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NM_000525.4(KCNJ11):c.601C>T (p.Arg201Cys) AND Diabetes mellitus, permanent neonatal 2

Clinical significance:Pathogenic (Last evaluated: Jan 1, 2005)

Review status:(0/4) 0 stars out of maximum of 4 stars

no assertion criteria provided

Based on:
1 submission [Details]
Record status:

Allele description [Variation Report for NM_000525.4(KCNJ11):c.601C>T (p.Arg201Cys)]

NM_000525.4(KCNJ11):c.601C>T (p.Arg201Cys)

KCNJ11:potassium inwardly rectifying channel subfamily J member 11 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Genomic location:
Preferred name:
NM_000525.4(KCNJ11):c.601C>T (p.Arg201Cys)
  • NC_000011.10:g.17387491G>A
  • NG_012446.1:g.6169C>T
  • NM_000525.4:c.601C>TMANE SELECT
  • NM_001166290.2:c.340C>T
  • NM_001377296.1:c.340C>T
  • NM_001377297.1:c.340C>T
  • NP_000516.3:p.Arg201Cys
  • NP_000516.3:p.Arg201Cys
  • NP_001159762.1:p.Arg114Cys
  • NP_001364225.1:p.Arg114Cys
  • NP_001364226.1:p.Arg114Cys
  • NC_000011.9:g.17409038G>A
  • NM_000525.3:c.601C>T
Protein change:
R114C; ARG201CYS
OMIM: 600937.0004; dbSNP: rs80356625
NCBI 1000 Genomes Browser:
Molecular consequence:
  • NM_000525.4:c.601C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001166290.2:c.340C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001377296.1:c.340C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001377297.1:c.340C>T - missense variant - [Sequence Ontology: SO:0001583]


Diabetes mellitus, permanent neonatal 2
MONDO: MONDO:0030087; MedGen: C5394296; OMIM: 618856

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
SCV000029420OMIMno assertion criteria providedPathogenic
(Jan 1, 2005)
germlineliterature only

PubMed (4)
[See all records that cite these PMIDs]

Gloyn, A. L., Pearson, E. R., Antcliff, J. F., Proks, P., Bruining, G. J., Slingerland, A. S., Howard, N., Srinivasan, S., Silva, J. M. C. L., Molnes, J., Edghill, E. L., Frayling, T. M., and 13 others Activating mutations in the gene encoding the ATP-sensitive potassium-channel subunit Kir6.2 and permanent neonatal diabetes. New Eng. J. Med. 350: 1838-1849, 2004. Note: Erratum: New Eng. J. Med. 351: 1470 only, 2004.

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only



Molecular basis for Kir6.2 channel inhibition by adenine nucleotides.

Ribalet B, John SA, Weiss JN.

Biophys J. 2003 Jan;84(1):266-76.

PubMed [citation]

Molecular basis of Kir6.2 mutations associated with neonatal diabetes or neonatal diabetes plus neurological features.

Proks P, Antcliff JF, Lippiat J, Gloyn AL, Hattersley AT, Ashcroft FM.

Proc Natl Acad Sci U S A. 2004 Dec 14;101(50):17539-44. Epub 2004 Dec 6.

PubMed [citation]
See all PubMed Citations (4)

Details of each submission

From OMIM, SCV000029420.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (4)


In a patient with permanent neonatal diabetes mellitus (PNDM2; 618856), Gloyn et al. (2004) identified a heterozygous arg201-to-cys (R201C) mutation in the Kir6.2 gene. The patient was diagnosed at 4 weeks of age and had no additional neurologic or dysmorphic features. The arg201 residue lies close to the ATP-binding site and was implicated in ATP sensitivity (Ribalet et al., 2003).

Proks et al. (2004) stated that the 2 mutations in residue arg201, R201H (600937.0002) and R201C, which lie in the ATP-binding site of Kir6.2, cause milder PNDM disease without neurologic features; however, Massa et al. (2005) identified the R201C mutation in a patient with PNDM who also had muscle weakness and delayed motor development.

Gloyn et al. (2004) described a family in which 2 affected paternal half-sibs were heterozygous for the R201C mutation. Direct sequencing of leukocyte DNA showed that their clinically unaffected mothers and father were genotypically normal. Quantitative real-time PCR analysis of the father's leukocyte DNA detected no trace of mutant DNA. These results were consistent with the father being mosaic for the mutation, which was restricted to his germline. Gloyn et al. (2004) concluded that the high percentage of permanent neonatal diabetes cases due to de novo KCNJ11 mutations (Gloyn et al., 2004) suggests that germline mosaicism may be common.

OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot providednot providednot providednot providednot provided

Last Updated: Feb 7, 2023