CD74

Summary

CD74 (CD74 molecule, HGNC:1697) is a protein-coding gene on chromosome 5q33.1, encoding HLA class II histocompatibility antigen gamma chain (P04233). 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….

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.

Source: NCBI Gene 972 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 63 total
• Druggable target: yes — 4 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001025159

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1697
Approved symbol	CD74
Name	CD74 molecule
Location	5q33.1
Locus type	gene with protein product
Status	Approved
Aliases	CLIP
Ensembl gene	ENSG00000019582
Ensembl biotype	protein_coding
OMIM	142790
Entrez	972

Gene structure

Transcript identifiers

Ensembl transcripts: 26 — 17 protein_coding, 6 retained_intron, 3 nonsense_mediated_decay

ENST00000009530, ENST00000353334, ENST00000377795, ENST00000517752, ENST00000517791, ENST00000518797, ENST00000522153, ENST00000522246, ENST00000523208, ENST00000523813, ENST00000523836, ENST00000524315, ENST00000881211, ENST00000881212, ENST00000881213, ENST00000881214, ENST00000881215, ENST00000881216, ENST00000881217, ENST00000881218, ENST00000881219, ENST00000881220, ENST00000881221, ENST00000881222, ENST00000881223, ENST00000949574

RefSeq mRNA: 5 — MANE Select: NM_001025159 NM_001025158, NM_001025159, NM_001364083, NM_001364084, NM_004355

CCDS: CCDS34276, CCDS47308, CCDS47309

Canonical transcript exons

ENST00000009530 — 9 exons

Exon	Start	End
ENSE00000841201	150404680	150404767
ENSE00002129676	150401639	150402250
ENSE00003494107	150402563	150402625
ENSE00003554133	150403121	150403312
ENSE00003569785	150406259	150406321
ENSE00003578099	150405085	150405180
ENSE00003671108	150407152	150407324
ENSE00003680132	150406881	150406960
ENSE00003929500	150412625	150412910

Expression profiles

Bgee: expression breadth ubiquitous, 300 present calls, max score 99.93.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 895.3092 / max 39437.5779, expressed in 1300 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
64243	893.8111	1299
64230	0.4835	225
64229	0.4656	220
64231	0.3828	191
64228	0.1662	96

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	99.93	gold quality
leukocyte	CL:0000738	99.93	gold quality
mononuclear cell	CL:0000842	99.93	gold quality
granulocyte	CL:0000094	99.92	gold quality
vermiform appendix	UBERON:0001154	99.92	gold quality
spleen	UBERON:0002106	99.92	gold quality
lymph node	UBERON:0000029	99.90	gold quality
gall bladder	UBERON:0002110	99.89	gold quality
right lung	UBERON:0002167	99.89	gold quality
upper lobe of lung	UBERON:0008948	99.88	gold quality
lower lobe of lung	UBERON:0008949	99.88	gold quality
upper lobe of left lung	UBERON:0008952	99.88	gold quality
ileal mucosa	UBERON:0000331	99.87	gold quality
caecum	UBERON:0001153	99.86	gold quality
jejunal mucosa	UBERON:0000399	99.82	gold quality
right coronary artery	UBERON:0001625	99.79	gold quality
metanephros cortex	UBERON:0010533	99.77	gold quality
ileum	UBERON:0002116	99.76	silver quality
small intestine Peyer’s patch	UBERON:0003454	99.76	gold quality
peripheral nervous system	UBERON:0000010	99.74	gold quality
nerve	UBERON:0001021	99.74	gold quality
tibial nerve	UBERON:0001323	99.74	gold quality
duodenum	UBERON:0002114	99.73	gold quality
right uterine tube	UBERON:0001302	99.72	gold quality
trigeminal ganglion	UBERON:0001675	99.72	gold quality
rectum	UBERON:0001052	99.71	gold quality
adult organism	UBERON:0007023	99.71	gold quality
small intestine	UBERON:0002108	99.70	gold quality
nasal cavity epithelium	UBERON:0005384	99.69	gold quality
bone marrow cell	CL:0002092	99.67	gold quality

Single-cell (SCXA)

Detected in 91 experiment(s), a significant marker in 75.

Experiment	Marker?	Max mean expression
E-CURD-120	yes	77636.53
E-MTAB-8207	yes	49418.44
E-MTAB-8142	yes	45074.94
E-HCAD-15	yes	37451.17
E-CURD-122	yes	33955.64
E-CURD-79	yes	33342.70
E-CURD-89	yes	33230.30
E-MTAB-6678	yes	33205.64
E-MTAB-10042	yes	32506.53
E-CURD-55	yes	29654.84
E-MTAB-6701	yes	29546.18
E-MTAB-9906	yes	28277.82
E-HCAD-24	yes	28209.99
E-GEOD-134144	yes	26741.09
E-GEOD-84465	yes	25925.26

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
CCL2	Activation

Upstream regulators (CollecTRI, top): AHR, AP1, AR, ASCL3, ATF1, ATF2, ATF6B, CEBPA, CEBPB, CEBPD, CEBPG, CREB1, CREB3, CREB3L2, CTCF, DLX5, DNMT3B, E2F1, E2F5, EGR1, ESR1, ESRRA, ETS1, EZH2, FOS, FOXP3, FUBP1, GATA1, GATA2, GLI3, GTF2I, HAND1, HBP1, HIF1A, HIVEP1, HNF4A, HNF4G, HOXB1, HR, ID2

miRNA regulators (miRDB)

40 targeting CD74, 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-4283	100.00	66.42	2097
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-8082	99.95	67.27	1170
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-576-5P	99.84	70.46	2582
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-320A-3P	99.77	69.73	2107
HSA-MIR-320B	99.77	69.73	2107
HSA-MIR-320C	99.77	69.73	2107
HSA-MIR-320D	99.77	69.73	2107
HSA-MIR-4429	99.77	69.62	2111
HSA-MIR-6763-5P	99.76	64.68	1767
HSA-MIR-6745	99.74	65.33	1321
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-24-3P	99.59	69.97	1934
HSA-MIR-4489	99.50	65.56	785
HSA-MIR-4498	99.47	67.42	2360
HSA-MIR-363-5P	99.46	64.51	1015
HSA-MIR-5001-5P	99.05	66.76	1972
HSA-MIR-6846-5P	98.81	65.86	1121
HSA-MIR-6848-5P	98.81	65.49	1126
HSA-MIR-4700-5P	98.63	67.43	1915
HSA-MIR-6776-5P	98.54	67.43	1304
HSA-MIR-541-5P	98.24	67.77	1181
HSA-MIR-6778-5P	98.19	66.59	1239
HSA-MIR-4443	98.02	66.25	1928
HSA-MIR-5087	98.01	69.09	965

Literature-anchored findings (GeneRIF, showing 40)

• Coordinate expression of Ii/CD74 and MHC class II antigens was identified in most fetal tissues (PMID:11897800)
• its cytoplasmic tail regulates endosome fusion and morphology (PMID:12058053)
• 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)
• CD74 represents a novel and promising target for treatment of multiple myeloma. (PMID:15475450)
• Downregulation of HLA-DG is associated with early intrahepatic recurrence of hepatocellular carcinoma (PMID:15688398)
• H.pylori binds to CD74 on gastric epithelial cells & stimulates interleukin-8 production; binding of H. pylori to CD74 presents a novel insight into an interaction of H. pylori with the gastric epithelium leading to upregulation of inflammatory responses (PMID:15845476)
• CD74 is expressed on the surface of gastric cells, and Helicobacter pylori can use this receptor as a point of attachment to gastric epithelial cells, which lead to IL-8 production. (PMID:15972644)
• We demonstrate that CD74-ICD translocates to the nucleus and induces the activation of the p65 member of NF-kappaB in this compartment. (PMID:16107560)
• H. pylori urease B binds to CD74 on gastric epithelial cells and initiates NF-kappaB activation and interleukin-8 production. (PMID:16428763)
• Residues favoring AP3 binding introduced into a protein that is transported via the PM such as the invariant chain can re-route such protein into direct sorting to late endosomal/lysosomal structures. (PMID:16542748)
• link the disruption of transmembrane helix interactions to previously reported losses of invariant chain function (PMID:16618111)
• Ii can also be detected in the class I MHC peptide loading complex. (PMID:16678175)
• Prostate cancer cell lines had increased MIF gene expression and protein levels; cell growth and invasion required MIF activated signal transduction pathways that were not necessary for growth or viability of androgen-dependent prostate cells (PMID:17142775)
• analysis of interaction between a secreted hookworm Macrophage Migration Inhibitory Factor (MIF) and the human MIF receptor CD74 (PMID:17567581)
• The cytoplasmic region of Vpu was found to interact with the 30-amino-acid cytoplasmic tail of CD74. (PMID:17959659)
• These findings identify Ii and lipid rafts as key regulators of CD1a organization on the surface of immature DCs and of its immunological function as Ag-presenting molecule (PMID:18178838)
• This study provides several lines of evidence to demonstrate the complex interactions of major histocompatibility (MHC) class II invariant chain (Ii) with neonatal Fc receptor for IgG (FcRn). (PMID:18684948)
• The observations indicate that CD74 and the AGTR1 become associated in the early biosynthetic pathway, and that CD74 is a negative regulator of AGTR1 expression. (PMID:18719072)
• Expression of Ii by breast tumor cells may quantitatively and qualitatively alter the presentation of antigens on those cells. (PMID:18828016)
• CD74 acts as a receptor for MIF in podocytes and may play a role in the pathogenesis of diabetic nephropathy (PMID:18842989)
• Increased expression of CD74 can enhance kidney cancer cell proliferation, anchorage independence, invasion, and tumor cell-induced human umbilical vein endothelial cell migration in vitro as well as tumor growth and metastasis in vivo. (PMID:18941249)
• We found intense CD74 expression by immunohistochemistry in 57 of 70 human specimens of non-small cell lung cancer (PMID:19131591)
• CD74 levels are increased in plaques and PBMC from patients with carotid stenosis and are associated with intima-medial thickness in subjects free from clinical cardiovascular diseases. (PMID:19423618)
• at late stages of Vaccinia virus infection, reductions in cellular invariant chain levels coupled with changes in lysosomal protease activity, contribute in part to defects in class II presentation (PMID:19592662)
• Data show that CD74 forms functional complexes with CXCR4 that mediate MIF-specific signaling. (PMID:19665027)
• CD74 activation inhibits in a dose-dependent manner up to 90% of in vitro migration of MSCs, with consistent effects observed among multiple MSC donor preparations. (PMID:20198449)
• CD74 and its target gene transcripts (TA)p63 and very late antigen (VLA)-4 facilitate migration of chronic lymphocytic leukemia cells back to the bone marrow (BM), where they interact with the supportive BM environment that rescues them from apoptosis. (PMID:20357260)
• CD74 is expressed in a subset of high grade gliomas and may contribute to temozolomide resistance (PMID:20443131)
• Overexpression of MIF and CD74 in the placenta may up-regulate the CRP level in maternal blood, which may be involved in the pathogenesis of preeclampsia. (PMID:20646540)
• Simultaneous inhibition of TAP and Ii completely down-modulated the expression of HLA-DR, demonstrating that together these molecules form the key mediators of HLA class II antigen presentation in leukemic blasts. (PMID:20820776)
• These findings are supportive of a role for CD74 in the development and maintenance of gastrointestinal neoplasia. (PMID:21228923)
• Studies indicate that in chronic lymphocytic leukemia cells, binding of MIF to CD74 induces nuclear factor-kappaB activation and up-regulation of TAp63 expression, resulting in the secretion of interleukin 8, which in turn promotes cell survival. (PMID:21417823)
• Synergistic TLR agonist stimulation in combination with IFN-alpha and IFN-gamma was the best method for regulating CD38 and CD74 expression (PMID:21423200)
• CatG was found to be dispensable in invariant chain conversion within intact primary human B cells and dendritic cells. (PMID:21543057)
• These results suggest that cancer cells in the PNI areas could acquired a growth advantage that could be triggered by the growth factor receptors EGFR and CD74. (PMID:21748758)
• overexpression of MIF and CD74 in cervical squamous cell carcinomas and its precancerous lesions and upregulation of VEGF secretion in cervical cancer cells indicate MIF and CD74 may play critical roles in pathogenesis and angiogenesis of cervical cancer (PMID:21792010)
• This is the first study reporting that Ii chain up-regulation occurs on naturally infected antigen presenting cells obtained directly from HIV(+) subjects. (PMID:21945129)
• HIV-1 glycoprotein 41 ectodomain induces activation of the CD74 protein-mediated extracellular signal-regulated kinase/mitogen-activated protein kinase pathway to enhance viral infection. (PMID:22039051)
• Data show that FTY720-mediated disruption of the autophagic-lysosomal pathway led to increased levels of CD74, a potential therapeutic target in mantle cell lymphoma (MCL) that is degraded in the lysosomal compartment. (PMID:22042694)
• Class I homozygosity at 5’VNTR is a significant risk factor of T1DM and acts independently from HLA haplotype in determining the actual risk of diabetes in children. (PMID:22069105)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	cd74a	ENSDARG00000009087
danio_rerio	cd74b	ENSDARG00000036628
mus_musculus	Cd74	ENSMUSG00000024610
rattus_norvegicus	Cd74	ENSRNOG00000018735

