KCNN1
protein-codingpotassium calcium-activated channel subfamily N member 1, the group of Potassium calcium-activated channels
Gene summary
Action potentials in vertebrate neurons are followed by an afterhyperpolarization (AHP) that may persist for several seconds and may have profound consequences for the firing pattern of the neuron. Each component of the AHP is kinetically distinct and is mediated by different calcium-activated potassium channels. The protein encoded by this gene is activated before membrane hyperpolarization and is thought to regulate neuronal excitability by contributing to the slow component of synaptic AHP. The encoded protein is an integral membrane protein that forms a voltage-independent calcium-activated channel with three other calmodulin-binding subunits. This gene is a member of the KCNN family of potassium channel genes. [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 ~48.8 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 KCNN1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001386974.1. 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 | 2 | |||
| missense | 73 | 1 | 74 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 73 | 2 | 1 | 76 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001373903.1 | 9 | MANE Select | |
| Ensembl | ENSP00000507021.1 | 9 | MANE Select | |
| RefSeq | NP_001373904.1 | 10 | Standard | |
| RefSeq | NP_001373905.1 | 10 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Insulin secretion - Homo sapiens (human)
- Neuronal System
- Ca2+ activated K+ channels
- Potassium Channels
Biological Process
- potassium ion transport
- chemical synaptic transmission
- potassium ion transmembrane transport
Molecular Function
- calmodulin binding
- calcium-activated potassium channel activity
- small conductance calcium-activated potassium channel activity
- protein heterodimerization activity
Cellular Component
- plasma membrane
- voltage-gated potassium channel complex
- neuron projection
- neuronal cell body
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000222249
- Coding exons
- 9
- Length
- 48788
- Individuals with no LoFs
- 125663
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 8
- Defined
- 125671
- p
- 0.0000318
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.41 | 237 | 367 | 0.646 | 0.0000261 | 3471 |
| Missense (PolyPhen) | 38 | 96.105 | 0.3954 | 810 | ||
| Synonymous | 0.697 | 155 | 166 | 0.931 | 0.0000130 | 1142 |
| Loss of Function | 3.46 | 3 | 19.5 | 0.154 | 8.35e-7 | 223 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000065 | 0.000062 | rare |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0.00010 | 0.000099 | rare |
| East Asian | 0.000056 | 0.000054 | rare |
| Finnish | 0.000093 | 0.000092 | rare |
| European (Non-Finnish) | 0.0000089 | 0.0000088 | rare |
| South Asian | 0.000038 | 0.000033 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Forms a voltage-independent potassium channel activated by intracellular calcium. Activation is followed by membrane hyperpolarization. Thought to regulate neuronal excitability by contributing to the slow component of synaptic afterhyperpolarization. The channel is blocked by apamin (By similarity). {ECO:0000250}.;
Recessive Scores
- pRec
- 0.122
Essentials
- Indispensability pred.
- E
- Indispensability score
- 0.737
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |