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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 15 days ago
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KCNIP1
potassium voltage-gated channel interacting protein 1
Chromosome 5 Β· 5q35.1
NCBI Gene: 30820Ensembl: ENSG00000182132.15HGNC: HGNC:15521UniProt: Q9NZI2
42PubMed Papers
20Diseases
0Drugs
1Pathogenic Variants
FUNCTIONAL ROLE
Ion ChannelTransporter
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
protein bindingregulation of potassium ion transmembrane transportcytoplasmpotassium channel regulator activitygeneralised epilepsyovarian neoplasmdiaphragm diseaseenteritis
✦AI Summary

KCNIP1 (potassium channel-interacting protein 1) functions as a regulatory subunit of Kv4 voltage-gated potassium channels, particularly Kv4.1 and Kv4.2 1. It modulates channel density, inactivation kinetics, and recovery from inactivation in a calcium-dependent manner 1. Structurally, KCNIP1 captures both the N and C termini of Kv4.2 to prevent N-type inactivation and stabilize gating helices, thereby enabling rapidly activating and inactivating A-type currents that prevent backpropagation of action potentials 1. KCNIP1 is expressed differentially across brain regions and tissues, with alternatively spliced variants contributing to functional diversity 2. Clinically, KCNIP1 dysregulation associates with multiple conditions. A common copy number variant in KCNIP1's first intron strongly predicts atrial fibrillation risk 3, with overexpression inducing arrhythmias in zebrafish 3. KCNIP1 copy number gains associate with type 2 diabetes susceptibility, correlating with elevated fasting glucose and impaired insulin secretion 4, 5. KCNIP1 inhibition increases glucose-dependent insulin secretion 5. Additionally, KCNIP1 polymorphisms associate with attention-deficit/hyperactivity disorder risk 6, and DNA methylation changes at KCNIP1 correlate with depression severity 7.

Sources cited
1
KCNIP1 is a regulatory subunit of Kv4 channels, modulates channel gating by capturing N and C termini of Kv4.2 to prevent N-type inactivation and stabilize S6 gating helices
PMID: 34552243
2
KCNIP1 mRNAs are expressed differentially in brain regions and tissues with alternative splicing generating functional diversity
PMID: 16112838
3
A KCNIP1 copy number variant strongly associates with atrial fibrillation risk; overexpression causes inducible AF in zebrafish
PMID: 26831368
4
KCNIP1 copy number gain is associated with type 2 diabetes risk and correlates with elevated fasting glucose and impaired insulin levels
PMID: 29491224
5
KCNIP1 inhibition increases glucose-dependent insulin secretion, indicating KCNIP1 dysregulation alters insulin production in T2D
PMID: 24886904
6
KCNIP1 polymorphisms associate with ADHD risk in the studied population
PMID: 34573389
7
DNA methylation at KCNIP1 CpG sites associates with depression severity in epigenome-wide association study
PMID: 34341332
Disease Associationsβ“˜20
generalised epilepsyOpen Targets
0.33Weak
ovarian neoplasmOpen Targets
0.33Weak
diaphragm diseaseOpen Targets
0.30Weak
enteritisOpen Targets
0.26Weak
hyperpituitarismOpen Targets
0.25Weak
StutteringOpen Targets
0.24Weak
TicsOpen Targets
0.24Weak
migraine disorderOpen Targets
0.12Weak
atrial fibrillationOpen Targets
0.08Suggestive
MODYOpen Targets
0.07Suggestive
eosinophil peroxidase deficiencyOpen Targets
0.07Suggestive
immunodeficiency 88Open Targets
0.06Suggestive
linear and whorled nevoid hypermelanosisOpen Targets
0.06Suggestive
maturity-onset diabetes of the young type 3Open Targets
0.05Suggestive
chronic myeloproliferative disorderOpen Targets
0.05Suggestive
attention deficit hyperactivity disorderOpen Targets
0.05Suggestive
3-hydroxy-3-methylglutaryl-CoA synthase deficiencyOpen Targets
0.05Suggestive
AnxietyOpen Targets
0.05Suggestive
hyperproinsulinemiaOpen Targets
0.05Suggestive
substance-related disorderOpen Targets
0.05Suggestive
Pathogenic Variants1
NM_014592.4(KCNIP1):c.328G>A (p.Asp110Asn)Pathogenic
Idiopathic generalized epilepsy
β˜†β˜†β˜†β˜†β†’ Residue 110
View on ClinVar β†—
Related Genes
DPP6Protein interaction100%KCNC1Protein interaction100%KCND1Protein interaction95%VAPBProtein interaction82%RMDN3Protein interaction82%HABP2Protein interaction81%
Tissue Expression6 tissues
Brain
100%
Heart
8%
Ovary
4%
Lung
3%
Bone Marrow
3%
Liver
1%
Gene Interaction Network
Click a node to explore
KCNIP1DPP6KCNC1KCND1VAPBRMDN3HABP2
PROTEIN STRUCTURE
Preparing viewer…
PDB1S1E Β· 2.30 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.75LoF Tolerant
pLIβ“˜
0.22Tolerant
Observed/Expected LoF0.43 [0.26–0.75]
RankingsWhere KCNIP1 stands among ~20K protein-coding genes
  • #9,891of 20,598
    Most Researched42
  • #5,152of 5,498
    Most Pathogenic Variants1
  • #5,890of 17,882
    Most Constrained (LOEUF)0.75
Genes detectedKCNIP1
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Structural basis of gating modulation of Kv4 channel complexes.
PMID: 34552243
Nature Β· 2021
1.00
2
Structure, alternative splicing, and expression of the human and mouse KCNIP gene family.
PMID: 16112838
Genomics Β· 2005
0.90
3
Genome-wide screening identifies a KCNIP1 copy number variant as a genetic predictor for atrial fibrillation.
PMID: 26831368
Nat Commun Β· 2016
0.80
4
Divergent patterns of genic copy number variation in KCNIP1 gene reveal risk locus of type 2 diabetes in Chinese population.
PMID: 29491224
Endocr J Β· 2018
0.70
5
Common and Unique Genetic Background between Attention-Deficit/Hyperactivity Disorder and Excessive Body Weight.
PMID: 34573389
Genes (Basel) Β· 2021
0.60