MIF

Summary

MIF (macrophage migration inhibitory factor, HGNC:7097) is a protein-coding gene on chromosome 22q11.23, encoding Macrophage migration inhibitory factor (P14174). Pro-inflammatory cytokine involved in the innate immune response to bacterial pathogens.

This gene encodes a lymphokine involved in cell-mediated immunity, immunoregulation, and inflammation. It plays a role in the regulation of macrophage function in host defense through the suppression of anti-inflammatory effects of glucocorticoids. This lymphokine and the JAB1 protein form a complex in the cytosol near the peripheral plasma membrane, which may indicate an additional role in integrin signaling pathways.

Source: NCBI Gene 4282 — RefSeq curated summary.

At a glance

• Gene–disease (curated): cystic fibrosis (Supportive, GenCC) — +1 more curated relationship
• GWAS associations: 5
• Clinical variants (ClinVar): 34 total
• Druggable target: yes — 10 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_002415

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7097
Approved symbol	MIF
Name	macrophage migration inhibitory factor
Location	22q11.23
Locus type	gene with protein product
Status	Approved
Aliases	GIF
Ensembl gene	ENSG00000240972
Ensembl biotype	protein_coding
OMIM	153620
Entrez	4282

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 4 protein_coding, 2 retained_intron

ENST00000215754, ENST00000465752, ENST00000498385, ENST00000857232, ENST00000921386, ENST00000921387

RefSeq mRNA: 1 — MANE Select: NM_002415 NM_002415

CCDS: CCDS13819

Canonical transcript exons

ENST00000215754 — 3 exons

Exon	Start	End
ENSE00001839840	23895040	23895223
ENSE00001922200	23894383	23894582
ENSE00003694118	23894772	23894944

Expression profiles

Bgee: expression breadth ubiquitous, 147 present calls, max score 99.68.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 1122.0184 / max 6625.9934, expressed in 1825 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
191342	1079.5071	1825
191343	32.1945	1801
191344	9.6381	1660
191345	0.6787	400

Top tissues by expression

147 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
pituitary gland	UBERON:0000007	99.68	gold quality
adenohypophysis	UBERON:0002196	99.68	gold quality
cortex of kidney	UBERON:0001225	99.67	gold quality
right adrenal gland	UBERON:0001233	99.67	gold quality
left adrenal gland	UBERON:0001234	99.62	gold quality
superior frontal gyrus	UBERON:0002661	99.62	gold quality
metanephros cortex	UBERON:0010533	99.62	gold quality
Brodmann (1909) area 9	UBERON:0013540	99.62	gold quality
lower esophagus mucosa	UBERON:0035834	99.62	gold quality
right uterine tube	UBERON:0001302	99.61	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	99.61	gold quality
left adrenal gland cortex	UBERON:0035825	99.61	gold quality
right adrenal gland cortex	UBERON:0035827	99.60	gold quality
hypothalamus	UBERON:0001898	99.59	gold quality
primary visual cortex	UBERON:0002436	99.59	gold quality
adult mammalian kidney	UBERON:0000082	99.58	gold quality
Ammon’s horn	UBERON:0001954	99.56	gold quality
right lobe of thyroid gland	UBERON:0001119	99.55	gold quality
esophagus mucosa	UBERON:0002469	99.55	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	99.55	gold quality
nucleus accumbens	UBERON:0001882	99.54	gold quality
left lobe of thyroid gland	UBERON:0001120	99.52	gold quality
temporal lobe	UBERON:0001871	99.52	gold quality
amygdala	UBERON:0001876	99.52	gold quality
anterior cingulate cortex	UBERON:0009835	99.52	gold quality
prostate gland	UBERON:0002367	99.50	gold quality
right frontal lobe	UBERON:0002810	99.50	gold quality
putamen	UBERON:0001874	99.48	gold quality
caudate nucleus	UBERON:0001873	99.46	gold quality
substantia nigra	UBERON:0002038	99.46	gold quality

Single-cell (SCXA)

Detected in 32 experiment(s), a significant marker in 16.

Experiment	Marker?	Max mean expression
E-ENAD-20	yes	3179.07
E-MTAB-8495	yes	2459.26
E-HCAD-38	yes	1949.03
E-GEOD-111727	yes	769.53
E-MTAB-10287	yes	34.24
E-ANND-3	yes	23.24
E-MTAB-9067	yes	20.94
E-CURD-112	yes	14.54
E-CURD-122	yes	11.91
E-MTAB-10042	yes	11.86
E-MTAB-7316	yes	9.28
E-MTAB-6678	yes	8.05
E-MTAB-9801	yes	6.28
E-GEOD-130148	yes	6.17
E-HCAD-35	yes	4.79

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

2 targets.

Target	Regulation
HBA1	Repression
HBB	Repression

Upstream regulators (CollecTRI, top): CEBPA, CEBPD, CREB1, HBP1, HIF1A, MAF, MYC, NFKB1, PAX3, PPARG, RELA, SP1, STAT3, TNF, TP53

miRNA regulators (miRDB)

3 targeting MIF, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-629-3P	99.85	67.99	1875
HSA-MIR-451A	91.68	64.18	71
HSA-MIR-1537-3P	90.51	63.57	105

Literature-anchored findings (GeneRIF, showing 40)

• increased expression seen in prostate carcinoma; may serve as prognostic marker (PMID:11920501)
• MIF is highly concentrated inside milk fat globules. milk MIF may protect the newborn against infection and play a role in preserving the functionality of the lactating mammary gland. (PMID:11978887)
• MIF seems to play a role in tumor-stroma interactions of primary breast cancers (PMID:11985788)
• role of tautomerase active site as target for discovery of novel anti-inflammatory agents (PMID:11997397)
• Monocyte chemotactic protein-1 and macrophage migration inhibitory factor production by peritoneal macrophages may contribute to paracrine and autocrine activation and to macrophage accumulation in peritoneal cavity of women with endometriosis. (PMID:12009356)
• a novel CATT-tetranucleotide repeat polymorphism correlated with low disease severity in a cohort of rheumatoid arthritis patients (PMID:12070782)
• capacity of MMIF to induce increased functional capacity of dendritic cells, and to produce IL-1beta and IL-8 from monocytes and DC, indicate a role of MMIF in the induction and/or perpetuation of the inflammatory environment in ulcerative colitis. (PMID:12109441)
• The serum level of MIF and PBMC MIF expression increased in acute respiratory distress syndrome patients (PMID:12126556)
• The MIF 173 C allele is associated with a significantly increased risk of developing sarcoidosis in patients with erythema nodosum. (PMID:12180727)
• released from lung epithelial cells rendered necrotic by influenza A virus infection (PMID:12186913)
• We found that the murine NB cell line, Neuro2a, secretes macrophage migration inhibitory factor, MIF, a multifunctional cytokine with the potential to block effective immune responses to a tumor (PMID:12218292)
• role of MIF in IgA nephropathy (PMID:12218308)
• Local and systemic up-regulation of MIF expression is associated with and precedes the occurrence of acute GVHD, suggesting a pathogenetic role. (PMID:12235522)
• The -173-MIF*C allele confers increased risk of susceptibility to juvenile idiopathic arthritis. (PMID:12355488)
• upregulation in intervillous blood is asociated with placental malaria (PMID:12402212)
• expression of MIF in human glioblastomas, a close relationship with VEGF expression. (PMID:12445161)
• Polymeric IgA increases the expression of this factor by human mesangial cells in IgA nephropathy. (PMID:12480958)
• up-regulation of MIF expression during hypoxic and hypoglycemic stress might play a critical role for the neovascularization of glial tumors (PMID:12507885)
• High levels of this factor are associated with risk of recurrernce after resection of lung cancer. (PMID:12576459)
• The increased secretion of MIF in AF at term, particularly at term labor, suggests that MIF contributes to the inflammatory events leading to labor. (PMID:12607777)
• Macrophage migration inhibitory factor is a critical mediator of severe acute pancreatitis. (PMID:12612911)
• Decreased serum MIF during early gestation were found in recurrent miscarriage with normal fetal chromosome karyotype. Might be related to aetiology of miscarriage. (PMID:12615835)
• MIF has potent anti-apoptotic activities and suppresses pro-oxidative stress-induced apoptosis. (PMID:12626594)
• The late morning peak of macrophage migration inhibitory factor, by antagonizing cortisol-mediated pro-inflammatory cytokine suppression may prolong the duration of early morning inflammation (PMID:12631237)
• Review. MIF is a critical upstream regulator of immune response. It is released under a variety of circumstances, regulates cytokine secretion & immune receptor expression, inhibits p53 function, & activates components of the MAP kinase & Jab-1 pathways. (PMID:12667094)
• interaction with apoptosis-associated protein BNIPL (PMID:12681488)
• the interaction between MIF and endotoxin may promote fluid collection in the middle ear, particularly in adults (PMID:12738641)
• MIF binds two peptides, hepatitis B surface antigen (HBsAg) and insulin B (InsB) with high affinity for HLA class II allo-types, HLA-DP2 and HLA-DQ8, respectively (PMID:12740374)
• Our study shows the functional relevance of the MIF-173 polymorphism and suggests that the MIF-173*C allele is a predictor of poor outcome in systemic-onset JIA. (PMID:12746913)
• MIF binds to the extracellular domain of CD74, and CD74 is required for MIF-induced activation of the extracellular signal-regulated kinase-1/2 MAP kinase cascade (PMID:12782713)
• MIF-(50-65) exhibits redox activity and has MIF-like biological functions (PMID:12796500)
• role for MIF in the regulation of p53 expression and p53-mediated events in the inflamed synovium and is of critical importance in the pathogenesis of RA. (PMID:12847682)
• Secretion of macrophage migration inhibitory factor is mediated by a non-classical pathway involving an ABCA1 transporter. (PMID:12965208)
• Macrophage migration inhibitory factor is a regulator of innate immunity. (PMID:14502271)
• MIF gene polymorphism is associated with susceptibility to but not severity of inflammatroy arthritis. (PMID:14551601)
• MIF is involved in the up-regulation of UVA-induced MMP-1 in dermal fibroblasts through PKC-, PKA-, Src family tyrosine kinase-, MAPK-, c-Jun-, and AP-1-dependent pathways. (PMID:14581488)
• MIF, TNF-alpha and IL-6 may participate in pathological process of chronic hepatitis B and cirrhosis. IL-6 may play important role in ascites formation. Serum MIF, TNF-alpha and IL-6 appear to reflect severity of tissue injury in hepatitis B. (PMID:14607690)
• MIF contributes to the inflammatory phase of the wound healing process in concert with thrombin and FXa via PAR-1 and PAR-2. (PMID:14736878)
• MIF is overexpressed in patients with systemic lupus erythematosus and while partly explained by corticosteroid use, there is evidence of an association between MIF and lupus-related disease damage. (PMID:14760795)
• MIF may play an important role in the migration of inflammatory cells into the synovium of rheumatoid joints via induction of IL-8. (PMID:15146413)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	mif	ENSDARG00000071336
mus_musculus	Mif	ENSMUSG00000033307
rattus_norvegicus	Mif	ENSRNOG00000006589
rattus_norvegicus	LOC120102174	ENSRNOG00000033673
rattus_norvegicus	AC127887.1	ENSRNOG00000034106
caenorhabditis_elegans		WBGENE00003234

