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50 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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MIF
macrophage migration inhibitory factor
Chromosome 22 · 22q11.23
NCBI Gene: 4282Ensembl: ENSG00000240972.3HGNC: HGNC:7097UniProt: I4AY87
891PubMed Papers
1Diseases
0Drugs
0Pathogenic Variants
RESEARCH IMPACT
Highly StudiedTrending
CLINICAL
OMIM Disease Gene
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
positive regulation of cell population proliferationdopachrome isomerase activitycytokine activitycytokine receptor bindingRheumatoid arthritis systemic juvenile
✦AI Summary

MIF (macrophage migration inhibitory factor) is a 12.5 kDa pro-inflammatory cytokine that functions as a pivotal regulator of innate and adaptive immunity 1. Expressed ubiquitously across hematopoietic, epithelial, endothelial, mesenchymal, and neuronal cells, MIF operates in autocrine and paracrine modes by binding multiple receptors including CD74/CD44, CXCR2, CXCR4, and CXCR7, activating downstream pathways such as ERK1/2, AMPK, and AKT 2. MIF promotes pathogen clearance during infections but conversely exacerbates detrimental inflammation and supports cancer progression 1. A critical mechanism involves counteracting glucocorticoid anti-inflammatory activity 3. While MIF possesses dopachrome tautomerase activity in vitro, physiological relevance of this enzymatic function remains unclear 4. Clinically, elevated MIF associates with inflammatory diseases (sepsis, rheumatoid arthritis, spondyloarthritis), organ pathologies (heart failure, acute kidney injury), and autoimmune conditions 25. MIF promotes endothelial cell death during ischemic stroke through RIPK1-mediated pathways 6 and drives CD8+ T cell activation in vitiligo 7. MIF expression and function are regulated by genetic polymorphisms and post-translational modifications, with MIF inhibitors and receptor antagonists showing therapeutic potential across multiple conditions 1.

Sources cited
1
MIF is a 12.5 kDa ubiquitously expressed proinflammatory cytokine involved in innate and adaptive immunity; plays both protective and pathological roles in infection, inflammation, and cancer
PMID: 34673115
2
MIF receptor signaling through CD74/CD44, CXCR2, CXCR4, and CXCR7 activates ERK1/2, AMPK, and AKT pathways; alters expression associates with sepsis, lupus, rheumatoid arthritis, heart failure, myocardial infarction, acute kidney injury, organ fibrosis, and malignancies
PMID: 30682543
3
MIF counteracts the anti-inflammatory activity of glucocorticoids
PMID: 15908412
4
MIF has dopachrome tautomerase activity in vitro but physiological substrate and relevance are unclear
PMID: 11439086
5
MIF drives spondyloarthritis pathology by intensifying type 3 immunity and promoting T regulatory cell conversion to TH17 phenotype; associated with human disease
PMID: 34669443
6
Myeloid-derived MIF promotes RIPK1-mediated cerebromicrovascular endothelial cell death and blood-brain barrier disruption in ischemic stroke
PMID: 36693098
7
MIF inhibition suppresses CD8+ T cell activation and proliferation, ameliorating vitiligo progression
PMID: 36852981
8
CD74 functions as a high-affinity MIF receptor that is upregulated on activated CD4+ T cells and involved in MIF-induced T cell migration
PMID: 38992165
Disease Associationsⓘ1
Rheumatoid arthritis systemic juvenileUniProt
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
CXCR2Protein interaction100%CD44Protein interaction100%CXCR4Protein interaction99%COPS5Protein interaction98%GOT2Protein interaction93%GOT1Protein interaction92%
Tissue Expression

No tissue expression data available for this gene.

Gene Interaction Network
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MIFCXCR2CD44CXCR4COPS5GOT2GOT1
PROTEIN STRUCTURE
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PDB9BNQ · 1.09 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.96LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF1.78 [1.13–1.96]
RankingsWhere MIF stands among ~20K protein-coding genes
  • #198of 20,598
    Most Researched891 · top 1%
  • #17,741of 17,882
    Most Constrained (LOEUF)1.96
Genes detectedMIF
Sources retrieved50 papers
Response time—
📄 Sources
50▼
1
Evolving complexity of MIF signaling.
PMID: 30682543
Cell Signal · 2019
1.00
2
Macrophage migration inhibitory factor (MIF): A multifaceted cytokine regulated by genetic and physiological strategies.
PMID: 34673115
Pharmacol Ther · 2022
0.90
3
Associations between circulating macrophage migration inhibitory factor (MIF) levels and rheumatoid arthritis, and between
PMID: 28912189
Postgrad Med J · 2018
0.90
4
CD44/POU2F2/BCL9L axis mediates MIF-driven SPP1
PMID: 41800265
Int J Biol Sci · 2026
0.88
5
Plant MDL proteins synergize with the cytokine MIF at CXCR2 and CXCR4 receptors in human cells.
PMID: 37988455
Sci Signal · 2023
0.84