This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
ClinVar Genomic variation as it relates to human health
NM_000525.4(KCNJ11):c.67A>G (p.Lys23Glu)
Germline
Classification
Help
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
(19)
Help
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
Benign/Likely benign
19
criteria provided, multiple submitters, no conflicts
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_000525.4(KCNJ11):c.67A>G (p.Lys23Glu)
Variation ID: 8678 Accession: VCV000008678.31
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 11p15.1 11: 17388025 (GRCh38) [ NCBI UCSC ] 11: 17409572 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Apr 4, 2013 Oct 8, 2024 Feb 1, 2024 - HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_000525.4:c.67A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000516.3:p.Lys23Glu missense NM_001166290.2:c.-16-179A>G intron variant NM_001377296.1:c.-24A>G 5 prime UTR NM_001377297.1:c.-16-179A>G intron variant NC_000011.10:g.17388025T>C NC_000011.9:g.17409572T>C NG_012446.1:g.5635A>G - Protein change
- K23E
- Other names
-
E23K
- Canonical SPDI
- NC_000011.10:17388024:T:C
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- -
-
Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
-
0.26298 (T)
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
-
The Genome Aggregation Database (gnomAD), exomes 0.64020
Exome Aggregation Consortium (ExAC) 0.64710
The Genome Aggregation Database (gnomAD) 0.72048
Trans-Omics for Precision Medicine (TOPMed) 0.72968
1000 Genomes Project 0.73702
1000 Genomes Project 30x 0.74001
- Links
Genes
| Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
|---|---|---|---|---|---|---|
| HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
|||
| ABCC8 | - | - |
GRCh38 GRCh37 |
2370 | 2502 | |
| KCNJ11 | - | - |
GRCh38 GRCh37 |
466 | 492 | |
Conditions - Germline
| Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
|---|---|---|---|---|
| risk factor (1) |
no assertion criteria provided
|
Dec 1, 2009 | RCV000009214.19 | |
| drug response (1) |
no assertion criteria provided
|
Dec 1, 2009 | RCV000009215.19 | |
| Benign (3) |
criteria provided, single submitter
|
Jun 14, 2016 | RCV000020356.16 | |
| Benign (2) |
criteria provided, multiple submitters, no conflicts
|
Nov 26, 2014 | RCV000146116.21 | |
| Likely benign (1) |
criteria provided, single submitter
|
Jun 14, 2016 | RCV000281825.15 | |
| Likely benign (1) |
criteria provided, single submitter
|
Jun 14, 2016 | RCV000294608.15 | |
| Likely benign (1) |
criteria provided, single submitter
|
Jun 14, 2016 | RCV000385348.13 | |
| Benign/Likely benign (3) |
criteria provided, multiple submitters, no conflicts
|
Feb 1, 2024 | RCV001512207.18 | |
| Likely benign (1) |
criteria provided, single submitter
|
Apr 27, 2017 | RCV001093985.12 | |
| Likely benign (1) |
criteria provided, single submitter
|
Apr 27, 2017 | RCV001105584.12 | |
| Benign/Likely benign (2) |
criteria provided, multiple submitters, no conflicts
|
Apr 28, 2017 | RCV000576501.14 | |
| Benign (1) |
criteria provided, single submitter
|
- | RCV002226643.9 | |
|
KCNJ11-related disorder
|
Benign (1) |
no assertion criteria provided
|
Apr 15, 2024 | RCV004734506.1 |
| click to load more click to collapse | ||||
Submissions - Germline
| Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
|
|---|---|---|---|---|---|
|
Benign
(Feb 08, 2013)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
(Autosomal unknown)
Affected status: unknown
Allele origin:
germline
|
Genetic Services Laboratory, University of Chicago
Accession: SCV000193333.1
First in ClinVar: Nov 23, 2014 Last updated: Nov 23, 2014 |
|
|
|
Likely benign
(Jun 14, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
Maturity Onset Diabetes of the Young
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV000369190.2
First in ClinVar: Dec 06, 2016 Last updated: Dec 06, 2016 |
|
|
|
Likely benign
(Jun 14, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
Transient Neonatal Diabetes, Dominant
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV000369189.2
First in ClinVar: Dec 06, 2016 Last updated: Dec 06, 2016 |
|
|
|
Benign
(Jun 14, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
Permanent Neonatal Diabetes Mellitus
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV000483236.2