Paralogs (2): DDTL (ENSG00000099974), DDT (ENSG00000099977)

Protein

Protein identifiers

Macrophage migration inhibitory factor — P14174 (reviewed: P14174)

Alternative names: Glycosylation-inhibiting factor, L-dopachrome isomerase, L-dopachrome tautomerase, Phenylpyruvate tautomerase

All UniProt accessions (2): P14174, I4AY87

UniProt curated annotations — full annotation on UniProt →

Function. Pro-inflammatory cytokine involved in the innate immune response to bacterial pathogens. The expression of MIF at sites of inflammation suggests a role as mediator in regulating the function of macrophages in host defense. Counteracts the anti-inflammatory activity of glucocorticoids. Has phenylpyruvate tautomerase and dopachrome tautomerase activity (in vitro), but the physiological substrate is not known. It is not clear whether the tautomerase activity has any physiological relevance, and whether it is important for cytokine activity.

Subunit / interactions. Homotrimer. Interacts with CXCR2 extracellular domain. Interacts with the CD74 extracellular domain, USO1, COPS5 and BNIPL.

Subcellular location. Secreted. Cytoplasm.

Disease relevance. Rheumatoid arthritis systemic juvenile (RASJ) [MIM:604302] An inflammatory articular disorder with systemic onset beginning before the age of 16. It represents a subgroup of juvenile arthritis associated with severe extraarticular features and occasionally fatal complications. During active phases of the disorder, patients display a typical daily spiking fever, an evanescent macular rash, lymphadenopathy, hepatosplenomegaly, serositis, myalgia and arthritis. Disease susceptibility is associated with variants affecting the gene represented in this entry.

Induction. Up-regulated in concanavalin-A-treated lymphocytes. Up-regulated in macrophages upon exposure to M.tuberculosis antigens.

Miscellaneous. Serum levels of MIF are elevated in patients with severe sepsis or septic shock. High levels of MIF are correlated with low survival. Drugs that inhibit tautomerase activity protect against death due to sepsis.

Similarity. Belongs to the MIF family.

RefSeq proteins (1): NP_002406* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001398	Macrophage_inhib_fac	Family
IPR014347	Tautomerase/MIF_sf	Homologous_superfamily
IPR019829	Macrophage_inhib_fac_CS	Conserved_site

Pfam: PF01187

Enzyme classification (BRENDA):

• EC 5.3.2.1 — phenylpyruvate tautomerase (BRENDA: 15 organisms, 36 substrates, 162 inhibitors, 39 Km, 40 kcat entries)
• EC 5.3.3.12 — L-dopachrome isomerase (BRENDA: 15 organisms, 23 substrates, 32 inhibitors, 2 Km, 0 kcat entries)

Substrate kinetics (BRENDA)

12 substrates with measured Km, best-characterized 12. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ENOL-PHENYLPYRUVATE	0.02–0.31	14
ENOL-(P-HYDROXYPHENYL)PYRUVATE	0.107–0.582	8
(4-HYDROXYPHENYL)PYRUVATE	0.072–2.4	4
PHENYLENOLPYRUVATE	0.11–3.5	3
PHENYLPYRUVATE	6–8	3
(4-HYDROXYPHENYL)ENOLPYRUVATE	0.79–0.89	2
DOPACHROME	0.1–1	2
4-(HYDROXYPHENYL)PYRUVATE	0.1	1
CIS-3-CHLOROACRYLATE	0.152	1
KETO-(P-HYDROXYPHENYL)PYRUVATE	2.77	1
KETO-PHENYLPYRUVATE	4.9	1
TRANS-3-CHLOROACRYLATE	96	1

Catalyzed reactions (Rhea), 2 shown:

• L-dopachrome = 5,6-dihydroxyindole-2-carboxylate (RHEA:13041)
• 3-phenylpyruvate = enol-phenylpyruvate (RHEA:17097)

UniProt features (28 total): strand 7, sequence conflict 6, helix 6, binding site 3, modified residue 2, initiator methionine 1, chain 1, active site 1, mutagenesis site 1

Structure

Experimental structures (PDB)

118 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
9JIT	X-RAY DIFFRACTION	1.08
9BNQ	X-RAY DIFFRACTION	1.09
6B1K	X-RAY DIFFRACTION	1.17
9JIY	X-RAY DIFFRACTION	1.2
7EE8	X-RAY DIFFRACTION	1.22
3DJH	X-RAY DIFFRACTION	1.25
3IJJ	X-RAY DIFFRACTION	1.25
4GRN	X-RAY DIFFRACTION	1.25
9JIV	X-RAY DIFFRACTION	1.25
9JJ0	X-RAY DIFFRACTION	1.25
7EDQ	X-RAY DIFFRACTION	1.27
4GRP	X-RAY DIFFRACTION	1.27
7XTX	X-RAY DIFFRACTION	1.28
8IMR	X-RAY DIFFRACTION	1.3
9JIZ	X-RAY DIFFRACTION	1.3
5B4O	X-RAY DIFFRACTION	1.37
7E47	X-RAY DIFFRACTION	1.38
6FVH	X-RAY DIFFRACTION	1.4
6FVE	X-RAY DIFFRACTION	1.41
7E45	X-RAY DIFFRACTION	1.43
4GRR	X-RAY DIFFRACTION	1.47
7E4A	X-RAY DIFFRACTION	1.48
1GD0	X-RAY DIFFRACTION	1.5
4Z1T	X-RAY DIFFRACTION	1.5
6BG6	X-RAY DIFFRACTION	1.52
4F2K	X-RAY DIFFRACTION	1.53
6OY8	X-RAY DIFFRACTION	1.53
6OYB	X-RAY DIFFRACTION	1.53
6OYE	X-RAY DIFFRACTION	1.53
9BNR	X-RAY DIFFRACTION	1.53

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P14174-F1	98.60	1.00

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 2 (proton acceptor; via imino nitrogen)

Ligand- & substrate-binding residues (3): 33; 65; 98

Post-translational modifications (2): 78, 78

Mutagenesis-validated functional residues (1):

Position	Phenotype
111	causes formation of interchain disulfide bonds with cys-81 from another subunit.

