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Intellectual disability syndromic and non-syndromic

Gene: KCNK3

Amber List (moderate evidence)

KCNK3 (potassium two pore domain channel subfamily K member 3)
EnsemblGeneIds (GRCh38): ENSG00000171303
EnsemblGeneIds (GRCh37): ENSG00000171303
OMIM: 603220, Gene2Phenotype
KCNK3 is in 9 panels

2 reviews

Krithika Murali (Victorian Clinical Genetics Services)

Green List (high evidence)

PMID 36195757 Sörmann et al 2022 report 9 unrelated individuals with de novo heterozygous KCNK3 missense variants (21 weeks to 25 years old). All 8 living probands (3-25 years) had hypotonia, global developmental delay, central and/or obstructive sleep apnoea and feeding difficulties. 7/9 probands had additional anomalies including microcephaly (at least 3/9), arthrogryposis/flexion contractures/foot deformities (7/9), scoliosis, cleft palate (2/9), and ambiguous genitalia/undescended testes (5/6) and dysmorphism. IUGR reported in 3/9 probands and polyhdramnios in 2/9.

KCNK3 encodes the TASK-1 K2P channel expressed throughout the central nervous system. All identified variants clustered near the X-gate and are involved in inter- or intra-subunit interaction likely to hold the X-gate closed. Individuals with variants located in the M2 transmembrane helix had a more severe phenotype than those with variants in the M4 helix. Functional studies support a gain of function disease mechanism with increased channel activation. TASK-1 K+ channel inhibitors (some in clinical use) have been raised as a possible therapeutic strategy.

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Heterozygous LoF variants associated with a different disorder - primary pulmonary arterial hypertension
Created: 6 Oct 2022, 1:15 a.m. | Last Modified: 6 Oct 2022, 1:15 a.m.
Panel Version: 0.4959

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Neurodevelopmental disorder, MONDO:0700092, KCNK3-related; developmental delay with sleep apnoea (DDSA)

Publications

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

I don't know

Established pulmonary hypertension gene.

PMID: 33057194 - Has been identified as a gene with significant de novo enrichment in a large trio study from the Deciphering Developmental Disorders study. 8 de novo variants (7 missense, 1 synonymous) identified in ~10,000 cases with developmental disorders (no other phenotype info provided).
Sources: Expert Review
Created: 14 Mar 2022, 6:16 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Neurodevelopmental disorder, MONDO:0700092, KCNK3-related

Publications

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Amber
  • Expert Review
Phenotypes
  • Neurodevelopmental disorder, MONDO:0700092, KCNK3-related
OMIM
603220
Clinvar variants
Variants in KCNK3
Penetrance
None
Publications
Panels with this gene

History Filter Activity

14 Mar 2022, Gel status: 2

Entity classified by Genomics England curator

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Gene: kcnk3 has been classified as Amber List (Moderate Evidence).

14 Mar 2022, Gel status: 2

Entity classified by Genomics England curator

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Gene: kcnk3 has been classified as Amber List (Moderate Evidence).

14 Mar 2022, Gel status: 2

Entity classified by Genomics England curator

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Gene: kcnk3 has been classified as Amber List (Moderate Evidence).

14 Mar 2022, Gel status: 1

Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

gene: KCNK3 was added gene: KCNK3 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review Mode of inheritance for gene: KCNK3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: KCNK3 were set to 33057194 Phenotypes for gene: KCNK3 were set to Neurodevelopmental disorder, MONDO:0700092, KCNK3-related Review for gene: KCNK3 was set to AMBER