Protein / target

T-cell surface glycoprotein CD3 gamma chain

CD3GP09693Homo sapiensSwiss-Prot
Clinically validated
Therapeutic maturity
11
Approved medicines
30
Clinical trials
Small-molecule tractable
Druggability
Structure with Ligand

Protein at a glance

Biological role

Signaling receptor complex adaptor activity

Primary system

Immune system

Strongest disease association

combined immunodeficiency due to CD3gamma deficiency

Genetic evidence · score 0.86

Therapeutic maturity

Clinically validated target

11 approved medicines against this target

Druggability

Small molecule

Open Targets tractability · Structure with Ligand

Clinical development

11 approved · 5 in clinical development

30 linked trials

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

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 to this role of signal transduction in T-cell activation, CD3G plays an essential role in the dynamic regulation of TCR expression at the cell surface (PubMed:8187769). Indeed, constitutive TCR cycling is dependent on the di-leucine-based (diL) receptor-sorting motif present in CD3G

Subcellular location

Cell membrane
Domains and Gene Ontology detail (21)

Domains & features

Ig-likeITAM

Gene Ontology

  • Calpha-beta T cell receptor complex
  • Cclathrin-coated endocytic vesicle membrane
  • Cexternal side of plasma membrane
  • Cplasma membrane
  • Fidentical protein binding
  • Fsignaling receptor complex adaptor activity
  • FT cell receptor binding
  • Ftransmembrane signaling receptor activity
  • Padaptive immune response
  • Palpha-beta T cell activation
  • Pcell surface receptor signaling pathway
  • Pestablishment or maintenance of cell polarity

182 aa · 20 kDa

Biological roles

Reactome v97

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

Immune signallingUniProt · GOSynaptic signallingReactomeKinase signallingReactomeApoptosis & cell deathGO
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 binding
  • ·adaptive immune response

Synaptic signalling

  • ·Translocation of ZAP-70 to Immunological synapse

Kinase signalling

  • ·Phosphorylation of CD3 and TCR zeta chains

Apoptosis & cell death

  • ·regulation of lymphocyte apoptotic process
View underlying pathways (13)

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.

CD3ECD3DCD247ZAP70SYKCD8ACD8BCD4TRAT1B2MCD3G

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.

Drugs targeting this protein

1

Whether each drug engages this protein directly or through a complex, and how many other targets are recorded for it. Direct binders with few recorded targets are listed first.

blinatumomab
ApprovedCross-linking agent

T cell surface glycoprotein CD3 cross-linking agent

Appears in clinical studies involving acute lymphoblastic leukemia, B-cell acute lymphoblastic leukemia, lymphoid leukemia, neoplasm

Acts on a complex — shared with CD3E, CD3D · 1 of 4 recorded protein targets

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

Translational evidence

Open Targets 26

Why this target matters therapeutically — disease associations, drugs in development, tractability and safety, from Open Targets.

Strongest genetic associations

Human genetic evidence — the most direct causal link between this target and a disease.

combined immunodeficiency due to CD3gamma deficiency0.86

Genetic · overall 0.77

severe combined immunodeficiency0.76

Genetic literature · overall 0.56

Highest-confidence therapeutic associations

Diseases where a drug acting on this target has already reached clinical development.

plasma cell myeloma0.98

Clinical · overall 0.60

follicular lymphoma0.95

Clinical · overall 0.58

diffuse large B-cell lymphoma0.95

Clinical · overall 0.59

neoplasm0.94

Clinical · overall 0.58

small cell lung carcinoma0.92

Clinical · overall 0.56

Highest overall evidence

Remaining associations by Open Targets' aggregated evidence score.

cutaneous leishmaniasis0.58

Pathway

acute lymphoblastic leukemia0.56

Clinical

Ascites0.51

Clinical

Show all associations
combined immunodeficiency due to CD3gamma deficiency0.77
plasma cell myeloma0.60
diffuse large B-cell lymphoma0.59
cutaneous leishmaniasis0.58
follicular lymphoma0.58
neoplasm0.58
acute lymphoblastic leukemia0.56
severe combined immunodeficiency0.56
small cell lung carcinoma0.56
Ascites0.51

Open Targets ranks 263 associations for this target and we store the top 10 by aggregated score. The long tail is largely literature co-mention and RNA-expression evidence, not evidence that this target drives those diseases.

Known drugs · 16 total

ELRANATAMABApproval

plasma cell myeloma · neoplasm · smoldering plasma cell myeloma

IMC-GP100Early Phase 1

melanoma

TALQUETAMABApproval

plasma cell myeloma · neoplasm · plasma cell myeloma

GLOFITAMABApproval

diffuse large B-cell lymphoma · neoplasm · diffuse large B-cell lymphoma

FLOTETUZUMABPhase 2

acute leukemia of ambiguous lineage · acute myeloid leukemia by FAB classification · hematopoietic and lymphoid cell neoplasm

BLINATUMOMABApproval

acute lymphoblastic leukemia · B-cell acute lymphoblastic leukemia · lymphoid leukemia

TECLISTAMABApproval

plasma cell myeloma · neoplasm · plasma cell myeloma

ODRONEXTAMABApproval

follicular lymphoma · neoplasm · follicular lymphoma

MOSUNETUZUMABApproval

follicular lymphoma · neoplasm · high grade B-cell lymphoma

MUROMONAB-CD3Approval

graft versus host disease · acute lymphoblastic leukemia · renal cell carcinoma

Tractability

SM · Structure with LigandAB · Approved DrugAB · UniProt loc high confAB · GO CC high confAB · UniProt SigP or TMHMMAB · Human Protein Atlas locPR · Database Ubiquitination

Clinical trials

30

Trials of drugs that target this protein — reached indirectly through those drugs, so a trial listed here studies the drug, not the protein.

Show remaining trials (24)

RECRUITING · via blinatumomab · NCT07294677

ClinicalTrials.gov via the drug-target graph.

Forefront confidence

Synthesis

Our own weighting of the evidence behind each disease association. Human genetics and clinical evidence count for most; literature co-mention counts for little, because two entities sharing an abstract is not evidence that one drives the other.

combined immunodeficiency due to CD3gamma deficiencyWell supported
0.88
agreement 0.761.00
Genetic86%Animal model14%Genetic literaturedup

Open Targets aggregate 0.77 · 2 independent evidence families · 1 not counted as duplicate

plasma cell myelomaModerately supported
0.73
agreement 0.580.89
Clinical99%Literature1%

Open Targets aggregate 0.60 · 2 independent evidence families

diffuse large B-cell lymphomaModerately supported
0.73
agreement 0.570.88
Clinical93%Literature7%

Open Targets aggregate 0.59 · 2 independent evidence families

follicular lymphomaModerately supported
0.72
agreement 0.550.88
Clinical100%

Open Targets aggregate 0.58 · 1 independent evidence family

neoplasmModerately supported
0.71
agreement 0.560.87
Clinical96%Literature4%

Open Targets aggregate 0.58 · 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 underlying per-type scores are shown above so the calculation can be checked.

What's happening now

4

Recent activity around this target, drawn from one canonical event stream. Every item is reached through a drug that targets this protein, so each event is news about that drug rather than about the protein directly.

  1. New publication2020-07-03
    Curative outcomes following blinatumomab in adults with minimal residual disease B-cell precursor acute lymphoblastic leukemia.

    Leukemia & lymphoma · 2020 · 71 citations · Europe PMC · via blinatumomab

  2. 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

  3. 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

  4. Regulatory approval2015-11-23

    Approval: Blincyto (EMA)

    ema · regulatory · ema · 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.