CD74

Chr 5

CD74 molecule

Also known as: CLIP, DHLAG, HLADG, II, Ia-GAMMA, p33

NCBI Gene: 972ENSG00000019582UniProt: P04233

The protein encoded by this gene associates with class II major histocompatibility complex (MHC) and is an important chaperone that regulates antigen presentation for immune response. It also serves as cell surface receptor for the cytokine macrophage migration inhibitory factor (MIF) which, when bound to the encoded protein, initiates survival pathways and cell proliferation. This protein also interacts with amyloid precursor protein (APP) and suppresses the production of amyloid beta (Abeta). Multiple alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Aug 2011]

0
ClinVar variants
0
Pathogenic / LP
0.25
pLI score
1
Active trials
Clinical Summary— CD74
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.25) despite low pLI — interpret in context.
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
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.
0.56LOEUF
pLI 0.249
Z-score 2.81
OE 0.25 (0.12–0.56)
Moderately 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.
1.40Z-score
OE missense 0.70 (0.61–0.82)
125 obs / 177.4 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.0.25 (0.12–0.56)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.70 (0.61–0.82)
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.0.93
0≤1.21.6
LoF obs/exp: 4 / 16.2Missense obs/exp: 125 / 177.4Syn Z: 0.46

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

CD74 · 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
CD74 ANTIGEN; CD74
MIM #142790 · *
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Unveiling inflammatory and prehypertrophic cell populations as key contributors to knee cartilage degeneration in osteoarthritis using multi-omics data integration.
Fan Y et al.·Ann Rheum Dis
2024
Single-Cell Transcriptomic Analysis of Primary and Metastatic Tumor Ecosystems in Esophageal Squamous Cell Carcinoma.
Jia Y et al.·Adv Sci (Weinh)
2023
Single-cell atlas of human gingiva unveils a NETs-related neutrophil subpopulation regulating periodontal immunity.
Qiu W et al.·J Adv Res
2025
A constitutive interferon-high immunophenotype defines response to immunotherapy in colorectal cancer.
Acha-Sagredo A et al.·Cancer Cell
2025
Single-Cell Analyses Reveal Diverse Mechanisms of Resistance to EGFR Tyrosine Kinase Inhibitors in Lung Cancer.
Kashima Y et al.·Cancer Res
2021Functional
Spatial transcriptome profiling identifies DTX3L and BST2 as key biomarkers in esophageal squamous cell carcinoma tumorigenesis.
Li R et al.·Genome Med
2024
DPSCs regulate epithelial-T cell interactions in oral submucous fibrosis.
Wang SY et al.·Stem Cell Res Ther
2024
CD74 supports accumulation and function of regulatory T cells in tumors.
Bonnin E et al.·Nat Commun
2024
A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.
Steele L et al.·Nat Immunol
2025
CD47-amyloid-β-CD74 signaling triggers adaptive immunosuppression in sepsis.
Feng Z et al.·EMBO Rep
2025
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Ectopic B lymphocyte follicles exacerbate ischemic brain damage via MIF-CD74/CXCR4 and interferon signaling.
Yang S et al.·J Clin Invest
2026🔓 Open Access
Lactate-induced metabolic reprogramming of TAMs impairs antigen presentation capacity via C/EBPα-CD74 axis in oral squamous cell carcinoma.
Wang M et al.·Clin Transl Med
2026🔓 Open Access
MIF-CD74 axis facilitates MDSC infiltration in the tumor microenvironment of pancreatic ductal adenocarcinoma.
Fukuda H et al.·Cancer Lett
2026
Anti-CD74 IgA is not associated with modic changes in the Northern Finland Birth Cohort.
Steimer A et al.·Clin Rheumatol
2026Cohort
The CD74-MIF axis contributes to acute uveitic injury by upregulating proinflammatory cytokine secretion in murine cytomegalovirus intracameral infection mouse models.
Sheng Q et al.·Exp Eye Res
2026Functional
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Solid Tumor, Adult

Patritumab Deruxtecan in Patients With Solid Tumor Harboring an NRG1 Fusion

RECRUITING
NCT06383884Phase PHASE2Samsung Medical CenterStarted 2024-08-13
Patritumab Deruxtecan

External Resources

Links to major genomics databases and tools