NM_000525.4(KCNJ11):c.844G>A (p.Glu282Lys) AND Hyperinsulinemic hypoglycemia, familial, 2

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Jan 5, 2015
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000009223.12

Allele description [Variation Report for NM_000525.4(KCNJ11):c.844G>A (p.Glu282Lys)]

NM_000525.4(KCNJ11):c.844G>A (p.Glu282Lys)

Gene:

KCNJ11:potassium inwardly rectifying channel subfamily J member 11 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

11p15.1

Genomic location:

Preferred name:

NM_000525.4(KCNJ11):c.844G>A (p.Glu282Lys)

HGVS:

NC_000011.10:g.17387248C>T
NG_012446.1:g.6412G>A
NM_000525.4:c.844G>AMANE SELECT
NM_001166290.2:c.583G>A
NM_001377296.1:c.583G>A
NM_001377297.1:c.583G>A
NP_000516.3:p.Glu282Lys
NP_000516.3:p.Glu282Lys
NP_001159762.1:p.Glu195Lys
NP_001364225.1:p.Glu195Lys
NP_001364226.1:p.Glu195Lys
NC_000011.9:g.17408795C>T
NC_000011.9:g.17408795C>T
NM_000525.3:c.844G>A

Protein change:

E195K; GLU282LYS

Links:

OMIM: 600937.0022; dbSNP: rs267607196

NCBI 1000 Genomes Browser:

rs267607196

Molecular consequence:

NM_000525.4:c.844G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001166290.2:c.583G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001377296.1:c.583G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001377297.1:c.583G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Hyperinsulinemic hypoglycemia, familial, 2
Synonyms:: HYPERINSULINEMIC HYPOGLYCEMIA, PERSISTENT; HYPERINSULINISM, NEONATAL
Identifiers:: MONDO: MONDO:0011153; MedGen: C2931833; Orphanet: 276580; Orphanet: 276603; OMIM: 601820

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000029441	OMIM	no assertion criteria provided	Pathogenic (Jul 1, 2009)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV000247655	Genetic Services Laboratory, University of Chicago	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jan 5, 2015)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000029441

OMIM

no assertion criteria provided

Pathogenic
(Jul 1, 2009)

germline

literature only

PubMed (1)
[See all records that cite this PMID]

SCV000247655

Genetic Services Laboratory, University of Chicago

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Jan 5, 2015)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

Sar1-GTPase-dependent ER exit of KATP channels revealed by a mutation causing congenital hyperinsulinism.

Taneja TK, Mankouri J, Karnik R, Kannan S, Smith AJ, Munsey T, Christesen HB, Beech DJ, Sivaprasadarao A.

Hum Mol Genet. 2009 Jul 1;18(13):2400-13. doi: 10.1093/hmg/ddp179. Epub 2009 Apr 8.

PubMed [citation]

PMID:: 19357197

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From OMIM, SCV000029441.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

Description

In a Swedish patient with hyperinsulinemic hypoglycemia (HHF2; 601820) with focal adenomatous hyperplasia, Taneja et al. (2009) identified an 844G-A transition in the KCNJ11 gene, resulting in a glu282-to-lys (E282K) substitution within a diacidic endoplasmic reticulum (ER) exit signal DXE at codons 280 to 282. The paternal E282K mutation abrogated the exit signal and prevented the ER export and surface expression of the channel. Since in focal hyperinsulinemic hypoglycemia, the maternal chromosome containing the K(ATP) channel genes are lost, beta-cells of the patient would lack wildtype Kir6.2 to rescue the mutant Kir6.2 subunit expressed from the paternal chromosome.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Genetic Services Laboratory, University of Chicago, SCV000247655.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Apr 28, 2025

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