KCNK1
potassium two pore domain channel subfamily K member 1, the group of Potassium two pore domain channel subfamily K |MicroRNA protein coding host genes
Basic information
Region (hg38): 1:233614106-233672514
Links
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the KCNK1 gene is commonly pathogenic or not.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 0 | |||||
| missense | 23 | 23 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region | 0 | |||||
| non coding | 0 | |||||
| Total | 0 | 0 | 23 | 0 | 0 |
Variants in KCNK1
This is a list of pathogenic ClinVar variants found in the KCNK1 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 1-233614244-T-A | not specified | Uncertain significance (May 30, 2022) | ||
| 1-233614320-A-G | not specified | Uncertain significance (Jan 16, 2024) | ||
| 1-233614374-A-C | not specified | Uncertain significance (Mar 30, 2024) | ||
| 1-233614405-C-G | not specified | Uncertain significance (Mar 28, 2023) | ||
| 1-233614406-C-A | not specified | Uncertain significance (Jun 16, 2023) | ||
| 1-233614412-C-G | not specified | Uncertain significance (Aug 05, 2024) | ||
| 1-233614422-A-C | not specified | Uncertain significance (Apr 07, 2023) | ||
| 1-233614490-G-T | not specified | Uncertain significance (Mar 30, 2024) | ||
| 1-233666609-G-A | not specified | Uncertain significance (Sep 29, 2023) | ||
| 1-233666627-G-A | not specified | Uncertain significance (Feb 28, 2023) | ||
| 1-233666654-G-A | not specified | Uncertain significance (May 25, 2022) | ||
| 1-233666702-C-T | not specified | Uncertain significance (Nov 10, 2024) | ||
| 1-233666717-G-T | not specified | Uncertain significance (Jul 25, 2023) | ||
| 1-233666724-G-A | not specified | Uncertain significance (May 01, 2024) | ||
| 1-233666738-T-C | not specified | Uncertain significance (Jun 11, 2024) | ||
| 1-233666771-G-A | not specified | Uncertain significance (Jun 17, 2022) | ||
| 1-233666946-G-A | not specified | Uncertain significance (Oct 27, 2021) | ||
| 1-233666969-C-T | not specified | Uncertain significance (Dec 18, 2023) | ||
| 1-233671344-A-T | not specified | Uncertain significance (Jul 12, 2022) | ||
| 1-233671405-C-T | not specified | Uncertain significance (Jan 06, 2023) | ||
| 1-233671472-A-G | not specified | Uncertain significance (May 26, 2024) | ||
| 1-233671496-C-T | not specified | Uncertain significance (Apr 28, 2023) | ||
| 1-233671510-G-A | not specified | Uncertain significance (Feb 11, 2022) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| KCNK1 | protein_coding | protein_coding | ENST00000366621 | 3 | 58509 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.0312 | 0.930 | 125739 | 0 | 8 | 125747 | 0.0000318 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 0.722 | 164 | 192 | 0.853 | 0.00000997 | 2169 |
| Missense in Polyphen | 44 | 72.319 | 0.60841 | 856 | ||
| Synonymous | -0.223 | 91 | 88.3 | 1.03 | 0.00000494 | 692 |
| Loss of Function | 1.78 | 4 | 10.1 | 0.396 | 4.27e-7 | 123 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000293 | 0.0000293 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000455 | 0.0000439 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.0000328 | 0.0000327 |
| Other | 0.000163 | 0.000163 |
dbNSFP
Source:
- Function
- FUNCTION: Ion channel that contributes to passive transmembrane potassium transport and to the regulation of the resting membrane potential in brain astrocytes, but also in kidney and in other tissues (PubMed:15820677, PubMed:21653227). Forms dimeric channels through which potassium ions pass in accordance with their electrochemical gradient. The channel is selective for K(+) ions at physiological potassium concentrations and at neutral pH, but becomes permeable to Na(+) at subphysiological K(+) levels and upon acidification of the extracellular medium (PubMed:21653227, PubMed:22431633). The homodimer has very low potassium channel activity, when expressed in heterologous systems, and can function as weakly inward rectifying potassium channel (PubMed:8605869, PubMed:8978667, PubMed:15820677, PubMed:21653227, PubMed:22431633, PubMed:23169818, PubMed:25001086). Channel activity is modulated by activation of serotonin receptors (By similarity). Heterodimeric channels containing KCNK1 and KCNK2 have much higher activity, and may represent the predominant form in astrocytes (By similarity). Heterodimeric channels containing KCNK1 and KCNK3 or KCNK9 have much higher activity (PubMed:23169818). Heterodimeric channels formed by KCNK1 and KCNK9 may contribute to halothane- sensitive currents (PubMed:23169818). Mediates outward rectifying potassium currents in dentate gyrus granule cells and contributes to the regulation of their resting membrane potential (By similarity). Contributes to the regulation of action potential firing in dentate gyrus granule cells and down-regulates their intrinsic excitability (By similarity). In astrocytes, the heterodimer formed by KCNK1 and KCNK2 is required for rapid glutamate release in response to activation of G-protein coupled receptors, such as F2R and CNR1 (By similarity). Required for normal ion and water transport in the kidney (By similarity). Contributes to the regulation of the resting membrane potential of pancreatic beta cells (By similarity). The low channel activity of homodimeric KCNK1 may be due to sumoylation (PubMed:15820677, PubMed:20498050, PubMed:23169818). The low channel activity may be due to rapid internalization from the cell membrane and retention in recycling endosomes (PubMed:19959478). {ECO:0000250|UniProtKB:O08581, ECO:0000250|UniProtKB:Q9Z2T2, ECO:0000269|PubMed:15820677, ECO:0000269|PubMed:17693262, ECO:0000269|PubMed:19959478, ECO:0000269|PubMed:20498050, ECO:0000269|PubMed:21653227, ECO:0000269|PubMed:22282804, ECO:0000269|PubMed:22431633, ECO:0000269|PubMed:23169818, ECO:0000269|PubMed:25001086, ECO:0000269|PubMed:8605869, ECO:0000269|PubMed:8978667}.;
- Pathway
- Antiarrhythmic Pathway, Pharmacodynamics;Disopyramide Action Pathway;Procainamide (Antiarrhythmic) Action Pathway;Phenytoin (Antiarrhythmic) Action Pathway;Fosphenytoin (Antiarrhythmic) Action Pathway;Bopindolol Action Pathway;Timolol Action Pathway;Carteolol Action Pathway;Bevantolol Action Pathway;Practolol Action Pathway;Dobutamine Action Pathway;Isoprenaline Action Pathway;Arbutamine Action Pathway;Amiodarone Action Pathway;Levobunolol Action Pathway;Metipranolol Action Pathway;Mexiletine Action Pathway;Lidocaine (Antiarrhythmic) Action Pathway;Quinidine Action Pathway;Sotalol Action Pathway;Epinephrine Action Pathway;Betaxolol Action Pathway;Atenolol Action Pathway;Alprenolol Action Pathway;Acebutolol Action Pathway;Muscle/Heart Contraction;Diltiazem Action Pathway;Propranolol Action Pathway;Pindolol Action Pathway;Penbutolol Action Pathway;Oxprenolol Action Pathway;Metoprolol Action Pathway;Esmolol Action Pathway;Bisoprolol Action Pathway;Bupranolol Action Pathway;Nebivolol Action Pathway;Amlodipine Action Pathway;Verapamil Action Pathway;Nitrendipine Action Pathway;Nisoldipine Action Pathway;Nimodipine Action Pathway;Ibutilide Action Pathway;Tocainide Action Pathway;Flecainide Action Pathway;Isradipine Action Pathway;Nifedipine Action Pathway;Felodipine Action Pathway;Nadolol Action Pathway;Carvedilol Action Pathway;Labetalol Action Pathway;Neuronal System;Phase 4 - resting membrane potential;Cardiac conduction;Muscle contraction;Tandem of pore domain in a weak inwardly rectifying K+ channels (TWIK);Tandem pore domain potassium channels;Potassium Channels
(Consensus)
Recessive Scores
- pRec
- 0.148
Intolerance Scores
- loftool
- 0.352
- rvis_EVS
- -0.27
- rvis_percentile_EVS
- 34.32
Haploinsufficiency Scores
- pHI
- 0.271
- hipred
- Y
- hipred_score
- 0.788
- ghis
- 0.607
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.655
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Kcnk1
- Phenotype
- renal/urinary system phenotype; homeostasis/metabolism phenotype;
Zebrafish Information Network
- Gene name
- kcnk1b
- Affected structure
- post-vent region
- Phenotype tag
- abnormal
- Phenotype quality
- increased curvature
Gene ontology
- Biological process
- potassium ion transport;stabilization of membrane potential;response to nicotine;sodium ion transmembrane transport;regulation of resting membrane potential;cardiac conduction;potassium ion transmembrane transport
- Cellular component
- plasma membrane;integral component of plasma membrane;voltage-gated potassium channel complex;integral component of membrane;apical plasma membrane;cell junction;dendrite;brush border membrane;potassium channel complex;perikaryon;intracellular membrane-bounded organelle;synapse;recycling endosome;inward rectifier potassium channel complex
- Molecular function
- inward rectifier potassium channel activity;voltage-gated potassium channel activity;potassium channel activity;sodium channel activity;protein binding;potassium ion leak channel activity;identical protein binding