Function

Pathways and Gene Ontology

Reactome pathways

10 pathways

ID	Pathway
R-HSA-202733	Cell surface interactions at the vascular wall
R-HSA-6798695	Neutrophil degranulation
R-HSA-8950505	Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation
R-HSA-109582	Hemostasis
R-HSA-1280215	Cytokine Signaling in Immune system
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System
R-HSA-447115	Interleukin-12 family signaling
R-HSA-449147	Signaling by Interleukins
R-HSA-9020591	Interleukin-12 signaling

MSigDB gene sets: 564 (showing top): GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_REGULATION_OF_LEUKOCYTE_PROLIFERATION, GOBP_INTRINSIC_APOPTOTIC_SIGNALING_PATHWAY_IN_RESPONSE_TO_DNA_DAMAGE_BY_P53_CLASS_MEDIATOR, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_REGULATION_OF_ICOSANOID_SECRETION, SHIPP_DLBCL_VS_FOLLICULAR_LYMPHOMA_UP, GOBP_B_CELL_HOMEOSTASIS, GOBP_MYELOID_LEUKOCYTE_MIGRATION, HARRIS_HYPOXIA, GOBP_CELL_CHEMOTAXIS, GOBP_NEGATIVE_REGULATION_OF_INTRINSIC_APOPTOTIC_SIGNALING_PATHWAY_BY_P53_CLASS_MEDIATOR, GOBP_REGULATION_OF_PROSTAGLANDIN_SECRETION, GOBP_REGULATION_OF_PHOSPHORYLATION, GOBP_REGULATION_OF_ORGANIC_ACID_TRANSPORT, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM

GO Biological Process (36): prostaglandin biosynthetic process (GO:0001516), positive regulation of cytokine production (GO:0001819), negative regulation of mature B cell apoptotic process (GO:0002906), inflammatory response (GO:0006954), cell surface receptor signaling pathway (GO:0007166), positive regulation of cell population proliferation (GO:0008284), negative regulation of gene expression (GO:0010629), negative regulation of macrophage chemotaxis (GO:0010760), carboxylic acid metabolic process (GO:0019752), DNA damage response, signal transduction by p53 class mediator (GO:0030330), negative regulation of cell migration (GO:0030336), positive regulation of B cell proliferation (GO:0030890), positive regulation of lipopolysaccharide-mediated signaling pathway (GO:0031666), positive regulation of tumor necrosis factor production (GO:0032760), negative regulation of myeloid cell apoptotic process (GO:0033033), positive regulation of phosphorylation (GO:0042327), regulation of macrophage activation (GO:0043030), negative regulation of apoptotic process (GO:0043066), negative regulation of DNA damage response, signal transduction by p53 class mediator (GO:0043518), innate immune response (GO:0045087), positive regulation of fibroblast proliferation (GO:0048146), negative regulation of protein metabolic process (GO:0051248), obsolete positive regulation of prostaglandin secretion involved in immune response (GO:0061078), positive regulation of myeloid leukocyte cytokine production involved in immune response (GO:0061081), protein homotrimerization (GO:0070207), positive regulation of ERK1 and ERK2 cascade (GO:0070374), positive regulation of arachidonate secretion (GO:0090238), cellular senescence (GO:0090398), positive regulation of cAMP/PKA signal transduction (GO:0141163), negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator (GO:1902166), positive regulation of chemokine (C-X-C motif) ligand 2 production (GO:2000343), negative regulation of cellular senescence (GO:2000773), immune system process (GO:0002376), regulation of cell population proliferation (GO:0042127), positive chemotaxis (GO:0050918), regulation of cellular response to stress (GO:0080135)

GO Molecular Function (9): protease binding (GO:0002020), dopachrome isomerase activity (GO:0004167), cytokine activity (GO:0005125), cytokine receptor binding (GO:0005126), chemoattractant activity (GO:0042056), identical protein binding (GO:0042802), phenylpyruvate tautomerase activity (GO:0050178), protein binding (GO:0005515), isomerase activity (GO:0016853)

GO Cellular Component (11): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886), cell surface (GO:0009986), vesicle (GO:0031982), secretory granule lumen (GO:0034774), extracellular exosome (GO:0070062), ficolin-1-rich granule lumen (GO:1904813)

Reactome top-level categories

Rollup of top-7 pathways:

Category	Pathways
Immune System	2
Hemostasis	1
Innate Immune System	1
Interleukin-12 signaling	1
Signaling by Interleukins	1
Cytokine Signaling in Immune system	1
Interleukin-12 family signaling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
receptor ligand activity	2
prostaglandin metabolic process	1
prostanoid biosynthetic process	1
cytokine production	1
regulation of cytokine production	1
positive regulation of gene expression	1
positive regulation of multicellular organismal process	1
mature B cell apoptotic process	1
negative regulation of B cell apoptotic process	1
regulation of mature B cell apoptotic process	1
defense response	1
signal transduction	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
gene expression	1
regulation of gene expression	1
negative regulation of macromolecule biosynthetic process	1
negative regulation of leukocyte chemotaxis	1
regulation of macrophage chemotaxis	1
macrophage chemotaxis	1
negative regulation of macrophage migration	1
oxoacid metabolic process	1
signal transduction in response to DNA damage	1
signal transduction by p53 class mediator	1
cell migration	1
regulation of cell migration	1
negative regulation of cell motility	1
regulation of B cell proliferation	1
B cell proliferation	1
positive regulation of lymphocyte proliferation	1
positive regulation of B cell activation	1
positive regulation of response to biotic stimulus	1
positive regulation of signal transduction	1
lipopolysaccharide-mediated signaling pathway	1
regulation of lipopolysaccharide-mediated signaling pathway	1
positive regulation of response to external stimulus	1
tumor necrosis factor production	1
regulation of tumor necrosis factor production	1

Protein interactions and networks

STRING

2644 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MIF	CD74	P04233	998
MIF	CXCR2	P25025	991
MIF	CXCR4	P30991	991
MIF	COPS5	Q92905	940
MIF	CD44	P16070	862
MIF	CCL2	P13500	837
MIF	KRT7	P08729	759
MIF	CCL5	P13501	755
MIF	CXCL12	P48061	738
MIF	ACKR3	P25106	716
MIF	IL6	P05231	708
MIF	IL1B	P01584	670
MIF	IL17A	Q16552	670
MIF	TNF	P01375	657
MIF	CXCL8	P10145	645

IntAct

111 interactions, top by confidence:

A	B	Type	Score
MIF	MIF	psi-mi:“MI:0915”(physical association)	0.830
MIF	MIF	psi-mi:“MI:0407”(direct interaction)	0.830
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
NTAQ1	MIF	psi-mi:“MI:0915”(physical association)	0.670
MIF	NTAQ1	psi-mi:“MI:0915”(physical association)	0.670
MIF	EGFR	psi-mi:“MI:0915”(physical association)	0.590
COPS5	MIF	psi-mi:“MI:0915”(physical association)	0.590
MIF	COPS5	psi-mi:“MI:0915”(physical association)	0.590
MIF	COPS5	psi-mi:“MI:0407”(direct interaction)	0.590
MIF	BCL2L11	psi-mi:“MI:0915”(physical association)	0.580
BCL2L11	MIF	psi-mi:“MI:0915”(physical association)	0.580
GCD7	MIF	psi-mi:“MI:0915”(physical association)	0.560
MIF	HTRA1	psi-mi:“MI:0915”(physical association)	0.530
MIF	HTRA1	psi-mi:“MI:0407”(direct interaction)	0.530
CFTR	PLEKHG3	psi-mi:“MI:0914”(association)	0.480

