CD28
Chr 2ARCD28 molecule
Also known as: IMD123, Tp44
The protein encoded by this gene is essential for T-cell proliferation and survival, cytokine production, and T-helper type-2 development. Several alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Jul 2011]
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 — mechanism propensity
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.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Modified Immune Cells (CD19 CAR T Cells) and Acalabrutinib for the Treatment of Relapsed or Refractory Mantle Cell Lymphoma
RECRUITINGiC9-GD2-CAR-VZV-CTLs/Refractory or Metastatic GD2-positive Sarcoma and Neuroblastoma
ACTIVE NOT RECRUITINGActivated T-Cells Expressing 2nd or 3rd Generation CD19-Specific CAR, Advanced B-Cell NHL, ALL, and CLL (SAGAN)
RECRUITINGGD2-CAR T Cells for Pediatric Brain Tumours
RECRUITINGCellular Immunotherapy Following Chemotherapy in Treating Patients With Recurrent Non-Hodgkin Lymphomas, Chronic Lymphocytic Leukemia, or B-Cell Prolymphocytic Leukemia
ACTIVE NOT RECRUITINGTRAC and Power3 (SPPL3) Genes Knock-out Allogeneic CD19-targeting CAR-T Cell Therapy in r/r B-NHL
RECRUITINGHer2 Chimeric Antigen Receptor Expressing T Cells in Advanced Sarcoma
ACTIVE NOT RECRUITINGChimeric Antigen Receptor T Cell Redirected to Target CD4 Positive Relapsed Refractory Acute Myeloid Leukemia (AML ) as a Bridge to Allogeneic Stem Cell Transplant
RECRUITINGHER2 Chimeric Antigen Receptor (CAR) T Cells in Combination With Checkpoint Blockade in Patients With Advanced Sarcoma
RECRUITINGNext-gen Flow Cytometry to Find Immune Profiles, Treatment Response, and Toxicity Markers in Skin Cancer Patients Treated With Cemiplimab.
RECRUITINGCD4CAR for CD4+ Leukemia and Lymphoma
RECRUITINGIntracerebroventricular Administration of CD19-CAR T Cells (CD19CAR-CD28-CD3zeta-EGFRt-expressing Tn/Mem T-lymphocytes) for the Treatment of Central Nervous System Lymphoma
RECRUITINGExternal Resources
Links to major genomics databases and tools