CTLA4

Inhibitory receptor acting as a major negative regulator of T-cell responses. The affinity of CTLA4 for its natural B7 family ligands, CD80 and CD86, is considerably stronger than the affinity of their cognate stimulatory coreceptor CD28.

Systemic lupus erythematosus

SLE

A chronic, relapsing, inflammatory, and often febrile multisystemic disorder of connective tissue, characterized principally by involvement of the skin, joints, kidneys and serosal membranes. It is of unknown etiology, but is thought to represent a failure of the regulatory mechanisms of the autoimmune system. The disease is marked by a wide range of system dysfunctions, an elevated erythrocyte sedimentation rate, and the formation of LE cells in the blood or bone marrow.

None

Disease susceptibility is associated with variants affecting the gene represented in this entry.

Genetic variations in CTLA4 may influence susceptibility to Graves disease, an autoimmune disorder associated with overactivity of the thyroid gland and hyperthyroidism.

Type 1 diabetes mellitus 12

T1D12

A multifactorial disorder of glucose homeostasis that is characterized by susceptibility to ketoacidosis in the absence of insulin therapy. Clinical features are polydipsia, polyphagia and polyuria which result from hyperglycemia-induced osmotic diuresis and secondary thirst. These derangements result in long-term complications that affect the eyes, kidneys, nerves, and blood vessels.

None

Disease susceptibility is associated with variants affecting the gene represented in this entry.

Celiac disease 3

CELIAC3

A multifactorial, chronic disorder of the small intestine caused by intolerance to gluten. It is characterized by immune-mediated enteropathy associated with failed intestinal absorption, and malnutrition. In predisposed individuals, the ingestion of gluten-containing food such as wheat and rye induces a flat jejunal mucosa with infiltration of lymphocytes.

None

Disease susceptibility is associated with variants affecting the gene represented in this entry.

Immune dysregulation with autoimmunity, immunodeficiency, and lymphoproliferation

IDAIL

An autosomal dominant primary immunodeficiency characterized by severe autoimmunity, infiltration of non-lymphoid organs, such as the intestine, lungs and brain, by hyperactive T cells and B cells, autoimmune cytopenias, and hypogammaglobulinemia in early childhood.

None

The disease is caused by variants affecting the gene represented in this entry.

N-glycosylation is important for dimerization.

Phosphorylation at Tyr-201 prevents binding to the AP-2 adapter complex, blocks endocytosis, and leads to retention of CTLA4 on the cell surface.

Widely expressed with highest levels in lymphoid tissues. Detected in activated T-cells where expression levels are 30- to 50-fold less than CD28, the stimulatory coreceptor, on the cell surface following activation.

• Cell membrane
• Single-pass type I membrane protein
• Exists primarily an intracellular antigen whose surface expression is tightly regulated by restricted trafficking to the cell surface and rapid internalization.

CD152, CTLA4, Cytotoxic T-lymphocyte protein 4, Cytotoxic T-lymphocyte-associated antigen 4, CTLA-4

• entrezGene:1493
• omim:123890
• swissprot:P16410

Proteins

Immuno-oncology

• Immunology & Infectious Disease

24656Da