UniProtKB/Swiss-Prot P01308: Variant p.Arg55Cys

Insulin
Gene: INS
Chromosomal location: 11p15.5
Variant information

Variant position:  55
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 Arginine (R) to Cysteine (C) at position 55 (R55C, p.Arg55Cys).
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 large size and basic (R) to medium size and polar (C)
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:  Diabetes mellitus, insulin-dependent, 2 (IDDM2) [MIM:125852]: A multifactorial disorder of glucose homeostasis that is characterized by susceptibility to ketoacidosis in the absence of insulin therapy. Clinical features are polydipsia, polyphagia and polyuria which result from hyperglycemia-induced osmotic diuresis and secondary thirst. These derangements result in long-term complications that affect the eyes, kidneys, nerves, and blood vessels. 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 IDDM2.
Any additional useful information about the variant.

Other resources:  
Links to websites of interest for the variant.



Sequence information

Variant position:  55
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  110
The length of the canonical sequence.

Location on the sequence:   LVEALYLVCGERGFFYTPKT  R REAEDLQVGQVELGGGPGAG
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                         LVEALYLVCGERGFFYTPKTRREAEDLQVG--QVELGGGPGAG

Gorilla                       LVEALYLVCGERGFFYTPKTRREAEDLQVG--QVELGGGPG

Chimpanzee                    LVEALYLVCGERGFFYTPKTRREAEDLQVG--QVELGGGPG

Pig                           LVEALYLVCGERGFFYTPKARREAENPQAG--AVELGG--G

Bovine                        LVEALYLVCGERGFFYTPKARREVEGPQVG--ALELAGGPG

Rabbit                        LVEALYLVCGERGFFYTPKSRREVEELQVG--QAELGGGPG

Goat                          LVEALYLVCGERGFFYTPKA---------------------

Sheep                         LVEALYLVCGERGFFYTPKARREVEGPQVG--ALELAGGPG

Cat                           LVEALYLVCGERGFFYTPKARREAEDLQGK--DAELGEAPG

Dog                           LVEALYLVCGERGFFYTPKARREVEDLQVR--DVELAGAPG

Horse                         LVEALYLVCGERGFFYTPKAXXEAEDPQVG--EVELGGGPG

Chicken                       LVEALYLVCGERGFFYSPKARRDVEQPLVS--SPLRGE---

Zebrafish                     LVDALYLVCGPTGFFYNPK--RDVE-PLLGFLPPKSAQETE

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
Disulfide bond 31 – 96 Interchain (between B and A chains)
Disulfide bond 43 – 109 Interchain (between B and A chains)


Literature citations

Mutations in the insulin gene can cause MODY and autoantibody-negative type 1 diabetes.
Molven A.; Ringdal M.; Nordbo A.M.; Raeder H.; Stoy J.; Lipkind G.M.; Steiner D.F.; Philipson L.H.; Bergmann I.; Aarskog D.; Undlien D.E.; Joner G.; Sovik O.; Bell G.I.; Njolstad P.R.;
Diabetes 57:1131-1135(2008)
Cited for: VARIANT MODY10 GLN-46; VARIANT IDDM2 CYS-55;

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.