KCNS3
protein-codingpotassium voltage-gated channel modifier subfamily S member 3, the group of Potassium voltage-gated channels
Gene summary
Voltage-gated potassium channels form the largest and most diversified class of ion channels and are present in both excitable and nonexcitable cells. Their main functions are associated with the regulation of the resting membrane potential and the control of the shape and frequency of action potentials. The alpha subunits are of 2 types: those that are functional by themselves and those that are electrically silent but capable of modulating the activity of specific functional alpha subunits. The protein encoded by this gene is not functional by itself but can form heteromultimers with member 1 and with member 2 (and possibly other members) of the Shab-related subfamily of potassium voltage-gated channel proteins. This gene belongs to the S subfamily of the potassium channel family. Alternatively spliced transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Sep 2013]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~483.8 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 KCNS3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_002252.5. 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 | 1 | ||||
| missense | 74 | 2 | 1 | 77 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 74 | 3 | 1 | 78 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_002243.3 | 1 | MANE Select | |
| Ensembl | ENSP00000305824.4 | 1 | MANE Select | |
| RefSeq | NP_001269357.1 | 1 | Standard | |
| Ensembl | ENSP00000385968.1 | 1 | Standard |
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
- potassium ion transport
- regulation of ion transmembrane transport
- regulation of insulin secretion
- protein homooligomerization
- potassium ion transmembrane transport
Molecular Function
- voltage-gated potassium channel activity
- delayed rectifier potassium channel activity
- potassium channel regulator activity
Cellular Component
- Golgi apparatus
- cytosol
- plasma membrane
- voltage-gated potassium channel complex
- integral component of membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000403915
- Coding exons
- 1
- Length
- 483769
- Individuals with no LoFs
- 125713
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 35
- Defined
- 125748
- p
- 0.000139
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.02 | 234 | 282 | 0.829 | 0.0000165 | 3263 |
| Missense (PolyPhen) | 63 | 93.07 | 0.67691 | 1150 | ||
| Synonymous | -0.702 | 128 | 118 | 1.08 | 0.00000765 | 952 |
| Loss of Function | 1.83 | 7 | 14.5 | 0.482 | 7.95e-7 | 166 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00012 | 0.00012 | rare |
| Latino/Admixed American | 0.00023 | 0.00023 | rare |
| Ashkenazi Jewish | 0.00020 | 0.00020 | rare |
| East Asian | 0.00011 | 0.00011 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00013 | 0.00013 | rare |
| South Asian | 0.00013 | 0.00013 | rare |
| Other | 0.00033 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Potassium channel subunit that does not form functional channels by itself. Can form functional heterotetrameric channels with KCNB1; modulates the delayed rectifier voltage-gated potassium channel activation and deactivation rates of KCNB1 (PubMed:10484328). Heterotetrameric channel activity formed with KCNB1 show increased current amplitude with the threshold for action potential activation shifted towards more negative values in hypoxic-treated pulmonary artery smooth muscle cells (By similarity). {ECO:0000250|UniProtKB:O88759, ECO:0000269|PubMed:10484328}.;
Recessive Scores
- pRec
- 0.138
Intolerance Scores
- LoFtool
- 0.131
- RVIS EVS
- 0.44
- RVIS percentile EVS
- 77.91
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.811
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |