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UniProtKB/Swiss-Prot P01730: Variant p.Arg265Trp

T-cell surface glycoprotein CD4
Gene: CD4
Variant information

Variant position:  265
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  LB/B
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 Tryptophan (W) at position 265 (R265W, p.Arg265Trp).
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

Polymorphism:  The OKT monoclonal antibodies are widely used for the analysis of human peripheral blood T-lymphocytes. OKT4 reacts with T-helper/inducer lymphocytes. The OKT4 epitope of the CD4 cell-surface protein is polymorphic in white, black, and Japanese populations. The variable phenotypic expression is due a CD4 polymorphism. OKT4 positive individuals carry Arg-265 and OKT4 negative individuals carry Trp-265 [MIM:613949].
Additional information on the polymorphism described.

Variant description:  In OKT4-negative populations.
Any additional useful information about the variant.

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



Sequence information

Variant position:  265
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  458
The length of the canonical sequence.

Location on the sequence:   ASSSKSWITFDLKNKEVSVK  R VTQDPKLQMGKKLPLHLTLP
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                         ASSSKSWITFDLKNKEVSVKRVTQDPKLQMGKKLPLHLTLP

                              ASSSLLWISFTLENRKLSMKEAHAPLKLQMKESLPLRFTLP

Rhesus macaque                ASSSKSWITFDLKNKEVSVKRVTQDPKLQMGKKLPLHLTLP

Chimpanzee                    ASSSKSWITFDLKNKEVSVKRVTQDPKLQMGKKLPLHLTLP

Mouse                         DSFFQPWISFSIKNKEVSVQKSTKDLKLQLKETLPLTLKIP

Rat                           APSSQSWITFSLKNQKVSVQKSTSNPKFQLSETLPLTLQIP

Rabbit                        ASSAQSWVSFSLEDRKVSVQKILPDLKIQMSKGLPLSLTLP

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 26 – 458 T-cell surface glycoprotein CD4
Topological domain 26 – 396 Extracellular
Domain 204 – 317 Ig-like C2-type 2
Mutagenesis 265 – 265 R -> A. Has no effect on the interaction with MHCII. Impairs recognition by OKT4 antibody.


Literature citations

Humans with OKT4-epitope deficiency have a single nucleotide base change in the CD4 gene, resulting in substitution of TRP240 for ARG240.
Hodge T.W.; Sasso D.R.; McDougal J.S.;
Hum. Immunol. 30:99-104(1991)
Cited for: NUCLEOTIDE SEQUENCE [MRNA]; POLYMORPHISM; VARIANT TRP-265; TOPOLOGY;

Submission
NIEHS SNPs program;
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]; VARIANTS GLU-191; SER-227 AND TRP-265;

A single amino acid substitution in a common African allele of the CD4 molecule ablates binding of the monoclonal antibody, OKT4.
Lederman S.; DeMartino J.A.; Daugherty B.L.; Foeldvari I.; Yellin M.J.; Cleary A.M.; Berkowitz N.; Lowy I.; Braunstein N.S.; Mark G.E.;
Mol. Immunol. 28:1171-1181(1991)
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 250-280; POLYMORPHISM; VARIANT TRP-265;

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.