BioGRID (355): MIF (Two-hybrid), WDYHV1 (Two-hybrid), MIF (Affinity Capture-MS), GORASP2 (Two-hybrid), MIF (Co-fractionation), MIF (Co-fractionation), MIF (Co-fractionation), MIF (Co-fractionation), MIF (Co-fractionation), MIF (Co-fractionation), MIF (Co-fractionation), MIF (Co-fractionation), MIF (Co-fractionation), MIF (Co-fractionation), MIF (Co-fractionation)

ESM2 similar proteins: A3QK15, F6V515, O46560, O55052, O88958, P14174, P29401, P30904, P32929, P34884, P36959, P40142, P50137, P80177, P80928, P82197, Q02960, Q0II59, Q0II68, Q1ZZU7, Q259G4, Q2KHU0, Q3T186, Q3ZBV9, Q4R549, Q5R4C1, Q5R8T8, Q5ZJ01, Q5ZLG0, Q60HG7, Q64422, Q6DCC5, Q6DEY3, Q6DN04, Q6P8M1, Q6PA43, Q6UWP2, Q71R50, Q7XPW5, Q7ZV22

Diamond homologs: A5PK65, A6NHG4, O35215, O55052, P14174, P30046, P80177, P80254, P80928, P81529, P91850, Q1ZZU7, Q28J83, Q4R549, Q5ZMG0, Q640C5, Q68FI3, Q6DN04, A9JSE7, P30904, P34884, Q02960, Q18785, O44786, P81748, Q76BK2, P90835

SIGNOR signaling

7 interactions.

A	Effect	B	Mechanism
MIF	up-regulates	CD74	binding
MIF	“down-regulates quantity by repression”	HBB	“transcriptional regulation”
MIF	“down-regulates quantity by repression”	HBA1	“transcriptional regulation”
MIF	“up-regulates activity”	CD74	binding
MIF	“up-regulates activity”	CXCR2	binding
MIF	“up-regulates activity”	CXCR4	binding
MIF	“down-regulates quantity by destabilization”	SOD1	relocalization

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 84 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Macroautophagy	7	13.0×	4e-04

GO biological processes:

GO term	Partners	Fold	FDR
mitophagy	6	26.1×	3e-05
autophagosome maturation	5	24.1×	4e-04
autophagosome assembly	7	21.6×	1e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

34 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	23
Likely benign	4
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

755 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:23895098:T:C	F114L	0.994
22:23895100:C:A	F114L	0.994
22:23895100:C:G	F114L	0.994
22:23894836:C:A	A58E	0.990
22:23894843:C:G	C60W	0.990
22:23894853:A:C	S64R	0.989
22:23894855:C:A	S64R	0.989
22:23894855:C:G	S64R	0.989
22:23894892:A:C	S77R	0.989
22:23894894:C:A	S77R	0.989
22:23894894:C:G	S77R	0.989
22:23894491:T:A	V6E	0.988
22:23894573:G:C	K33N	0.988
22:23894573:G:T	K33N	0.988
22:23894501:C:A	N9K	0.987
22:23894501:C:G	N9K	0.987
22:23895081:G:A	G108D	0.987
22:23894841:T:C	C60R	0.985
22:23894944:G:T	R94M	0.984
22:23894834:C:G	C57W	0.983
22:23894811:T:C	F50L	0.982
22:23894813:C:A	F50L	0.982
22:23894813:C:G	F50L	0.982
22:23894860:G:T	G66V	0.982
22:23895078:T:A	V107E	0.982
22:23895080:G:C	G108R	0.982
22:23895099:T:G	F114C	0.982
22:23894479:C:A	P2Q	0.981
22:23894571:A:G	K33E	0.981
22:23895040:G:C	R94S	0.979

dbSNP variants (sampled 300 via entrez): RS1002019906 (22:23892795 T>C), RS1002472066 (22:23895714 T>A,C), RS1002754971 (22:23895533 C>A,T), RS1002990502 (22:23894523 G>A,C,T), RS1003021375 (22:23894386 G>A), RS1003902382 (22:23893085 T>A), RS1004935039 (22:23894342 G>A,C), RS1006348019 (22:23895145 C>G,T), RS1006350782 (22:23893249 C>A,T), RS1006419656 (22:23893096 A>C,G), RS1006804948 (22:23893112 T>C,G), RS1008737878 (22:23893859 G>A,C), RS1008810167 (22:23893441 A>G), RS1009522178 (22:23894228 G>A), RS1009883182 (22:23893807 G>A)

Disease associations

OMIM: gene MIM:153620 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
cystic fibrosis	Supportive	Autosomal recessive
juvenile idiopathic arthritis	Limited	Autosomal dominant

Mondo (2): cystic fibrosis (MONDO:0009061), juvenile idiopathic arthritis (MONDO:0011429)

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST001277_19	Liver enzyme levels (gamma-glutamyl transferase)	2.000000e-09
GCST004423_17	Macrophage Migration Inhibitory Factor levels	5.000000e-10
GCST006585_945	Blood protein levels	8.000000e-26
GCST90011898_167	Alanine aminotransferase levels	2.000000e-09
GCST90011900_16	Serum alkaline phosphatase levels	8.000000e-17

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004532	serum gamma-glutamyl transferase measurement
EFO:0004533	alkaline phosphatase measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D001171	Arthritis, Juvenile	C05.550.114.122; C05.799.056; C17.300.775.049; C20.111.198
D003550	Cystic Fibrosis	C06.689.202; C08.381.187; C16.320.190; C16.614.213

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL2085 (SINGLE PROTEIN), CHEMBL2111430 (PROTEIN-PROTEIN INTERACTION), CHEMBL6193804 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

10 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 275,498 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1201319	METARAMINOL	4	3,794
CHEMBL19449	IBUDILAST	4	7,461
CHEMBL496	HEXACHLOROPHENE	4	26,164
CHEMBL90	HISTAMINE	4	169,677
CHEMBL2107455	IGURATIMOD	3	1,446
CHEMBL48802	SULFORAPHANE	3	7,981
CHEMBL51085	EBSELEN	3	13,237
CHEMBL1627201	L-SULFORAPHANE	2	48
CHEMBL6246	ELLAGIC ACID	2	23,148
CHEMBL233248	ALLYL ISOTHIOCYANATE	1	22,542

PharmGKB: 1 entry (VIP=true, CPIC=false)

Binding affinities (BindingDB)

