KCNK9

protein-coding

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

Gene summary

This gene encodes a protein that contains multiple transmembrane regions and two pore-forming P domains and functions as a pH-dependent potassium channel. Amplification and overexpression of this gene have been observed in several types of human carcinomas. This gene is imprinted in the brain, with preferential expression from the maternal allele. A mutation in this gene was associated with Birk-Barel dysmorphism syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2017]

MANE transcript

NM_001282534.2

Inheritance

ClinVar variants

P:9U:63B:22

Top phenotype

Birk-Barel syndrome

gnomAD constraint

pLI —, LoF o/e 0

Max pathogenic AF

—

Genomic locus

chr8:139,600,838-139,704,109

External References & Databases

Ensembl (ENSG00000169427)

Transcript & Mutation Effects

hg38 • Region Span ~103.3 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

Birk-Barel syndromeSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0012856

Submitter: Illumina

Birk-Barel syndromeLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0012856

Submitter: G2P

Birk-Barel syndromeMODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0012856

Submitter: Ambry Genetics

Birk-Barel syndromeSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0012856

Submitter: PanelApp Australia

Birk-Barel syndromeSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0012856

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Birk-Barel syndromeAD

Manifestation: Craniofacial; Dental; Musculoskeletal; Neurologic

Intervention: General

Rationale: 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

Refs: 18678320

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to KCNK9 variants in ClinVar

7 Conditions Cataloged

not providedTotal: 63

Birk-Barel syndromeTotal: 19

KCNK9-related disorderTotal: 9

Inborn genetic diseasesTotal: 8

not specifiedTotal: 7

Autism spectrum disorderTotal: 1

Developmental disorderTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001282534.2. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	15 clinvar	4 clinvar	20
missense	2 clinvar	7 clinvar	55 clinvar	3 clinvar		67
nonsense			6 clinvar			6
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)						0
Total	2	7	63	18	4	94

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 13 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001282534.2	RefSeq	NP_001269463.1	2	MANE Select
ENST00000520439.3	Ensembl	ENSP00000430676.1	2	MANE Select
ENST00000303015.2	Ensembl	ENSP00000302166.1	2	Standard
ENST00000303015.3	Ensembl	ENSP00000302166.1	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Aldosterone synthesis and secretion - Homo sapiens (human)
Nicotine Pathway (Dopaminergic Neuron), Pharmacodynamics
Nicotine Activity on Dopaminergic Neurons
Neuronal System
Phase 4 - resting membrane potential

Biological Process

potassium ion transport
stabilization of membrane potential
potassium ion transmembrane transport

Molecular Function

potassium channel activity
potassium ion leak channel activity

Cellular Component

plasma membrane
integral component of plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000520439
Coding exons: 2
Length: 102219
Individuals with no LoFs: 125638
Homozygous LoFs: 0
Heterozygous LoFs: 1
Defined: 125639
p: 0.00000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.90	118	246	0.479	0.0000164	2457
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.0000088	0.0000088	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: pH-dependent, voltage-insensitive, background potassium channel protein. {ECO:0000269|PubMed:11042359, ECO:0000269|PubMed:11431495, ECO:0000269|PubMed:23169818}.;

Recessive Scores

pRec: 0.128

Intolerance Scores

LoFtool: 0.0561
RVIS EVS: -0.38
RVIS percentile EVS: 27.42

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Indispensability pred.: N
Indispensability score: 0.186

Gene Damage Prediction

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