KCNK2

potassium two pore domain channel subfamily K member 2, the group of Potassium two pore domain channel subfamily K

Basic information

Region (hg38): 1:215005774-215237090

Links

ENSG00000082482 ∙ NCBI:3776 ∙ OMIM:603219 ∙ HGNC:6277 ∙ Uniprot:O95069 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the KCNK2 gene.

• Inborn genetic diseases (5 variants)
• not provided (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the KCNK2 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		1
missense			5			5
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				1		1
non coding						0
Total	0	0	5	1	0

Variants in KCNK2

This is a list of pathogenic ClinVar variants found in the KCNK2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
1-215083401-T-C		not specified	Uncertain significance (Dec 09, 2023)
1-215086371-C-T		not specified	Uncertain significance (Sep 19, 2022)
1-215086455-C-A		not specified	Uncertain significance (Feb 15, 2023)
1-215086482-T-C		not specified	Uncertain significance (Feb 15, 2023)
1-215169219-C-T		not specified	Uncertain significance (Feb 17, 2024)
1-215169328-A-G		not specified	Uncertain significance (Aug 08, 2022)
1-215194960-C-T			Likely benign (Dec 31, 2019)
1-215195099-A-C			Likely benign (Dec 31, 2019)
1-215234970-T-C		not specified	Uncertain significance (Nov 19, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
KCNK2	protein_coding	protein_coding	ENST00000444842	7	231319

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0191	0.977	125742	0	6	125748	0.0000239

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.31	147	250	0.589	0.0000139	2752
Missense in Polyphen		46	103.82	0.44307		1150
Synonymous	0.758	92	102	0.904	0.00000646	882
Loss of Function	2.54	6	17.5	0.343	8.24e-7	209

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000152	0.000152
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000264	0.0000264
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Ion channel that contributes to passive transmembrane potassium transport (PubMed:23169818). Reversibly converts between a voltage-insensitive potassium leak channel and a voltage- dependent outward rectifying potassium channel in a phosphorylation-dependent manner (PubMed:11319556). In astrocytes, forms mostly heterodimeric potassium channels with KCNK1, with only a minor proportion of functional channels containing homodimeric KCNK2. 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). {ECO:0000250|UniProtKB:P97438, ECO:0000269|PubMed:10784345, ECO:0000269|PubMed:11319556, ECO:0000269|PubMed:23169818}.
• Pathway: Cortisol synthesis and secretion - Homo sapiens (human);Cushing,s syndrome - Homo sapiens (human);Gastric acid secretion - Homo sapiens (human);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: 0.480
• rvis_EVS: -0.45
• rvis_percentile_EVS: 24

Haploinsufficiency Scores

• pHI: 0.128
• hipred: Y
• hipred_score: 0.837
• ghis: 0.521

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.114

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Kcnk2
• Phenotype: behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); homeostasis/metabolism phenotype

Gene ontology

• Biological process: cardiac ventricle development;G protein-coupled receptor signaling pathway;memory;response to mechanical stimulus;positive regulation of cell death;stabilization of membrane potential;regulation of membrane potential;response to axon injury;negative regulation of cardiac muscle cell proliferation;cellular response to hypoxia;potassium ion transmembrane transport;cochlea development;positive regulation of cellular response to hypoxia;negative regulation of DNA biosynthetic process
• Cellular component: nucleus;endoplasmic reticulum membrane;plasma membrane;integral component of plasma membrane;voltage-gated potassium channel complex;cell surface;apical plasma membrane;neuronal cell body;calyx of Held;astrocyte projection
• Molecular function: outward rectifier potassium channel activity;potassium ion leak channel activity