KCNH6

Chr 17

potassium voltage-gated channel subfamily H member 6

Also known as: ERG-2, ERG2, HERG2, Kv11.2, hERG-2

NCBI Gene: 81033ENSG00000173826UniProt: Q9H252

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 H. This member is a pore-forming (alpha) subunit. Alternative splicing results in multiple transcript variants that encode different isoforms. [provided by RefSeq, Jul 2013]

0
Active trials
10
Pathogenic / LP
207
ClinVar variants
6
Pubs (1 yr)
-0.2
Missense Z
1.40
LOEUF
Clinical Summary— KCNH6
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
10 Pathogenic / Likely Pathogenic· 185 VUS of 207 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.40LOEUF
pLI 0.000
Z-score -0.53
OE 1.09 (0.85–1.40)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.21Z-score
OE missense 1.02 (0.96–1.09)
632 obs / 617.6 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE1.09 (0.85–1.40)
0≤0.351.4
Missense OE1.02 (0.96–1.09)
0≤0.61.4
Synonymous OE1.00
0≤1.21.6
LoF obs/exp: 44 / 40.4Missense obs/exp: 632 / 617.6Syn Z: 0.00
GOFDN
DN
0.75top 25%
GOF
0.83top 10%
LOF
0.3940th %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

207 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic10
VUS185
Likely Benign11
Benign1
10
Pathogenic
185
VUS
11
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
10
0
10
Likely Pathogenic
0
0
0
0
0
VUS
0
184
1
0
185
Likely Benign
0
9
0
2
11
Benign
0
0
0
1
1
Total0193113207

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

View in ClinVar →

KCNH6 · 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

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Landmark / reviewRecent case evidence
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 4 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 4 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients