|Coordinate||124,872,977 bp (GRCm38)|
|Base Change||A ⇒ G (forward strand)|
|Gene Name||CD4 antigen|
|Chromosomal Location||124,864,692-124,888,221 bp (-)|
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a membrane glycoprotein of T lymphocytes that interacts with major histocompatibility complex class II antigenes and is also a receptor for the human immunodeficiency virus. This gene is expressed not only in T lymphocytes, but also in B cells, macrophages, and granulocytes. It is also expressed in specific regions of the brain. The protein functions to initiate or augment the early phase of T-cell activation, and may function as an important mediator of indirect neuronal damage in infectious and immune-mediated diseases of the central nervous system. Multiple alternatively spliced transcript variants encoding different isoforms have been identified in this gene. [provided by RefSeq, Aug 2010]
PHENOTYPE: Mice homozygous for knock-out alleles exhibit abnormal immune system morphology and physiology. [provided by MGI curators]
|Amino Acid Change||Valine changed to Alanine|
|Institutional Source||Australian Phenomics Network|
|Gene Model||not available|
AA Change: V125A
|Predicted Effect||possibly damaging
PolyPhen 2 Score 0.807 (Sensitivity: 0.84; Specificity: 0.93)
|Meta Mutation Damage Score||Not available|
|Is this an essential gene?||Non Essential (E-score: 0.000)|
|Candidate Explorer Status||CE: no linkage results|
Linkage Analysis Data
|Alleles Listed at MGI|
|Mode of Inheritance||Autosomal Recessive|
Australian Phenome Bank: 4588
|Last Updated||2016-05-13 3:09 PM by Peter Jurek|
|Record Created||2010-10-14 9:47 AM by Nora G. Smart|
The seshat phenotype was identified in a flow cytometry screen of blood from N-ethyl-N-nitrosourea (ENU)-mutagenized mice. Homozygous seshat mice display reduced numbers of peripheral T cells and reduced CD4+ (cluster of differentiation 4) expression (Figure 1).
|Nature of Mutation|
The Cd4 gene was directly sequenced as a candidate gene due to the reduced expression of CD4 in seshat mice, and corresponds to a T to C transition at position 543 of the Cd4 transcript, in exon 9 of 13 total exons using Genbank record NM_013488.
The mutated nucleotide is indicated in red lettering and causes a valine to alanine change at amino acid 125 of the encoded protein.
|Illustration of Mutations in
Gene & Protein
The seshat mutation alters an amino acid located near the C-terminal end of the first immunoglobulin-like domain (D1) (Figure 2).
Please see the record for thoth for more information on Cd4.
The reduced numbers, but not absence, of CD4+ T cells suggests that the seshat mutation is hypomorphic. This is compatible with the missense nature of the mutation. The seshat mutation is located in the D1 domain of CD4, which is known to bind to major histocompatibility complex (MHC) class II molecules. The mutation may affect the binding of the D1 domain to MHC class II although Val 125 is not a key binding residue. The reduced expression of CD4 in seshat animals may be due to instability of the missense protein or to reduced CD4 function that may cause increased numbers of non-MHC binding CD4+ T cells and subsequent elimination during the positive/negative stage of T cell development.
|Primers||Primers cannot be located by automatic search.|
Genotyping protocols are from the Australian PhenomeBank.
|Science Writers||Nora G. Smart|
|Illustrators||Diantha La Vine|
|Authors||Christopher C. Goodnow|