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Genetic Epilepsy

Gene: KCNJ11

Green List (high evidence)

KCNJ11 (potassium voltage-gated channel subfamily J member 11)
EnsemblGeneIds (GRCh38): ENSG00000187486
EnsemblGeneIds (GRCh37): ENSG00000187486
OMIM: 600937, Gene2Phenotype
KCNJ11 is in 14 panels

1 review

Elena Savva (Victorian Clinical Genetics Services)

Green List (high evidence)

Congenital hyperinsulinism (HI) variants are generally reported in heterozygous patients where they also carry a somatic 2nd hit, or have isodisomy of the paternal allele (focal HI), or in bilallelic patients (diffuse HI). This condition can be dominant (but rarely), where patients with these missense are diazoxide-responsive. Patients with recessively inherited variants are diazoxide-unresponsive (OMIM, PMID:11395395, PMID: 23275527, PMID: 23345197).

Genotype-phenotype correlation:
Permanent neonatal diabetes – GOF (OMIM)
Permanent neonatal diabetes + other features – GOF (OMIM)
Congenital hyperinsulinism – LOF (PMID:18250167).

PTCs - LOF
Missense - Loss and gain of function
LOF – cause reduce channel expression, channel activity and increase current decay (PMID:18250167)
GOF - impair ATP-based sensitivity, more open state channel (OMIM)

Mutations generally occur on the paternal allele (PMID: 23345197).
Created: 15 Apr 2020, 3:29 a.m. | Last Modified: 15 Apr 2020, 3:29 a.m.
Panel Version: 0.2280
Congenital hyperinsulinism (HI) variants are generally reported in heterozygous patients where they also carry a somatic 2nd hit, or have isodisomy of the paternal allele (focal HI), or in bilallelic patients (diffuse HI). This condition can be dominant (but rarely), where patients with these missense are diazoxide-responsive. Patients with recessively inherited variants are diazoxide-unresponsive (OMIM, PMID:11395395, PMID: 23275527, PMID: 23345197).

Genotype-phenotype correlation:
Permanent neonatal diabetes – GOF (OMIM)
Permanent neonatal diabetes + other features – GOF (OMIM)
Congenital hyperinsulinism – LOF (PMID:18250167).

PTCs - LOF
Missense - Loss and gain of function
LOF – cause reduce channel expression, channel activity and increase current decay (PMID:18250167)
GOF - impair ATP-based sensitivity, more open state channel (OMIM)

Mutations generally occur on the paternal allele (PMID: 23345197).
Created: 15 Apr 2020, 3:29 a.m. | Last Modified: 15 Apr 2020, 3:29 a.m.
Panel Version: 0.2280

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
{Diabetes mellitus, type 2, susceptibility to} 125853; Diabetes mellitus, transient neonatal, 3 610582; Diabetes, permanent neonatal, with or without neurologic features 606176; Hyperinsulinemic hypoglycemia, familial, 2 601820; Maturity-onset diabetes of the young, type 13 616329 AD

Publications

Mode of pathogenicity
Other

Details

Mode of Inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Victorian Clinical Genetics Services
  • Australian Genomics Health Alliance Epilepsy Flagship
Phenotypes
  • Diabetes mellitus, transient neonatal, 3 610582
  • Diabetes, permanent neonatal, with or without neurologic features 606176
  • Hyperinsulinemic hypoglycemia, familial, 2 601820
OMIM
600937
Clinvar variants
Variants in KCNJ11
Penetrance
None
Publications
Panels with this gene

History Filter Activity

24 Mar 2024, Gel status: 3

Entity classified by Genomics England curator

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Gene: kcnj11 has been classified as Green List (High Evidence).

24 Mar 2024, Gel status: 3

Set Phenotypes

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Phenotypes for gene: KCNJ11 were changed from to Diabetes mellitus, transient neonatal, 3 610582; Diabetes, permanent neonatal, with or without neurologic features 606176; Hyperinsulinemic hypoglycemia, familial, 2 601820

24 Mar 2024, Gel status: 3

Set publications

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Publications for gene: KCNJ11 were set to

24 Mar 2024, Gel status: 3

Set mode of inheritance

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Mode of inheritance for gene: KCNJ11 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal

17 Nov 2019, Gel status: 3

Created, Added New Source, Set mode of inheritance

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

gene: KCNJ11 was added gene: KCNJ11 was added to Genetic Epilepsy_AustralianGenomics_VCGS. Sources: Australian Genomics Health Alliance Epilepsy Flagship,Expert Review Green,Victorian Clinical Genetics Services Mode of inheritance for gene: KCNJ11 was set to Unknown