38 measured of 57 human assays (58 total across all organisms); most potent 38 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
3-[2-[1-(3-fluoro-4-hydroxyphenyl)triazol-4-yl]quinolin-5-yl]oxybenzoic acid	KI	23 nM	US-10336721: Biaryltriazole inhibitors of macrophage migration inhibitory factor
3-[2-[1-(3-fluoro-4-hydroxyphenyl)triazol-4-yl]quinolin-6-yl]oxypropyl formate	KI	34 nM	US-10336721: Biaryltriazole inhibitors of macrophage migration inhibitory factor
3-[2-[1-(3-fluoro-4-hydroxyphenyl)triazol-4-yl]quinolin-7-yl]oxypropyl formate	KI	43 nM	US-10336721: Biaryltriazole inhibitors of macrophage migration inhibitory factor
2-[2-[1-(3-fluoro-4-hydroxyphenyl)triazol-4-yl]quinolin-6-yl]oxyethoxymethyl formate	KI	45 nM	US-10336721: Biaryltriazole inhibitors of macrophage migration inhibitory factor
2-fluoro-4-[4-[5-[3-(2-methoxyethoxy)phenoxy]quinolin-2-yl]triazol-1-yl]phenol	KI	82 nM	US-10336721: Biaryltriazole inhibitors of macrophage migration inhibitory factor
HEXACHLOROPHENE	IC50	98.3 nM
4-[2-[1-(3-fluoro-4-hydroxyphenyl)triazol-4-yl]quinolin-5-yl]oxybenzoic acid	KI	110 nM	US-10336721: Biaryltriazole inhibitors of macrophage migration inhibitory factor
[3-[2-[1-(3-fluoro-4-hydroxyphenyl)triazol-4-yl]quinolin-8-yl]oxyphenyl] formate	KI	112 nM	US-10336721: Biaryltriazole inhibitors of macrophage migration inhibitory factor
2-fluoro-4-[4-[5-[3-[2-(2-morpholin-4-ylethoxy)ethoxy]phenoxy]quinolin-2-yl]triazol-1-yl]phenol	KI	128 nM	US-10336721: Biaryltriazole inhibitors of macrophage migration inhibitory factor
2-fluoro-4-[4-[6-[2-(2-morpholin-4-ylethoxy)ethoxy]quinolin-2-yl]triazol-1-yl]phenol	KI	150 nM	US-10336721: Biaryltriazole inhibitors of macrophage migration inhibitory factor
2-fluoro-4-[4-[7-[2-(2-morpholin-4-ylethoxy)ethoxy]quinolin-2-yl]triazol-1-yl]phenol	KI	290 nM	US-10336721: Biaryltriazole inhibitors of macrophage migration inhibitory factor
[4-[2-[1-(3-fluoro-4-hydroxyphenyl)triazol-4-yl]quinolin-8-yl]oxyphenyl] formate	KI	296 nM	US-10336721: Biaryltriazole inhibitors of macrophage migration inhibitory factor
2-[2-(2-ethynylquinolin-6-yl)oxyethoxy]-N-tritylethanamine	KI	330 nM	US-10336721: Biaryltriazole inhibitors of macrophage migration inhibitory factor
4-[4-[5-[4-(2-methoxyethoxy)phenoxy]quinolin-2-yl]triazol-1-yl]phenol	KI	360 nM	US-10336721: Biaryltriazole inhibitors of macrophage migration inhibitory factor
4-[4-(5-phenoxyquinolin-2-yl)triazol-1-yl]phenol	KI	370 nM	US-10336721: Biaryltriazole inhibitors of macrophage migration inhibitory factor
4-[4-[6-[2-(2-morpholin-4-ylethoxy)ethoxy]quinolin-2-yl]triazol-1-yl]phenol	KI	410 nM	US-10336721: Biaryltriazole inhibitors of macrophage migration inhibitory factor
4-[4-[5-[3-(aminomethyl)phenoxy]quinolin-2-yl]triazol-1-yl]-2-fluorophenol	KI	568 nM	US-10336721: Biaryltriazole inhibitors of macrophage migration inhibitory factor
4-[4-[6-(2-methoxyethoxy)quinolin-2-yl]triazol-1-yl]phenol	KI	570 nM	US-10336721: Biaryltriazole inhibitors of macrophage migration inhibitory factor
4-(4-quinolin-2-yltriazol-1-yl)phenol	KI	590 nM	US-10336721: Biaryltriazole inhibitors of macrophage migration inhibitory factor
4-[4-[6-[2-(2-aminoethoxy)ethoxy]quinolin-2-yl]triazol-1-yl]phenol	KI	770 nM	US-10336721: Biaryltriazole inhibitors of macrophage migration inhibitory factor
4-[4-[7-[2-(2-morpholin-4-ylethoxy)ethoxy]quinolin-2-yl]triazol-1-yl]phenol	KI	850 nM	US-10336721: Biaryltriazole inhibitors of macrophage migration inhibitory factor
4-[4-(1,8-naphthyridin-2-yl)triazol-1-yl]phenol	KI	1480 nM	US-10336721: Biaryltriazole inhibitors of macrophage migration inhibitory factor
4-[4-[6-(3-morpholin-4-ylpropoxy)quinolin-2-yl]triazol-1-yl]phenol	KI	1950 nM	US-10336721: Biaryltriazole inhibitors of macrophage migration inhibitory factor
[2-[1-(3-fluoro-4-hydroxyphenyl)triazol-4-yl]quinolin-7-yl]oxymethyl formate	KI	2240 nM	US-10336721: Biaryltriazole inhibitors of macrophage migration inhibitory factor
4-[4-(4-methylquinolin-2-yl)triazol-1-yl]phenol	KI	2300 nM	US-10336721: Biaryltriazole inhibitors of macrophage migration inhibitory factor
4-[4-[6-(2-methoxyethoxy)quinazolin-2-yl]triazol-1-yl]phenol	KI	2350 nM	US-10336721: Biaryltriazole inhibitors of macrophage migration inhibitory factor
2-(2-adamantyloxy)-5-(1H-pyrazol-4-yl)benzoic acid	KI	2600 nM	US-11999723: Pyrazole-containing macrophage migration inhibitory factor inhibitors
4-[4-(8-phenoxyquinolin-2-yl)triazol-1-yl]phenol	KI	2950 nM	US-10336721: Biaryltriazole inhibitors of macrophage migration inhibitory factor
4-[4-[3-methyl-6-(3-morpholin-4-ylpropoxy)quinolin-2-yl]triazol-1-yl]phenol	KI	3120 nM	US-10336721: Biaryltriazole inhibitors of macrophage migration inhibitory factor
2,6-difluoro-4-[4-[6-[2-(2-morpholin-4-ylethoxy)ethoxy]quinolin-2-yl]triazol-1-yl]phenol	KI	3750 nM	US-10336721: Biaryltriazole inhibitors of macrophage migration inhibitory factor
[3-[2-[1-(3,4-difluorophenyl)triazol-4-yl]quinolin-5-yl]oxyphenyl] formate	KI	4930 nM	US-10336721: Biaryltriazole inhibitors of macrophage migration inhibitory factor
4-[4-(3-methylquinolin-2-yl)triazol-1-yl]phenol	KI	7300 nM	US-10336721: Biaryltriazole inhibitors of macrophage migration inhibitory factor
2-[1-(4-fluorophenyl)triazol-4-yl]-6-(2-methoxyethoxy)quinoline	KI	8900 nM	US-10336721: Biaryltriazole inhibitors of macrophage migration inhibitory factor
(5,5-dimethyl-3-oxidanylidene-cyclohexen-1-yl) 4-chloranylbenzoate	IC50	15500 nM
US8618147, ISO-1	KI	21000 nM	US-10336721: Biaryltriazole inhibitors of macrophage migration inhibitory factor
4-[2-[2-[2-[1-(4-fluorophenyl)triazol-4-yl]quinolin-6-yl]oxyethoxy]ethyl]morpholine	KI	29600 nM	US-10336721: Biaryltriazole inhibitors of macrophage migration inhibitory factor
2-[1-(4-fluorophenyl)triazol-4-yl]-8-methoxyquinoline	KI	56000 nM	US-10336721: Biaryltriazole inhibitors of macrophage migration inhibitory factor
2-[1-(4-fluorophenyl)triazol-4-yl]-8-(2-methoxyethoxy)quinoline	KI	64000 nM	US-10336721: Biaryltriazole inhibitors of macrophage migration inhibitory factor

ChEMBL bioactivities

449 potent at pChembl≥5 of 698 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.02	Ki	0.96	nM	CHEMBL4763772
8.72	Kd	1.918	nM	CHEMBL3752910
8.65	ED50	2.239	nM	CHEMBL3752910
8.12	IC50	7.5	nM	CHEMBL1256233
8.00	IC50	10	nM	CHEMBL1255975
7.85	Ki	14	nM	CHEMBL3917143
7.80	Kd	16	nM	CHEMBL4779696
7.64	Ki	23	nM	CHEMBL3917143
7.62	Ki	24	nM	CHEMBL3918231
7.47	Ki	34	nM	CHEMBL5999957
7.47	Ki	34	nM	CHEMBL3927658
7.43	Ki	37	nM	CHEMBL3890541
7.42	Ki	38	nM	CHEMBL13486
7.42	IC50	38	nM	CHEMBL13486
7.42	IC50	38	nM	CHEMBL1089054
7.41	Ki	39	nM	CHEMBL3927658
7.37	Ki	43	nM	CHEMBL5936436
7.37	Ki	43	nM	CHEMBL5784808
7.35	Ki	45	nM	CHEMBL5987981
7.35	Ki	45	nM	CHEMBL3890541
7.32	Ki	48	nM	CHEMBL3899123
7.30	IC50	50	nM	CHEMBL1253380
7.29	Ki	51	nM	CHEMBL5591863
7.28	Ki	52	nM	CHEMBL3797437
7.26	Ki	55	nM	CHEMBL5589606
7.26	Ki	55	nM	CHEMBL5594739
7.25	Ki	56	nM	CHEMBL4208992
7.24	Ki	57	nM	CHEMBL3917143
7.20	Kd	63	nM	CHEMBL3927658
7.19	Ki	65	nM	CHEMBL5590917
7.17	Ki	67	nM	CHEMBL4208079
7.16	Kd	68.6	nM	BTZO-1
7.15	Ki	71	nM	CHEMBL4779696
7.15	Ki	71	nM	CHEMBL5592539
7.15	IC50	71	nM	BTZO-1
7.13	Ki	74	nM	CHEMBL3957289
7.12	Ki	75	nM	CHEMBL4160035
7.10	IC50	80	nM	CHEMBL1253382
7.10	IC50	80	nM	CHEMBL1256304
7.09	Ki	82	nM	CHEMBL3918231
7.07	Ki	86	nM	CHEMBL5583909
7.06	Kd	88	nM	BTZO-1
7.05	Ki	90	nM	CHEMBL4170679
7.05	IC50	90	nM	CHEMBL1255976
7.03	Kd	94	nM	CHEMBL4170679
7.00	Ki	100	nM	CHEMBL4094592
7.00	Ki	100	nM	CHEMBL4794376
6.96	IC50	110	nM	CHEMBL3797982
6.96	Kd	111	nM	CHEMBL4160035
6.96	Kd	110	nM	CHEMBL4794376