First in ClinVar: Dec 06, 2016 Last updated: Dec 06, 2016 |
|
|
|
Likely benign
(Jun 14, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
Hyperinsulinism, Dominant/Recessive
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV000369188.2
First in ClinVar: Dec 06, 2016 Last updated: Dec 06, 2016 |
|
|
|
Benign
(Nov 26, 2014)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
germline
|
Eurofins Ntd Llc (ga)
Accession: SCV000224239.5
First in ClinVar: Jun 29, 2015 Last updated: Oct 02, 2016 |
Number of individuals with the variant: 3
Sex: mixed
|
|
|
Likely benign
(Apr 27, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
Diabetes mellitus, transient neonatal, 3
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV000483235.3
First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020 |
Comment:
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, … (more)
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. (less)
|
|
|
Likely benign
(Apr 27, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
Hyperinsulinemic hypoglycemia, familial, 2
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV000483234.3
First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020 |
Comment:
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, … (more)
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. (less)
|
|
|
Likely benign
(Apr 27, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
Maturity-onset diabetes of the young type 13
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV001262568.1
First in ClinVar: May 31, 2020 Last updated: May 31, 2020 |
Comment:
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, … (more)
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. (less)
|
|
|
Benign
(-)
|
criteria provided, single submitter
Method: research
|
Type 2 diabetes mellitus
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
somatic
|
Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic
Accession: SCV002505643.1
First in ClinVar: May 07, 2022 Last updated: May 07, 2022 |
Comment:
Mutations in KCNJ11 gene can cause decreased production and secretion of insulin. This can lead to MODY which is responsive to oral sulfonylureas. KCNJ11 rs5219- … (more)
Mutations in KCNJ11 gene can cause decreased production and secretion of insulin. This can lead to MODY which is responsive to oral sulfonylureas. KCNJ11 rs5219- E23K is associated with Type II Diabetes Mellitus. It doesnt cause any sensitivity towards mild hypoglycemia, an adverse effect of Sulfonylurea treatment. (less)
|
|
|
Benign
(Apr 28, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
Hyperinsulinemic hypoglycemia, familial, 2
Affected status: unknown
Allele origin:
germline
|
Athena Diagnostics
Accession: SCV000677330.1
First in ClinVar: Jan 07, 2018 Last updated: Jan 07, 2018 |
|
|
|
Benign
(Sep 04, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV001852181.1
First in ClinVar: Sep 12, 2021 Last updated: Sep 12, 2021 |
Comment:
This variant is associated with the following publications: (PMID: 28252621, 15111507, 25625107, 25165692, 24332549, 31118516, 29632382, 28082085, 25725792, 27535653, 25955821, 24996284, 26551672, 27398621, 26315042, 9867219, … (more)
This variant is associated with the following publications: (PMID: 28252621, 15111507, 25625107, 25165692, 24332549, 31118516, 29632382, 28082085, 25725792, 27535653, 25955821, 24996284, 26551672, 27398621, 26315042, 9867219, 24741969, 16733889, 24710510, 22163043, 22209866, 24241377, 22264780, 23054005, 23412854, 19498446, 17823772, 19578796, 19685080, 19214942, 22082043, 19491206, 15855351, 12196481, 20424228, 19587354, 17257281, 16455067, 19233137, 22704848, 18758683) (less)
|
|
|
Benign
(Feb 01, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV001719579.4
First in ClinVar: Jun 15, 2021 Last updated: Feb 20, 2024 |
|
|
|
Likely benign
(-)
|
criteria provided, single submitter
Method: not provided
|
not provided
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
|
Breakthrough Genomics, Breakthrough Genomics
Accession: SCV005221359.1
First in ClinVar: Sep 29, 2024 Last updated: Sep 29, 2024 |
|
|
|
Benign
(Sep 16, 2020)
|
no assertion criteria provided
Method: clinical testing
|
Permanent neonatal diabetes mellitus
Affected status: unknown
Allele origin:
germline
|
Natera, Inc.
