KCND2

Chr 7

potassium voltage-gated channel subfamily D member 2

Also known as: KV4.2, RK5

NCBI Gene: 3751ENSG00000184408UniProt: Q9NZV8

Voltage-gated potassium (Kv) channels represent the most complex class of voltage-gated ion channels from both functional and structural standpoints. Their diverse functions include regulating neurotransmitter release, heart rate, insulin secretion, neuronal excitability, epithelial electrolyte transport, smooth muscle contraction, and cell volume. Four sequence-related potassium channel genes - shaker, shaw, shab, and shal - have been identified in Drosophila, and each has been shown to have human homolog(s). This gene encodes a member of the potassium channel, voltage-gated, shal-related subfamily, members of which form voltage-activated A-type potassium ion channels and are prominent in the repolarization phase of the action potential. This member mediates a rapidly inactivating, A-type outward potassium current which is not under the control of the N terminus as it is in Shaker channels. [provided by RefSeq, Jul 2008]

0
ClinVar variants
0
Pathogenic / LP
0.01
pLI score
0
Active trials
Clinical Summary— KCND2
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.32) despite low pLI — interpret in context.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Missense constrained — critical functional residues
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.57LOEUF
pLI 0.012
Z-score 3.17
OE 0.32 (0.19–0.57)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
3.51Z-score
OE missense 0.49 (0.44–0.56)
189 obs / 382.3 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.32 (0.19–0.57)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.49 (0.44–0.56)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.95
0≤1.21.6
LoF obs/exp: 8 / 25.1Missense obs/exp: 189 / 382.3Syn Z: 0.45

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

KCND2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

KCND2-related neurodevelopmental disorder with or without seizures

moderate
ADUndeterminedAltered Gene Product Structure
Dev. Disorders
G2P ↗
missense variant

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
📖
GeneReview available — KCND2
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Promoting proliferation and tumorigenesis of breast cancer: KCND2's significance as a prognostic factor.
Yang S et al.·Funct Integr Genomics
2023
KCND2 variants associated with global developmental delay differentially impair Kv4.2 channel gating.
Zhang Y et al.·Hum Mol Genet
2021
Constructing a novel prognostic model for triple-negative breast cancer based on genes associated with vasculogenic mimicry.
Ren Y et al.·Aging (Albany NY)
2024Functional
Exome sequencing identifies de novo gain of function missense mutation in KCND2 in identical twins with autism and seizures that slows potassium channel inactivation.
Lee H et al.·Hum Mol Genet
2014
Transgenic mouse models of sodium and potassium channelopathies in epilepsy: insights into disease mechanisms and therapeutics.
Hammer MF·Biosci Rep
2025Review
Potassium voltage-gated channel subfamily D member 2 induces an aggressive phenotype in lung adenocarcinoma.
Lu X et al.·Neoplasma
2021
Evaluation of genes encoding for the transient outward current (Ito) identifies the KCND2 gene as a cause of J-wave syndrome associated with sudden cardiac death.
Perrin MJ et al.·Circ Cardiovasc Genet
2014
Identification of genes promoting skin youthfulness by genome-wide association study.
Chang ALS et al.·J Invest Dermatol
2014
Potassium Channel Gain of Function in Epilepsy: An Unresolved Paradox.
Niday Z et al.·Neuroscientist
2018
Six genes as potential diagnosis and prognosis biomarkers for hepatocellular carcinoma through data mining.
Zhang Y et al.·J Cell Physiol
2019
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools