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Protein / target

HLA class II histocompatibility antigen gamma chain

Encoded byCD74P04233Homo sapiensSwiss-Prot
Clinically validated
Therapeutic maturity
1
Approved medicines
Open Targets target-level
View by indication →
12
Clinical trials
Small-molecule tractable
Druggability
Approved Drug

Protein at a glance

Biological role

MHC class II protein binding, via antigen binding groove

Strongest disease association

Carcinoma, Non-Small-Cell Lung

Via encoding gene CD74 · Clinical evidence · score 0.63

Therapeutic position

Established drug target

Small molecules and 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

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 bindi…

View complete UniProt function annotation

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.

Cell migrationGOImmune signallingUniProt · GO · ReactomeApoptosis & cell deathGO
View supporting evidence

Cell migration

  • ·negative regulation of cell migration
  • ·positive regulation of neutrophil chemotaxis

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
View underlying pathways (3)

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.

Approved medicines with mapped indications

1 medicine · 1 area

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.

Neoplasms1 medicine

Approved indications from ChEMBL (phase-4), via the canonical drug→disease graph.

Drugs targeting this protein

1

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.

repotrectinib
ApprovedInhibitor

CD74-ROS1 inhibitor

Indicated for Neoplasms

Direct interaction with this protein · 1 of 6 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 CD74

Gene-level evidence surfaced through the gene CD74that 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.

Carcinoma, Non-Small-Cell Lung
0.81Well supported

Clinical evidence dominant · Open Targets 0.63

Neoplasms
0.54Moderately supported

Clinical evidence dominant · Open Targets 0.40

Adenocarcinoma of Lung
0.42Limited support

Somatic mutation evidence dominant · Open Targets 0.38

Squamous cell lung carcinoma
0.42Limited support

Somatic mutation evidence dominant · Open Targets 0.38

Leukemia, Lymphocytic, Chronic, B-Cell
0.40Limited support

Somatic mutation evidence dominant · Open Targets 0.30

View evidence synthesis (5)
Carcinoma, Non-Small-Cell LungWell supported
0.81
agreement 0.690.93
Clinical57%Somatic mutation35%Literature8%

Open Targets aggregate 0.63 · 3 independent evidence families

NeoplasmsModerately supported
0.54
agreement 0.380.69
Clinical76%Literature24%

Open Targets aggregate 0.40 · 2 independent evidence families

Adenocarcinoma of LungLimited support
0.42
agreement 0.280.56
Somatic mutation92%Literature8%RNA expression0%

Open Targets aggregate 0.38 · 3 independent evidence families

Squamous cell lung carcinomaLimited support
0.42
agreement 0.260.58
Somatic mutation92%Literature8%

Open Targets aggregate 0.38 · 2 independent evidence families

Leukemia, Lymphocytic, Chronic, B-CellLimited support
0.40
agreement 0.280.52
Somatic mutation66%Clinical21%Literature13%

Open Targets aggregate 0.30 · 3 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
Carcinoma, Non-Small-Cell Lung0.63
Neoplasms0.40
Adenocarcinoma of Lung0.38
Squamous cell lung carcinoma0.38
Lymphoid neoplasm0.37
Acinar lung adenocarcinoma0.37
Breast Neoplasms0.30
Leukemia, Lymphocytic, Chronic, B-Cell0.30
Leukemia, Myeloid, Acute0.30

Drug development

2 compounds recorded · 1 approved · 1 in clinical development

Open Targets' development universe — every compound recorded against the target at any stage, not all approved medicines. Distinct from the 1 drug that targets this protein in Forefront's canonical graph (1 with a mapped approved indication, shown above): these count different sets and are not a subset relation.

View all recorded compounds (2)
REPOTRECTINIBApproval
MILATUZUMABPhase 1 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 moleculesStrong

Approved Drug and High-Quality Ligand support this modality.

AntibodiesStrong

Advanced Clinical and UniProt loc high conf support this modality.

Protein degradersEmerging

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

View underlying tractability evidence (10)
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

Raw Open Targets tractability assessment buckets, by modality.

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. Ranked by active status, then clinical phase and recency, and spread across the targeting drugs.

View all trials (8)

ClinicalTrials.gov via the drug-target graph.

What's happening now

2

Recent therapeutic activity around this target — regulatory actions, clinical trials and safety signals for a drug that targets 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.

  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.