Accession: SCV001459969.1
First in ClinVar: Jan 02, 2021 Last updated: Jan 02, 2021 |
|
|
|
drug response
(Dec 01, 2009)
|
no assertion criteria provided
Method: literature only
|
EXERCISE STRESS RESPONSE, IMPAIRED, ASSOCIATION WITH
Affected status: not provided
Allele origin:
germline
|
OMIM
Accession: SCV000029433.5
First in ClinVar: Apr 04, 2013 Last updated: Mar 10, 2024 |
Comment on evidence:
Hani et al. (1998) identified a glu23-to-lys (E23K) amino acid substitution in the KCNJ11 gene by molecular screening using SSCP and direct sequencing in 72 … (more)
Hani et al. (1998) identified a glu23-to-lys (E23K) amino acid substitution in the KCNJ11 gene by molecular screening using SSCP and direct sequencing in 72 French Caucasian families with type 2 diabetes (125853). They genotyped this variant in French cohorts of 191 unrelated type 2 diabetic probands and 119 normoglycemic control subjects and performed association studies. Homozygosity for lys23 (KK) was more frequent in type 2 diabetic than in control subjects (27 vs 14%; p = 0.015). Analyses in a recessive model (KK vs EK/EE) showed a stronger association of the K allele with diabetes. In a metaanalysis of their data for the E23K variant and data obtained from 3 other Caucasian groups, Hani et al. (1998) found the E23K variant to be significantly associated with type 2 diabetes. Hansen et al. (2005) investigated the separate and combined effects of the PPARG pro12-to-ala (P12A; 601487.0002) and the KCNJ11 E23K polymorphisms on risk of type 2 diabetes. The combined analysis involved 1,164 type 2 diabetic patients and 4,733 middle-aged, glucose-tolerant subjects. In the separate analyses, the K allele of KCNJ11 E23K associated with type 2 diabetes (odds ratio, 1.19; p = 0.0002), whereas PPARG P12A showed no significant association with type 2 diabetes. The combined analysis indicated that the 2 polymorphisms acted in an additive manner to increase the risk of type 2 diabetes, and the authors found no evidence for a synergistic interaction between them. Together, the 2 polymorphisms conferred a population-attributable risk for type 2 diabetes of 28%. The authors concluded that their results showed no evidence of a synergistic interaction between the KCNJ11 E23K and PPARG P12A polymorphisms, but indicated that they may act in an additive manner to increase the risk of type 2 diabetes. Laukkanen et al. (2004) found an additive effect of a high risk ABCC8 (600509) haplotype, composed of a silent polymorphism (AGG-AGA; arg1273 to arg) and 3 promoter polymorphisms, and the 23K allele of the KCNJ11 gene. In genomewide association studies of type 2 diabetes involving genotype data from a variety of international consortia, the Diabetes Genetics Initiative of Broad Institute of Harvard and MIT, Lund University, and Novartis Institutes for BioMedical Research (2007), Zeggini et al. (2007), and Scott et al. (2007) confirmed association of the E23K polymorphism (rs5219) with diabetes susceptibility. Although this association was not strongly observed in any single scan, all-data metaanalyses resulted in genomewide significant association (OR = 1.14, p = 6.7 x 10(-11)). Association with Impaired Exercise Stress Response Reyes et al. (2009) found that the E23K polymorphism was overrepresented in 115 individuals with dilated cardiomyopathy (see 115200) and congestive heart failure (CHF) compared to 2,031 community-based controls (p less than 0.001). In addition, the KK genotype, which was present in 18% of the CHF patients, was associated with abnormal cardiopulmonary exercise stress testing: despite similar baseline heart rates among genotype subgroups, individuals with the KK genotype had a significantly reduced heart rate increase at matched workload, at 75% of maximum oxygen consumption, and at peak VO(2), compared to those with the EE or EK genotypes. Noting that the glu23 residue is located within the functionally relevant intracellular slide helix region, Reyes et al. (2009) suggested that E23K might represent a biomarker for impaired stress performance. (less)
|
|
|
risk factor
(Dec 01, 2009)
|
no assertion criteria provided
Method: literature only
|
TYPE 2 DIABETES MELLITUS, SUSCEPTIBILITY TO
Affected status: not provided
Allele origin:
germline
|
OMIM
Accession: SCV000029432.5
First in ClinVar: Apr 04, 2013 Last updated: Mar 10, 2024 |
Comment on evidence:
Hani et al. (1998) identified a glu23-to-lys (E23K) amino acid substitution in the KCNJ11 gene by molecular screening using SSCP and direct sequencing in 72 … (more)
