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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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KCNIP4
potassium voltage-gated channel interacting protein 4
Chromosome 4 · 4p15.31-p15.2
NCBI Gene: 80333Ensembl: ENSG00000185774.17HGNC: HGNC:30083UniProt: A8K4N3
37PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Ion ChannelTransporter
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
calcium ion bindingprotein bindingcytoplasmperoxisomemathematical abilitysmoking initiationresponse to angiotensin-converting enzyme inhibitorAbruptio Placentae
✦AI Summary

KCNIP4 is a regulatory subunit of Kv4/D-type voltage-gated A-type potassium channels that modulates channel density, inactivation kinetics, and recovery rates in a calcium-dependent manner 123. It regulates both KCND2 and KCND3/Kv4.3 currents, with certain isoforms negatively regulating surface expression 23. Functionally, KCNIP4 enhances A-type potassium currents that provide neuroprotection against glutamate-induced excitotoxicity in ischemic stroke models 4. In disease relevance, KCNIP4 variants are associated with multiple psychiatric and neurological disorders: asthma and airway hyperresponsiveness 5, adult ADHD and personality disorders 67, and post-traumatic stress disorder in the dorsolateral prefrontal cortex 8. The gene is expressed in cerebellar neurons with regional enrichment in granule cell layers 9. Additionally, KCNIP4 disruption has been identified in renal cell cancer patients with constitutional translocations, suggesting potential tumor suppressor involvement 10. Alternative splicing generates functionally distinct isoforms with tissue-specific expression patterns 11, contributing to the gene's diverse physiological roles.

Sources cited
1
KCNIP4 modulates KCND2 channel properties in calcium-dependent manner
PMID: 11847232
2
KCNIP4 isoforms differentially regulate KCND2 membrane expression and channel kinetics
PMID: 18957440
3
KCNIP4 modulates both KCND2 and KCND3/Kv4.3 currents
PMID: 23576435
4
KCNIP4 upregulation enhances A-type potassium currents protecting against glutamate excitotoxicity
PMID: 31792968
5
KCNIP4 associated with asthma and airway hyperresponsiveness in integrated mouse-human GWAS
PMID: 23457522
6
KCNIP4 variants associated with adult ADHD and personality disorders
PMID: 22981920
7
KCNIP4 identified as PTSD-associated gene in dorsolateral prefrontal cortex with cell-type specific regulation
PMID: 40533550
8
KCNIP4 associated with adult ADHD as part of neurite outgrowth network
PMID: 28097908
9
KCNIP4 expressed as cerebellar granule cell layer marker in human stem cell-derived organoids
PMID: 35896708
10
KCNIP4 disrupted in renal cell cancer patients and highly expressed in normal kidney cells
PMID: 17981209
11
KCNIP4 undergoes alternative splicing generating tissue-specific variants with differential expression
PMID: 16112838
Disease Associationsⓘ20
mathematical abilityOpen Targets
0.44Moderate
smoking initiationOpen Targets
0.41Moderate
response to angiotensin-converting enzyme inhibitorOpen Targets
0.40Weak
Abruptio PlacentaeOpen Targets
0.38Weak
COVID-19Open Targets
0.38Weak
insomniaOpen Targets
0.37Weak
CoughOpen Targets
0.36Weak
spontaneous abortionOpen Targets
0.32Weak
ovarian dysfunctionOpen Targets
0.32Weak
severe acute respiratory syndromeOpen Targets
0.32Weak
chronic obstructive pulmonary diseaseOpen Targets
0.30Weak
diabetic ketoacidosisOpen Targets
0.29Weak
placental retentionOpen Targets
0.29Weak
acute tonsillitisOpen Targets
0.28Weak
vascular diseaseOpen Targets
0.28Weak
preeclampsiaOpen Targets
0.27Weak
cardiomyopathyOpen Targets
0.25Weak
kidney diseaseOpen Targets
0.25Weak
knee fractureOpen Targets
0.25Weak
premature birthOpen Targets
0.25Weak
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
KCND2Protein interaction97%KCND1Protein interaction97%KCND3Protein interaction97%KCNIP2Protein interaction97%KCNC1Protein interaction94%PSEN2Protein interaction81%
Tissue Expression6 tissues
Brain
100%
Bone Marrow
12%
Ovary
8%
Heart
5%
Lung
2%
Liver
2%
Gene Interaction Network
Click a node to explore
KCNIP4KCND2KCND1KCND3KCNIP2KCNC1PSEN2
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q3YAB7
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.85LoF Tolerant
pLIⓘ
0.24Tolerant
Observed/Expected LoF0.43 [0.24–0.85]
RankingsWhere KCNIP4 stands among ~20K protein-coding genes
  • #10,639of 20,598
    Most Researched37
  • #7,440of 17,882
    Most Constrained (LOEUF)0.85
Genes detectedKCNIP4
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Single-cell transcriptomic and chromatin dynamics of the human brain in PTSD.
PMID: 40533550
Nature · 2025
1.00
2
Integration of mouse and human genome-wide association data identifies KCNIP4 as an asthma gene.
PMID: 23457522
PLoS One · 2013
0.90
3
KCNIP4 as a candidate gene for personality disorders and adult ADHD.
PMID: 22981920
Eur Neuropsychopharmacol · 2013
0.80
4
Down-regulation of miR-3068-3p enhances kcnip4-regulated A-type potassium current to protect against glutamate-induced excitotoxicity.
PMID: 31792968
J Neurochem · 2020
0.70
5
Phenotypic, metabolic, and biogenesis properties of human stem cell-derived cerebellar spheroids.
PMID: 35896708
Sci Rep · 2022
0.60