Variant information:

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Variant position: 18

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

Type of variant: Disease [Disclaimer: Variants classification is intended for research purposes only, not for clinical and diagnostic use. The label disease variant is assigned according to literature reports on probable disease-association that can be based on theoretical reasons. This label must not be considered as a definitive proof for the pathogenic role of a variant.]

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 18 (C18R, p.Cys18Arg).

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: Defects in PDX1 are the cause of maturity-onset diabetes of the young type 4 (MODY4) [MIM:606392]; also symbolized MODY-4. MODY is a form of diabetes that is characterized by an autosomal dominant mode of inheritance, onset in childhood or early adulthood (usually before 25 years of age), a primary defect in insulin secretion and frequent insulin-independence at the beginning of the disease.

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 MODY4.

Any additional useful information about the variant.

Other resources: 

Links to websites of interest for the variant.

• GeneReviews

Sequence information:

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Variant position: 18

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

Protein sequence length: 283

The length of the canonical sequence.

Location on the sequence:  MNGEEQYYAATQLYKDP  C AFQRGPAPEFSASPPACLYM

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.

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
Chain	1 – 283	Pancreas/duodenum homeobox protein 1
Region	13 – 73	Transactivation domain

Literature citations

Missense mutations in the insulin promoter factor-1 gene predispose to type 2 diabetes.
Macfarlane W.M.; Frayling T.M.; Ellard S.; Evans J.C.; Allen L.I.; Bulman M.P.; Ayres S.; Shepherd M.; Clark P.; Millward A.; Demaine A.; Wilkin T.; Docherty K.; Hattersley A.T.;
J. Clin. Invest. 104:R33-R39(1999)
Cited for: VARIANTS MODY4 ARG-18; ASN-76 AND HIS-197;