Protein / target

T-cell surface glycoprotein CD3 delta chain

Encoded byCD3DP04234Homo sapiensSwiss-Prot

UniProt: P04234 Ensembl: ENSG00000167286 HGNC: HGNC:1673 NCBI Gene: 915

Clinically validated

Therapeutic maturity

Approved medicines

Open Targets target-level

View by indication →

Clinical trials

Small-molecule tractable

Druggability

Structure with Ligand

Protein at a glance

Biological role

Transmembrane signaling receptor

Strongest disease association

Immunodeficiency 19

Via encoding gene CD3D · Genetic evidence · score 0.92

Therapeutic position

Established drug target

Antibodies

Derived from structured UniProt, Open Targets and literature data on this page.

Protein profile

UniProt 2026_02

Canonical identity and biological annotation from UniProt.

Function overview

Part of the TCR-CD3 complex present on T-lymphocyte cell surface that plays an essential role in adaptive immune response.

View complete UniProt function annotation

Part of the TCR-CD3 complex present on T-lymphocyte cell surface that plays an essential role in adaptive immune response. When antigen presenting cells (APCs) activate T-cell receptor (TCR), TCR-mediated signals are transmitted across the cell membrane by the CD3 chains CD3D, CD3E, CD3G and CD247/CD3Z. All CD3 chains contain immunoreceptor tyrosine-based activation motifs (ITAMs) in their cytoplasmic domain. Upon TCR engagement, these motifs become phosphorylated by Src family protein tyrosine kinases LCK and FYN, resulting in the activation of downstream signaling pathways (PubMed:2470098). In addition of this role of signal transduction in T-cell activation, CD3D plays an essential role in thymocyte differentiation. Indeed, participates in correct intracellular TCR-CD3 complex assembly and surface expression. In absence of a functional TCR-CD3 complex, thymocytes are unable to differentiate properly. Interacts with CD4 and CD8 and thus serves to establish a functional link between the TCR and coreceptors CD4 and CD8, which is needed for activation and positive selection of CD4 or CD8 T-cells (PubMed:12215456)

Subcellular location

Cell membrane

Domains and Gene Ontology detail (14)

Domains & features

ITAM

Gene Ontology

Calpha-beta T cell receptor complex
Cclathrin-coated endocytic vesicle membrane
Ccytoplasm
Cexternal side of plasma membrane
Cplasma membrane
CT cell receptor complex
Fidentical protein binding
Ftransmembrane signaling receptor activity
Padaptive immune response
Palpha-beta T cell activation
Pcell surface receptor signaling pathway
Ppositive thymic T cell selection

171 aa · 19 kDa · 2 isoforms

Biological roles

Reactome v97

What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.

Immune signallingUniProt · GO

View supporting evidence

Immune signalling

·Part of the TCR-CD3 complex present on T-lymphocyte cell surface that plays an essential…
·alpha-beta T cell receptor complex
·T cell receptor complex
·adaptive immune response

View underlying pathways (8)

Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell

Downstream TCR signaling

Phosphorylation of CD3 and TCR zeta chains

Translocation of ZAP-70 to Immunological synapse

Generation of second messenger molecules

Co-inhibition by PD-1

Cargo recognition for clathrin-mediated endocytosis

Clathrin-mediated endocytosis

Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.

Interaction neighbourhood

STRING v12.0

Proteins with the strongest functional or physical association. Node size and line weight reflect STRING confidence; hover or select a partner to inspect one association.

10 strongest partners — larger node and heavier line mean higher confidence

Functional and physical associations from STRING v12.0. Only associations with this protein are drawn — partner-to-partner links are not part of this evidence.

Approved medicines with mapped indications

7 medicines · 6 areas

Approved therapies targeting this protein, grouped by what they are approved to treat — the disease-first view of the medicines below. Relationships come from the canonical approved-indication graph (ChEMBL phase-4), the same source as the drug cards.

Multiple Myeloma3 medicines

elranatamab talquetamab teclistamab

Lymphoma, Large B-Cell, Diffuse2 medicines

epcoritamab glofitamab

Lymphoma, Follicular1 medicine

epcoritamab

Precursor B-Cell Lymphoblastic Leukemia-Lymphoma1 medicine

blinatumomab

Precursor Cell Lymphoblastic Leukemia-Lymphoma1 medicine

blinatumomab

Neoplasms7 medicines

blinatumomab catumaxomab elranatamab epcoritamab glofitamab talquetamab teclistamab

11 medicines meet Open Targets' target-level approved-medicine definition; the 7 shown here are those on this page with a canonical approved disease indication in the graph. Approved indications from ChEMBL (phase-4), via the canonical drug→disease graph.

Drugs targeting this protein

How approved and investigational drugs engage this protein — mechanism and action type, direct vs complex targeting, and how broadly each acts across other targets. A drug-first view (the section above groups the approved ones disease-first); direct binders with few recorded targets are listed first.

blinatumomab

ApprovedCross-linking agent

T cell surface glycoprotein CD3 cross-linking agent

Indicated for Precursor B-Cell Lymphoblastic Leukemia-Lymphoma, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Neoplasms

Acts on a complex — shared with CD3E, CD3G · 1 of 4 recorded protein targets

glofitamab

ApprovedBinding agent

T cell surface glycoprotein CD3 binding agent

Indicated for Lymphoma, Large B-Cell, Diffuse, Neoplasms

Acts on a complex — shared with CD3E, CD3G · 1 of 4 recorded protein targets

catumaxomab

ApprovedCross-linking agent

T cell surface glycoprotein CD3 cross-linking agent

Indicated for Neoplasms

Acts on a complex — shared with CD3E, CD3G · 1 of 4 recorded protein targets

elranatamab

ApprovedBinding agent

T cell surface glycoprotein CD3 binding agent

Indicated for Multiple Myeloma, Neoplasms

Acts on a complex — shared with CD3E, CD3G · 1 of 4 recorded protein targets

epcoritamab

ApprovedBinding agent

T cell surface glycoprotein CD3 binding agent

Indicated for Lymphoma, Follicular, Lymphoma, Large B-Cell, Diffuse, Neoplasms

Acts on a complex — shared with CD3E, CD3G · 1 of 4 recorded protein targets

talquetamab

ApprovedBinding agent

T cell surface glycoprotein CD3 binding agent

Indicated for Multiple Myeloma, Neoplasms

Acts on a complex — shared with CD3E, CD3G · 1 of 3 recorded protein targets — narrow recorded profile

View all 7 targeting drugs

teclistamab

ApprovedBinding agent

T cell surface glycoprotein CD3 binding agent

Indicated for Multiple Myeloma, Neoplasms

Acts on a complex — shared with CD3E, CD3G · 1 of 4 recorded protein targets

ChEMBL mechanism, action type, target identity and approved indications. Open Targets clinical status.

Translational evidence

Open Targets 26

Why this target matters therapeutically, strongest evidence first. Disease associations are gene-level (via the gene that encodes this protein) and open into the full confidence synthesis; the development universe, tractability and safety annotations are target-level, from Open Targets.

Strongest disease associations · via encoding gene CD3D

Gene-level evidence surfaced through the gene CD3Dthat encodes this protein — not a direct protein–disease relationship. Ranked by Forefront's causal-directness weighting, so genetically- and clinically-evidenced diseases lead over ones that merely share the literature.

Immunodeficiency 19

0.93Well supported

Genetic evidence dominant · Open Targets 0.74

Neoplasms

0.74Moderately supported

Clinical evidence dominant · Open Targets 0.59

Multiple Myeloma

0.73Moderately supported

Clinical evidence dominant · Open Targets 0.60

Lymphoma, Large B-Cell, Diffuse

0.72Moderately supported

Clinical evidence dominant · Open Targets 0.58

Precursor Cell Lymphoblastic Leukemia-Lymphoma

0.69Moderately supported

Clinical evidence dominant · Open Targets 0.56

View evidence synthesis (5)

Immunodeficiency 19Well supported

0.93

agreement 0.81–1.00

Genetic89%Animal model11%Literature0%Genetic literaturedup

Open Targets aggregate 0.74 · 3 independent evidence families · 1 not counted as duplicate

NeoplasmsModerately supported

0.74

agreement 0.58–0.89

Clinical87%Literature13%

Open Targets aggregate 0.59 · 2 independent evidence families

Multiple MyelomaModerately supported

0.73

agreement 0.58–0.89

Clinical99%Literature1%

Open Targets aggregate 0.60 · 2 independent evidence families

Lymphoma, Large B-Cell, DiffuseModerately supported

0.72

agreement 0.56–0.87

Clinical98%Literature2%

Open Targets aggregate 0.58 · 2 independent evidence families

Precursor Cell Lymphoblastic Leukemia-LymphomaModerately supported

0.69

agreement 0.54–0.85

Clinical96%Literature5%

Open Targets aggregate 0.56 · 2 independent evidence families

The evidence agreement range shows how closely the independent evidence families agree — it is not a statistical confidence interval, and nothing here is fitted to outcome data. Derived from Open Targets evidence types under Forefront weighting; the per-type scores above show the calculation.

Show all associations

Immunodeficiency 190.74

Multiple Myeloma0.60

Neoplasms0.59

Lymphoma, Large B-Cell, Diffuse0.58

Precursor Cell Lymphoblastic Leukemia-Lymphoma0.56

T-B- severe combined immunodeficiency0.46

Drug development

16 compounds recorded · 11 approved · 5 in clinical development

Open Targets' development universe — every compound recorded against the target at any stage, not all approved medicines. Distinct from the 7 drugs that target this protein in Forefront's canonical graph (7 with a mapped approved indication, shown above): these count different sets and are not a subset relation.

View all recorded compounds (10)

IMC-GP100Early Phase 1

EPCORITAMABApproval

MUROMONAB-CD3Approval

FLOTETUZUMABPhase 2

CATUMAXOMABApproval

GLOFITAMABApproval

BLINATUMOMABApproval

ODRONEXTAMABApproval

MOSUNETUZUMABApproval

FORALUMABPhase 2

Open Targets known-drugs universe. Drug name and highest clinical stage only — the disease relationship is NOT read from this slice (it carries trial-context noise); approved indications come from the canonical graph above.

Tractability

Small molecules — Emerging

Feasibility evidence (structure with ligand) — no clinical-stage drug of this modality recorded.

Antibodies — Strong

Approved Drug and GO CC high conf support this modality.

Protein degraders — Emerging

Feasibility evidence (database ubiquitination and half-life data) — no clinical-stage drug of this modality recorded.

View underlying tractability evidence (7)

SM · Structure with LigandAB · Approved DrugAB · GO CC high confAB · UniProt loc med confAB · UniProt SigP or TMHMMPR · Database UbiquitinationPR · Half-life Data

Raw Open Targets tractability assessment buckets, by modality.

Clinical trials

Trials of drugs that target this protein — reached indirectly through those drugs, so a trial listed here studies the drug, not the protein. Ranked by active status, then clinical phase and recency, and spread across the targeting drugs.

Prospective Clinical Study of Glofitamab for Consolidation After First-line Treatment of High-risk Large B-cell LymphomaPHASE4

NOT_YET_RECRUITING · via glofitamab · NCT06956092

An Open Label, Multicenter, Phase IV Study of Teclistamab to Evaluate Its Safety in Indian Participants With Relapsed and Refractory Multiple Myeloma Who Have Previously Received at Least 3 Prior Lines of Therapy Including an Immunomodulatory Agent, a Proteasome Inhibitor and an Anti-CD38 Antibody and Have Demonstrated Disease Progression on the Last TherapyPHASE4

RECRUITING · via teclistamab · NCT07030517

ELRANATAMAB POST TRIAL ACCESS: AN OPEN-LABEL, SINGLE-ARM STUDY FOR PARTICIPANTS WITH MULTIPLE MYELOMA CONTINUING FROM PFIZER-SPONSORED ELRANATAMAB CLINICAL STUDIESPHASE4

