UniProtKB/Swiss-Prot Q14654: Variant p.Cys42Arg

ATP-sensitive inward rectifier potassium channel 11
Gene: KCNJ11
Chromosomal location: 11p15.1
Variant information

Variant position:  42
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Disease [Disclaimer]
The variants are classified into three categories: Disease, Polymorphism and Unclassified.
  • Disease: Variants have been found in patients and disease-association is reported in literature. However, this classification is not a definitive assessment of variant pathogenicity.
  • Polymorphism: No disease-association has been reported.
  • Unclassified: Variants have been found in patients but disease-association remains unclear.

Residue change:  From Cysteine (C) to Arginine (R) at position 42 (C42R, p.Cys42Arg).
Indicates the amino acid change of the variant. The one-letter and three-letter codes for amino acids used in UniProtKB/Swiss-Prot are those adopted by the commission on Biochemical Nomenclature of the IUPAC-IUB.

Physico-chemical properties:  Change from medium size and polar (C) to large size and basic (R)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -3
The score within a Blosum matrix for the corresponding wild-type to variant amino acid change. The log-odds score measures the logarithm for the ratio of the likelihood of two amino acids appearing by chance. The Blosum62 substitution matrix is used. This substitution matrix contains scores for all possible exchanges of one amino acid with another:
  • Lowest score: -4 (low probability of substitution).
  • Highest score: 11 (high probability of substitution).
More information can be found on the following page

Involvement in disease:  Transient neonatal diabetes mellitus 3 (TNDM3) [MIM:610582]: Neonatal diabetes mellitus, defined as insulin-requiring hyperglycemia within the first month of life, is a rare entity. In about half of the neonates, diabetes is transient and resolves at a median age of 3 months, whereas the rest have a permanent form of diabetes. In a significant number of patients with transient neonatal diabetes mellitus, diabetes type 2 appears later in life. The onset and severity of TNDM3 is variable with childhood-onset diabetes, gestational diabetes or adult-onset diabetes described. Note=The disease is caused by mutations affecting the gene represented in this entry.
The name and a short description of the disease associated with the variant. For more information about the disease, the user can refer to OMIM, following the link provided after the disease acronym.

Variant description:  In TNDM3; increased spontaneous open probability; reduced ATP sensitivity; reduced expression at the cell surface of the functional ATP-sensitive form.
Any additional useful information about the variant.



Sequence information

Variant position:  42
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  390
The length of the canonical sequence.

Location on the sequence:   AEPRYRARQRRARFVSKKGN  C NVAHKNIREQGRFLQDVFTT
The residue change on the sequence. Unless the variant is located at the beginning or at the end of the protein sequence, both residues upstream (20) and downstream (20) of the variant will be shown.

Residue conservation: 
The multiple alignment of the region surrounding the variant against various orthologous sequences.

Human                         AEPRYRARQRRARFVSKKGNCNVAHKNIREQGRFLQDVFTT

Mouse                         AEPRYRTRERRARFVSKKGNCNVAHKNIREQGRFLQDVFTT

Rat                           TEPRYRTRERRARFVSKKGNCNVAHKNIREQGRFLQDVFTT

Rabbit                        AEPRYRARERRARFVSKKGNCNVAHKNIREQGRFLQDVFTT

Sequence annotation in neighborhood:  
The regions or sites of interest surrounding the variant. In general the features listed are posttranslational modifications, binding sites, enzyme active sites, local secondary structure or other characteristics reported in the cited references. The "Sequence annotation in neighborhood" lines have a fixed format:
  • Type: the type of sequence feature.
  • Positions: endpoints of the sequence feature.
  • Description: contains additional information about the feature.

TypePositionsDescription
Chain 1 – 390 ATP-sensitive inward rectifier potassium channel 11
Topological domain 1 – 68 Cytoplasmic
Alternative sequence 1 – 87 Missing. In isoform 2.


Literature citations

The C42R mutation in the Kir6.2 (KCNJ11) gene as a cause of transient neonatal diabetes, childhood diabetes, or later-onset, apparently type 2 diabetes mellitus.
Yorifuji T.; Nagashima K.; Kurokawa K.; Kawai M.; Oishi M.; Akazawa Y.; Hosokawa M.; Yamada Y.; Inagaki N.; Nakahata T.;
J. Clin. Endocrinol. Metab. 90:3174-3178(2005)
Cited for: VARIANT TNDM3 ARG-42; CHARACTERIZATION OF VARIANT TNDM3 ARG-42;

Disclaimer: Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. They are not in any way intended to be used as a substitute for professional medical advice, diagnostic, treatment or care.