UniProtKB/Swiss-Prot P55895: Variant p.Gly451Ala

V(D)J recombination-activating protein 2
Gene: RAG2
Chromosomal location: 11p13
Variant information

Variant position:  451
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 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 Glycine (G) to Alanine (A) at position 451 (G451A, p.Gly451Ala).
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 glycine (G) to small size and hydrophobic (A)
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

Involvement in disease:  Combined cellular and humoral immune defects with granulomas (CHIDG) [MIM:233650]: Immunodeficiency disease with granulomas in the skin, mucous membranes, and internal organs. Other characteristics include hypogammaglobulinemia, a diminished number of T and B-cells, and sparse thymic tissue on ultrasonography. 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 CHIDG; reduced recombination activity.
Any additional useful information about the variant.



Sequence information

Variant position:  451
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  527
The length of the canonical sequence.

Location on the sequence:   VPFYSTELNKPAMIYCSHGD  G HWVHAQCMDLAERTLIHLSA
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                         VPFYSTELNKPAMIYCSHGD-GHWVHAQCMDLAERTLIHLSA

Mouse                         VPFYSTELNKPAMIYCSHGD-GHWVHAQCMDLEERTLIHLS

Rabbit                        VPFYSTELNKPAMIYCSHGD-GHWVHAKCMDLAERTLIHLS

Chicken                       VPFYSTELNKPAMILCSSGS-GHWVHAQCMDLSESMLLQLS

Xenopus laevis                EPFYSTELNKPSMIFCSKDG-GHWVHSQCMDLSETMLKYLS

Zebrafish                     EPYYSTELTRPAMIFCSRGEGGHWVHAQCMELPESLLLQLS

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 – 527 V(D)J recombination-activating protein 2
Zinc finger 416 – 484 PHD-type; atypical
Metal binding 446 – 446 Zinc 2
Metal binding 452 – 452 Zinc 2
Metal binding 455 – 455 Zinc 1
Metal binding 458 – 458 Zinc 1


Literature citations

An immunodeficiency disease with RAG mutations and granulomas.
Schuetz C.; Huck K.; Gudowius S.; Megahed M.; Feyen O.; Hubner B.; Schneider D.T.; Manfras B.; Pannicke U.; Willemze R.; Knuechel R.; Goebel U.; Schulz A.; Borkhardt A.; Friedrich W.; Schwarz K.; Niehues T.;
N. Engl. J. Med. 358:2030-2038(2008)
Cited for: VARIANTS CHIDG ASN-77 AND ALA-451; CHARACTERIZATION OF VARIANTS CHIDG ASN-77 AND ALA-451;

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.