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UniProtKB/Swiss-Prot Q9BZS1: Variant p.Arg347His

Forkhead box protein P3
Gene: FOXP3
Variant information

Variant position:  347
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 Histidine (H) at position 347 (R347H, p.Arg347His).
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 (H)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  0
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 IPEX; mild phenotype; no loss of protein expression; impairs its ability to confer inhibitory function to regulatory T-cells; no loss of DNA-binding when associated with A-373.
Any additional useful information about the variant.

Other resources:  
Links to websites of interest for the variant.



Sequence information

Variant position:  347
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:   NMDYFKFHNMRPPFTYATLI  R WAILEAPEKQRTLNEIYHWF
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                         NMDYFKFHNMRPPFTYATLIRWAILEAPEKQRTLNEIYHWF

Mouse                         NMDYFKYHNMRPPFTYATLIRWAILEAPERQRTLNEIYHWF

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
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.
Helix 342 – 351


Literature citations

Structure of a domain-swapped FOXP3 dimer on DNA and its function in regulatory T cells.
Bandukwala H.S.; Wu Y.; Feuerer M.; Chen Y.; Barboza B.; Ghosh S.; Stroud J.C.; Benoist C.; Mathis D.; Rao A.; Chen L.;
Immunity 34:479-491(2011)
Cited for: X-RAY CRYSTALLOGRAPHY (2.80 ANGSTROMS) OF 336-417 IN COMPLEX WITH DNA AND NFATC2; FUNCTION; SUBUNIT; DOMAIN FORK-HEAD; INTERACTION WITH NFATC2; CHARACTERIZATION OF VARIANTS IPEX GLU-251 DEL; HIS-347; CYS-371 AND ALA-373; MUTAGENESIS OF TRP-348; MET-370 AND ALA-372;

Clinical and molecular profile of a new series of patients with immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome: inconsistent correlation between forkhead box protein 3 expression and disease severity.
Gambineri E.; Perroni L.; Passerini L.; Bianchi L.; Doglioni C.; Meschi F.; Bonfanti R.; Sznajer Y.; Tommasini A.; Lawitschka A.; Junker A.; Dunstheimer D.; Heidemann P.H.; Cazzola G.; Cipolli M.; Friedrich W.; Janic D.; Azzi N.; Richmond E.; Vignola S.; Barabino A.; Chiumello G.; Azzari C.; Roncarolo M.G.; Bacchetta R.;
J. Allergy Clin. Immunol. 122:1105-1112(2008)
Cited for: VARIANTS IPEX PRO-242; LEU-324; ALA-339; HIS-347; ALA-373; CYS-374 AND THR-384; CHARACTERIZATION OF VARIANTS IPEX PRO-242; LEU-324; ALA-339; HIS-347; ALA-373; CYS-374 AND THR-384;

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.