RECRUITING · via elranatamab · NCT06057402

A Phase 2/3, Randomized, Open-Label, Comparison Study of MK-1045 Versus Blinatumomab in Participants With Relapsed or Refractory CD19+ B-Cell Acute Lymphoblastic Leukemia (B-ALL)PHASE2/PHASE3

RECRUITING · via blinatumomab · NCT07570173

View all trials (26)

Accelerate Improvement in Multiple Myeloma for Newly Diagnosed Transplant-Eligible PatientsPHASE3

NOT_YET_RECRUITING · via teclistamab · NCT07671287

A Phase 3 Randomized Study Comparing JNJ-79635322 Versus Teclistamab in Participants With Relapsed or Refractory Multiple Myeloma After 1 to 3 Prior Lines of Therapy, Including an Anti-CD38 Antibody and LenalidomidePHASE3

RECRUITING · via teclistamab · NCT07518186

International Study for Treatment of Childhood Relapsed Precursor B-Cell ALL 2020 A Randomized Phase III Study Conducted by the Resistant Disease Committee of the International BFM Study GroupPHASE3

NOT_YET_RECRUITING · via blinatumomab · NCT07476729

Framework for Optimizing, Refining, and Unifying Management of HSCT in Pediatric ALLPHASE2/PHASE3

NOT_YET_RECRUITING · via blinatumomab · NCT07297914

A Phase 3, Open-label, Controlled, Randomized Study of Newly Diagnosed Multiple Myeloma Treatment, Designed to Evaluate the Efficacy and Safety of the Elranatamab-lenalidomide Combination as a Replacement for Chemotherapy Followed by Autologous Stem Cell Transplant in the Consolidation Phase, and to Compare Elranatamab With Standard of Care in the Maintenance PhasePHASE3

RECRUITING · via elranatamab · NCT06918002

Chinese Children's Cancer Group-2025 Protocol for Newly Diagnosed Low Risk Childhood B-cell Acute Lymphoblastic LeukemiaPHASE2/PHASE3

RECRUITING · via blinatumomab · NCT06882057

Chinese Children's Cancer Group-2025 Protocol for Newly Diagnosed for Intermediate/High Risk Childhood B-cell ALLPHASE2/PHASE3

RECRUITING · via blinatumomab · NCT06764238

Efficacy Study of Blinatumomab Clean Up Early Residual Disease for Newly Diagnosed Pediatric B Lymphoblastic LeukemiaPHASE2/PHASE3

RECRUITING · via blinatumomab · NCT06607419

64407564MMY3009: A Phase 3 Randomized Study Comparing Talquetamab in Combination With Pomalidomide (Tal-P), Talquetamab in Combination With Teclistamab (Tal-Tec), and Investigator's Choice of Either Elotuzumab, Pomalidomide, and Dexamethasone (EPd) or PomPHASE3

ACTIVE_NOT_RECRUITING · via talquetamab · NCT06208150

A Phase III, Open-Label, Multicenter Randomized Study Evaluating Glofitamab as a Single Agent Versus Investigator's Choice in Patients With Relapsed/Refractory Mantle Cell LymphomaPHASE3

RECRUITING · via glofitamab · NCT06084936

A Phase 3 Randomized Study Comparing Teclistamab Monotherapy Versus Pomalidomide, Bortezomib, Dexamethasone (PVd) or Carfilzomib, Dexamethasone (Kd) in Participants With Relapsed or Refractory Multiple Myeloma Who Have Received 1 to 3 Prior Lines of Therapy, Including an Anti-CD38 Monoclonal Antibody and LenalidomidePHASE3

ACTIVE_NOT_RECRUITING · via teclistamab · NCT05572515

Interfant-21 International Collaborative Treatment Protocol for Infants Under One Year With KMT2A-rearranged Acute Lymphoblastic Leukemia or Mixed Phenotype Acute Leukemia.PHASE3

