UniProtKB/Swiss-Prot Q9BZS1: Variant p.Ile363Val

Forkhead box protein P3
Gene: FOXP3
Chromosomal location: Xp11.23
Variant information

Variant position:  363
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 Isoleucine (I) to Valine (V) at position 363 (I363V, p.Ile363Val).
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:  Similar physico-chemical property. Both residues are medium size and hydrophobic.
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:  Immunodeficiency polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) [MIM:304790]: Characterized by neonatal onset insulin-dependent diabetes mellitus, infections, secretory diarrhea, thrombocytopenia, anemia and eczema. It is usually lethal in infancy. {ECO:0000269|PubMed:11120765, ECO:0000269|PubMed:11137992, ECO:0000269|PubMed:11137993, ECO:0000269|PubMed:11768393, ECO:0000269|PubMed:18951619, ECO:0000269|PubMed:21458306}. 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 IPEX.
Any additional useful information about the variant.



Sequence information

Variant position:  363
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  431
The length of the canonical sequence.

Location on the sequence:   ATLIRWAILEAPEKQRTLNE  I YHWFTRMFAFFRNHPATWKN
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                         ATLIRWAILEAPEKQRTLNEIYHWFTRMFAFFRNHPATWKN

Mouse                         ATLIRWAILEAPERQRTLNEIYHWFTRMFAYFRNHPATWKN

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 – 431 Forkhead box protein P3
Chain 1 – 417 Forkhead box protein P3, C-terminally processed
Chain 52 – 417 Forkhead box protein P3 41 kDa form
DNA binding 337 – 423 Fork-head
Alternative sequence 382 – 382 K -> KVSSSEVAVTGMASSAIAAQSGQAWVWAHRHIGEERDVGCWWWLLASEVDAHLLPVPGLPQ. In isoform 3.
Mutagenesis 348 – 348 W -> Q. No loss of DNA-binding. Disrupts dimerization but does not affect DNA-binding; when associated with T-370. Disrupts dimerization, does not affect DNA-binding, causes dysregulated expression of a subset of FOXP3 target genes and impairs its ability to confer inhibitory function to regulatory T-cells; when associated with T-370 and P-372.
Mutagenesis 370 – 370 M -> T. Disrupts dimerization but does not affect DNA-binding; when associated with Q-348. Disrupts dimerization, does not affect DNA-binding, causes dysregulated expression of a subset of FOXP3 target genes and impairs its ability to confer inhibitory function to regulatory T-cells; when associated with Q-348 and P-372.
Mutagenesis 372 – 372 A -> P. Disrupts dimerization, does not affect DNA-binding, causes dysregulated expression of a subset of FOXP3 target genes and impairs its ability to confer inhibitory function to regulatory T-cells; when associated with Q-348 and T-370.
Helix 360 – 371


Literature citations

Novel mutations of FOXP3 in two Japanese patients with immune dysregulation, polyendocrinopathy, enteropathy, X linked syndrome (IPEX).
Kobayashi I.; Shiari R.; Yamada M.; Kawamura N.; Okano M.; Yara A.; Iguchi A.; Ishikawa N.; Ariga T.; Sakiyama Y.; Ochs H.D.; Kobayashi K.;
J. Med. Genet. 38:874-876(2001)
Cited for: VARIANT IPEX VAL-363;

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.