PubChem BioAssay actives

383 with measured affinity, of 1231 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148750: Binding affinity to human MIF incubated for 45 mins by Kinobead based pull down assay	kd	0.0019	uM
3-[(3-hydroxyphenyl)methyl]-6-methyl-1,3-benzoxazol-2-one	516521: Inhibition of human recombinant MIF tautomerase	ic50	0.0075	uM
3-[(3-hydroxyphenyl)methyl]-5-methyl-1,3-benzoxazol-2-one	516521: Inhibition of human recombinant MIF tautomerase	ic50	0.0100	uM
3-[2-[1-(3-fluoro-4-hydroxyphenyl)triazol-4-yl]quinolin-5-yl]oxybenzoic acid	1331426: Inhibition of recombinant human MIF tautomerase activity expressed in Escherichia coli assessed as borate-enol complex formation using 4-hydroxyphenyl pyruvic acid as substrate preincubated for 20 mins followed by substrate addition measured for 175 sec by fluorescence based analysis	ki	0.0140	uM
4-[4-(7-hydroxy-2-oxochromen-3-yl)phenyl]benzoic acid	1697392: Binding affinity to C-terminal His-tagged recombinant human MIF expressed in Escherichia coli BL21 (DE3) at 200 nM by fluorescence assay	kd	0.0160	uM
2-fluoro-4-[4-[5-[3-(2-methoxyethoxy)phenoxy]quinolin-2-yl]triazol-1-yl]phenol	1331426: Inhibition of recombinant human MIF tautomerase activity expressed in Escherichia coli assessed as borate-enol complex formation using 4-hydroxyphenyl pyruvic acid as substrate preincubated for 20 mins followed by substrate addition measured for 175 sec by fluorescence based analysis	ki	0.0240	uM
2-[2-[2-[1-(3-fluoro-4-hydroxyphenyl)triazol-4-yl]quinolin-6-yl]oxyethoxy]acetic acid	1331426: Inhibition of recombinant human MIF tautomerase activity expressed in Escherichia coli assessed as borate-enol complex formation using 4-hydroxyphenyl pyruvic acid as substrate preincubated for 20 mins followed by substrate addition measured for 175 sec by fluorescence based analysis	ki	0.0370	uM
3-(3,4-dihydroxyphenyl)chromen-4-one	464889: Inhibition of MIF	ic50	0.0380	uM
3-(3,4-dihydroxyphenyl)-7-hydroxychromen-4-one	106681: Inhibitory activity against tautomerase macrophage migration inhibitory factor (MIF)	ki	0.0380	uM
4-[2-[1-(3-fluoro-4-hydroxyphenyl)triazol-4-yl]quinolin-6-yl]oxybutanoic acid	1331426: Inhibition of recombinant human MIF tautomerase activity expressed in Escherichia coli assessed as borate-enol complex formation using 4-hydroxyphenyl pyruvic acid as substrate preincubated for 20 mins followed by substrate addition measured for 175 sec by fluorescence based analysis	ki	0.0390	uM
2-[2-[1-(3-fluoro-4-hydroxyphenyl)triazol-4-yl]quinolin-6-yl]oxyacetic acid	1331426: Inhibition of recombinant human MIF tautomerase activity expressed in Escherichia coli assessed as borate-enol complex formation using 4-hydroxyphenyl pyruvic acid as substrate preincubated for 20 mins followed by substrate addition measured for 175 sec by fluorescence based analysis	ki	0.0480	uM
(6-phenylpyridazin-3-yl) thiophene-2-carboxylate	513953: Inhibition of human MIF tautomerase activity	ic50	0.0500	uM
7-[[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]amino]-N-[4-(7-hydroxy-2-oxo-4H-1,3-benzoxazin-3-yl)phenyl]heptanamide	2115088: Binding affinity to MIF in human A549 cells assessed as inhibition constant	ki	0.0510	uM
6-[morpholin-4-yl-[4-(trifluoromethyl)phenyl]methyl]-1,3-benzodioxol-5-ol	1298946: Covalent inhibition of recombinant human MIF tautomerase activity expressed in Escherichia coli using 4-hydroxyphenyl pyruvic acid as substrate assessed as borate-enol complex formation incubated for 30 mins followed substrate addition by microplate reader	ki	0.0520	uM
N-[4-(7-hydroxy-2-oxo-4H-1,3-benzoxazin-3-yl)phenyl]-8-[[2-(1-methyl-2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]amino]octanamide	2115088: Binding affinity to MIF in human A549 cells assessed as inhibition constant	ki	0.0550	uM
4-[[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]amino]-N-[4-(7-hydroxy-2-oxo-4H-1,3-benzoxazin-3-yl)phenyl]butanamide	2115088: Binding affinity to MIF in human A549 cells assessed as inhibition constant	ki	0.0550	uM
N-[5-[(3’,6’-dihydroxy-3-oxospiro[2-benzofuran-1,9’-xanthene]-5-yl)carbamothioylamino]pentyl]-4-[2-[1-(3-fluoro-4-hydroxyphenyl)triazol-4-yl]quinolin-6-yl]oxybutanamide	1384612: Inhibition of recombinant human MIF expressed in Escherichia coli using HPP as substrate preincubated for 30 mins followed by substrate addition	ki	0.0560	uM
10-[[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]amino]-N-[4-(7-hydroxy-2-oxo-4H-1,3-benzoxazin-3-yl)phenyl]decanamide	2115088: Binding affinity to MIF in human A549 cells assessed as inhibition constant	ki	0.0650	uM
5-(5-fluoro-1H-pyrazol-4-yl)-2-[3-[4-(3-morpholin-4-ylpropoxy)phenyl]phenoxy]benzoic acid	1384624: Inhibition of recombinant human MIF expressed in Escherichia coli using HPP as substrate preincubated for 20 mins followed by substrate addition measured for 175 secs	ki	0.0670	uM
8-[[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]amino]-N-[4-(7-hydroxy-2-oxo-4H-1,3-benzoxazin-3-yl)phenyl]octanamide	2115088: Binding affinity to MIF in human A549 cells assessed as inhibition constant	ki	0.0710	uM
2-pyridin-2-yl-1,3-benzothiazin-4-one	2194556: Inhibition of [3H]-BTZO-1 binding to recombinant human C-terminal His-tagged MIF expressed in Escherichia coli BL21 (DE3) measured after 3 hrs by SPA	ic50	0.0710	uM
2-fluoro-4-[4-[6-[2-(2-morpholin-4-ylethoxy)ethoxy]quinolin-2-yl]triazol-1-yl]phenol	1331426: Inhibition of recombinant human MIF tautomerase activity expressed in Escherichia coli assessed as borate-enol complex formation using 4-hydroxyphenyl pyruvic acid as substrate preincubated for 20 mins followed by substrate addition measured for 175 sec by fluorescence based analysis	ki	0.0740	uM
2-[1-(3-fluoro-4-hydroxyphenyl)triazol-4-yl]-7-methyl-1,7-naphthyridin-8-one	1504968: Inhibition of recombinant human MIF tautomerase activity expressed in Escherichia coli assessed as decrease in formation of borate complex of enol product using 4-HPP as substrate incubated for 30 mins followed by substrate addition measured for 175 secs	ki	0.0750	uM
butyl 1,3-benzoxazol-2-ylsulfanylformate	513953: Inhibition of human MIF tautomerase activity	ic50	0.0800	uM
3-[(3-hydroxyphenyl)methyl]-5-methoxy-1,3-benzoxazol-2-one	516522: Inhibition of human recombinant biotinylated MIF/CD74 interaction after 30 mins	ic50	0.0800	uM
5-[[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]amino]-N-[4-(7-hydroxy-2-oxo-4H-1,3-benzoxazin-3-yl)phenyl]pentanamide	2115088: Binding affinity to MIF in human A549 cells assessed as inhibition constant	ki	0.0860	uM