Protein

Protein identifiers

HLA class II histocompatibility antigen gamma chain — P04233 (reviewed: P04233)

Alternative names: HLA-DR antigens-associated invariant chain, Ia antigen-associated invariant chain

All UniProt accessions (4): P04233, E7EQJ3, H0YBZ2, H0YBZ8

UniProt curated annotations — full annotation on 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. Binds to the peptide-binding site of MHC class II alpha/beta heterodimers forming an alpha-beta-CLIP complex, thereby preventing the loading of antigenic peptides to the MHC class II complex until its release by HLA-DM in the endosome. Stabilizes the conformation of mature CTSL by binding to its active site and serving as a chaperone to help maintain a pool of mature enzyme in endocytic compartments and extracellular space of antigen-presenting cells (APCs). Has antiviral activity by stymieing the endosomal entry of Ebola virus and coronaviruses, including SARS-CoV-2. Disrupts cathepsin-mediated Ebola virus glycoprotein processing, which prevents viral fusion and entry. This antiviral activity is specific to p41 isoform.

Subunit / interactions. Homotrimer. In the endoplasmic reticulum (ER) it forms a heterononameric MHC II-Ii complex: 3 MHC class II molecules (heterodimers of an alpha and a beta subunit) bind to the CD74 homotrimer (also known as invariant chain or HLA class II histocompatibility antigen gamma chain). In the endosomal/lysosomal system, the CD74 component undergoes sequential degradation by various proteases, including CTSS and CTSL, leaving a small fragment termed CLIP (class-II-associated invariant chain peptide) attached to the MHC class II molecule (alpha-beta-CLIP complex). This processed complex interacts with HLA_DM and HLA_DO heterodimers in order to release CLIP and facilitate the binding of antigenic peptides to the MHC class II molecules. Interacts with CD44; this complex is essential for the MIF-induced signaling cascade that results in B cell survival. Interacts with the mature form of CTSL; the complex survive in neutral pH environment.

Subcellular location. Cell membrane. Endoplasmic reticulum membrane. Golgi apparatus. trans-Golgi network. Endosome. Lysosome. Secreted Late endosome.

Tissue specificity. Detected in urine (at protein level). In B cells, represents 10% of total CD74 expression. In B cells, represents 70% of total CD74 expression.

Post-translational modifications. O-glycosylated with core 1 or possibly core 8 glycans. Contains chondroitin sulfate.

Disease relevance. A chromosomal aberration involving CD74 is found in a non-small cell lung tumor. Results in the formation of a CD74-ROS1 chimeric protein.

Domain organisation. Antiviral activity requires delivery of the thyroglobulin domain to the endosomal membrane.

Isoforms (5)

UniProt ID	Names	Canonical?
P04233-1	p45, Long	yes
P04233-2	p35, Short
P04233-3	3
P04233-4	p41
P04233-5	p33

RefSeq proteins (5): NP_001020329, NP_001020330, NP_001351012, NP_001351013, NP_004346 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000716	Thyroglobulin_1	Domain
IPR011988	MHC_II-assoc_invariant_trimer	Domain
IPR015386	MHC_II-assoc_invar/CLIP_MHC-bd	Domain
IPR022339	MHC_II-assoc_invar_chain	Family
IPR036613	MHCII_invariant_trimer_sf	Homologous_superfamily
IPR036857	Thyroglobulin_1_sf	Homologous_superfamily
IPR043530	CD74_antigen	Family
IPR052001	MHC-II_Gamma/Thyroglobulin	Family

Pfam: PF00086, PF08831, PF09307

UniProt features (38 total): glycosylation site 6, helix 5, splice variant 4, strand 4, disulfide bond 3, region of interest 3, topological domain 2, mutagenesis site 2, chain 1, peptide 1, site 1, modified residue 1, sequence conflict 1, transmembrane region 1, turn 1, domain 1, compositionally biased region 1

Structure

Experimental structures (PDB)

24 structures.

PDB	Method	Resolution (Å)
4X5W	X-RAY DIFFRACTION	1.34
7YX9	X-RAY DIFFRACTION	1.76
3PDO	X-RAY DIFFRACTION	1.95
1ICF	X-RAY DIFFRACTION	2
7YXB	X-RAY DIFFRACTION	2.1
7Z0Q	X-RAY DIFFRACTION	2.1
1MUJ	X-RAY DIFFRACTION	2.15
5KSV	X-RAY DIFFRACTION	2.19
4AEN	X-RAY DIFFRACTION	2.2
8VSJ	ELECTRON MICROSCOPY	2.28
3QXD	X-RAY DIFFRACTION	2.3
4AH2	X-RAY DIFFRACTION	2.36
9EJH	X-RAY DIFFRACTION	2.45
3PGC	X-RAY DIFFRACTION	2.66
3QXA	X-RAY DIFFRACTION	2.71
3PGD	X-RAY DIFFRACTION	2.72
5KSU	X-RAY DIFFRACTION	2.73
1A6A	X-RAY DIFFRACTION	2.75
8VRW	ELECTRON MICROSCOPY	3.03
8VSP	ELECTRON MICROSCOPY	3.12
9CYM	X-RAY DIFFRACTION	3.84
9CYL	X-RAY DIFFRACTION	4.66
1IIE	SOLUTION NMR
1L3H	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P04233-F1	70.49	0.26

Antibody-complex structures (SAbDab): 1 — 8VSJ

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): 208–209 (breakpoint for translocation to form a cd74-ros1 fusion protein)

Post-translational modifications (1): 25

Disulfide bonds (3): 213–232, 243–250, 252–271

Glycosylation sites (6): 130, 136, 203, 256, 281, 282

Mutagenesis-validated functional residues (2):

Position	Phenotype
225–226	decreases inhibition of ebola virus infection.
225–226	no effect on inhibition of ebola virus infection.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-202733	Cell surface interactions at the vascular wall
R-HSA-2132295	MHC class II antigen presentation
R-HSA-9925563	Developmental Lineage of Pancreatic Ductal Cells

MSigDB gene sets: 665 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, GOBP_REGULATION_OF_CELL_ACTIVATION, RNGTGGGC_UNKNOWN, CREL_01, GOBP_REGULATION_OF_LEUKOCYTE_PROLIFERATION, GOBP_ANTIGEN_PROCESSING_AND_PRESENTATION_OF_PEPTIDE_OR_POLYSACCHARIDE_ANTIGEN_VIA_MHC_CLASS_II, GOBP_INTRINSIC_APOPTOTIC_SIGNALING_PATHWAY_IN_RESPONSE_TO_DNA_DAMAGE_BY_P53_CLASS_MEDIATOR, KOBAYASHI_EGFR_SIGNALING_24HR_UP, GOBP_NEGATIVE_REGULATION_OF_CELL_DEVELOPMENT, GOBP_B_CELL_HOMEOSTASIS, MCLACHLAN_DENTAL_CARIES_UP, GOBP_POSITIVE_REGULATION_OF_HEMOPOIESIS, GOBP_MYELOID_LEUKOCYTE_MIGRATION, GOBP_CELL_CHEMOTAXIS, GOBP_NEGATIVE_REGULATION_OF_INTRINSIC_APOPTOTIC_SIGNALING_PATHWAY_BY_P53_CLASS_MEDIATOR

GO Biological Process (52): prostaglandin biosynthetic process (GO:0001516), positive regulation of cytokine-mediated signaling pathway (GO:0001961), T cell activation involved in immune response (GO:0002286), positive regulation of dendritic cell antigen processing and presentation (GO:0002606), negative regulation of peptide secretion (GO:0002792), positive regulation of type 2 immune response (GO:0002830), negative regulation of mature B cell apoptotic process (GO:0002906), intracellular protein transport (GO:0006886), positive regulation of gene expression (GO:0010628), immunoglobulin mediated immune response (GO:0016064), antigen processing and presentation (GO:0019882), antigen processing and presentation of endogenous antigen (GO:0019883), antigen processing and presentation of exogenous peptide antigen via MHC class II (GO:0019886), negative regulation of cell migration (GO:0030336), positive regulation of B cell proliferation (GO:0030890), positive regulation of prostaglandin biosynthetic process (GO:0031394), positive regulation of chemokine production (GO:0032722), positive regulation of interleukin-6 production (GO:0032755), positive regulation of interleukin-8 production (GO:0032757), response to type II interferon (GO:0034341), macrophage migration inhibitory factor signaling pathway (GO:0035691), regulation of macrophage activation (GO:0043030), negative regulation of apoptotic process (GO:0043066), positive regulation of canonical NF-kappaB signal transduction (GO:0043123), negative regulation of DNA damage response, signal transduction by p53 class mediator (GO:0043518), T cell selection (GO:0045058), positive thymic T cell selection (GO:0045059), negative thymic T cell selection (GO:0045060), negative regulation of T cell differentiation (GO:0045581), positive regulation of T cell differentiation (GO:0045582), positive regulation of monocyte differentiation (GO:0045657), host-mediated suppression of symbiont invasion (GO:0046597), positive regulation of fibroblast proliferation (GO:0048146), protein stabilization (GO:0050821), positive regulation of macrophage cytokine production (GO:0060907), protein-containing complex assembly (GO:0065003), protein trimerization (GO:0070206), positive regulation of ERK1 and ERK2 cascade (GO:0070374), positive regulation of neutrophil chemotaxis (GO:0090023), negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator (GO:1902166)

GO Molecular Function (12): amyloid-beta binding (GO:0001540), cytokine receptor activity (GO:0004896), cytokine binding (GO:0019955), MHC class II protein complex binding (GO:0023026), macrophage migration inhibitory factor binding (GO:0035718), MHC class II protein binding (GO:0042289), CD4 receptor binding (GO:0042609), MHC class II protein binding, via antigen binding groove (GO:0042658), identical protein binding (GO:0042802), protein folding chaperone (GO:0044183), nitric-oxide synthase binding (GO:0050998), protein binding (GO:0005515)

GO Cellular Component (29): Golgi membrane (GO:0000139), nucleus (GO:0005634), cytoplasm (GO:0005737), lysosome (GO:0005764), lysosomal membrane (GO:0005765), late endosome (GO:0005770), multivesicular body (GO:0005771), vacuole (GO:0005773), plasma membrane (GO:0005886), external side of plasma membrane (GO:0009897), cell surface (GO:0009986), ER to Golgi transport vesicle membrane (GO:0012507), membrane (GO:0016020), transport vesicle membrane (GO:0030658), endocytic vesicle membrane (GO:0030666), clathrin-coated endocytic vesicle membrane (GO:0030669), trans-Golgi network membrane (GO:0032588), protein-containing complex (GO:0032991), macrophage migration inhibitory factor receptor complex (GO:0035692), NOS2-CD74 complex (GO:0035693), MHC class II protein complex (GO:0042613), lysosomal lumen (GO:0043202), extracellular exosome (GO:0070062), lumenal side of endoplasmic reticulum membrane (GO:0098553), extracellular region (GO:0005576), endosome (GO:0005768), endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), Golgi apparatus (GO:0005794)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Hemostasis	1
Adaptive Immune System	1
Developmental Cell Lineages of the Exocrine Pancreas	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
positive regulation of cytokine production	3
bounding membrane of organelle	3
cellular anatomical structure	3
cytokine-mediated signaling pathway	2
cytokine binding	2
protein binding	2
intracellular membrane-bounded organelle	2
cytoplasmic vesicle membrane	2
prostaglandin metabolic process	1
prostanoid biosynthetic process	1
regulation of cytokine-mediated signaling pathway	1
positive regulation of signal transduction	1
positive regulation of response to cytokine stimulus	1
lymphocyte activation involved in immune response	1
immune response	1
T cell activation	1
dendritic cell antigen processing and presentation	1
positive regulation of antigen processing and presentation	1
regulation of dendritic cell antigen processing and presentation	1
peptide secretion	1
regulation of peptide secretion	1
negative regulation of secretion	1
regulation of type 2 immune response	1
type 2 immune response	1
positive regulation of immune response	1
mature B cell apoptotic process	1
negative regulation of B cell apoptotic process	1
regulation of mature B cell apoptotic process	1
intracellular protein localization	1
protein transport	1
intracellular transport	1
gene expression	1
regulation of gene expression	1
positive regulation of macromolecule biosynthetic process	1
B cell mediated immunity	1
immune system process	1
antigen processing and presentation	1
antigen processing and presentation of exogenous peptide antigen	1
antigen processing and presentation of peptide antigen via MHC class II	1
cell migration	1

Protein interactions and networks

STRING

6539 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CD74	MIF	P14174	998
CD74	CD44	P16070	993
CD74	CXCR2	P25025	992
CD74	CXCR4	P30991	992
CD74	APP	P05067	985
CD74	DDT	P30046	965
CD74	ROS1	P08922	776
CD74	CTSS	P25774	764
CD74	HLA-DQB2	P05538	742
CD74	CIITA	P33076	733
CD74	HLA-DMA	P28067	720
CD74	HLA-DRB1	P01911	708
CD74	HLA-DQA2	P01906	683
CD74	SLC34A2	O95436	679
CD74	HLA-DRA	P01903	664

IntAct

114 interactions, top by confidence:

A	B	Type	Score
HLA-DQB1	HLA-DQA1	psi-mi:“MI:0915”(physical association)	0.860
HLA-DMA	HLA-DRA	psi-mi:“MI:0914”(association)	0.620
CD74	HLA-DRA	psi-mi:“MI:0914”(association)	0.560
CXCR4	CD74	psi-mi:“MI:0403”(colocalization)	0.560
CXCR4	CD74	psi-mi:“MI:0915”(physical association)	0.560
CD74	CXCR4	psi-mi:“MI:0915”(physical association)	0.560
CD74	HLA-DRA	psi-mi:“MI:0915”(physical association)	0.560
HADHA	CD74	psi-mi:“MI:0915”(physical association)	0.550
CD74	dnaK	psi-mi:“MI:0407”(direct interaction)	0.540
dnaK	HLA-DRB1	psi-mi:“MI:0915”(physical association)	0.540
dnaK	CD74	psi-mi:“MI:0915”(physical association)	0.540
hspa1a_hspa1b_human-1	CD74	psi-mi:“MI:0407”(direct interaction)	0.540
hspa1a_hspa1b_human-1	CD74	psi-mi:“MI:0915”(physical association)	0.540
HLA-DQA1	CD74	psi-mi:“MI:2364”(proximity)	0.540
HLA-DQA1	CD74	psi-mi:“MI:0915”(physical association)	0.540
CD74	PGRMC1	psi-mi:“MI:0914”(association)	0.530
CD74	CXCR2	psi-mi:“MI:0915”(physical association)	0.520

BioGRID (164): CD74 (Two-hybrid), CD74 (Biochemical Activity), CD74 (Affinity Capture-MS), COPG1 (Affinity Capture-MS), COPG2 (Affinity Capture-MS), HLA-DPB1 (Affinity Capture-MS), HLA-DQA1 (Co-localization), nef (Affinity Capture-Western), CD74 (Affinity Capture-MS), COPG1 (Affinity Capture-MS), COPG2 (Affinity Capture-MS), CD44 (FRET), MIF (Reconstituted Complex), MIF (Affinity Capture-Western), AKAP8 (Affinity Capture-MS)

ESM2 similar proteins: A2AM05, A2BDC9, A2VD12, A2VE10, A5D8S1, B1AJZ9, O00461, O75071, P04233, P04441, P07106, P10247, P24054, P70663, Q08D19, Q14515, Q32N32, Q4KLH6, Q4V9H3, Q5BJK8, Q5PQS2, Q5R5X4, Q5R6R3, Q5R8Y4, Q5R9L2, Q5T8D3, Q5TB80, Q5ZHQ6, Q5ZKQ5, Q5ZM60, Q640L3, Q6P2L7, Q6P4E1, Q6Y685, Q6ZQ06, Q70YC5, Q86TE4, Q8BG89, Q8BMK4, Q8BVV7

Diamond homologs: A0A1D0C023, B3F211, B5DFC9, P04233, P04441, P10247, P10493, P31226, P81439, P84032, Q08629, Q14112, Q62288, Q8BKV0, Q8BLY1, Q8CD91, Q92563, Q9ER58, Q9H3U7, Q9H4F8, A2ARV4, B3EWY9, B3NBB6, B4HVU2, B4PD96, F1RRV3, O08523, O08710, O42182, O73775, O75095, O75197, O75443, O75581, O77469, O88322, O88572, P01130, P01131, P01266

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
MIF	up-regulates	CD74	binding
CD74	up-regulates	CXCR4	binding
MIF	“up-regulates activity”	CD74	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 53 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
Interferon gamma signaling	6	37.6×	1e-06
MHC class II antigen presentation	5	22.3×	6e-05

GO biological processes:

GO term	Partners	Fold	FDR
peptide antigen assembly with MHC class II protein complex	6	274.8×	6e-12
antigen processing and presentation of exogenous peptide antigen via MHC class II	6	141.8×	3e-10
positive regulation of immune response	6	125.6×	4e-10
positive regulation of T cell activation	6	115.7×	5e-10
immune response	9	18.4×	2e-08
adaptive immune response	5	18.3×	2e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	32
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1116 predictions. Top by Δscore:

Variant	Effect	Δscore
5:150402623:ACTC:A	acceptor_loss	1.0000
5:150402624:CT:C	acceptor_gain	1.0000
5:150402624:CTCT:C	acceptor_loss	1.0000
5:150402625:TCTG:T	acceptor_loss	1.0000
5:150402626:C:CC	acceptor_gain	1.0000
5:150403120:CCA:C	donor_gain	1.0000
5:150403308:CAGTA:C	acceptor_gain	1.0000
5:150403309:AGTA:A	acceptor_gain	1.0000
5:150403310:GTA:G	acceptor_gain	1.0000
5:150403311:TA:T	acceptor_gain	1.0000
5:150403313:C:CC	acceptor_gain	1.0000
5:150403319:C:CT	acceptor_gain	1.0000
5:150403320:G:T	acceptor_gain	1.0000
5:150403327:A:C	acceptor_gain	1.0000
5:150405087:T:TA	donor_gain	1.0000
5:150405177:CATT:C	acceptor_gain	1.0000
5:150405179:TT:T	acceptor_gain	1.0000
5:150406254:CTCA:C	donor_loss	1.0000
5:150406255:TCA:T	donor_loss	1.0000
5:150406256:CACCT:C	donor_loss	1.0000
5:150406257:A:AC	donor_gain	1.0000
5:150406257:A:AT	donor_loss	1.0000
5:150406258:C:CC	donor_gain	1.0000
5:150406258:C:CG	donor_loss	1.0000
5:150406317:ATGGG:A	acceptor_gain	1.0000
5:150406318:TGGG:T	acceptor_gain	1.0000
5:150406319:GGG:G	acceptor_gain	1.0000
5:150406320:GG:G	acceptor_gain	1.0000
5:150406322:C:CC	acceptor_gain	1.0000
5:150406324:G:C	acceptor_gain	1.0000

AlphaMissense

1962 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:150403185:C:A	W251C	0.998
5:150403185:C:G	W251C	0.998
5:150403243:C:G	C232S	0.998
5:150403244:A:T	C232S	0.998
5:150403300:C:G	C213S	0.998
5:150403301:A:T	C213S	0.998
5:150403168:C:A	G257V	0.996
5:150403231:C:A	G236V	0.995
5:150403244:A:G	C232R	0.994
5:150403301:A:G	C213R	0.994
5:150407265:G:T	A62D	0.994
5:150403225:T:C	Y238C	0.993
5:150405088:C:A	W178C	0.993
5:150405088:C:G	W178C	0.993
5:150403169:C:A	G257C	0.992
5:150403183:C:G	C252S	0.992
5:150403184:A:T	C252S	0.992
5:150403210:C:G	C243S	0.992
5:150403211:A:T	C243S	0.992
5:150403299:G:C	C213W	0.992
5:150407262:C:T	G63D	0.992
5:150403226:A:C	Y238D	0.991
5:150403243:C:T	C232Y	0.991
5:150404739:A:G	L189P	0.991
5:150405116:A:G	L169P	0.991
5:150403242:G:C	C232W	0.990
5:150403184:A:G	C252R	0.988
5:150403243:C:A	C232F	0.988
5:150407256:G:T	A65D	0.988
5:150403212:C:A	Q242H	0.987

dbSNP variants (sampled 300 via entrez): RS1000084815 (5:150408399 G>A), RS1000442955 (5:150406816 T>G), RS1000519043 (5:150412000 T>C), RS1000794707 (5:150408768 T>C), RS1000860894 (5:150402894 G>A,C,T), RS1001160146 (5:150409083 C>A), RS1001806547 (5:150406037 CTGAGATTACAGGCA>C), RS1001886535 (5:150409961 C>G,T), RS1002087935 (5:150405426 A>G,T), RS1002191758 (5:150410680 A>T), RS1002520352 (5:150408778 G>A), RS1003167720 (5:150406590 G>C), RS1003593534 (5:150411214 T>C), RS1003717394 (5:150401720 G>A), RS1003917054 (5:150410013 G>A,C)

Disease associations

OMIM: gene MIM:142790 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST003264_240	Post bronchodilator FEV1/FVC ratio	4.000000e-06
GCST004131_47	Inflammatory bowel disease	3.000000e-15
GCST004132_24	Crohn’s disease	2.000000e-19

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004713	FEV/FVC ratio

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL2111430 (PROTEIN-PROTEIN INTERACTION), CHEMBL4680046 (CHIMERIC PROTEIN), CHEMBL4692 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

4 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 24,673 (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
CHEMBL3286830	LORLATINIB	4	3,598
CHEMBL3545311	BRIGATINIB	4	5,634
CHEMBL4298138	REPOTRECTINIB	4	1,038
CHEMBL601719	CRIZOTINIB	4	14,403

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

PharmGKB variants

2 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1560661	CD74		0.00	0
rs2748249	CD74		0.00	0

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: other protein — CD molecules

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
milatuzumab	Binding	9.3	pKd

ChEMBL bioactivities

46 potent at pChembl≥5 of 52 total, top 45 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.64	IC50	0.23	nM	LORLATINIB
9.52	IC50	0.3	nM	LORLATINIB
9.15	IC50	0.7	nM	REPOTRECTINIB
8.80	IC50	1.6	nM	CHEMBL6165880
8.41	IC50	3.9	nM	CRIZOTINIB
7.88	IC50	13.2	nM	BRIGATINIB
7.75	IC50	18	nM	BRIGATINIB
7.60	IC50	25	nM	CRIZOTINIB
7.10	IC50	80	nM	CHEMBL1256304
7.05	IC50	90	nM	CHEMBL1255976
6.94	IC50	115	nM	CHEMBL1257465
6.39	IC50	410	nM	CHEMBL201461
6.12	IC50	750	nM	CHEMBL408418
6.09	IC50	810	nM	CHEMBL206745
6.05	IC50	900	nM	CHEMBL377511
6.05	IC50	900	nM	CHEMBL1289631
6.03	IC50	930	nM	CHEMBL207003
6.02	IC50	950	nM	CHEMBL204525
6.01	IC50	980	nM	CHEMBL377684
5.96	IC50	1100	nM	CHEMBL205748
5.96	IC50	1100	nM	CHEMBL205919
5.92	IC50	1200	nM	CHEMBL1289632
5.89	IC50	1300	nM	CHEMBL203102
5.89	IC50	1300	nM	CHEMBL239179
5.89	IC50	1300	nM	CHEMBL414587
5.85	IC50	1400	nM	CHEMBL381369
5.85	IC50	1400	nM	CHEMBL208344
5.82	IC50	1500	nM	CHEMBL206035
5.82	IC50	1500	nM	CHEMBL523238
5.80	IC50	1600	nM	CHEMBL380361
5.80	IC50	1600	nM	CHEMBL383835
5.75	IC50	1800	nM	CHEMBL379769
5.75	IC50	1800	nM	CHEMBL406247
5.72	IC50	1900	nM	CHEMBL377683
5.70	IC50	2000	nM	CHEMBL208103
5.70	IC50	2000	nM	CHEMBL379351
5.60	IC50	2500	nM	CHEMBL498412
5.60	IC50	2500	nM	CHEMBL498410
5.58	IC50	2600	nM	CHEMBL380541
5.57	IC50	2700	nM	CHEMBL379770
5.46	IC50	3500	nM	CHEMBL1288977
5.40	IC50	4000	nM	CHEMBL496155
5.36	IC50	4400	nM	CHEMBL206067
5.16	IC50	7000	nM	CHEMBL1257355
5.10	IC50	8000	nM	CHEMBL496373

