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    KCNIP4 potassium voltage-gated channel interacting protein 4 [ Homo sapiens (human) ]

    Gene ID: 80333, updated on 27-Dec-2024

    Summary

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    Official Symbol
    KCNIP4provided by HGNC
    Official Full Name
    potassium voltage-gated channel interacting protein 4provided by HGNC
    Primary source
    HGNC:HGNC:30083
    See related
    Ensembl:ENSG00000185774 MIM:608182; AllianceGenome:HGNC:30083
    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
    CALP; KCHIP4
    Summary
    This gene encodes a member of the family of voltage-gated potassium (Kv) channel-interacting proteins (KCNIPs), which belong to the recoverin branch of the EF-hand superfamily. Members of the KCNIP family are small calcium binding proteins. They all have EF-hand-like domains, and differ from each other in the N-terminus. They are integral subunit components of native Kv4 channel complexes. They may regulate A-type currents, and hence neuronal excitability, in response to changes in intracellular calcium. This protein member also interacts with presenilin. Multiple alternatively spliced transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]
    Expression
    Broad expression in brain (RPKM 3.7), endometrium (RPKM 1.2) and 15 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See KCNIP4 in Genome Data Viewer
    Location:
    4p15.31-p15.2
    Exon count:
    14
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 4 NC_000004.12 (20728606..21948772, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 4 NC_060928.1 (20710285..21930631, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 4 NC_000004.11 (20730229..21950395, complement)

    Chromosome 4 - NC_000004.12Genomic Context describing neighboring genes Neighboring gene slit guidance ligand 2 Neighboring gene NANOG hESC enhancer GRCh37_chr4:20590873-20591475 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr4:20618190-20618690 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr4:20631231-20631937 Neighboring gene H3K27ac hESC enhancer GRCh37_chr4:20634775-20635276 Neighboring gene H3K27ac hESC enhancer GRCh37_chr4:20635277-20635776 Neighboring gene microRNA 218-1 Neighboring gene uncharacterized LOC105374515 Neighboring gene ReSE screen-validated silencer GRCh37_chr4:20675647-20675822 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 21365 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_77676 Neighboring gene parkin coregulated like Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_77702 Neighboring gene Sharpr-MPRA regulatory region 6369 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_77709 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr4:21305572-21306072 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr4:21367838-21368378 Neighboring gene uncharacterized LOC124900677 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr4:21544835-21545753 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_77794 Neighboring gene uncharacterized LOC105374516 Neighboring gene microRNA 7978 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_77821 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_77853 Neighboring gene ribosomal protein L31 pseudogene 25 Neighboring gene KCNIP4 intronic transcript 1 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr4:21950342-21950842 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr4:21950843-21951343 Neighboring gene RNA, U6 small nuclear 420, pseudogene Neighboring gene MED14-independent group 3 enhancer GRCh37_chr4:22205027-22206226 Neighboring gene Sharpr-MPRA regulatory region 2159 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr4:22269927-22271126 Neighboring gene uncharacterized LOC100505912

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: Tissue-specific circular RNA induction during human fetal development
    • Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
    • BioProject: PRJNA270632
    • Publication: PMID 26076956
    • Analysis date: Mon Apr 2 22:54:59 2018

    Bibliography

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    Related articles in PubMed

    1. RNA polymerase III drives alternative splicing of the potassium channel-interacting protein contributing to brain complexity and neurodegeneration. Massone S, et al. J Cell Biol, 2011 May 30. PMID 21624954, Free PMC Article
    2. A genome-wide association study identifies variants in KCNIP4 associated with ACE inhibitor-induced cough. Mosley JD, et al. Pharmacogenomics J, 2016 Jun. PMID 26169577, Free PMC Article
    3. Mapping of constitutional translocation breakpoints in renal cell cancer patients: identification of KCNIP4 as a candidate gene. Bonne A, et al. Cancer Genet Cytogenet, 2007 Nov. PMID 17981209
    4. KCNIP4 as a candidate gene for personality disorders and adult ADHD. Weißflog L, et al. Eur Neuropsychopharmacol, 2013 Jun. PMID 22981920
    5. Auxiliary KChIP4a suppresses A-type K+ current through endoplasmic reticulum (ER) retention and promoting closed-state inactivation of Kv4 channels. Tang YQ, et al. J Biol Chem, 2013 May 24. PMID 23576435, Free PMC Article

    See all (37) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Results indicate that SNPs in KCNIP4 may modulate ACE inhibitor-induced cough risk.
      Title: A genome-wide association study identifies variants in KCNIP4 associated with ACE inhibitor-induced cough.
    2. Subunit counting by single-molecule imaging revealed that the bound number of KChIP4 in each Kv4.2.KChIP4 complex was dependent on the expression level of KChIP4.
      Title: The stoichiometry and biophysical properties of the Kv4 potassium channel complex with K+ channel-interacting protein (KChIP) subunits are variable, depending on the relative expression level.
    3. genetic association studies in populations in Germany: Data suggest that multiple SNPs in KCNIP4 are associated not only with attention deficit disorder with hyperactivity in children and adults but also with personality disorders.
      Title: KCNIP4 as a candidate gene for personality disorders and adult ADHD.
    4. Genome-wide association study identifies KCNIP4 as an asthma gene in human and in mouse.
      Title: Integration of mouse and human genome-wide association data identifies KCNIP4 as an asthma gene.
    5. KChIP4a suppresses A-type Kv4 current via ER retention and enhancement of Kv4 closed-state inactivation.
      Title: Auxiliary KChIP4a suppresses A-type K+ current through endoplasmic reticulum (ER) retention and promoting closed-state inactivation of Kv4 channels.
    6. The synthesis of the variant KCNIP4 isoform is also detrimental to brain physiology, as it results in the concomitant blockade of the fast kinetics of potassium channels.
      Title: RNA polymerase III drives alternative splicing of the potassium channel-interacting protein contributing to brain complexity and neurodegeneration.
    7. Observational study and genome-wide association study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
      Title: Genome-wide association study of increasing suicidal ideation during antidepressant treatment in the GENDEP project.
    8. Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator)
      Title: Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.
    9. These data demonstrate that PKA phosphorylation of Kv4.2 plays an important role in the trafficking of Kv4.2 through its specific interaction with KChIP4a.
      Title: KChIP4a regulates Kv4.2 channel trafficking through PKA phosphorylation.
    10. Clinical trial and genome-wide association study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
      Title: Molecular genetics of successful smoking cessation: convergent genome-wide association study results.
    Submit: New GeneRIF Correction See all GeneRIFs (17)

    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 suggests contrasting associations in ACPA-positive versus ACPA-negative rheumatoid arthritis.
    EBI GWAS Catalog
    Genome-wide association study of increasing suicidal ideation during antidepressant treatment in the GENDEP project.
    EBI GWAS Catalog
    Loci associated with N-glycosylation of human immunoglobulin G show pleiotropy with autoimmune diseases and haematological cancers.
    EBI GWAS Catalog
    Novel genetic loci identified for the pathophysiology of childhood obesity in the Hispanic population.
    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)

    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

    • MGC44947

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables calcium ion binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables calcium ion binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables potassium channel activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables potassium channel regulator activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables potassium channel regulator activity ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in potassium ion transmembrane transport IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in protein localization to plasma membrane ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in regulation of potassium ion transmembrane transport IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in regulation of potassium ion transmembrane transport ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in regulation of signal transduction IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    Component Evidence Code Pubs
    located_in cytoplasm IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in cytosol ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    located_in dendrite IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in endoplasmic reticulum IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in neuronal cell body IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in peroxisome IDA
    Inferred from Direct Assay
    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
    		  
    located_in plasma membrane TAS
    Traceable Author Statement
    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 ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  

    General protein information

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    Preferred Names
    Kv channel-interacting protein 4
    Names
    Kv channel interacting protein 4
    a-type potassium channel modulatory protein 4
    calsenilin-like protein

    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_052969.1 RefSeqGene

      Range
      4980..1225146
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001035003.2 → NP_001030175.1  Kv channel-interacting protein 4 isoform 5

      See identical proteins and their annotated locations for NP_001030175.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (5) has an alternate exon which contains an in-frame start codon, as compared to variant 1. The encoded isoform (5) thus has an alternate N-terminus, as compared to isoform 1.
      Source sequence(s)
      AC096576, AC104065, BX648990, DQ148490
      Consensus CDS
      CCDS43217.1
      UniProtKB/TrEMBL
      A8K0U6
      Related
      ENSP00000371583.3, ENST00000382148.7
      Conserved Domains (1) summary
      COG5126
      Location:55 → 214
      FRQ1; Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms]

    2. NM_001035004.2 → NP_001030176.1  Kv channel-interacting protein 4 isoform 3

      See identical proteins and their annotated locations for NP_001030176.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (6) has an alternate exon which lacks an in-frame start codon, as compared to variant 1. Use of a downstream start codon results in an isoform (3) that has a shorter N-terminus, as compared to isoform 1. Variants 3 and 6 encode the same isoform (3).
      Source sequence(s)
      AC096576, AC104065, AK290998, BX648990, DQ148491
      Consensus CDS
      CCDS47035.1
      UniProtKB/TrEMBL
      A8K0U6
      Related
      ENSP00000423257.1, ENST00000509207.1
      Conserved Domains (1) summary
      COG5126
      Location:18 → 177
      FRQ1; Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms]