2-[2-[1-(3-fluoro-4-hydroxyphenyl)triazol-4-yl]-8-oxo-1,7-naphthyridin-7-yl]acetic acid	1504968: Inhibition of recombinant human MIF tautomerase activity expressed in Escherichia coli assessed as decrease in formation of borate complex of enol product using 4-HPP as substrate incubated for 30 mins followed by substrate addition measured for 175 secs	ki	0.0900	uM
3-[(2-methoxyphenyl)methyl]-5-methyl-1,3-benzoxazol-2-one	516522: Inhibition of human recombinant biotinylated MIF/CD74 interaction after 30 mins	ic50	0.0900	uM
3-[(3-hydroxyphenyl)methyl]-5-methyl-1,3-benzoxazole-2-thione	1490032: Inhibition of recombinant human MIF tautomerase activity using 4-HPP as substrate preincubated for 15 mins followed by substrate addition measured after 360 secs	ki	0.1000	uM
3-(3,4-dimethoxyphenyl)-7-hydroxy-4H-1,3-benzoxazin-2-one	1697390: Inhibition of C-terminal His-tagged recombinant human MIF expressed in Escherichia coli BL21 (DE3) using 4-HPP as substrate preincubated for 10 mins followed by substrate addition by UV absorption spectrum analysis	ki	0.1000	uM
4-imidazo[1,2-a]pyridin-3-ylbenzene-1,2-diol	1298951: Inhibition of MIF (unknown origin) tautomerase activity using dopachrome as substrate	ic50	0.1100	uM
3-[(3-methoxyphenyl)methyl]-5,6-dimethyl-1,3-benzoxazol-2-one	516522: Inhibition of human recombinant biotinylated MIF/CD74 interaction after 30 mins	ic50	0.1150	uM
2-fluoro-4-[(E)-[(4-methoxyphenyl)hydrazinylidene]methyl]phenol	281494: Inhibition of MIF tautomerase activity by spectrophotometric assay	ic50	0.1300	uM
4-[4-[6-[2-(2-aminoethoxy)ethoxy]quinolin-2-yl]triazol-1-yl]-2-fluorophenol;2,2,2-trifluoroacetic acid	1331426: Inhibition of recombinant human MIF tautomerase activity expressed in Escherichia coli assessed as borate-enol complex formation using 4-hydroxyphenyl pyruvic acid as substrate preincubated for 20 mins followed by substrate addition measured for 175 sec by fluorescence based analysis	ki	0.1440	uM
4-[4-[6-[2-(2-methoxyethoxy)ethoxy]quinolin-2-yl]triazol-1-yl]phenol	1331426: Inhibition of recombinant human MIF tautomerase activity expressed in Escherichia coli assessed as borate-enol complex formation using 4-hydroxyphenyl pyruvic acid as substrate preincubated for 20 mins followed by substrate addition measured for 175 sec by fluorescence based analysis	ki	0.1470	uM
4-[4-[6-[2-(2-morpholin-4-ylethoxy)ethoxy]quinolin-2-yl]triazol-1-yl]phenol	1504968: Inhibition of recombinant human MIF tautomerase activity expressed in Escherichia coli assessed as decrease in formation of borate complex of enol product using 4-HPP as substrate incubated for 30 mins followed by substrate addition measured for 175 secs	ki	0.1600	uM
N-(2-aminophenyl)-4-[[2-[4-(7-hydroxy-2-oxo-4H-1,3-benzoxazin-3-yl)phenyl]acetyl]amino]benzamide	2136674: Inhibition of MIF (unknown origin) tautomerase activity incubated for 10 mins by microplate reader analysis	ic50	0.1800	uM
(4,8-dioxo-3-oxa-9-azatetracyclo[7.6.1.02,7.012,16]hexadeca-1(15),2(7),5,12(16),13-pentaen-6-yl) 4-fluorobenzoate	1799792: Tautomerase Enzyme Assay from Article 10.1074/jbc.M110.113951: “Identification and characterization of novel classes of macrophage migration inhibitory factor (MIF) inhibitors with distinct mechanisms of action.”	ki	0.1900	uM
2-[2-[1-(4-hydroxyphenyl)triazol-4-yl]quinolin-6-yl]oxyacetic acid	1331426: Inhibition of recombinant human MIF tautomerase activity expressed in Escherichia coli assessed as borate-enol complex formation using 4-hydroxyphenyl pyruvic acid as substrate preincubated for 20 mins followed by substrate addition measured for 175 sec by fluorescence based analysis	ki	0.2000	uM
4-[4-[6-(2-methoxyethoxy)quinolin-2-yl]triazol-1-yl]phenol	1331426: Inhibition of recombinant human MIF tautomerase activity expressed in Escherichia coli assessed as borate-enol complex formation using 4-hydroxyphenyl pyruvic acid as substrate preincubated for 20 mins followed by substrate addition measured for 175 sec by fluorescence based analysis	ki	0.2000	uM
2-[1-(4-hydroxyphenyl)triazol-4-yl]-7-methyl-1,7-naphthyridin-8-one	1504970: Inhibition of recombinant human MIF tautomerase activity assessed as decrease in formation of borate complex of enol product using 4-HPP as substrate incubated for 20 mins by fluorescence polarization method	kd	0.2130	uM
2-chloro-4-[(E)-[(4-methoxyphenyl)hydrazinylidene]methyl]phenol	281494: Inhibition of MIF tautomerase activity by spectrophotometric assay	ic50	0.2200	uM
(2-oxo-1-phenylquinolin-4-yl) benzoate	1799792: Tautomerase Enzyme Assay from Article 10.1074/jbc.M110.113951: “Identification and characterization of novel classes of macrophage migration inhibitory factor (MIF) inhibitors with distinct mechanisms of action.”	ki	0.2300	uM
4-(4-quinolin-2-yltriazol-1-yl)phenol	1331426: Inhibition of recombinant human MIF tautomerase activity expressed in Escherichia coli assessed as borate-enol complex formation using 4-hydroxyphenyl pyruvic acid as substrate preincubated for 20 mins followed by substrate addition measured for 175 sec by fluorescence based analysis	ki	0.2300	uM
3-isothiocyanatoprop-1-ene	1198788: Inhibition of macrophage migration inhibitory factor tautomerase activity in human Jurkat T cells using L-dopachrome methyl ester as substrate incubated for 30 mins prior to substrate addition measured for 2 mins by spectrophotometric analysis	ic50	0.2500	uM
4-[4-[6-(2-aminoethoxy)quinolin-2-yl]triazol-1-yl]phenol;2,2,2-trifluoroacetic acid	1331426: Inhibition of recombinant human MIF tautomerase activity expressed in Escherichia coli assessed as borate-enol complex formation using 4-hydroxyphenyl pyruvic acid as substrate preincubated for 20 mins followed by substrate addition measured for 175 sec by fluorescence based analysis	ki	0.2600	uM
4-[4-[6-(oxan-2-ylmethoxy)quinolin-2-yl]triazol-1-yl]phenol	1331426: Inhibition of recombinant human MIF tautomerase activity expressed in Escherichia coli assessed as borate-enol complex formation using 4-hydroxyphenyl pyruvic acid as substrate preincubated for 20 mins followed by substrate addition measured for 175 sec by fluorescence based analysis	ki	0.2700	uM
7-hydroxy-3-[4-(2-oxochromen-3-yl)-1,3-thiazol-2-yl]chromen-2-one	106681: Inhibitory activity against tautomerase macrophage migration inhibitory factor (MIF)	ki	0.2800	uM
1-phenyl-3-(1,3,4-thiadiazol-2-yl)thiourea	513953: Inhibition of human MIF tautomerase activity	ic50	0.3000	uM
3-[(4-fluoro-3-hydroxyphenyl)methyl]-5-(trifluoromethyl)-1,3-benzoxazole-2-thione	1490032: Inhibition of recombinant human MIF tautomerase activity using 4-HPP as substrate preincubated for 15 mins followed by substrate addition measured after 360 secs	ki	0.3000	uM

