UniProtKB/SwissProt variant VAR

Variant information

Variant position:

46

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

Type of variant:

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:

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:

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:

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:

In MODY10; reduces binding affinity to INSR; reduces biological activity; reduces folding properties.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs121908260 [ dbSNP | Ensembl ]

Sequence information

Variant position:

46

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:

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:

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

Human                         VNQHLCGSHLVEALYLVCGERGFFYTPKTRREAEDLQVG--QV

Gorilla                       VNQHLCGSHLVEALYLVCGERGFFYTPKTRREAEDLQVG--

                              VNQHLCGSHLVEALYLVCGERGFFYTPKARREVEDLQVR--

Chimpanzee                    VNQHLCGSHLVEALYLVCGERGFFYTPKTRREAEDLQVG--

Pig                           VNQHLCGSHLVEALYLVCGERGFFYTPKARREAENPQAG--

Bovine                        VNQHLCGSHLVEALYLVCGERGFFYTPKARREVEGPQVG--

Rabbit                        VNQHLCGSHLVEALYLVCGERGFFYTPKSRREVEELQVG--

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

Sheep                         VNQHLCGSHLVEALYLVCGERGFFYTPKARREVEGPQVG--

Cat                           VNQHLCGSHLVEALYLVCGERGFFYTPKARREAEDLQGK--

Horse                         VNQHLCGSHLVEALYLVCGERGFFYTPKAXXEAEDPQVG--

Chicken                       ANQHLCGSHLVEALYLVCGERGFFYSPKARRDVEQPLVS--

Zebrafish                     TPQHLCGSHLVDALYLVCGPTGFFYNPK--RDVE-PLLGFL

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.

Type	Positions	Description
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 IDDM2 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;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P01308: Variant p.Arg46Gln