Protein / target

HLA class II histocompatibility antigen gamma chain

CD74P04233Homo sapiensSwiss-Prot
UniProt: P04233Ensembl: ENSG00000019582HGNC: HGNC:1697NCBI Gene: 972
Clinically validated
Therapeutic maturity
1
Approved medicines
12
Clinical trials
Small-molecule tractable
Druggability
Approved Drug

Protein at a glance

Biological role

MHC class II protein binding, via antigen binding groove

Primary system

Immune system

Strongest disease association

non-small cell lung carcinoma

Clinical evidence · score 0.63

Therapeutic maturity

Clinically validated target

1 approved medicine against this target

Druggability

Small molecule

Open Targets tractability · Approved Drug

Clinical development

1 approved · 1 in clinical development

12 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

Plays a critical role in MHC class II antigen processing by stabilizing peptide-free class II alpha/beta heterodimers in a complex soon after their synthesis and directing transport of the complex from the endoplasmic reticulum to the endosomal/lysosomal system where the antigen processing and binding of antigenic peptides to MHC class II takes place. Serves as cell surface receptor for the cytokine MIF

Subcellular location

Cell membraneEndoplasmic reticulum membraneGolgi apparatus, trans-Golgi networkEndosomeLysosomeSecretedLate endosome
Domains and Gene Ontology detail (74)

Domains & features

Thyroglobulin type-1

Gene Ontology

  • Ccell surface
  • Cclathrin-coated endocytic vesicle membrane
  • Ccytoplasm
  • Cendocytic vesicle membrane
  • CER to Golgi transport vesicle membrane
  • Cexternal side of plasma membrane
  • Cextracellular exosome
  • CGolgi apparatus
  • CGolgi membrane
  • Clate endosome
  • Clumenal side of endoplasmic reticulum membrane
  • Clysosomal lumen

296 aa · 34 kDa · 5 isoforms

Biological roles

Reactome v97

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

Immune signallingUniProt · GO · ReactomeApoptosis & cell deathGOTranscriptional regulationGO
View supporting evidence

Immune signalling

  • ·Plays a critical role in MHC class II antigen processing by stabilizing peptide-free cla…
  • ·cytokine binding
  • ·cytokine receptor activity
  • ·MHC class II protein binding, via antigen binding groove

Apoptosis & cell death

  • ·negative regulation of apoptotic process
  • ·negative regulation of mature B cell apoptotic process

Transcriptional regulation

  • ·positive regulation of gene expression
View underlying pathways (3)
Cell surface interactions at the vascular wall
MHC class II antigen presentation
Developmental Lineage of Pancreatic Ductal Cells

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.

CD44MIFHLA-DRAHLA-DQ…FAUHLA-DR…CXCR4HLA-DMAHLA-DQ…CXCR2CD74

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.

repotrectinib
ApprovedInhibitor

CD74-ROS1 inhibitor

Appears in clinical studies involving non-small cell lung carcinoma, non-small cell lung carcinoma, non-small cell lung carcinoma, cancer

Direct interaction with this protein · 1 of 6 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.

Highest-confidence therapeutic associations

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

non-small cell lung carcinoma0.87

Clinical · overall 0.63

neoplasm0.61

Clinical · overall 0.40

cancer0.61

Clinical · overall 0.39

B-cell chronic lymphocytic leukemia0.13

Clinical · overall 0.30

Highest overall evidence

Remaining associations by Open Targets' aggregated evidence score.

lung adenocarcinoma0.38

Somatic mutation

squamous cell lung carcinoma0.38

Somatic mutation

lymphoid neoplasm0.37

Somatic mutation

acinar lung adenocarcinoma0.37

Somatic mutation

breast carcinoma0.30

Literature

Show all associations
non-small cell lung carcinoma0.63
neoplasm0.40
cancer0.39
lung adenocarcinoma0.38
squamous cell lung carcinoma0.38
lymphoid neoplasm0.37
acinar lung adenocarcinoma0.37
breast carcinoma0.30
B-cell chronic lymphocytic leukemia0.30
acute myeloid leukemia0.30

Open Targets ranks 694 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 · 2 total

REPOTRECTINIBApproval

non-small cell lung carcinoma · non-small cell lung carcinoma · non-small cell lung carcinoma

MILATUZUMABPhase 1 2

B-cell chronic lymphocytic leukemia · plasma cell myeloma · non-Hodgkin lymphoma

Tractability

SM · Approved DrugSM · High-Quality LigandSM · High-Quality PocketAB · Advanced ClinicalAB · UniProt loc high confAB · GO CC high confAB · UniProt SigP or TMHMMPR · Database UbiquitinationPR · Half-life DataPR · Small Molecule Binder

Clinical trials

12

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

Phase II Study of REPotrectinib With or Without Fulvestrant in Patients With Hormone Receptor-positive Human Epidermal Growth Factor 2-negative Metastatic Invasive LObular Carcinoma Who Received a Prior Endocrine Therapy in Combination With Cyclin-dependent Kinase 4 and 6 Inhibitor (REPLOT Trial)PHASE2

