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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P01308: Variant p.Arg46Gln

Insulin
Gene: INS
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Variant information Variant position: help 46 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: help LP/P [Disclaimer] The variants are classified into three categories: LP/P, LB/B and US.
  • LP/P: likely pathogenic or pathogenic.
  • LB/B: likely benign or benign.
  • US: uncertain significance
Residue change: help From Arginine (R) to Glutamine (Q) at position 46 (R46Q, p.Arg46Gln). 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: help Change from large size and basic (R) to medium size and polar (Q) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help 1 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
Variant description: help In MODY10; reduces binding affinity to INSR; reduces biological activity; reduces folding properties. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 46 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 110 The length of the canonical sequence.
Location on the sequence: help VNQHLCGSHLVEALYLVCGE R GFFYTPKTRREAEDLQVGQV 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: help The multiple alignment of the region surrounding the variant against various orthologous sequences. 
Human                         VNQHLCGSHLVEALYLVCGERGFFYTPKTRREAEDLQVGQV

Gorilla                       VNQHLCGSHLVEALYLVCGERGFFYTPKTRREAEDLQVGQV

                              VNQHLCGSHLVEALYLVCGERGFFYTPKARREVEDLQVRDV

Chimpanzee                    VNQHLCGSHLVEALYLVCGERGFFYTPKTRREAEDLQVGQV

Pig                           VNQHLCGSHLVEALYLVCGERGFFYTPKARREAENPQAGAV

Bovine                        VNQHLCGSHLVEALYLVCGERGFFYTPKARREVEGPQVGAL

Rabbit                        VNQHLCGSHLVEALYLVCGERGFFYTPKSRREVEELQVGQA

Goat                          VNQHLCGSHLVEALYLVCGERGFFYTPKA------------

Sheep                         VNQHLCGSHLVEALYLVCGERGFFYTPKARREVEGPQVGAL

Cat                           VNQHLCGSHLVEALYLVCGERGFFYTPKARREAEDLQGKDA

Horse                         VNQHLCGSHLVEALYLVCGERGFFYTPKAXXEAEDPQVGEV

Chicken                       ANQHLCGSHLVEALYLVCGERGFFYSPKARRDVEQPLVSS-

Zebrafish                     TPQHLCGSHLVDALYLVCGPTGFFYNPK--RDVE-PLLGFL
Sequence annotation in neighborhood: help 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
Peptide 25 – 54 Insulin B chain
Disulfide bond 31 – 96 Interchain (between B and A chains)
Disulfide bond 43 – 109 Interchain (between B and A chains)
Helix 44 – 46



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 T1D2 CYS-55; Further evidence that mutations in INS can be a rare cause of Maturity-Onset Diabetes of the Young (MODY).
Boesgaard T.W.; Pruhova S.; Andersson E.A.; Cinek O.; Obermannova B.; Lauenborg J.; Damm P.; Bergholdt R.; Pociot F.; Pisinger C.; Barbetti F.; Lebl J.; Pedersen O.; Hansen T.;
BMC Med. Genet. 11:42-42(2010)
Cited for: VARIANTS MODY10 HIS-6 AND GLN-46; Structural and functional study of the GlnB22-insulin mutant responsible for maturity-onset diabetes of the young.
Krizkova K.; Veverka V.; Maletinska L.; Hexnerova R.; Brzozowski A.M.; Jiracek J.; Zakova L.;
PLoS ONE 9:E112883-E112883(2014)
Cited for: VARIANT MODY10 GLN-46; CHARACTERIZATION OF VARIANT MODY10 GLN-46; STRUCTURE BY NMR OF 90-110 AND 25-54; DISULFIDE BONDS OF VARIANT MODY10 GLN-46; SUBUNIT;
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.