CTD chemical–gene interactions

94 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, decreases expression, increases expression, increases secretion, decreases reaction (+1 more)	6
Particulate Matter	increases abundance, affects expression, increases reaction, increases expression, decreases expression	4
Arsenic Trioxide	affects binding, decreases reaction, decreases expression	3
sodium arsenite	increases abundance, increases expression	2
rottlerin	decreases reaction, increases expression	2
monomethylarsonous acid	increases expression	2
Air Pollutants	decreases expression, increases abundance, increases expression	2
Arsenic	affects expression, increases abundance, increases expression	2
Vehicle Emissions	affects expression, increases reaction, increases expression	2
Lipopolysaccharides	decreases expression, decreases reaction, increases expression, affects cotreatment	2
Mustard Gas	decreases expression, increases secretion	2
Oxygen	increases expression	2
Tetradecanoylphorbol Acetate	affects binding, decreases reaction, affects cotreatment, decreases expression	2
aristolochic acid I	increases expression	1
ginger extract	increases expression, decreases reaction, increases abundance	1
tungsten carbide	affects cotreatment, increases expression	1
tetrachloroisophthalonitrile	decreases expression	1
sodium arsenate	decreases expression	1
titanium dioxide	affects binding, increases secretion	1
trichostatin A	increases expression	1
arsenite	affects binding, increases reaction	1
zinc chloride	decreases expression	1
cobaltous chloride	increases expression	1
2-bromopalmitate	decreases reaction, increases abundance, increases palmitoylation	1
1,10-phenanthroline	increases expression	1
butylidenephthalide	increases expression	1
cobalt sulfate	increases expression	1
cadmium acetate	increases expression	1
4-aminophenylarsenoxide	affects binding, decreases reaction	1
artemisic acid	decreases expression	1

ChEMBL screening assays

205 unique, capped per target: 202 binding, 3 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1010227	Binding	Activity of human recombinant MIF tautomerase by LB plot in presence of 3 uM ZINC00806272	Discovery of human macrophage migration inhibitory factor (MIF)-CD74 antagonists via virtual screening. — J Med Chem
CHEMBL1291797	Functional	Agonist activity at human MIF tautomerase using 4-hydroxyphenylpyruvate as substrate at 100 uM	Receptor agonists of macrophage migration inhibitory factor. — Bioorg Med Chem Lett

Cellosaurus cell lines

4 cell lines: 3 cancer cell line, 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_D2BY	Abcam HCT 116 MIF KO	Cancer cell line	Male
CVCL_SY37	HAP1 MIF (-) 1	Cancer cell line	Male
CVCL_T386	Psi-CRIP-MFGhMIF	Transformed cell line	Male
CVCL_XQ55	HAP1 MIF (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

300 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00157690	PHASE4	COMPLETED	Study of Alendronate to Prevent and Treat Osteoporosis in Cystic Fibrosis Patients
NCT00208078	PHASE4	TERMINATED	Effect of Non-Invasive Ventilation in Cystic Fibrosis Patient With Chronic Respiratory Failure.
NCT00244270	PHASE4	COMPLETED	Cystic Fibrosis and Totally Implantable Vascular Access Devices
NCT00333385	PHASE4	TERMINATED	Continuous Versus Short Infusions of Ceftazidime in Cystic Fibrosis
NCT00411736	PHASE4	COMPLETED	Scandinavian Cystic Fibrosis Azithromycin Study
NCT00418470	PHASE4	TERMINATED	Prolonging the Duration of Peripheral Venous Catheters in Cystic Fibrosis People
NCT00431964	PHASE4	COMPLETED	Effect of Azithromycin on Lung Function in 6-18 Year-olds With Cystic Fibrosis (CF) Not Infected With P. Aeruginosa
NCT00434278	PHASE4	TERMINATED	A Trial of Pulmozyme Withdrawal on Exercise Tolerance in Cystic Fibrosis Subjects With Severe Lung Disease (TOPIC)
NCT00483769	PHASE4	COMPLETED	One Year Glargine Treatment in CFRD Children and Adolescents
NCT00528190	PHASE4	COMPLETED	Treatment of Aspergillus Fumigatus (a Fungal Infection) in Patients With Cystic Fibrosis
NCT00557089	PHASE4	COMPLETED	The Effect of rhDNase on Ventilation Inhomogeneity in Patients With Cystic Fibrosis
NCT00572975	PHASE4	COMPLETED	Malabsorption Blood Test:Toward a Novel Approach to Quantify Steatorrhea
NCT00680316	PHASE4	TERMINATED	A Study of Pulmozyme® (Dornase Alpha) in 3- to 5-Year-Old Patients With Cystic Fibrosis
NCT00685035	PHASE4	COMPLETED	Comparison of Airway Clearance Therapy in Cystic Fibrosis Using the Same VEST Therapy Device But With Different Settings
NCT00744250	PHASE4	TERMINATED	Intraduodenal Aspiration Study to Assess the Bioavailability of Oral Pancrecarb® Compared to Placebo Control
NCT00787917	PHASE4	TERMINATED	An Exploratory Study to Assess Multiple Doses of Omalizumab in Patients With Cystic Fibrosis Complicated by Acute Bronchopulmonary Aspergillosis (ABPA)
NCT00843817	PHASE4	COMPLETED	RhDNase and Biodistribution of PMN Serine Proteases in Cystic Fibrosis Sputum
NCT00890370	PHASE4	COMPLETED	Should Any One Airway Clearance Technique be Recommended for People With Cystic Fibrosis?
NCT00996424	PHASE4	TERMINATED	The Effect of Inhaled N-Acetylcysteine Compared to Normal Saline on Sputum Rheology and Lung Function
NCT01044719	PHASE4	UNKNOWN	Duration of Antibiotics in Infective Exacerbations of Cystic Fibrosis
NCT01100606	PHASE4	COMPLETED	A Study to Evaluate the Mode of Administration and Safety of EUR-1008 (APT-1008) in Infants 1 to 12 Months of Age
NCT01131507	PHASE4	COMPLETED	PR-018: An Open-Label, Safety Extension of Study PR-011
NCT01207245	PHASE4	COMPLETED	Circadian Rhythm In Tobramycin Elimination In Cystic Fibrosis
NCT01323101	PHASE4	COMPLETED	Doxycycline Effects on Inflammation in Cystic Fibrosis
NCT01327703	PHASE4	COMPLETED	Control of Steatorrhea in Participants With Cystic Fibrosis and Exocrine Pancreatic Insufficiency
NCT01377792	PHASE4	COMPLETED	Study of Long-term Treatment With Hypertonic Saline in Patients With Cystic Fibrosis
NCT01400750	PHASE4	COMPLETED	Comparison of 2 Treatment Regimens for Eradication of P Aeruginosa Infection in Children With Cystic Fibrosis
NCT01429259	PHASE4	COMPLETED	Population Pharmacokinetics of Prolonged Infusion Meropenem in Cystic Fibrosis (CF) Children
NCT01608555	PHASE4	COMPLETED	Tobramycin 300 mg Once-a-day (o.d.) Aerosol in Adults With Cystic Fibrosis
NCT01667094	PHASE4	UNKNOWN	A Study Comparing Continuous Infusion Antibiotics to Standard Treatment for Lung Infections in Cystic Fibrosis
NCT01694069	PHASE4	TERMINATED	Continuous Infusion Piperacillin-tazobactam for the Treatment of Cystic Fibrosis
NCT01702415	PHASE4	WITHDRAWN	Zoledronic Acid in Cystic Fibrosis
NCT01712334	PHASE4	COMPLETED	A Study of the Comparable Efficacy and Safety of Pulmozyme (Dornase Alfa) Delivered by the eRapid Nebulizer System in Patients With Cystic Fibrosis
NCT01737983	PHASE4	COMPLETED	Effect of Lactobacillus Reuteri in Cystic Fibrosis
NCT01844778	PHASE4	COMPLETED	Ease of Use and Microbial Contamination of Tobramycin Inhalation Powder (TIP) Versus Nebulised Tobramycin Inhalation Solution (TIS) and Nebulised Colistimethate (COLI)
NCT01880346	PHASE4	COMPLETED	Comparison of Absorption of Vitamin D in Cystic Fibrosis
NCT01882400	PHASE4	COMPLETED	Assessment of Response to Treatment of Osteoporosis With Oral Bisphosphonates in Patients With Muscular Dystrophy
NCT01937325	PHASE4	UNKNOWN	CPET in CF Patients With One G551D Mutation Taking VX770
NCT02015663	PHASE4	TERMINATED	Tobramycin Inhalation Powder (TIP) Administered Once Daily Continuously Versus TIP Administered BID in 28 Day on / 28 Day Off Cycles
NCT02048592	PHASE4	UNKNOWN	Impact of Immunonutrition on the Patients With Cystic Fibrosis