CD19

Chr 16AR

CD19 molecule

NCBI Gene: 930ENSG00000177455UniProt: P15391

Functions as a coreceptor for the B-cell antigen receptor complex (BCR) on B-lymphocytes (PubMed:29523808). Decreases the threshold for activation of downstream signaling pathways and for triggering B-cell responses to antigens (PubMed:1373518, PubMed:16672701, PubMed:2463100). Activates signaling pathways that lead to the activation of phosphatidylinositol 3-kinase and the mobilization of intracellular Ca(2+) stores (PubMed:12387743, PubMed:16672701, PubMed:9317126, PubMed:9382888). Is not required for early steps during B cell differentiation in the blood marrow (PubMed:9317126). Required for normal differentiation of B-1 cells (By similarity). Required for normal B cell differentiation and proliferation in response to antigen challenges (PubMed:1373518, PubMed:2463100). Required for normal levels of serum immunoglobulins, and for production of high-affinity antibodies in response to antigen challenge (PubMed:12387743, PubMed:16672701, PubMed:9317126)

Primary Disease Associations & Inheritance

Immunodeficiency, common variable, 3MIM #613493
AR
575
ClinVar variants
86
Pathogenic / LP
0.90
pLI score· haploinsufficient
12
Active trials
Clinical Summary— CD19
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.90). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
86 Pathogenic / Likely Pathogenic· 196 VUS of 575 total submissions
💊
Clinical Trials
12 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
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?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.03Z-score
OE missense 0.84 (0.76–0.93)
270 obs / 321.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.17 (0.09–0.35)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.84 (0.76–0.93)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.02
0≤1.21.6
LoF obs/exp: 5 / 29.6Missense obs/exp: 270 / 321.8Syn Z: -0.22

ClinVar Variant Classifications

575 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic75
Likely Pathogenic11
VUS196
Likely Benign188
Benign12
Conflicting14
75
Pathogenic
11
Likely Pathogenic
196
VUS
188
Likely Benign
12
Benign
14
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
2
0
73
0
75
Likely Pathogenic
4
1
6
0
11
VUS
2
156
35
3
196
Likely Benign
1
5
77
105
188
Benign
0
0
10
2
12
Conflicting
—14
Total9162201110496

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View 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.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
CD19 ANTIGEN; CD19
MIM #107265 · *

Immunodeficiency, common variable, 3

MIM #613493

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
An iPSC-derived CD19/BCMA CAR-NK therapy in a patient with systemic sclerosis.
Wang X et al.·Cell
2025Case report
CD19-targeted chimeric antigen receptor T cell therapy in two patients with multiple sclerosis.
Fischbach F et al.·Med
2024Case report
4-1BB costimulation ameliorates T cell exhaustion induced by tonic signaling of chimeric antigen receptors.
Long AH et al.·Nat Med
2015
CAR-T Cell-Mediated B-Cell Depletion in Central Nervous System Autoimmunity.
Gupta S et al.·Neurol Neuroimmunol Neuroinflamm
2023
CD22-targeted CAR T cells induce remission in B-ALL that is naive or resistant to CD19-targeted CAR immunotherapy.
Fry TJ et al.·Nat Med
2018Clinical trial
Can autoimmune disease be cured by deep CD19+ cell depletion?
Suan D et al.·J Immunol
2025
Identification of Potent CD19 scFv for CAR T Cells through scFv Screening with NK/T-Cell Line.
Kang CH et al.·Int J Mol Sci
2020
T cell lymphoma and secondary primary malignancy risk after commercial CAR T cell therapy.
Ghilardi G et al.·Nat Med
2024
Mapping variant effects on anti-tumor hallmarks of primary human T cells with base-editing screens.
Walsh ZH et al.·Nat Biotechnol
2025
In Vivo Generation of CAR T Cells Selectively in Human CD4(+) Lymphocytes.
Agarwal S et al.·Mol Ther
2020
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
ITK-targeted immune remodeling enhanced the efficacy of anti-CD19 CAR-T cell therapy.
Li Z et al.·Cell Death Discov
2026Functional
Dual-Targeting BCMA-CD19 CAR-T Cell Therapy in Systemic Lupus Erythematosus: Single-Cell and Immune Repertoire Analysis Reveals Mechanisms of Immune Reconstitution.
He Z et al.·Arthritis Rheumatol
2026Functional
Anti-CD19 chimeric antigen receptor T-cell therapy for relapsed or refractory Philadelphia chromosome-positive B cell acute lymphoblastic leukemia: a multicenter retrospective study.
Yu J et al.·BMC Med
2026
Differential Expression of CD79B, CD19, and PD-L1 in de Novo and Transformed CD20-Negative Large B-Cell Lymphomas.
Kaimi Y et al.·Hematol Oncol
2026
Racial and clinical determinants of response in 2304 large B-cell lymphomas treated with CD19 CAR T in clinical trials.
Kho SJ et al.·Blood Adv
2026🔓 Open Access
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
B Cell Lymphoma

Efficacy and Safety Evaluation of U01(ssCART-19) in B-Cell Lymphoma

RECRUITING
NCT06987916Phase PHASE1, PHASE2Shanghai Tongji Hospital, Tongji University School of MedicineStarted 2025-04-22
ssCART-19
Sickle Cell DiseaseSickle-Cell Disease With Crisis

Investigation Into the Use of BAH243 Lentiviral Vector for Gene Therapy in Treating Sickle Cell Disease

RECRUITING
NCT06399107Phase PHASE1, PHASE2Essen BiotechStarted 2024-08-01
Drug Product is administered by IV infusion following myeloablative conditioning with busulfan
Malnutrition PregnancyMalnutrition in ChildrenMalnutrition (Calorie)

Early Life Malnutrition, Environmental Enteric Dysfunction and Microbiome Trajectories

RECRUITING
NCT07195006University of ZimbabweStarted 2025-01-27
Malnutrition in pregnancy as exposurePoor WASH living conditions as exposure
Childhood-onset Systemic Lupus Erythematosus

Immune Profiling of Refractory cSLE Exposed to CD3×CD19 BiTE

RECRUITING
NCT07352332The Children's Hospital of Zhejiang University School of MedicineStarted 2025-09-30
Severe Congenital NeutropeniaGATA2 Deficiency

Total Lymphoid Irradiation Pre-HSCT in Severe Congenital Neutropenia

NOT YET RECRUITING
NCT04844177Phase PHASE2Federal Research Institute of Pediatric Hematology, Oncology and ImmunologyStarted 2021-04-14
conditioning with TLI
B-cell Malignancies

Combination CAR-T Cell Therapy Targeting Hematological Malignancies

RECRUITING
NCT03125577Phase PHASE1, PHASE2Shenzhen Geno-Immune Medical InstituteStarted 2025-08-01
4SCAR19 and 4SCAR224SCAR19 and 4SCAR384SCAR19 and 4SCAR20
Acute Lymphoblastic LeukemiaNon-Hodgkin Lymphoma of Soft Tissue

A Study of Murine CD19 CAR-T Therapy for Patients With Relapsed or Refractory CD19+ B-cell Hematological Malignancies

RECRUITING
NCT04532281Phase EARLY_PHASE1Zhejiang UniversityStarted 2020-11-01
Murine CD19 CAR-T cells
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
Refractory Lupus NephritisMyasthaenia GravisStiff Person Syndrome

A Long-Term Follow-Up Study for Participants Previously Treated With KYV-101

RECRUITING
NCT07403188Kyverna TherapeuticsStarted 2025-11-24
KYV-101
Leukemia, Lymphoblastic, Acute, Lymphoma

Immunotherapy for High Risk/Relapsed CD19+ Acute Lymphoblastic Leukaemia, B-cell Non-Hodgkin's Lymphoma (B-NHL) and Chronic Lymphocytic Leukaemia (CLL)/ Small Lymphocytic Lymphoma (SLL) Using CAR T-cells to Target CD19

ACTIVE NOT RECRUITING
NCT02935257Phase PHASE1University College, LondonStarted 2017-09-29
CD19CAT-41BBZ CAR T-cells
LymphomaLymphoma, B-CellImmune System Diseases

Anti-CD19 CAR-T Cells With Inducible Caspase 9 Safety Switch for B-cell Lymphoma

ACTIVE NOT RECRUITING
NCT03696784Phase PHASE1UNC Lineberger Comprehensive Cancer CenterStarted 2019-03-12
iC9-CAR19 T cellsBendamustineFludarabine
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

RECRUITING
NCT07166419Phase PHASE1Ohio State University Comprehensive Cancer CenterStarted 2026-02-01
Autologous Anti-CD19/CD20/CD22 CAR T-cellsBiospecimen CollectionBone Marrow Aspiration

External Resources

Links to major genomics databases and tools