Hani et al. (1998) identified a glu23-to-lys (E23K) amino acid substitution in the KCNJ11 gene by molecular screening using SSCP and direct sequencing in 72 French Caucasian families with type 2 diabetes (125853). They genotyped this variant in French cohorts of 191 unrelated type 2 diabetic probands and 119 normoglycemic control subjects and performed association studies. Homozygosity for lys23 (KK) was more frequent in type 2 diabetic than in control subjects (27 vs 14%; p = 0.015). Analyses in a recessive model (KK vs EK/EE) showed a stronger association of the K allele with diabetes. In a metaanalysis of their data for the E23K variant and data obtained from 3 other Caucasian groups, Hani et al. (1998) found the E23K variant to be significantly associated with type 2 diabetes. Hansen et al. (2005) investigated the separate and combined effects of the PPARG pro12-to-ala (P12A; 601487.0002) and the KCNJ11 E23K polymorphisms on risk of type 2 diabetes. The combined analysis involved 1,164 type 2 diabetic patients and 4,733 middle-aged, glucose-tolerant subjects. In the separate analyses, the K allele of KCNJ11 E23K associated with type 2 diabetes (odds ratio, 1.19; p = 0.0002), whereas PPARG P12A showed no significant association with type 2 diabetes. The combined analysis indicated that the 2 polymorphisms acted in an additive manner to increase the risk of type 2 diabetes, and the authors found no evidence for a synergistic interaction between them. Together, the 2 polymorphisms conferred a population-attributable risk for type 2 diabetes of 28%. The authors concluded that their results showed no evidence of a synergistic interaction between the KCNJ11 E23K and PPARG P12A polymorphisms, but indicated that they may act in an additive manner to increase the risk of type 2 diabetes. Laukkanen et al. (2004) found an additive effect of a high risk ABCC8 (600509) haplotype, composed of a silent polymorphism (AGG-AGA; arg1273 to arg) and 3 promoter polymorphisms, and the 23K allele of the KCNJ11 gene. In genomewide association studies of type 2 diabetes involving genotype data from a variety of international consortia, the Diabetes Genetics Initiative of Broad Institute of Harvard and MIT, Lund University, and Novartis Institutes for BioMedical Research (2007), Zeggini et al. (2007), and Scott et al. (2007) confirmed association of the E23K polymorphism (rs5219) with diabetes susceptibility. Although this association was not strongly observed in any single scan, all-data metaanalyses resulted in genomewide significant association (OR = 1.14, p = 6.7 x 10(-11)). Association with Impaired Exercise Stress Response Reyes et al. (2009) found that the E23K polymorphism was overrepresented in 115 individuals with dilated cardiomyopathy (see 115200) and congestive heart failure (CHF) compared to 2,031 community-based controls (p less than 0.001). In addition, the KK genotype, which was present in 18% of the CHF patients, was associated with abnormal cardiopulmonary exercise stress testing: despite similar baseline heart rates among genotype subgroups, individuals with the KK genotype had a significantly reduced heart rate increase at matched workload, at 75% of maximum oxygen consumption, and at peak VO(2), compared to those with the EE or EK genotypes. Noting that the glu23 residue is located within the functionally relevant intracellular slide helix region, Reyes et al. (2009) suggested that E23K might represent a biomarker for impaired stress performance. (less)
|
|
|
Benign
(Apr 15, 2024)
|
no assertion criteria provided
Method: clinical testing
|
KCNJ11-related condition
Affected status: unknown
Allele origin:
germline
|
PreventionGenetics, part of Exact Sciences
Accession: SCV000304667.2
First in ClinVar: Oct 02, 2016 Last updated: Oct 08, 2024 |
Comment:
This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
|
|
|
not provided
(-)
|
no classification provided
Method: literature only
|
Permanent neonatal diabetes mellitus
Affected status: not provided
Allele origin:
unknown
|
GeneReviews
Accession: SCV000040740.2
First in ClinVar: Apr 04, 2013 Last updated: Oct 01, 2022 |
|
|
| click to load more click to collapse | |||||
Comment:
Comment:
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Comment:
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Comment:
Mutations in KCNJ11 gene can cause decreased production and secretion of insulin. This can lead to MODY which is responsive to oral sulfonylureas. KCNJ11 rs5219- E23K is associated with Type II Diabetes Mellitus. It doesnt cause any sensitivity towards mild hypoglycemia, an adverse effect of Sulfonylurea treatment.
Comment:
This variant is associated with the following publications: (PMID: 28252621, 15111507, 25625107, 25165692, 24332549, 31118516, 29632382, 28082085, 25725792, 27535653, 25955821, 24996284, 26551672, 27398621, 26315042, 9867219, 24741969, 16733889, 24710510, 22163043, 22209866, 24241377, 22264780, 23054005, 23412854, 19498446, 17823772, 19578796, 19685080, 19214942, 22082043, 19491206, 15855351, 12196481, 20424228, 19587354, 17257281, 16455067, 19233137, 22704848, 18758683)
Comment:
This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
Germline Functional Evidence
| There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Comment:
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Comment:
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Comment:
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Comment:
Mutations in KCNJ11 gene can cause decreased production and secretion of insulin. This can lead to MODY which is responsive to oral sulfonylureas. KCNJ11 rs5219- E23K is associated with Type II Diabetes Mellitus. It doesnt cause any sensitivity towards mild hypoglycemia, an adverse effect of Sulfonylurea treatment.
Comment:
This variant is associated with the following publications: (PMID: 28252621, 15111507, 25625107, 25165692, 24332549, 31118516, 29632382, 28082085, 25725792, 27535653, 25955821, 24996284, 26551672, 27398621, 26315042, 9867219, 24741969, 16733889, 24710510, 22163043, 22209866, 24241377, 22264780, 23054005, 23412854, 19498446, 17823772, 19578796, 19685080, 19214942, 22082043, 19491206, 15855351, 12196481, 20424228, 19587354, 17257281, 16455067, 19233137, 22704848, 18758683)
Comment:
This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Permanent Neonatal Diabetes Mellitus. | Adam MP | - | 2024 | PMID: 20301620 |
| Genetic polymorphisms in KCNJ11 (E23K, rs5219) and SDF-1β (G801A, rs1801157) genes are associated with the risk of type 2 diabetes mellitus. | Rizvi S | British journal of biomedical science | 2018 | PMID: 29893194 |
| Effects of single nucleotide polymorphisms in K(ATP) channel genes on type 2 diabetes in a Turkish population. | Gonen MS | Archives of medical research | 2012 | PMID: 22704848 |
| Association of KCNJ11 E23K gene polymorphism with hypoglycemia in sulfonylurea-treated type 2 diabetic patients. | Ragia G | Diabetes research and clinical practice | 2012 | PMID: 22591706 |
| Association between a common KCNJ11 polymorphism (rs5219) and new-onset posttransplant diabetes in patients treated with Tacrolimus. | Tavira B | Molecular genetics and metabolism | 2012 | PMID: 22264780 |
| Pharmacogenomic analysis of ATP-sensitive potassium channels coexpressing the common type 2 diabetes risk variants E23K and S1369A. | Lang VY | Pharmacogenetics and genomics | 2012 | PMID: 22209866 |
| The effect of KCNJ11 polymorphism on the risk of type 2 diabetes: a global meta-analysis based on 49 case-control studies. | Gong B | DNA and cell biology | 2012 | PMID: 22082043 |
| The KCNJ11 E23K polymorphism and progression of glycaemia in Southern Chinese: a long-term prospective study. | Cheung CY | PloS one | 2011 | PMID: 22163043 |
| Impact of common variants of PPARG, KCNJ11, TCF7L2, SLC30A8, HHEX, CDKN2A, IGF2BP2, and CDKAL1 on the risk of type 2 diabetes in 5,164 Indians. | Chauhan G | Diabetes | 2010 | PMID: 20424228 |
| KATP channel Kir6.2 E23K variant overrepresented in human heart failure is associated with impaired exercise stress response. | Reyes S | Human genetics | 2009 | PMID: 19685080 |
| Coexpression of the type 2 diabetes susceptibility gene variants KCNJ11 E23K and ABCC8 S1369A alter the ATP and sulfonylurea sensitivities of the ATP-sensitive K(+) channel. | Hamming KS | Diabetes | 2009 | PMID: 19587354 |
| Association of genetic variants with chronic kidney disease in individuals with different lipid profiles. | Yoshida T | International journal of molecular medicine | 2009 | PMID: 19578796 |
| The E23K variation in the KCNJ11 gene is associated with type 2 diabetes in Chinese and East Asian population. | Zhou D | Journal of human genetics | 2009 | PMID: 19498446 |
| Kir6.2 variant E23K increases ATP-sensitive K+ channel activity and is associated with impaired insulin release and enhanced insulin sensitivity in adults with normal glucose tolerance. | Villareal DT | Diabetes | 2009 | PMID: 19491206 |
| The effects of E23K polymorphism in Kir6.2 subunit on insulin sensitivity in skeletal muscle cells by long-chain fatty acyl CoA. | Wan J | Biochemical and biophysical research communications | 2009 | PMID: 19233137 |
| The E23K variant of KCNJ11 and the risk for severe sulfonylurea-induced hypoglycemia in patients with type 2 diabetes. | Holstein A | Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme | 2009 | PMID: 19214942 |
| Genetic variations in the pancreatic ATP-sensitive potassium channel, beta-cell dysfunction, and susceptibility to type 2 diabetes. | Chistiakov DA | Acta diabetologica | 2009 | PMID: 18758683 |
| SNPs in the KCNJ11-ABCC8 gene locus are associated with type 2 diabetes and blood pressure levels in the Japanese population. | Sakamoto Y | Journal of human genetics | 2007 | PMID: 17823772 |
| Replication of genome-wide association signals in UK samples reveals risk loci for type 2 diabetes. | Zeggini E | Science (New York, N.Y.) | 2007 | PMID: 17463249 |
| A genome-wide association study of type 2 diabetes in Finns detects multiple susceptibility variants. | Scott LJ | Science (New York, N.Y.) | 2007 | PMID: 17463248 |
| Genome-wide association analysis identifies loci for type 2 diabetes and triglyceride levels. | Diabetes Genetics Initiative of Broad Institute of Harvard and MIT, Lund University, and Novartis Institutes of BioMedical Research | Science (New York, N.Y.) | 2007 | PMID: 17463246 |
| Polymorphisms of KCNJ11 (Kir6.2 gene) are associated with Type 2 diabetes and hypertension in the Korean population. | Koo BK | Diabetic medicine : a journal of the British Diabetic Association | 2007 | PMID: 17257281 |
| The E23K polymorphism in Kir6.2 gene and coronary heart disease. | Xiong C | Clinica chimica acta; international journal of clinical chemistry | 2006 | PMID: 16455067 |
| Single nucleotide polymorphisms in K(ATP) channels: muscular impact on type 2 diabetes. | Li L | Diabetes | 2005 | PMID: 15855351 |
| Analysis of separate and combined effects of common variation in KCNJ11 and PPARG on risk of type 2 diabetes. | Hansen SK | The Journal of clinical endocrinology and metabolism | 2005 | PMID: 15797964 |
| Polymorphisms of the SUR1 (ABCC8) and Kir6.2 (KCNJ11) genes predict the conversion from impaired glucose tolerance to type 2 diabetes. The Finnish Diabetes Prevention Study. | Laukkanen O | The Journal of clinical endocrinology and metabolism | 2004 | PMID: 15579791 |
| Haplotype structure and genotype-phenotype correlations of the sulfonylurea receptor and the islet ATP-sensitive potassium channel gene region. | Florez JC | Diabetes | 2004 | PMID: 15111507 |
| The E23K variant of Kir6.2 associates with impaired post-OGTT serum insulin response and increased risk of type 2 diabetes. | Nielsen EM | Diabetes | 2003 | PMID: 12540638 |
| Large-scale association studies of variants in genes encoding the pancreatic beta-cell KATP channel subunits Kir6.2 (KCNJ11) and SUR1 (ABCC8) confirm that the KCNJ11 E23K variant is associated with type 2 diabetes. | Gloyn AL | Diabetes | 2003 | PMID: 12540637 |
| The common single nucleotide polymorphism E23K in K(IR)6.2 sensitizes pancreatic beta-cell ATP-sensitive potassium channels toward activation through nucleoside diphosphates. | Schwanstecher C | Diabetes | 2002 | PMID: 12475776 |
| The prevalent Glu23Lys polymorphism in the potassium inward rectifier 6.2 (KIR6.2) gene is associated with impaired glucagon suppression in response to hyperglycemia. | Tschritter O | Diabetes | 2002 | PMID: 12196481 |
| K(IR)6.2 polymorphism predisposes to type 2 diabetes by inducing overactivity of pancreatic beta-cell ATP-sensitive K(+) channels. | Schwanstecher C | Diabetes | 2002 | PMID: 11872696 |
| Genetic variability of the SUR1 promoter in relation to beta-cell function and Type II diabetes mellitus. | Hansen T | Diabetologia | 2001 | PMID: 11692183 |
| Association studies of variants in promoter and coding regions of beta-cell ATP-sensitive K-channel genes SUR1 and Kir6.2 with Type 2 diabetes mellitus (UKPDS 53). | Gloyn AL | Diabetic medicine : a journal of the British Diabetic Association | 2001 | PMID: 11318841 |
| Missense mutations in the pancreatic islet beta cell inwardly rectifying K+ channel gene (KIR6.2/BIR): a meta-analysis suggests a role in the polygenic basis of Type II diabetes mellitus in Caucasians. | Hani EH | Diabetologia | 1998 | PMID: 9867219 |
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Text-mined citations for rs5219 ...
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Record last updated Nov 10, 2024
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