KCNK9

potassium two pore domain channel subfamily K member 9, the group of Potassium two pore domain channel subfamily K

Basic information

Region (hg38): 8:139600837-139704109

Links

ENSG00000169427 ∙ NCBI:51305 ∙ OMIM:605874 ∙ HGNC:6283 ∙ Uniprot:Q9NPC2 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Birk-Barel syndrome (Limited), mode of inheritance: Autosomal dominant inheritance with paternal imprinting
• Birk-Barel syndrome (Moderate), mode of inheritance: AD
• Birk-Barel syndrome (Strong), mode of inheritance: AD
• Birk-Barel syndrome (Strong), mode of inheritance: AD
• Birk-Barel syndrome (Limited), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Birk-Barel 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	18678320

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the KCNK9 gene.

• not provided (1 variants)
• Birk-Barel syndrome (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the KCNK9 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				9	2	11
missense	1	2	27	2		32
nonsense			4			4
start loss						0
frameshift						0
inframe indel			1			1
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding					1	1
Total	1	2	32	11	3

Variants in KCNK9

This is a list of pathogenic ClinVar variants found in the KCNK9 region.

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

Position	Type	Phenotype	Significance	ClinVar
8-139612555-A-AG		Birk-Barel Intellectual Disability Dysmorphism Syndrome	Benign (Jun 14, 2016)
8-139618278-T-A			Uncertain significance (Apr 20, 2023)
8-139618327-G-C			Uncertain significance (Feb 01, 2024)
8-139618345-G-A			Benign (Apr 16, 2018)
8-139618405-G-A			Likely benign (Jun 09, 2018)
8-139618406-T-C			Uncertain significance (Dec 12, 2022)
8-139618410-G-T		Birk-Barel syndrome	Uncertain significance (Sep 11, 2023)
8-139618451-G-T		Birk-Barel syndrome	Uncertain significance (Apr 12, 2022)
8-139618454-C-G			Uncertain significance (May 30, 2019)
8-139618469-T-C		Inborn genetic diseases	Uncertain significance (Feb 26, 2022)
8-139618476-G-A		Autism spectrum disorder	association (-)
8-139618483-G-T			Likely benign (Mar 01, 2024)
8-139618520-G-A		KCNK9-related disorder	Uncertain significance (Jan 11, 2023)
8-139618536-G-A		Inborn genetic diseases	Uncertain significance (Mar 22, 2022)
8-139618558-G-A		KCNK9-related disorder	Benign/Likely benign (Mar 08, 2019)
8-139618580-C-T			Likely benign (Jan 01, 2023)
8-139618620-G-A		Inborn genetic diseases	Uncertain significance (Jan 25, 2022)
8-139618673-G-T		Birk-Barel syndrome	Likely pathogenic (Jan 01, 2019)
8-139618677-C-G		Birk-Barel syndrome	Pathogenic (Dec 12, 2016)
8-139618677-C-T		Birk-Barel syndrome	Pathogenic (Mar 17, 2024)
8-139618723-G-A			Likely benign (Jun 20, 2018)
8-139618747-A-G		not specified	Benign (-)
8-139618784-A-G		Birk-Barel syndrome	Uncertain significance (Aug 27, 2020)
8-139618801-G-A		KCNK9-related disorder	Likely benign (Sep 13, 2019)
8-139618818-C-T			Likely benign (Aug 21, 2020)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
KCNK9	protein_coding	protein_coding	ENST00000520439	2	102219

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.955	0.0447	125638	0	1	125639	0.00000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.90	118	246	0.479	0.0000164	2457
Missense in Polyphen		6	62.363	0.09621		661
Synonymous	-0.840	124	113	1.10	0.00000833	759
Loss of Function	2.89	0	9.74	0.00	4.20e-7	123

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00000880	0.00000880
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: pH-dependent, voltage-insensitive, background potassium channel protein. {ECO:0000269|PubMed:11042359, ECO:0000269|PubMed:11431495, ECO:0000269|PubMed:23169818}.
• Pathway: Aldosterone synthesis and secretion - Homo sapiens (human);Nicotine Pathway (Dopaminergic Neuron), 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: 0.128

Intolerance Scores

• loftool: 0.0561
• rvis_EVS: -0.38
• rvis_percentile_EVS: 27.42

Haploinsufficiency Scores

• pHI: 0.185
• hipred: Y
• hipred_score: 0.565
• ghis: 0.647

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.186

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Kcnk9
• Phenotype: 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); 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); homeostasis/metabolism phenotype; endocrine/exocrine gland phenotype

Gene ontology

• Biological process: potassium ion transport;stabilization of membrane potential;potassium ion transmembrane transport
• Cellular component: plasma membrane;integral component of plasma membrane
• Molecular function: potassium channel activity;potassium ion leak channel activity