KCNK3

potassium two pore domain channel subfamily K member 3, the group of Potassium two pore domain channel subfamily K

Basic information

Region (hg38): 2:26692721-26733420

Links

ENSG00000171303 ∙ NCBI:3777 ∙ OMIM:603220 ∙ HGNC:6278 ∙ Uniprot:O14649 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• heritable pulmonary arterial hypertension (Supportive), mode of inheritance: AD
• pulmonary hypertension, primary, 4 (Strong), mode of inheritance: AD
• pulmonary arterial hypertension (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Pulmonary hypertension, primary, 4	AD	Cardiovascular; Pulmonary	While prognosis is overall poor, medical therapy may be beneficial, though heart/lung transplantation may be required; Control of complications may be beneficial	Cardiovascular; Pulmonary	23883380

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the KCNK3 gene.

• Pulmonary hypertension, primary, 4 (137 variants)
• not provided (15 variants)
• Inborn genetic diseases (11 variants)
• Autism spectrum disorder (2 variants)
• not specified (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the KCNK3 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			2	57	2	61
missense	1	1	74	5		81
nonsense						0
start loss						0
frameshift			1			1
inframe indel			2			2
splice donor/acceptor (+/-2bp)						0
splice region				2		2
non coding				4	3	7
Total	1	1	79	66	5

Variants in KCNK3

This is a list of pathogenic ClinVar variants found in the KCNK3 region.

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

Position	Type	Phenotype	Significance	ClinVar
2-26692748-G-C			Likely benign (May 26, 2021)
2-26692756-G-T			Benign (Aug 25, 2018)
2-26692874-C-A		KCNK3-related disorder	Likely benign (Sep 10, 2019)
2-26692881-GC-G		Pulmonary hypertension, primary, 4	Uncertain significance (Aug 05, 2021)
2-26692892-T-C		Pulmonary hypertension, primary, 4	Uncertain significance (Feb 03, 2022)
2-26692898-C-A		Pulmonary hypertension, primary, 4	Pathogenic (-)
2-26692899-G-C		Pulmonary hypertension, primary, 4	Benign (Nov 17, 2023)
2-26692903-G-A		Pulmonary hypertension, primary, 4	Uncertain significance (Oct 13, 2020)
2-26692904-C-A		Pulmonary hypertension, primary, 4	Uncertain significance (Jun 07, 2022)
2-26692914-G-A		Pulmonary hypertension, primary, 4	Likely benign (Aug 30, 2021)
2-26692915-T-G		Pulmonary hypertension, primary, 4	Uncertain significance (Sep 30, 2023)
2-26692958-C-T		Inborn genetic diseases	Uncertain significance (Apr 08, 2022)
2-26692968-G-C		Pulmonary hypertension, primary, 4	Likely benign (Apr 07, 2022)
2-26692974-C-G		Pulmonary hypertension, primary, 4	Likely benign (Jun 06, 2022)
2-26692975-G-A		Pulmonary hypertension, primary, 4	Uncertain significance (Jun 19, 2017)
2-26692977-G-T		Pulmonary hypertension, primary, 4	Uncertain significance (Jul 31, 2022)
2-26692983-C-T		Pulmonary hypertension, primary, 4	Likely benign (May 31, 2023)
2-26692995-G-A		Pulmonary hypertension, primary, 4	Likely benign (Feb 20, 2022)
2-26692997-T-TGGAGCTGCGGCAGCA		Pulmonary hypertension, primary, 4	Uncertain significance (Nov 12, 2022)
2-26693022-G-A		Pulmonary hypertension, primary, 4	Likely benign (Sep 03, 2018)
2-26693027-G-T		Pulmonary hypertension, primary, 4	Uncertain significance (Dec 27, 2023)
2-26693042-A-T		Pulmonary hypertension, primary, 4	Uncertain significance (Sep 06, 2021)
2-26693047-G-A		Pulmonary hypertension, primary, 4	Uncertain significance (Jul 16, 2023)
2-26693053-G-C		Pulmonary hypertension, primary, 4	Uncertain significance (Dec 31, 2021)
2-26693077-C-A		Pulmonary hypertension, primary, 4	Uncertain significance (Nov 08, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
KCNK3	protein_coding	protein_coding	ENST00000302909	2	40670

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.900	0.0997	123670	0	2	123672	0.00000809

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.55	103	266	0.387	0.0000190	2467
Missense in Polyphen		13	105.16	0.12362		1002
Synonymous	3.49	84	136	0.619	0.0000113	819
Loss of Function	2.92	1	11.8	0.0844	5.78e-7	121

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000590	0.0000545
Finnish	0.00	0.00
European (Non-Finnish)	0.00000970	0.00000906
Middle Eastern	0.0000590	0.0000545
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: pH-dependent, voltage-insensitive, background potassium channel protein. Rectification direction results from potassium ion concentration on either side of the membrane. Acts as an outward rectifier when external potassium concentration is low. When external potassium concentration is high, current is inward. {ECO:0000269|PubMed:23169818, ECO:0000269|PubMed:9312005}.
• Pathway: Cortisol synthesis and secretion - Homo sapiens (human);Aldosterone synthesis and secretion - Homo sapiens (human);Cushing,s syndrome - Homo sapiens (human);Nicotine Pathway (Dopaminergic Neuron), Pharmacodynamics;Antiarrhythmic Pathway, Pharmacodynamics;Nicotine Activity on Dopaminergic Neurons;Neuronal System;Phase 4 - resting membrane potential;Cardiac conduction;Muscle contraction;TWIK-releated acid-sensitive K+ channel (TASK);Tandem pore domain potassium channels;Potassium Channels (Consensus)

Recessive Scores

• pRec: 0.230

Haploinsufficiency Scores

• pHI: 0.223
• ghis: 0.514

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.909

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Kcnk3
• Phenotype: endocrine/exocrine gland phenotype; homeostasis/metabolism phenotype; normal phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); 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)

Gene ontology

• Biological process: potassium ion transport;chemical synaptic transmission;brain development;stabilization of membrane potential;ion transmembrane transport;response to drug;negative regulation of cytosolic calcium ion concentration;cardiac conduction;cellular response to zinc ion;cellular response to hypoxia;potassium ion transmembrane transport;cochlea development
• Cellular component: plasma membrane;integral component of plasma membrane
• Molecular function: ion channel activity;open rectifier potassium channel activity;potassium channel activity;protein C-terminus binding;potassium ion leak channel activity;S100 protein binding