
KCND3provided by HGNC
Official Full Name
potassium voltage-gated channel subfamily D member 3provided by HGNC
Primary source
HGNC:HGNC:6239
See related
Ensembl:ENSG00000171385 MIM:605411; AllianceGenome:HGNC:6239
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
KV4.3; SCA19; SCA22; BRGDA9; KCND3L; KCND3S; KSHIVB
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. Four sequence-related potassium channel genes - shaker, shaw, shab, and shal - have been identified in Drosophila, and each has been shown to have human homolog(s). This gene encodes a member of the potassium channel, voltage-gated, shal-related subfamily, members of which form voltage-activated A-type potassium ion channels and are prominent in the repolarization phase of the action potential. This member includes two isoforms with different sizes, which are encoded by alternatively spliced transcript variants of this gene. [provided by RefSeq, Jul 2008]
Expression
Broad expression in brain (RPKM 4.9), prostate (RPKM 2.7) and 17 other tissues See more
Orthologs
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Genomic context

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Location:
1p13.2
Exon count:
14
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 1 NC_000001.11 (111770662..111989668, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 1 NC_060925.1 (111785561..112004582, complement)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 1 NC_000001.10 (112313284..112532290, complement)

Chromosome 1 - NC_000001.11Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC101928718 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 1508 Neighboring gene inka box actin regulator 2 Neighboring gene INKA2 antisense RNA 1 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 1509 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:112298273-112299157 Neighboring gene DEAD-box helicase 20 Neighboring gene uncharacterized LOC124904312 Neighboring gene NANOG-H3K4me1 hESC enhancer GRCh37_chr1:112397726-112398319 Neighboring gene MPRA-validated peak363 silencer Neighboring gene KCND3 intronic transcript 1 Neighboring gene MPRA-validated peak364 silencer Neighboring gene ReSE screen-validated silencer GRCh37_chr1:112441183-112441402 Neighboring gene KCND3 antisense RNA 1 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:112480069-112480569 Neighboring gene uncharacterized LOC105378906 Neighboring gene long intergenic non-protein coding RNA 1750

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • 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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Related articles in PubMed

  1. Novel KCND3 Variant Underlying Nonprogressive Congenital Ataxia or SCA19/22 Disrupt K(V)4.3 Protein Expression and K+ Currents with Variable Effects on Channel Properties. Zanni G, et al. Int J Mol Sci, 2021 May 7. PMID 34067185, Free PMC Article
  2. A Novel Gain-of-Function KCND3 Variant Associated with Brugada Syndrome. Li X, et al. Cardiology, 2020. PMID 32818936
  3. KCND3 potassium channel gene variant confers susceptibility to electrocardiographic early repolarization pattern. Teumer A, et al. JCI Insight, 2019 Dec 5. PMID 31600170, Free PMC Article
  4. Novel SCA19/22-associated KCND3 mutations disrupt human K(V) 4.3 protein biosynthesis and channel gating. Hsiao CT, et al. Hum Mutat, 2019 Nov. PMID 31293010
  5. Modulation of the transient outward current (Ito) in rat cardiac myocytes and human Kv4.3 channels by mefloquine. Perez-Cortes EJ, et al. Toxicol Appl Pharmacol, 2015 Oct 15. PMID 26216464

See all (75) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. A Novel Gain-of-Function KCND3 Variant Associated with Brugada Syndrome.
    Title: A Novel Gain-of-Function KCND3 Variant Associated with Brugada Syndrome.
  2. Novel KCND3 Variant Underlying Nonprogressive Congenital Ataxia or SCA19/22 Disrupt KV4.3 Protein Expression and K+ Currents with Variable Effects on Channel Properties.
    Title: Novel KCND3 Variant Underlying Nonprogressive Congenital Ataxia or SCA19/22 Disrupt K(V)4.3 Protein Expression and K+ Currents with Variable Effects on Channel Properties.
  3. Inter-Regulation of Kv4.3 and Voltage-Gated Sodium Channels Underlies Predisposition to Cardiac and Neuronal Channelopathies.
    Title: Inter-Regulation of K(v)4.3 and Voltage-Gated Sodium Channels Underlies Predisposition to Cardiac and Neuronal Channelopathies.
  4. KCND3 potassium channel gene variant confers susceptibility to electrocardiographic early repolarization pattern.
    Title: KCND3 potassium channel gene variant confers susceptibility to electrocardiographic early repolarization pattern.
  5. we utilized the NGS technology to identify two novel KCND3 mutations from two distinct pedigrees with molecularly unassigned SCA. Our clinical observations broaden the genotypic and phenotypic spectrum of SCA19/22 to include cerebellar ataxia, developmental delay, cognitive impairment, myoclonus, and dystonia, thereby emphasizing the significance of KCND3 mutations in a wide range of different neurological disorders.
    Title: Novel SCA19/22-associated KCND3 mutations disrupt human K(V) 4.3 protein biosynthesis and channel gating.
  6. The S248R and R250T mutations of SCN1Bbeta gene caused gain-of-function of Ito by associated with Kv4.3, which maybe underlie the early repolarization syndrome (ERS) phenotype of the probands.
    Title: SCN1Bβ mutations that affect their association with Kv4.3 underlie early repolarization syndrome.
  7. The alpha subunit of Ito Kv4.3 can interact with and modify the localization of the alpha subunit of IKr hERG, thus providing potentially novel insights into the molecular mechanism of the malignant ventricular arrhythmia in heart failure.
    Title: Kv4.3 Modulates the Distribution of hERG.
  8. This study Identified a new KCND3 phenotype and novel genes causing Dravet syndrome.
    Title: Gene mutational analysis in a cohort of Chinese children with unexplained epilepsy: Identification of a new KCND3 phenotype and novel genes causing Dravet syndrome.
  9. mutations cause a gainoffunction of KV4.3/KChIP2encoded channels by increasing membrane protein expression and slowing channel inactivation.
    Title: Two novel Brugada syndrome-associated mutations increase KV4.3 membrane expression and function.
  10. Mefloquine is a concentration-dependent Ito and hKv4.3 channel blocker.
    Title: Modulation of the transient outward current (Ito) in rat cardiac myocytes and human Kv4.3 channels by mefloquine.
Submit: New GeneRIF Correction See all GeneRIFs (48)

