KCNH6
protein-codingpotassium voltage-gated channel subfamily H member 6, the group of Potassium voltage-gated channels|PAS domain containing
Gene summary
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]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~25.6 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to KCNH6 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001278919.2. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 2 | 1 | 4 | ||
| missense | 178 | 8 | 186 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 179 | 10 | 1 | 190 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001265848.1 | 13 | MANE Select | |
| Ensembl | ENSP00000318212.5 | 13 | MANE Select | |
| RefSeq | NP_001265849.1 | 11 | Standard | |
| RefSeq | NP_110406.1 | 14 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| kcnh6a | Danio rerio | Structure: parachordal vessel Quality: present abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Neuronal System
- Voltage gated Potassium channels
- Potassium Channels
Biological Process
- regulation of ion transmembrane transport
- regulation of membrane potential
- potassium ion transmembrane transport
Molecular Function
- voltage-gated potassium channel activity
Cellular Component
- plasma membrane
- integral component of plasma membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000583023
- Coding exons
- 14
- Length
- 25644
- Individuals with no LoFs
- 125395
- Homozygous LoFs
- 1
- Heterozygous LoFs
- 352
- Defined
- 125748
- p
- 0.00140
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.205 | 632 | 618 | 1.02 | 0.0000395 | 6442 |
| Missense (PolyPhen) | 204 | 200.82 | 1.0158 | 1997 | ||
| Synonymous | 0.00222 | 272 | 272 | 1.00 | 0.0000186 | 2065 |
| Loss of Function | -0.529 | 44 | 40.4 | 1.09 | 0.00000207 | 424 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.0015 | 0.0015 | notable |
| Latino/Admixed American | 0.0015 | 0.0014 | notable |
| Ashkenazi Jewish | 0.0018 | 0.0018 | notable |
| East Asian | 0.0034 | 0.0033 | notable |
| Finnish | 0.00042 | 0.00042 | rare |
| European (Non-Finnish) | 0.0010 | 0.00098 | notable |
| South Asian | 0.0023 | 0.0023 | notable |
| Other | 0.0015 | 0.0015 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Pore-forming (alpha) subunit of voltage-gated potassium channel. Elicits a slowly activating, rectifying current (By similarity). Channel properties may be modulated by cAMP and subunit assembly. {ECO:0000250}.;
Recessive Scores
- pRec
- 0.169
Intolerance Scores
- LoFtool
- 0.0284
- RVIS EVS
- -0.61
- RVIS percentile EVS
- 17.51
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.367
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |