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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
    mouse all
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    Genomic context

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    See KCND3 in Genome Data Viewer
    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

    Gene LinkOut

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

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