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

EBI GWAS Catalog

Description
A genome wide association study (GWAS) providing evidence of an association between common genetic variants and late radiotherapy toxicity.
EBI GWAS Catalog
A meta-analysis of genome-wide association studies of the electrocardiographic early repolarization pattern.
EBI GWAS Catalog
Genetic determinants of P wave duration and PR segment.
EBI GWAS Catalog
Genome-wide analysis of polymorphisms associated with cytokine responses in smallpox vaccine recipients.
EBI GWAS Catalog
Genome-wide association for abdominal subcutaneous and visceral adipose reveals a novel locus for visceral fat in women.
EBI GWAS Catalog

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Clone Names

  • MGC142035, MGC142037

Gene Ontology Provided by GOA

Function Evidence Code Pubs
contributes_to A-type (transient outward) potassium channel activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables metal ion binding IEA
Inferred from Electronic Annotation
more info
  
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables transmembrane transporter binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables voltage-gated potassium channel activity IBA
Inferred from Biological aspect of Ancestor
more info
  
contributes_to voltage-gated potassium channel activity involved in cardiac muscle cell action potential repolarization TAS
Traceable Author Statement
more info
 PubMed 
contributes_to voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization IMP
Inferred from Mutant Phenotype
more info
 PubMed 
Process Evidence Code Pubs
involved_in action potential IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in membrane repolarization IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in membrane repolarization during cardiac muscle cell action potential TAS
Traceable Author Statement
more info
 PubMed 
involved_in membrane repolarization during ventricular cardiac muscle cell action potential IEA
Inferred from Electronic Annotation
more info
  
involved_in potassium ion export across plasma membrane IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in potassium ion export across plasma membrane IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in potassium ion export across plasma membrane ISS
Inferred from Sequence or Structural Similarity
more info
 PubMed 
involved_in potassium ion transport TAS
Traceable Author Statement
more info
 PubMed 
involved_in protein homooligomerization IEA
Inferred from Electronic Annotation
more info
  
involved_in regulation of heart rate by cardiac conduction IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in ventricular cardiac muscle cell membrane repolarization IMP
Inferred from Mutant Phenotype
more info
 PubMed 
Component Evidence Code Pubs
located_in GABA-ergic synapse IEA
Inferred from Electronic Annotation
more info
  
is_active_in dendritic spine IBA
Inferred from Biological aspect of Ancestor
more info
  
is_active_in neuronal cell body IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in plasma membrane TAS
Traceable Author Statement
more info
  
is_active_in postsynaptic membrane IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in postsynaptic specialization membrane IEA
Inferred from Electronic Annotation
more info
  
located_in sarcolemma 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 D member 3
Names
potassium channel, voltage gated Shal related subfamily D, member 3
potassium ionic channel Kv4.3
potassium voltage-gated channel long
potassium voltage-gated channel, Shal-related subfamily, member 3
sha1-related potassium channel Kv4.3
voltage-gated K+ channel
voltage-gated potassium channel subunit Kv4.3

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

  1. NG_032011.2 RefSeqGene

    Range
    5001..218324
    Download
    GenBank, FASTA, Sequence Viewer (Graphics), LRG_445

mRNA and Protein(s)

  1. NM_001378969.1 → NP_001365898.1  potassium voltage-gated channel subfamily D member 3 isoform 1

    Status: REVIEWED

    Source sequence(s)
    AL049557, AL450997, AL512665
    Consensus CDS
    CCDS843.1
    UniProtKB/Swiss-Prot
    O60576, O60577, Q14D71, Q5T0M0, Q9UH85, Q9UH86, Q9UK16, Q9UK17
    UniProtKB/TrEMBL
    B7ZKV0
    Related
    ENSP00000306923.4, ENST00000302127.5
    Conserved Domains (3) summary
    cd18419
    Location:6 → 143
    BTB_POZ_KCND3; BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in potassium voltage-gated channel subfamily D member 3 (KCND3)
    pfam00520
    Location:186 → 412
    Ion_trans; Ion transport protein
    pfam11879
    Location:442 → 563
    DUF3399; Domain of unknown function (DUF3399)

  2. NM_001378970.1 → NP_001365899.1  potassium voltage-gated channel subfamily D member 3 isoform 2

    Status: REVIEWED

    Source sequence(s)
    AL049557, AL450997, AL512665
    Consensus CDS
    CCDS844.1
    UniProtKB/TrEMBL
    B7ZKV0
    Related
    ENSP00000358711.1, ENST00000369697.5
    Conserved Domains (3) summary
    cd18419
    Location:6 → 143
    BTB_POZ_KCND3; BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in potassium voltage-gated channel subfamily D member 3 (KCND3)
    pfam00520
    Location:186 → 412
    Ion_trans; Ion transport protein
    pfam11879
    Location:442 → 544
    DUF3399; Domain of unknown function (DUF3399)

  3. NM_004980.5 → NP_004971.2  potassium voltage-gated channel subfamily D member 3 isoform 1

    See identical proteins and their annotated locations for NP_004971.2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1), also known as the long splice variant, encodes the longer isoform (1).
    Source sequence(s)
    AL049557, AL450997, AL512665
    Consensus CDS
    CCDS843.1
    UniProtKB/Swiss-Prot
    O60576, O60577, Q14D71, Q5T0M0, Q9UH85, Q9UH86, Q9UK16, Q9UK17
    UniProtKB/TrEMBL
    B7ZKV0
    Related
    ENSP00000319591.2, ENST00000315987.6
    Conserved Domains (3) summary
    cd18419
    Location:6 → 143
    BTB_POZ_KCND3; BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in potassium voltage-gated channel subfamily D member 3 (KCND3)
    pfam00520
    Location:186 → 412
    Ion_trans; Ion transport protein
    pfam11879
    Location:442 → 563
    DUF3399; Domain of unknown function (DUF3399)

  4. NM_172198.3 → NP_751948.1  potassium voltage-gated channel subfamily D member 3 isoform 2

    See identical proteins and their annotated locations for NP_751948.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2), also known as the shorter splice variant, lacks an in-frame exon in the 3' coding region, as compared to variant 1. It thus encodes an isoform (2) that is shorter than isoform 1.
    Source sequence(s)
    AL049557, AL450997, AL512665
    Consensus CDS
    CCDS844.1
    UniProtKB/TrEMBL
    B7ZKV0
    Conserved Domains (3) summary
    cd18419
    Location:6 → 143
    BTB_POZ_KCND3; BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in potassium voltage-gated channel subfamily D member 3 (KCND3)
    pfam00520
    Location:186 → 412
    Ion_trans; Ion transport protein
    pfam11879
    Location:442 → 544
    DUF3399; Domain of unknown function (DUF3399)

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

  1. NC_000001.11 Reference GRCh38.p14 Primary Assembly

    Range
    111770662..111989668 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_006710629.5 → XP_006710692.1  potassium voltage-gated channel subfamily D member 3 isoform X1

    See identical proteins and their annotated locations for XP_006710692.1

    UniProtKB/Swiss-Prot
    O60576, O60577, Q14D71, Q5T0M0, Q9UH85, Q9UH86, Q9UK16, Q9UK17
    UniProtKB/TrEMBL
    B7ZKV0
    Conserved Domains (3) summary
    cd18419
    Location:6 → 143
    BTB_POZ_KCND3; BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in potassium voltage-gated channel subfamily D member 3 (KCND3)
    pfam00520
    Location:186 → 412
    Ion_trans; Ion transport protein
    pfam11879
    Location:442 → 563
    DUF3399; Domain of unknown function (DUF3399)

  2. XM_017001244.3 → XP_016856733.1  potassium voltage-gated channel subfamily D member 3 isoform X1

    UniProtKB/Swiss-Prot
    O60576, O60577, Q14D71, Q5T0M0, Q9UH85, Q9UH86, Q9UK16, Q9UK17
    UniProtKB/TrEMBL
    B7ZKV0
    Conserved Domains (3) summary
    cd18419
    Location:6 → 143
    BTB_POZ_KCND3; BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in potassium voltage-gated channel subfamily D member 3 (KCND3)
    pfam00520
    Location:186 → 412
    Ion_trans; Ion transport protein
    pfam11879
    Location:442 → 563
    DUF3399; Domain of unknown function (DUF3399)

  3. XM_011541427.4 → XP_011539729.1  potassium voltage-gated channel subfamily D member 3 isoform X5

    See identical proteins and their annotated locations for XP_011539729.1

    Conserved Domains (2) summary
    cd18419
    Location:6 → 143
    BTB_POZ_KCND3; BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in potassium voltage-gated channel subfamily D member 3 (KCND3)
    pfam00520
    Location:186 → 369
    Ion_trans; Ion transport protein

  4. XM_006710632.4 → XP_006710695.1  potassium voltage-gated channel subfamily D member 3 isoform X4

    Conserved Domains (4) summary
    smart00225
    Location:42 → 139
    BTB; Broad-Complex, Tramtrack and Bric a brac
    pfam00520
    Location:217 → 369
    Ion_trans; Ion transport protein
    pfam02214
    Location:42 → 131
    BTB_2; BTB/POZ domain
    pfam11601
    Location:3 → 28
    Shal-type; Shal-type voltage-gated potassium channels

  5. XM_011541428.3 → XP_011539730.1  potassium voltage-gated channel subfamily D member 3 isoform X6

    See identical proteins and their annotated locations for XP_011539730.1

    Conserved Domains (2) summary
    cd18419
    Location:6 → 143
    BTB_POZ_KCND3; BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in potassium voltage-gated channel subfamily D member 3 (KCND3)
    pfam00520
    Location:186 → 369
    Ion_trans; Ion transport protein

  6. XM_011541426.3 → XP_011539728.1  potassium voltage-gated channel subfamily D member 3 isoform X3

    Conserved Domains (4) summary
    smart00225
    Location:42 → 139
    BTB; Broad-Complex, Tramtrack and Bric a brac
    pfam00520
    Location:217 → 369
    Ion_trans; Ion transport protein
    pfam02214
    Location:42 → 131
    BTB_2; BTB/POZ domain
    pfam11601
    Location:3 → 28
    Shal-type; Shal-type voltage-gated potassium channels

  7. XM_011541425.4 → XP_011539727.1  potassium voltage-gated channel subfamily D member 3 isoform X2

    Conserved Domains (4) summary
    smart00225
    Location:42 → 139
    BTB; Broad-Complex, Tramtrack and Bric a brac
    pfam00520
    Location:217 → 369
    Ion_trans; Ion transport protein
    pfam02214
    Location:42 → 131
    BTB_2; BTB/POZ domain
    pfam11601
    Location:3 → 28
    Shal-type; Shal-type voltage-gated potassium channels

  8. XM_017001245.3 → XP_016856734.1  potassium voltage-gated channel subfamily D member 3 isoform X2

    Related
    ENST00000703643.1
    Conserved Domains (4) summary
    smart00225
    Location:42 → 139
    BTB; Broad-Complex, Tramtrack and Bric a brac
    pfam00520
    Location:217 → 369
    Ion_trans; Ion transport protein
    pfam02214
    Location:42 → 131
    BTB_2; BTB/POZ domain
    pfam11601
    Location:3 → 28
    Shal-type; Shal-type voltage-gated potassium channels

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060925.1 Alternate T2T-CHM13v2.0

    Range
    111785561..112004582 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054336461.1 → XP_054192436.1  potassium voltage-gated channel subfamily D member 3 isoform X1

    UniProtKB/Swiss-Prot
    O60576, O60577, Q14D71, Q5T0M0, Q9UH85, Q9UH86, Q9UK16, Q9UK17

  2. XM_054336462.1 → XP_054192437.1  potassium voltage-gated channel subfamily D member 3 isoform X1

    UniProtKB/Swiss-Prot
    O60576, O60577, Q14D71, Q5T0M0, Q9UH85, Q9UH86, Q9UK16, Q9UK17

  3. XM_054336467.1 → XP_054192442.1  potassium voltage-gated channel subfamily D member 3 isoform X5

  4. XM_054336466.1 → XP_054192441.1  potassium voltage-gated channel subfamily D member 3 isoform X4

  5. XM_054336468.1 → XP_054192443.1  potassium voltage-gated channel subfamily D member 3 isoform X6

  6. XM_054336465.1 → XP_054192440.1  potassium voltage-gated channel subfamily D member 3 isoform X3

  7. XM_054336463.1 → XP_054192438.1  potassium voltage-gated channel subfamily D member 3 isoform X2

  8. XM_054336464.1 → XP_054192439.1  potassium voltage-gated channel subfamily D member 3 isoform X2

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q9UK17.3 GenPept UniProtKB/Swiss-Prot:Q9UK17

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