KCNG2

Chr 18

potassium voltage-gated channel modifier subfamily G member 2

Also known as: KCNF2, KV6.2

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. This gene encodes a member of the potassium channel, voltage-gated, subfamily G. This member is a gamma subunit of the voltage-gated potassium channel. The delayed-rectifier type channels containing this subunit may contribute to cardiac action potential repolarization. [provided by RefSeq, Jul 2008]

OMIMResearchGenerating clinical summary…
MultiplemechanismLOEUF 0.67
Clinical SummaryKCNG2
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.60) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
83 VUS of 89 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint?
0.67LOEUF
pLI 0.602
Z-score 2.13
OE 0.14 (0.050.67)
Moderately constrained

Typical tolerance to LoF variation

Missense Constraint?
1.75Z-score
OE missense 0.70 (0.620.79)
185 obs / 265.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.14 (0.050.67)
00.351.4
Missense OE?0.70 (0.620.79)
00.61.4
Synonymous OE?1.06
01.21.6
LoF obs/exp: 1 / 7.1Missense obs/exp: 185 / 265.0Syn Z: -0.53

This gene — mechanism propensity

DN
0.7133th %ile
GOF
0.89top 5%
LOF
0.3259th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median
DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

89 submitted variants in ClinVar

Classification Summary

VUS83
Likely Benign4
83
VUS
4
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
0
0
0
Likely Pathogenic
0
0
0
0
0
VUS
0
83
0
0
83
Likely Benign
0
2
0
2
4
Benign
0
0
0
0
0
Total0850287

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

165 pathogenic / likely-pathogenic (of 194) ClinVar copy-number / structural variants overlap KCNG2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →

Protein Context — Lollipop Plot

KCNG2 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →