KCNK4
Basic information
Region (hg38): 11:64291302-64300031
Links
Phenotypes
GenCC
Source:
- facial dysmorphism, hypertrichosis, epilepsy, intellectual/developmental delay, and gingival overgrowth syndrome (Limited), mode of inheritance: AD
- facial dysmorphism, hypertrichosis, epilepsy, intellectual/developmental delay, and gingival overgrowth syndrome (Strong), mode of inheritance: AD
Clinical Genomic Database
Source:
Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
---|---|---|---|---|---|
Facial dysmorphism, hypertrichosis, epilepsy, intellectual disability/developmental delay, and gingival overgrowth syndrome | AD | General | Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing | Craniofacial; Dental; Musculoskeletal; Neurologic; Ophthalmologic | 30290154 |
ClinVar
This is a list of variants' phenotypes submitted to
- Generalized hypertrichosis;Gingival overgrowth;Seizure;Abnormal facial shape;Intellectual disability (1 variants)
- Facial dysmorphism, hypertrichosis, epilepsy, intellectual/developmental delay, and gingival overgrowth syndrome (1 variants)
- not provided (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the KCNK4 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 | 103 | 107 | ||||
missense | 193 | 208 | ||||
nonsense | 5 | |||||
start loss | 0 | |||||
frameshift | 12 | 12 | ||||
inframe indel | 6 | |||||
splice donor/acceptor (+/-2bp) | 1 | |||||
splice region | 7 | 12 | 3 | 22 | ||
non coding | 14 | 19 | ||||
Total | 2 | 2 | 219 | 126 | 9 |
Variants in KCNK4
This is a list of pathogenic ClinVar variants found in the KCNK4 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
Position | Type | Phenotype | Significance | ClinVar |
---|---|---|---|---|
11-64293022-C-A | Uncertain significance (Aug 07, 2023) | |||
11-64293023-G-A | not specified | Uncertain significance (May 30, 2024) | ||
11-64293029-C-T | Uncertain significance (Dec 28, 2021) | |||
11-64293034-C-G | Uncertain significance (Jul 26, 2022) | |||
11-64293041-C-T | Uncertain significance (Oct 28, 2023) | |||
11-64293042-C-T | KCNK4-related disorder | Benign/Likely benign (Mar 01, 2024) | ||
11-64293051-G-A | Likely benign (Jan 01, 2023) | |||
11-64293054-G-T | Likely benign (Oct 01, 2022) | |||
11-64293060-G-A | Likely benign (Dec 03, 2022) | |||
11-64293072-G-A | Likely benign (Aug 23, 2023) | |||
11-64293073-T-C | Uncertain significance (Sep 07, 2022) | |||
11-64293073-T-G | Uncertain significance (May 25, 2022) | |||
11-64293081-C-T | Likely benign (Sep 19, 2023) | |||
11-64293091-C-G | Uncertain significance (Aug 18, 2023) | |||
11-64293092-G-A | Uncertain significance (Aug 17, 2021) | |||
11-64293095-C-T | Uncertain significance (Sep 21, 2021) | |||
11-64293098-T-C | Uncertain significance (Oct 14, 2022) | |||
11-64293105-G-A | Likely benign (Jul 07, 2023) | |||
11-64293111-C-A | not specified | Uncertain significance (Apr 29, 2024) | ||
11-64293113-A-G | Uncertain significance (Jul 25, 2023) | |||
11-64293121-G-T | Uncertain significance (Jul 17, 2023) | |||
11-64293122-C-T | Uncertain significance (Jul 28, 2023) | |||
11-64293130-G-C | Uncertain significance (Dec 23, 2023) | |||
11-64293145-C-T | Uncertain significance (Nov 03, 2022) | |||
11-64293146-G-A | Uncertain significance (Aug 18, 2023) |
GnomAD
Source:
Gene | Type | Bio Type | Transcript | Coding Exons | Length |
---|---|---|---|---|---|
KCNK4 | protein_coding | protein_coding | ENST00000539216 | 6 | 8730 |
pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
---|---|---|---|---|---|---|
0.00568 | 0.974 | 125718 | 0 | 27 | 125745 | 0.000107 |
Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
---|---|---|---|---|---|---|
Missense | 0.754 | 197 | 229 | 0.860 | 0.0000121 | 2440 |
Missense in Polyphen | 76 | 90.557 | 0.83925 | 940 | ||
Synonymous | -0.807 | 119 | 108 | 1.10 | 0.00000577 | 900 |
Loss of Function | 2.03 | 6 | 14.3 | 0.421 | 7.18e-7 | 151 |
LoF frequencies by population
Ethnicity | Sum of pLOFs | p |
---|---|---|
African & African-American | 0.000362 | 0.000360 |
Ashkenazi Jewish | 0.0000993 | 0.0000992 |
East Asian | 0.000163 | 0.000163 |
Finnish | 0.00 | 0.00 |
European (Non-Finnish) | 0.000110 | 0.000105 |
Middle Eastern | 0.000163 | 0.000163 |
South Asian | 0.0000653 | 0.0000653 |
Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Voltage-insensitive potassium channel (PubMed:22282805). Channel opening is triggered by mechanical forces that deform the membrane (PubMed:22282805, PubMed:25471887, PubMed:25500157). Channel opening is triggered by raising the intracellular pH to basic levels (By similarity). The channel is inactive at 24 degrees Celsius (in vitro); raising the temperature to 37 degrees Celsius increases the frequency of channel opening, with a further increase in channel activity when the temperature is raised to 42 degrees Celsius (By similarity). Plays a role in the perception of pain caused by heat (By similarity). Plays a role in the sensory perception of pain caused by pressure (By similarity). {ECO:0000250|UniProtKB:G3V8V5, ECO:0000250|UniProtKB:O88454, ECO:0000269|PubMed:22282805, ECO:0000269|PubMed:25471887, ECO:0000269|PubMed:25500157}.;
- Pathway
- Neuronal System;Phase 4 - resting membrane potential;Cardiac conduction;Muscle contraction;TWIK related potassium channel (TREK);Tandem pore domain potassium channels;Potassium Channels
(Consensus)
Intolerance Scores
- loftool
- 0.644
- rvis_EVS
- -0.2
- rvis_percentile_EVS
- 38.82
Haploinsufficiency Scores
- pHI
- 0.184
- hipred
- N
- hipred_score
- 0.482
- ghis
- 0.619
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
- Kcnk4
- Phenotype
Gene ontology
- Biological process
- potassium ion transport;memory;sensory perception of pain;stabilization of membrane potential;regulation of ion transmembrane transport;sensory perception of temperature stimulus;detection of mechanical stimulus involved in sensory perception of touch;cellular response to mechanical stimulus;cellular response to fatty acid;cellular response to alkaline pH;cellular response to temperature stimulus;potassium ion transmembrane transport
- Cellular component
- plasma membrane;integral component of plasma membrane;potassium channel complex
- Molecular function
- voltage-gated ion channel activity;potassium channel activity;potassium ion leak channel activity;temperature-gated cation channel activity;mechanosensitived potassium channel activity