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

Gene ID: 80333, updated on 5-Mar-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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Location:
4p15.31-p15.2
Exon count:
14
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 4 NC_000004.12 (20728606..21948772, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 4 NC_060928.1 (20710285..21930631, complement)
105.20220307 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: 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. 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
  2. KCNIP4 as a candidate gene for personality disorders and adult ADHD. Weißflog L, et al. Eur Neuropsychopharmacol, 2013 Jun. PMID 22981920
  3. 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
  4. 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
  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)

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

  • 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
  
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_2023_10

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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