PubChem BioAssay actives

42 with measured affinity, of 130 total; 40 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
Lorlatinib	1680101: Inhibition of CD74-ROS1 (unknown origin) expressed in mouse BaF3 cells assessed as reduction in cell viability	ic50	0.0002	uM
Crizotinib	1680101: Inhibition of CD74-ROS1 (unknown origin) expressed in mouse BaF3 cells assessed as reduction in cell viability	ic50	0.0039	uM
Brigatinib	2183019: Inhibition of CD74-ROS1 (unknown origin) expressed in mouse BaF3 cells assessed as inhibition of ROS1-driven cell viability incubated for 72 hrs by CellTiter 96 aqueous one solution assay	ic50	0.0180	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
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-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
4-[1-[2-hydroxy-3-[5-methylsulfonyl-3-[4-(trifluoromethyl)phenyl]-6,7-dihydro-4H-pyrazolo[4,3-c]pyridin-1-yl]propyl]piperidin-4-yl]-1,4-benzoxazin-3-one	263659: Inhibition of MHC2 invariant chain	ic50	0.4100	uM
1-[1-[3-[3-(4-bromophenyl)-5-methylsulfonyl-6,7-dihydro-4H-pyrazolo[4,3-c]pyridin-1-yl]-2-hydroxypropyl]piperidin-4-yl]-6-chloro-3,4-dihydroquinolin-2-one	263659: Inhibition of MHC2 invariant chain	ic50	0.7500	uM
4-[1-[3-[5-acetyl-3-[4-(trifluoromethyl)phenyl]-6,7-dihydro-4H-pyrazolo[4,3-c]pyridin-1-yl]propyl]piperidin-4-yl]-1,4-benzoxazin-3-one	263659: Inhibition of MHC2 invariant chain	ic50	0.8100	uM
4-[1-[3-[3-(4-bromophenyl)-5-methylsulfonyl-6,7-dihydro-4H-pyrazolo[4,3-c]pyridin-1-yl]-2-hydroxypropyl]piperidin-4-yl]pyrido[3,2-b][1,4]oxazin-3-one	263659: Inhibition of MHC2 invariant chain	ic50	0.9000	uM
4-[1-[(2,3-dimethoxyphenyl)methyl]triazol-4-yl]phenol	539283: Inhibition of human biotinylated MIF/CD74 interaction	ic50	0.9000	uM
1-[1-[2-hydroxy-3-[5-methylsulfonyl-3-[4-(trifluoromethyl)phenyl]-6,7-dihydro-4H-pyrazolo[4,3-c]pyridin-1-yl]propyl]piperidin-4-yl]-5H-4,1-benzoxazepin-2-one	263659: Inhibition of MHC2 invariant chain	ic50	0.9300	uM
4-[1-[3-[5-methylsulfonyl-3-[4-(trifluoromethyl)phenyl]-6,7-dihydro-4H-pyrazolo[4,3-c]pyridin-1-yl]propyl]piperidin-4-yl]-1,4-benzoxazin-3-one	263659: Inhibition of MHC2 invariant chain	ic50	0.9500	uM
6-chloro-1-[1-[2-hydroxy-3-[5-methylsulfonyl-3-[4-(trifluoromethyl)phenyl]-6,7-dihydro-4H-pyrazolo[4,3-c]pyridin-1-yl]propyl]piperidin-4-yl]-3,4-dihydroquinolin-2-one	263659: Inhibition of MHC2 invariant chain	ic50	0.9800	uM
4-[1-[3-[5-acetyl-3-[4-(trifluoromethyl)phenyl]-6,7-dihydro-4H-pyrazolo[4,3-c]pyridin-1-yl]-2-hydroxypropyl]piperidin-4-yl]-1,4-benzoxazin-3-one	263659: Inhibition of MHC2 invariant chain	ic50	1.1000	uM
1-[1-[3-[3-(4-bromophenyl)-5-methylsulfonyl-6,7-dihydro-4H-pyrazolo[4,3-c]pyridin-1-yl]-2-hydroxypropyl]piperidin-4-yl]-3,4-dihydroquinazolin-2-one	263659: Inhibition of MHC2 invariant chain	ic50	1.1000	uM
methyl 3-[[4-(4-hydroxyphenyl)triazol-1-yl]methyl]benzoate	539283: Inhibition of human biotinylated MIF/CD74 interaction	ic50	1.2000	uM
6-chloro-4-[1-[2-hydroxy-3-[5-methylsulfonyl-3-[4-(trifluoromethyl)phenyl]-6,7-dihydro-4H-pyrazolo[4,3-c]pyridin-1-yl]propyl]piperidin-4-yl]-1,4-benzoxazin-3-one	263659: Inhibition of MHC2 invariant chain	ic50	1.3000	uM
4-[1-[2-hydroxy-3-[5-methylsulfonyl-3-[4-(trifluoromethyl)phenyl]-6,7-dihydro-4H-pyrazolo[4,3-c]pyridin-1-yl]propyl]piperidin-4-yl]pyrido[3,2-b][1,4]oxazin-3-one	263659: Inhibition of MHC2 invariant chain	ic50	1.3000	uM
1-[4-(6-chloro-2,2-dioxo-3,4-dihydro-2lambda6,1,3-benzothiadiazin-1-yl)piperidin-1-yl]-3-[5-methylsulfonyl-3-[4-(trifluoromethyl)phenyl]-6,7-dihydro-4H-pyrazolo[4,3-c]pyridin-1-yl]propan-2-ol	263659: Inhibition of MHC2 invariant chain	ic50	1.3000	uM
1-[1-[2-hydroxy-3-[5-methylsulfonyl-3-[4-(trifluoromethyl)phenyl]-6,7-dihydro-4H-pyrazolo[4,3-c]pyridin-1-yl]propyl]piperidin-4-yl]-4H-3,1-benzoxazin-2-one	263659: Inhibition of MHC2 invariant chain	ic50	1.4000	uM
1-[1-[2-hydroxy-3-[5-methylsulfonyl-3-[4-(trifluoromethyl)phenyl]-6,7-dihydro-4H-pyrazolo[4,3-c]pyridin-1-yl]propyl]piperidin-4-yl]-3,4-dihydroquinazolin-2-one	263659: Inhibition of MHC2 invariant chain	ic50	1.4000	uM
3-benzyl-5-methyl-1,3-benzoxazol-2-one	410820: Inhibition of human MIF-CD74 binding	ic50	1.5000	uM
1-[1-[3-[3-(4-bromophenyl)-5-methylsulfonyl-6,7-dihydro-4H-pyrazolo[4,3-c]pyridin-1-yl]-2-hydroxypropyl]piperidin-4-yl]-6-chloro-3,4-dihydroquinazolin-2-one	263659: Inhibition of MHC2 invariant chain	ic50	1.5000	uM
4-[1-[3-[3-(4-bromophenyl)-5-methylsulfonyl-6,7-dihydro-4H-pyrazolo[4,3-c]pyridin-1-yl]propyl]piperidin-4-yl]-5-methyl-1,4-benzoxazin-3-one	263659: Inhibition of MHC2 invariant chain	ic50	1.6000	uM
4-[1-[3-[3-(4-bromophenyl)-5-methylsulfonyl-6,7-dihydro-4H-pyrazolo[4,3-c]pyridin-1-yl]propyl]piperidin-4-yl]-1,4-benzoxazin-3-one	263659: Inhibition of MHC2 invariant chain	ic50	1.6000	uM
