KCNK5
protein-codingpotassium two pore domain channel subfamily K member 5, the group of Potassium two pore domain channel subfamily K
Gene summary
This gene encodes one of the members of the superfamily of potassium channel proteins containing two pore-forming P domains. The message for this gene is mainly expressed in the cortical distal tubules and collecting ducts of the kidney. The protein is highly sensitive to external pH and this, in combination with its expression pattern, suggests it may play an important role in renal potassium transport. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~40.5 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 KCNK5 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_003740.4. 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 | 3 | 3 | ||||
| missense | 58 | 3 | 2 | 63 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 58 | 6 | 2 | 66 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_003731.1 | 5 | MANE Select | |
| Ensembl | ENSP00000352527.3 | 5 | MANE Select | |
| Ensembl | ENSP00000577404.1 | 5 | Standard | |
| Ensembl | ENSP00000577404.1 | 5 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| kcnk5b | Danio rerio | Structure: lepidotrichium segment Quality: increased variability of size abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Protein digestion and absorption - Homo sapiens (human)
- Taste transduction - Homo sapiens (human)
- Phase 4 - resting membrane potential
- Cardiac conduction
- Muscle contraction
Biological Process
- potassium ion transport
- excretion
- stabilization of membrane potential
- regulation of ion transmembrane transport
- potassium ion transmembrane transport
Molecular Function
- voltage-gated potassium channel activity
- potassium channel activity
- potassium ion leak channel activity
Cellular Component
- integral component of plasma membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000359534
- Coding exons
- 5
- Length
- 40478
- Individuals with no LoFs
- 125738
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 10
- Defined
- 125748
- p
- 0.0000398
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.97 | 203 | 299 | 0.680 | 0.0000185 | 3238 |
| Missense (PolyPhen) | 63 | 120.09 | 0.52462 | 1294 | ||
| Synonymous | -0.284 | 138 | 134 | 1.03 | 0.00000917 | 1027 |
| Loss of Function | 2.95 | 4 | 17.2 | 0.232 | 8.30e-7 | 199 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00019 | 0.00018 | rare |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000035 | 0.000035 | rare |
| South Asian | 0.000065 | 0.000065 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: pH-dependent, voltage insensitive, outwardly rectifying potassium channel. Outward rectification is lost at high external K(+) concentrations.;
Recessive Scores
- pRec
- 0.114
Intolerance Scores
- LoFtool
- 0.160
- RVIS EVS
- 0.0000761
- RVIS percentile EVS
- 53.98
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.587
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |