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

Summary

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

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_000004.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues 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?

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

D4S2620 (e-PCR), detects polymorphism
- UniSTS:61440

D4S893 (e-PCR)
- UniSTS:21506

G16780 (e-PCR)
- UniSTS:73731

SHGC-51650 (e-PCR)
- UniSTS:53766

SHGC-59487 (e-PCR)
- UniSTS:32519

SHGC-79761 (e-PCR)
- UniSTS:96011

G33687 (e-PCR)
- UniSTS:16666

D4S278 (e-PCR)
- UniSTS:42525

D4S2994 (e-PCR)
- UniSTS:76324

WI-20656 (e-PCR)
- UniSTS:42532

D4S1533 (e-PCR)
- UniSTS:68147

RH92764 (e-PCR)
- UniSTS:87094

D4S2707 (e-PCR)
- UniSTS:69435

G20630 (e-PCR)
- UniSTS:11324

D4S1546 (e-PCR)
- UniSTS:18748

D4S1562 (e-PCR), detects polymorphism
- UniSTS:14143

STS-H52461 (e-PCR)
- UniSTS:5189

D4S2792 (e-PCR)
- UniSTS:77897

D4S3020 (e-PCR)
- UniSTS:67147

SHGC-144186 (e-PCR)
- UniSTS:174159

RH93232 (e-PCR)
- UniSTS:93010

RH12353 (e-PCR)
- UniSTS:37974

D4S1593 (e-PCR), detects polymorphism
- UniSTS:9561

SHGC-67313 (e-PCR)
- UniSTS:84059

CHLC.GGAT14F06 (e-PCR)
- UniSTS:28001

D4S456 (e-PCR)
- UniSTS:48743

AB055381 (e-PCR)
- UniSTS:479853

SHGC-30526 (e-PCR)
- UniSTS:10608

G63700 (e-PCR)
- UniSTS:140662

G65558 (e-PCR)
- UniSTS:225400

D4S2511E (e-PCR)
- UniSTS:16513

D4S2708 (e-PCR)
- UniSTS:42117

SHGC-51639 (e-PCR)
- UniSTS:1414

RH120910 (e-PCR)
- UniSTS:133767

D4S2312 (e-PCR)
- UniSTS:149384

D4S323 (e-PCR)
- UniSTS:15502

D4S3349 (e-PCR), detects polymorphism
- UniSTS:58766

STS-F04275 (e-PCR)
- UniSTS:78992

GATA70E01 (e-PCR)
- UniSTS:498580

D4S1562 (e-PCR), detects polymorphism
- UniSTS:45460

D4S337 (e-PCR)
- UniSTS:12949

SHGC-50646 (e-PCR)
- UniSTS:38805

D4S2353 (e-PCR)
- UniSTS:81558

D4S2905 (e-PCR)
- UniSTS:49046

D4S1546 (e-PCR)
- UniSTS:35745

D4S337 (e-PCR)
- UniSTS:146594

SHGC-24820 (e-PCR)
- UniSTS:3235

SHGC-8260 (e-PCR)
- UniSTS:2472

SHGC-17216 (e-PCR)
- UniSTS:47529

D4S503 (e-PCR)
- UniSTS:46766

RH17093 (e-PCR)
- UniSTS:84912

WI-21155 (e-PCR)
- UniSTS:54195

SHGC-67835 (e-PCR)
- UniSTS:64451

RH119995 (e-PCR)
- UniSTS:133319

Kcnip4 (e-PCR), detects polymorphism
- UniSTS:478923

Kcnip4 (e-PCR), detects polymorphism
- UniSTS:478924

G63730 (e-PCR)
- UniSTS:140761

G33938 (e-PCR)
- UniSTS:24542

D4S2803 (e-PCR)
- UniSTS:37091

SHGC-81007 (e-PCR)
- UniSTS:102628

D4S3017 (e-PCR), detects polymorphism
- UniSTS:20199

D4S2525E (e-PCR)
- UniSTS:55272

G33915 (e-PCR)
- UniSTS:40173

SHGC-59731 (e-PCR)
- UniSTS:17646

SHGC-59718 (e-PCR)
- UniSTS:11503

RH118939 (e-PCR)
- UniSTS:138225

SHGC-24104 (e-PCR)
- UniSTS:49137

D4S1593 (e-PCR), detects polymorphism
- UniSTS:49649

RH122272 (e-PCR)
- UniSTS:134898

SHGC-50148 (e-PCR)
- UniSTS:39154

WI-18093 (e-PCR)
- UniSTS:23800

D4S3356 (e-PCR)
- UniSTS:76538

SHGC-67709 (e-PCR)
- UniSTS:79100

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

NG_052969.1 RefSeqGene

Range

4980..1225146

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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]
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]
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]
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]
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]
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]
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

NC_000004.12 Reference GRCh38.p14 Primary Assembly

Range

20728606..21948772 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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