RECRUITING · via blinatumomab · NCT05327894

A Phase 3 Randomized Study Comparing Teclistamab in Combination With Daratumumab SC and Lenalidomide (Tec-DR) and Talquetamab in Combination With Daratumumab SC and Lenalidomide (Tal-DR) Versus Daratumumab SC, Lenalidomide, and Dexamethasone (DRd) in Participants With Newly Diagnosed Multiple Myeloma Who Are Either Ineligible or Not Intended for Autologous Stem Cell Transplant as Initial TherapyPHASE3

RECRUITING · via teclistamab · NCT05552222

A Randomized, Open-Label, Phase 3 Trial of Epcoritamab vs Investigator's Choice Chemotherapy in Relapsed/Refractory Diffuse Large B-cell LymphomaPHASE3

ACTIVE_NOT_RECRUITING · via epcoritamab · NCT07226752

A Phase 3, Open-Label Study to Evaluate Safety and Efficacy of Epcoritamab in Combination With Rituximab and Lenalidomide (R2) Compared to R2 in Subjects With Relapsed or Refractory Follicular Lymphoma (EPCORE FL-1)PHASE3

ACTIVE_NOT_RECRUITING · via epcoritamab · NCT05409066

Phase 3 Study of Teclistamab in Combination With Lenalidomide and Teclistamab Alone Versus Lenalidomide Alone in Participants With Newly Diagnosed Multiple Myeloma as Maintenance Therapy Following Autologous Stem Cell Transplantation - MajesTEC-4PHASE3

RECRUITING · via teclistamab · NCT05243797

A RANDOMIZED, 2-ARM, PHASE 3 STUDY OF ELRANATAMAB (PF-06863135) VERSUS LENALIDOMIDE IN PATIENTS WITH NEWLY DIAGNOSED MULTIPLE MYELOMA AFTER UNDERGOING AUTOLOGOUS STEM-CELL TRANSPLANTATIONPHASE3

ACTIVE_NOT_RECRUITING · via elranatamab · NCT05317416

AN OPEN-LABEL, 3-ARM, MULTICENTER, RANDOMIZED PHASE 3 STUDY TO EVALUATE THE EFFICACY AND SAFETY OF ELRANATAMAB (PF-06863135) MONOTHERAPY AND ELRANATAMAB + DARATUMUMAB VERSUS DARATUMUMAB + POMALIDOMIDE + DEXAMETHASONE IN PARTICIPANTS WITH RELAPSED/REFRACTORY MULTIPLE MYELOMA WHO HAVE RECEIVED AT LEAST 1 PRIOR LINE OF THERAPY INCLUDING LENALIDOMIDE AND A PROTEASOME INHIBITORPHASE3

RECRUITING · via elranatamab · NCT05020236

A Phase 3 Trial Investigating Blinatumomab (NSC# 765986) in Combination With Chemotherapy in Patients With Newly Diagnosed Standard Risk or Down Syndrome B-Lymphoblastic Leukemia (B-ALL) and the Treatment of Patients With Localized B-Lymphoblastic Lymphoma (B-LLy)PHASE3

ACTIVE_NOT_RECRUITING · via blinatumomab · NCT03914625

Phase Ib/II of the Combination of Fludarabine, Cytarabine, Idarubicin, G-CSF (FLAG-Ida) With Venetoclax and Asciminib in Patients With Advanced Phase Chronic Myeloid Leukemia and Philadelphia Chromosome-Positive Acute Myeloid LeukemiaPHASE1/PHASE2

NOT_YET_RECRUITING · via blinatumomab · NCT07604233

Study of the Efficacy and Safety of a Bispecific Antibody, Teclistamab in Severe Rapidly Progressive Interstitial Lung Disease Associated With Anti-MDA5.PHASE2

NOT_YET_RECRUITING · via teclistamab · NCT07631208

A Phase II Randomized Study of Blinatumomab With or Without Revumenib for Patients With KMT2A-Translocation B-Cell Acute Lymphoblastic Leukemia (ALL)/ Acute Leukemia With Ambiguous Lineage (ALAL) With Persistent Measurable Residual Disease (MRD)PHASE2