TERMINATED · via repotrectinib · NCT06408168

Phase 1/2 Study of TPX-0005 (Repotrectinib) in Combination With Chemotherapy in Pediatric and Young Adult Subjects With Advanced or Metastatic Solid Tumors and Primary Central Nervous System TumorsPHASE1/PHASE2

RECRUITING · via repotrectinib · NCT05004116

Phase 1, 2-Cohort, Open-label, Fixed-sequence, Drug-drug Interaction Study to Evaluate the Effect of Repotrectinib on the Pharmacokinetics of Transporter and CYP P450 Probe Substrates in Healthy Adult ParticipantsPHASE1

COMPLETED · via repotrectinib · NCT07223671

A Phase I, Two-part, Single-center, Open-label, Drug-drug Interaction Study to Assess the Effect of Voriconazole (Part 1) and Quinidine (Part 2) on the Pharmacokinetics of a Single Dose of Repotrectinib (BMS-986472) in Healthy ParticipantsPHASE1

COMPLETED · via repotrectinib · NCT06493409

A Phase 1, Multicenter, Open-label, Single-dose Study to Assess the Pharmacokinetics of Repotrectinib in Healthy Participants and Those With Moderate and Severe Hepatic ImpairmentPHASE1

COMPLETED · via repotrectinib · NCT06352528

A Phase II Study Assessing Safety and Efficacy of REPotrectinib in ROS1-positive Non-small Cell Lung Cancer Patients With Active Brain mEtastasis (REPOSE Study)PHASE2

RECRUITING · via repotrectinib · NCT06315010

Show remaining trials (6)
A Phase 1/2, Open-Label, Safety, Tolerability, Pharmacokinetics, and Anti-Tumor Activity Study of Repotrectinib in Pediatric and Young Adult Subjects With Advanced or Metastatic Malignancies Harboring ALK, ROS1, NTRK1-3 AlterationsPHASE1/PHASE2

RECRUITING · via repotrectinib · NCT04094610

Phase I Clinical Study to Assess Safety and Efficacy of Repotrectinib Combined With Osimertinib in Patients With Advanced, Metastatic EGFR Mutant NSCLC (TOTEM).PHASE1

UNKNOWN · via repotrectinib · NCT04772235

Open-label Phase II Efficacy Study of Repotrectinib in Frail (PS ≥2) and/or Elderly Patients With ROS1-rearranged Advanced NSCLCPHASE2

RECRUITING · via repotrectinib · NCT06552234

Randomized, Open-label, Multicenter, Phase 3 Trial of Repotrectinib Versus Crizotinib in Participants With Locally Advanced or Metastatic Tyrosine Kinase Inhibitor (TKI)-naïve ROS1-positive Non-Small Cell Lung Cancer (NSCLC) (TRIDENT-3)PHASE3

ACTIVE_NOT_RECRUITING · via repotrectinib · NCT06140836

A Phase 1 Study to Assess the Effect of Hepatic Impairment on the Pharmacokinetics of Repotrectinib in Advanced Cancer PatientsPHASE1

WITHDRAWN · via repotrectinib · NCT05828277

A Phase 1/2, Open-Label, Multi-Center, First-in-Human Study of the Safety, Tolerability, Pharmacokinetics, and Anti-Tumor Activity of TPX-0005 in Patients With Advanced Solid Tumors Harboring ALK, ROS1, or NTRK1-3 Rearrangements (TRIDENT-1)PHASE1/PHASE2

RECRUITING · via repotrectinib · NCT03093116

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.

non-small cell lung carcinomaWell supported
0.81
agreement 0.69–0.93
Clinical57%Somatic mutation35%Literature8%

Open Targets aggregate 0.63 · 3 independent evidence families

neoplasmModerately supported
0.54
agreement 0.38–0.69
Clinical76%Literature24%

Open Targets aggregate 0.40 · 2 independent evidence families

cancerModerately supported
0.52
agreement 0.37–0.68
Clinical79%Literature21%

Open Targets aggregate 0.39 · 2 independent evidence families

lung adenocarcinomaLimited support
0.42
agreement 0.28–0.56
Somatic mutation92%Literature8%RNA expression0%

Open Targets aggregate 0.38 · 3 independent evidence families

squamous cell lung carcinomaLimited support
0.42
agreement 0.26–0.58
Somatic mutation92%Literature8%

Open Targets aggregate 0.38 · 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

2

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. Regulatory approval2025-01-13

    Approval: Augtyro (EMA)

    ema · regulatory · ema · via repotrectinib

  2. New publication2024-01-01
    Repotrectinib in <i>ROS1</i> Fusion-Positive Non-Small-Cell Lung Cancer.

    The New England journal of medicine · 2024 · 168 citations · Europe PMC · via repotrectinib

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.