KCNK4

potassium two pore domain channel subfamily K member 4, the group of Potassium two pore domain channel subfamily K

Basic information

Region (hg38): 11:64291302-64300031

Links

ENSG00000182450NCBI:50801OMIM:605720HGNC:6279Uniprot:Q9NYG8AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

Phenotypes

GenCC

Source: genCC

  • 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: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Facial dysmorphism, hypertrichosis, epilepsy, intellectual disability/developmental delay, and gingival overgrowth syndromeADGeneralGenetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testingCraniofacial; Dental; Musculoskeletal; Neurologic; Ophthalmologic30290154

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the KCNK4 gene.

  • 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
1
clinvar
103
clinvar
3
clinvar
107
missense
2
clinvar
2
clinvar
193
clinvar
8
clinvar
3
clinvar
208
nonsense
4
clinvar
1
clinvar
5
start loss
0
frameshift
12
clinvar
12
inframe indel
6
clinvar
6
splice donor/acceptor (+/-2bp)
1
clinvar
1
splice region
7
12
3
22
non coding
2
clinvar
14
clinvar
3
clinvar
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)2838717
11-64293023-G-A not specified Uncertain significance (May 30, 2024)2778395
11-64293029-C-T Uncertain significance (Dec 28, 2021)1367979
11-64293034-C-G Uncertain significance (Jul 26, 2022)1471850
11-64293041-C-T Uncertain significance (Oct 28, 2023)1406377
11-64293042-C-T KCNK4-related disorder Benign/Likely benign (Mar 01, 2024)1575952
11-64293051-G-A Likely benign (Jan 01, 2023)2641916
11-64293054-G-T Likely benign (Oct 01, 2022)2087030
11-64293060-G-A Likely benign (Dec 03, 2022)2781438
11-64293072-G-A Likely benign (Aug 23, 2023)2961817
11-64293073-T-C Uncertain significance (Sep 07, 2022)2046605
11-64293073-T-G Uncertain significance (May 25, 2022)1909319
11-64293081-C-T Likely benign (Sep 19, 2023)1603238
11-64293091-C-G Uncertain significance (Aug 18, 2023)2753688
11-64293092-G-A Uncertain significance (Aug 17, 2021)1375741
11-64293095-C-T Uncertain significance (Sep 21, 2021)1382771
11-64293098-T-C Uncertain significance (Oct 14, 2022)1466048
11-64293105-G-A Likely benign (Jul 07, 2023)1993985
11-64293111-C-A not specified Uncertain significance (Apr 29, 2024)1392368
11-64293113-A-G Uncertain significance (Jul 25, 2023)2783202
11-64293121-G-T Uncertain significance (Jul 17, 2023)1950183
11-64293122-C-T Uncertain significance (Jul 28, 2023)1432584
11-64293130-G-C Uncertain significance (Dec 23, 2023)1494442
11-64293145-C-T Uncertain significance (Nov 03, 2022)2783956
11-64293146-G-A Uncertain significance (Aug 18, 2023)1917484

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
KCNK4protein_codingprotein_codingENST00000539216 68730
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
0.005680.9741257180271257450.000107
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense0.7541972290.8600.00001212440
Missense in Polyphen7690.5570.83925940
Synonymous-0.8071191081.100.00000577900
Loss of Function2.03614.30.4217.18e-7151

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.0003620.000360
Ashkenazi Jewish0.00009930.0000992
East Asian0.0001630.000163
Finnish0.000.00
European (Non-Finnish)0.0001100.000105
Middle Eastern0.0001630.000163
South Asian0.00006530.0000653
Other0.000.00

dbNSFP

Source: dbNSFP

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

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

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