    3. NM_001363504.2 → NP_001350433.1  Kv channel-interacting protein 4 isoform 6

      Status: REVIEWED

      Description
      Transcript Variant: This variant (7) differs in the 5' UTR and coding sequence compared to variant 1. The resulting isoform (6) has a shorter and distinct N-terminus compared to isoform 1.
      Source sequence(s)
      AC097505, AC104065, AC109636
      Consensus CDS
      CCDS87210.1
      UniProtKB/TrEMBL
      A8K4N3, Q3YAB7
      Related
      ENSP00000494651.1, ENST00000382149.9
      Conserved Domains (1) summary
      COG5126
      Location:63 → 222
      FRQ1; Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms]

    4. NM_025221.6 → NP_079497.2  Kv channel-interacting protein 4 isoform 1

      See identical proteins and their annotated locations for NP_079497.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) encodes the longest isoform (1, also known as KCHIP4.1).
      Source sequence(s)
      AC097505, AC104065, AC113606, AF367023, BC032520, BI596848, BX648990
      Consensus CDS
      CCDS43216.1
      UniProtKB/Swiss-Prot
      Q3YAB8, Q3YAB9, Q3YAC0, Q3YAC1, Q3YAC2, Q4W5G8, Q6PIL6, Q8NEU0, Q9BWT2, Q9H294, Q9H2A4
      UniProtKB/TrEMBL
      A8K0U6
      Related
      ENSP00000371587.2, ENST00000382152.7
      Conserved Domains (1) summary
      COG5126
      Location:80 → 239
      FRQ1; Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms]

    5. NM_147181.4 → NP_671710.1  Kv channel-interacting protein 4 isoform 2

      See identical proteins and their annotated locations for NP_671710.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) lacks an in-frame exon in the coding region, as compared to variant 1. Isoform 2, also known as KCHIP4.2, is thus missing an internal segment, as compared to isoform 1.
      Source sequence(s)
      AC104065, AC113606, AF367024, BI596848, BX648990
      Consensus CDS
      CCDS43215.1
      UniProtKB/TrEMBL
      A8K0U6
      Related
      ENSP00000399080.2, ENST00000447367.6
      Conserved Domains (1) summary
      COG5126
      Location:46 → 205
      FRQ1; Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms]

    6. NM_147182.4 → NP_671711.1  Kv channel-interacting protein 4 isoform 3

      See identical proteins and their annotated locations for NP_671711.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) has an alternate exon which lacks an in-frame start codon, as compared to variant 1. Use of a downstream start codon results in an isoform (3, also known as KCHIP4.3) that has a shorter N-terminus, as compared to isoform 1. Variants 3 and 6 encode the same isoform (3).
      Source sequence(s)
      AC104065, AC113606, AY029176, BI596848, BX648990
      Consensus CDS
      CCDS47035.1
      UniProtKB/TrEMBL
      A8K0U6
      Conserved Domains (1) summary
      COG5126
      Location:18 → 177
      FRQ1; Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms]

    7. NM_147183.3 → NP_671712.1  Kv channel-interacting protein 4 isoform 4

      See identical proteins and their annotated locations for NP_671712.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) has an alternate exon which contains an in-frame start codon, as compared to variant 1. Isoform 4, also known as KCHIP4.4, thus has an alternate N-terminus, as compared to isoform 1.
      Source sequence(s)
      AC104065, AY118170, BX648990
      Consensus CDS
      CCDS3428.1
      UniProtKB/TrEMBL
      A8K4N3
      Related
      ENSP00000371585.4, ENST00000382150.8
      Conserved Domains (1) summary
      COG5126
      Location:59 → 218
      FRQ1; Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms]

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000004.12 Reference GRCh38.p14 Primary Assembly

      Range
      20728606..21948772 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_011513885.4 → XP_011512187.1  Kv channel-interacting protein 4 isoform X1

      Conserved Domains (2) summary
      cd00051
      Location:135 → 206
      EFh; EF-hand, calcium binding motif; A diverse superfamily of calcium sensors and calcium signal modulators; most examples in this alignment model have 2 active canonical EF hands. Ca2+ binding induces a conformational change in the EF-hand motif, leading to ...
      pfam13499
      Location:138 → 206
      EF-hand_7; EF-hand domain pair

    Reference GRCh38.p14 ALT_REF_LOCI_1

    Genomic

    1. NT_187540.1 Reference GRCh38.p14 ALT_REF_LOCI_1

      Range
      4291..183576 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060928.1 Alternate T2T-CHM13v2.0

      Range
      20710285..21930631 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054350900.1 → XP_054206875.1  Kv channel-interacting protein 4 isoform X1

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q6PIL6.1 GenPept UniProtKB/Swiss-Prot:Q6PIL6

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