NOT_YET_RECRUITING · via blinatumomab · NCT07636564

Phase 2 Study to Assess the Safety and Efficacy of Subcutaneous Blinatumomab in Patients With Measurable Residual Disease Positive B-cell Acute Lymphoblastic LeukemiaPHASE2

NOT_YET_RECRUITING · via blinatumomab · NCT07192237

Epcoritamab in Combination With Dose Adjusted R-EPOCH for High Risk Burkitt Lymphoma (BL) (BEDROCK Study)PHASE2

NOT_YET_RECRUITING · via epcoritamab · NCT07662928

A Phase II Study of Glofitamab for Relapsed/Refractory Mantle Cell Lymphoma in Patients Previously Treated With CD19-Directed CAR T-Cell TherapyPHASE2

RECRUITING · via glofitamab · NCT07003295

ELDORADO: a Randomized Phase II Trial of Elranatamab or Daratumumab in Combination With Lenalidomide, Bortezomib, and Dexamethasone (RVd Lite) in Newly Diagnosed, Transplant Ineligible/Deferred Multiple MyelomaPHASE2

NOT_YET_RECRUITING · via elranatamab · NCT07247097

ClinicalTrials.gov via the drug-target graph.

What's happening now

Recent therapeutic activity around this target — regulatory actions, clinical trials and safety signals for 6 drugs that target this protein, plus publications where such a drug is a genuine subject. Every item is reached indirectly through the drug, not the protein itself; incidental mentions (a paper that merely measures a drug) and press items are excluded.

Trial status changed2026-07-30
64407564MMY3009: A Phase 3 Randomized Study Comparing Talquetamab in Combination With Pomalidomide (Tal-P), Talquetamab in Combination With Teclistamab (Tal-Tec), and Investigator's Choice of Either Elotuzumab, Pomalidomide, and Dexamethasone (EPd) or Pom
Status changed to Active, not recruiting · ClinicalTrials.gov · via talquetamab
Trial status changed2026-07-20
A Phase II Trial of Teclistamab in Participants With Previously Treated Immunoglobulin Light-chain (AL) Amyloidosis
Status changed to Active, not recruiting · ClinicalTrials.gov · via teclistamab
Trial status changed2026-07-17
A Phase 1b Open-Label Study to Evaluate the Safety and Anti-cancer Activity of Loncastuximab Tesirine in Combination With Other Anti-cancer Agents in Patients With Relapsed or Refractory B-cell Non-Hodgkin Lymphoma (LOTIS-7)
Status changed to Active, not recruiting · ClinicalTrials.gov · via glofitamab
Label change2026-06-22
Label change: GLOFITAMAB (BLA761309)
fda · regulatory · fda · via glofitamab
Label change2026-06-17
Label change: EPCORITAMAB-BYSP (BLA761324)
fda · regulatory · fda · via epcoritamab
Label change2026-05-28
Label change: GLOFITAMAB (BLA761309)
fda · regulatory · fda · via glofitamab
Indication expanded2026-03-27
Indication expansion: EPCORITAMAB-BYSP (BLA761324)
fda · regulatory · fda · via epcoritamab
Indication expanded2025-11-18
Indication expansion: EPCORITAMAB-BYSP (BLA761324)
fda · regulatory · fda · via epcoritamab
Label change2025-10-27
Label change: GLOFITAMAB (BLA761309)
fda · regulatory · fda · via glofitamab
Regulatory approval2025-02-10
Approval: Korjuny (EMA)
ema · regulatory · ema · via catumaxomab
New publication2020-05-13
The BiTE (bispecific T-cell engager) platform: Development and future potential of a targeted immuno-oncology therapy across tumor types.
Cancer · 2020 · 180 citations · Europe PMC · via blinatumomab
New publication2018-01-22
Blinatumomab for minimal residual disease in adults with B-cell precursor acute lymphoblastic leukemia.
Blood · 2018 · 635 citations · Europe PMC · via blinatumomab

Objective event titles are shown unmodified; the event kind and significance line are derived from structured fields. Forefront AttentionEvent stream aggregating Europe PMC Regulatory filings ClinicalTrials.gov.