CD28
Chr 2ARCD28 molecule
Also known as: IMD123, Tp44
The CD28 protein is a T-cell receptor that is essential for T-cell activation, proliferation, and survival, and plays a critical role in cytokine production and maintaining immune homeostasis. Mutations cause primary immunodeficiency with autosomal recessive inheritance, leading to severe T-cell dysfunction and recurrent infections. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.711), suggesting some tolerance to heterozygous loss.
Moderate evidence — consider for supplementary testing
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
CD28 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Chimeric Antigen Receptor T-cells for The Treatment of AML Expressing CLL-1 Antigen
ACTIVE NOT RECRUITINGActivated T-Cells Expressing 2nd or 3rd Generation CD19-Specific CAR, Advanced B-Cell NHL, ALL, and CLL (SAGAN)
RECRUITINGAllogeneic CARCIK-CD19 in Adults/Pediatric B-cell NHL or Chronic Lymphocytic Leukemia
RECRUITINGCell Therapy for High Risk T-Cell Malignancies Using CD7-Specific CAR Expressed On Autologous T Cells
RECRUITINGPrecision Microbiota Interventions for Senoreduction Trial
NOT YET RECRUITINGActivated T Lymphocytes Expressing CARs, Relapsed CD19+ Malignancies Post-Allo HSCT(CARPASCIO)
ACTIVE NOT RECRUITINGGD2 Specific CAR and Interleukin-15 Expressing Autologous NKT Cells to Treat Children With Neuroblastoma
RECRUITINGGD2-CAR T Cells for Pediatric Brain Tumours
RECRUITINGCD19.CAR Allogeneic NKT for Patients With Relapsed or Refractory B-Cell Malignancies (ANCHOR)
ACTIVE NOT RECRUITINGModified Immune Cells (CD19 CAR T Cells) and Acalabrutinib for the Treatment of Relapsed or Refractory Mantle Cell Lymphoma
RECRUITINGHer2 Chimeric Antigen Receptor Expressing T Cells in Advanced Sarcoma
ACTIVE NOT RECRUITINGStudy of Kappa Chimeric Antigen Receptor (CAR) T Lymphocytes Co-Expressing the Kappa and CD28 CARs for Relapsed/Refractory Kappa+ Non-Hodgkin Lymphoma and Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma.
RECRUITINGExternal Resources
Links to major genomics databases and tools