UniProtKB/Swiss-Prot O43316: Variant p.Arg172Trp

Paired box protein Pax-4
Gene: PAX4
Chromosomal location: 7q32
Variant information

Variant position:  172
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 implicated in disease according to literature reports.
  • Polymorphism: Variants not reported to be implicated in disease.
  • Unclassified: Variants with uncertain implication in disease according to literature reports. Evidence against or in favor of a pathogenic role is limited and/or conflicting.

Residue change:  From Arginine (R) to Tryptophan (W) at position 172 (R172W, p.Arg172Trp).
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 large size and aromatic (W)
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:  Maturity-onset diabetes of the young 9 (MODY9) [MIM:612225]: 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. {ECO:0000269|PubMed:17426099}. 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 MODY9; the mutant sequence represses the activity of the insulin and glucagon promoters by only 35% compared to 50% and 57% respectively with wild-type sequence.
Any additional useful information about the variant.



Sequence information

Variant position:  172
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  350
The length of the canonical sequence.

Location on the sequence:   VLTPHSGSETPRGTHPGTGH  R NRTIFSPSQAEALEKEFQRG
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                         VLTPHSGSETPRGTHPGTGHRNRTIFSPSQAEALEKEFQRG

Mouse                         LPSPHSNCGAPRGPHPGTSHRNRTIFSPGQAEALEKEFQRG

Rat                           LPSPHSNCEAPRGPHPGTSHRNRTIFSPGQAEALEKEFQRG

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 – 350 Paired box protein Pax-4
DNA binding 170 – 229 Homeobox


Literature citations

PAX4 mutations in Thais with maturity onset diabetes of the young.
Plengvidhya N.; Kooptiwut S.; Songtawee N.; Doi A.; Furuta H.; Nishi M.; Nanjo K.; Tantibhedhyangkul W.; Boonyasrisawat W.; Yenchitsomanus P.-T.; Doria A.; Banchuin N.;
J. Clin. Endocrinol. Metab. 92:2821-2826(2007)
Cited for: VARIANT MODY9 TRP-172; VARIANTS GLN-39; CYS-191; HIS-200 AND SER-200; VARIANT PRO-321 (ISOFORM 3); CHARACTERIZATION OF VARIANT MODY9 TRP-172;

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.