CD19

Chr 16AR

CD19 molecule

Also known as: B4, CVID3

This gene encodes a member of the immunoglobulin gene superfamily. Expression of this cell surface protein is restricted to B cell lymphocytes. This protein is a reliable marker for pre-B cells but its expression diminishes during terminal B cell differentiation in antibody secreting plasma cells. The protein has two N-terminal extracellular Ig-like domains separated by a non-Ig-like domain, a hydrophobic transmembrane domain, and a large C-terminal cytoplasmic domain. This protein forms a complex with several membrane proteins including complement receptor type 2 (CD21) and tetraspanin (CD81) and this complex reduces the threshold for antigen-initiated B cell activation. Activation of this B-cell antigen receptor complex activates the phosphatidylinositol 3-kinase signalling pathway and the subsequent release of intracellular stores of calcium ions. This protein is a target of chimeric antigen receptor (CAR) T-cells used in the treatment of lymphoblastic leukemia. Mutations in this gene are associated with the disease common variable immunodeficiency 3 (CVID3) which results in a failure of B-cell differentiation and impaired secretion of immunoglobulins. CVID3 is characterized by hypogammaglobulinemia, an inability to mount an antibody response to antigen, and recurrent bacterial infections. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2020]

OMIMResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Immunodeficiency, common variable, 3MIM #613493
AR

Clinical highlights

Interpreting a novel variant
This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.
12
Active trials
2702
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
0.35
LOEUF
—
Mechanism

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint?
0.35LOEUF
pLI 0.905
Z-score 4.19
OE 0.17 (0.09–0.35)
Highly constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?
1.03Z-score
OE missense 0.84 (0.76–0.93)
270 obs / 321.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.17 (0.09–0.35)
0≤0.351.4
Missense OE?0.84 (0.76–0.93)
0≤0.61.4
Synonymous OE?1.02
0≤1.21.6
LoF obs/exp: 5 / 29.6Missense obs/exp: 270 / 321.8Syn Z: -0.22

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

CD19 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

Multiple Myeloma in RelapseRefractory Multiple MyelomaPlasmacytoid; Lymphoma

BCMA-CD19 cCAR in Multiple Myeloma and Plasmacytoid Lymphoma

RECRUITING
NCT04162353Phase PHASE1iCell Gene TherapeuticsStarted 2019-07-01
BCMA-CD19 cCAR T cells
B-cell Leukemia

CAR-T Immunotherapy Targeting CD19- ALL

NOT YET RECRUITING
NCT04016129Phase PHASE1, PHASE2Shenzhen Geno-Immune Medical InstituteStarted 2027-07-01
4SCAR-CD22/CD123/CD38/CD10/CD20/TSLPR
Blast Phase Chronic Myeloid Leukemia, BCR-ABL1 PositiveRecurrent Acute Lymphoblastic LeukemiaRecurrent Chronic Lymphocytic Leukemia

Anti-CD19/20/22 Chimeric Antigen Receptor T Cells (TriCAR19.20.22 T Cells) for the Treatment of Relapsed or Refractory Non-Hodgkin Lymphoma, Acute Lymphoblastic Leukemia, and Chronic Lymphocytic Leukemia

ACTIVE NOT RECRUITING
NCT07166419Phase PHASE1Ohio State University Comprehensive Cancer CenterStarted 2026-01-14
Autologous Anti-CD19/CD20/CD22 CAR T-cellsBiospecimen CollectionBone Marrow Aspiration
B Cell Lymphoma (BCL)

Multi-CAR-T Cells Targeting B Cell Lymphomas

NOT YET RECRUITING
NCT04429438Phase PHASE1, PHASE2Shenzhen Geno-Immune Medical InstituteStarted 2027-06-01
4SCAR19 and 4SCAR20/22/70/PSMA/13/79b/GD2
Acute Lymphoblastic Leukemia (ALL)Chronic Lymphocytic Leukemia (CLL)Non Hodgkin's Lymphoma

Multi-virus CTLs Expressing CD19 Chimeric Receptors, CD19 Positive Malignancies Post SCT, MULTIPRAT

ACTIVE NOT RECRUITING
NCT00840853Phase PHASE1Baylor College of MedicineStarted 2009-04
CD19CAR/virus specific T cellsBenadryl and Tylenol
Refractory B-Cell Non-Hodgkin LymphomaRefractory B-Cell Small Lymphocytic LymphomaRelapsed Adult ALL

CD19.CAR Allogeneic NKT for Patients With Relapsed or Refractory B-Cell Malignancies (ANCHOR)

ACTIVE NOT RECRUITING
NCT03774654Phase PHASE1Baylor College of MedicineStarted 2020-04-14
CD19.CAR-aNKT cells
B-cell Non-Hodgkin's Lymphoma

A Phase 1/2 Study of CT120 in Patient With Relapsed/Refractory B-cell Non-Hodgkin's Lymphoma

NOT YET RECRUITING
NCT05091541Phase PHASE1, PHASE2Nanjing IASO Biotechnology Co., Ltd.Started 2021-10-20
Fully Human Anti-CD19/CD22 Dual Target Chimeric Antigen Receptor Autologous T Cell Injection
Lymphoproliferative DisorderMultiple Myeloma

Understanding the Mechanisms of Clonal and Non-clonal Cytopenia Following CAR-T Therapy for Multiple Myeloma or CD19+ Lymphoproliferative Disorder (LPD)

RECRUITING
NCT06630104Phase NAMayo ClinicStarted 2024-11-22
Biospecimen CollectionBone Marrow AspirationElectronic Health Record Review
Relapse/Refractory B-cell Acute Lymphoblastic Leukemia

Safety and Efficacy of CAR T Cell Therapy in Patients with R/r B-ALL

RECRUITING
NCT06635330Phase PHASE1, PHASE2Kara Yakhteh Tajhiz Azma CompanyStarted 2024-05-20
anti-CD19 CAR T cell therapy
Inflammatory Myopathy

BCMA-CD19 cCAR-T for the Treatment of Refractory Inflammatory Myopathy

RECRUITING
NCT07715136Phase PHASE1iCell Gene TherapeuticsStarted 2025-03-20
ICG318, BCMA-CD19-IL-15/IL-15 sushi Compound CAR-T
Lymphoma, B-CellLymphoma, Non-Hodgkin (NHL)Lymphoma, Large B-Cell, Diffuse (DLBCL)

A Phase 1 Study of UB-VV111 With and Without Rapamycin in Relapsed/Refractory CD19+ B-cell Malignancies

RECRUITING
NCT06528301Phase PHASE1Umoja BiopharmaStarted 2025-03-10
UB-VV111rapamycin
Lymphoma Diffuse Large B-cellLeukemia and LymphomaLeukemia Relapse

Study of Allo-QuadCAR01-T, an Allogeneic CAR-T Targeting CD19/CD20, in Patients With Relapsed or Refractory B-Cell Malignancies

RECRUITING
NCT07284433Phase PHASE1, PHASE2AvenCell Therapeutics, Inc.Started 2026-01-06
Cyclophosphamide (Non-IMP, Lymphodepletion)Fludarabine (Non-IMP, Lymphodepletion)Allo-QuadCAR01-T