4-[1-[3-[3-(4-bromophenyl)-5-methylsulfonyl-6,7-dihydro-4H-pyrazolo[4,3-c]pyridin-1-yl]-2-hydroxypropyl]piperidin-4-yl]-1,4-benzoxazin-3-one	263659: Inhibition of MHC2 invariant chain	ic50	1.8000	uM
1-[1-[2-hydroxy-3-[5-methylsulfonyl-3-[4-(trifluoromethyl)phenyl]-6,7-dihydro-4H-pyrazolo[4,3-c]pyridin-1-yl]propyl]piperidin-4-yl]-3,4-dihydroquinolin-2-one	263659: Inhibition of MHC2 invariant chain	ic50	1.8000	uM
6-chloro-1-[1-[2-hydroxy-3-[5-methylsulfonyl-3-[4-(trifluoromethyl)phenyl]-6,7-dihydro-4H-pyrazolo[4,3-c]pyridin-1-yl]propyl]piperidin-4-yl]-3,4-dihydroquinazolin-2-one	263659: Inhibition of MHC2 invariant chain	ic50	1.9000	uM
1-[1-[3-[3-(4-bromophenyl)-5-methylsulfonyl-6,7-dihydro-4H-pyrazolo[4,3-c]pyridin-1-yl]-2-hydroxypropyl]piperidin-4-yl]-3,4-dihydroquinolin-2-one	263659: Inhibition of MHC2 invariant chain	ic50	2.0000	uM
5-methyl-4-[1-[3-[5-methylsulfonyl-3-[4-(trifluoromethyl)phenyl]-6,7-dihydro-4H-pyrazolo[4,3-c]pyridin-1-yl]propyl]piperidin-4-yl]-1,4-benzoxazin-3-one	263659: Inhibition of MHC2 invariant chain	ic50	2.0000	uM
7-[(3-fluoroanilino)-pyridin-2-ylmethyl]quinolin-8-ol	410820: Inhibition of human MIF-CD74 binding	ic50	2.5000	uM
[2-(1-benzofuran-2-yl)-4-oxo-3,1-benzoxazin-6-yl] acetate	410820: Inhibition of human MIF-CD74 binding	ic50	2.5000	uM
4-[1-[3-[3-(4-bromophenyl)-5-methylsulfonyl-6,7-dihydro-4H-pyrazolo[4,3-c]pyridin-1-yl]propyl]piperidin-4-yl]-6-chloro-1,4-benzoxazin-3-one	263659: Inhibition of MHC2 invariant chain	ic50	2.6000	uM
1-[3-(4-bromophenyl)-5-methylsulfonyl-6,7-dihydro-4H-pyrazolo[4,3-c]pyridin-1-yl]-3-[4-(6-chloro-2,2-dioxo-3,4-dihydro-2lambda6,1,3-benzothiadiazin-1-yl)piperidin-1-yl]propan-2-ol	263659: Inhibition of MHC2 invariant chain	ic50	2.7000	uM
4-(4-benzyltriazol-1-yl)phenol	539283: Inhibition of human biotinylated MIF/CD74 interaction	ic50	3.5000	uM
1-benzofuran-2-yl(2,3-dihydroindol-1-yl)methanone	410820: Inhibition of human MIF-CD74 binding	ic50	4.0000	uM
4-[1-[3-[3-(4-bromophenyl)-5-methylsulfonyl-6,7-dihydro-4H-pyrazolo[4,3-c]pyridin-1-yl]-2-hydroxypropyl]piperidin-4-yl]-6-chloro-1,4-benzoxazin-3-one	263659: Inhibition of MHC2 invariant chain	ic50	4.4000	uM
3-[(2,3-dimethoxyphenyl)methyl]-5-methyl-1,3-benzoxazol-2-one	516522: Inhibition of human recombinant biotinylated MIF/CD74 interaction after 30 mins	ic50	7.0000	uM
2-[(E)-2-(4-hydroxyphenyl)ethenyl]quinolin-8-ol	410820: Inhibition of human MIF-CD74 binding	ic50	8.0000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Particulate Matter	increases abundance, affects cotreatment, decreases reaction, increases expression, decreases expression	5
sodium arsenite	affects expression, decreases reaction, increases expression, decreases expression	4
Vehicle Emissions	decreases reaction, increases expression, affects cotreatment	3
trichostatin A	increases expression	2
Panobinostat	affects cotreatment, increases expression	2
Air Pollutants	decreases expression, increases abundance, increases expression	2
Benzo(a)pyrene	decreases expression, decreases methylation, affects methylation	2
Tobacco Smoke Pollution	decreases expression	2
Valproic Acid	affects expression, increases expression	2
Aflatoxin B1	increases methylation	2
aristolochic acid I	increases expression	1
sotorasib	affects cotreatment, increases expression	1
tremortin	decreases expression	1
triphenyl phosphate	affects expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
bisphenol A	affects expression	1
deoxynivalenol	decreases expression	1
nobiletin	decreases expression	1
quercitrin	affects expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
arsenite	increases methylation	1
sulforaphane	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium tungstate(VI)	increases expression	1
potassium chromate(VI)	decreases expression	1
nickel sulfate	decreases expression	1
tamibarotene	increases expression	1
bergamottin	decreases expression	1
N-(3-nitratopivaloyl)cysteine ethyl ester	decreases expression	1
CGP 52608	affects binding, increases reaction	1

ChEMBL screening assays

18 unique, capped per target: 18 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1021635	Binding	Inhibition of human MIF-CD74 binding	Discovery of human macrophage migration inhibitory factor (MIF)-CD74 antagonists via virtual screening. — J Med Chem

Cellosaurus cell lines

23 cell lines: 23 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1BL	Abcam Raji CD74 KO 1	Cancer cell line	Male
CVCL_B1BM	Abcam Raji CD74 KO 2	Cancer cell line	Male
CVCL_B8D7	Abcam HCT 116 CD74 KO	Cancer cell line	Male
CVCL_B8TQ	Abcam MCF-7 CD74 KO	Cancer cell line	Female
CVCL_B9FE	Abcam A-549 CD74 KO	Cancer cell line	Male
CVCL_C8SZ	CUTO-23	Cancer cell line
CVCL_C8T0	CUTO-33	Cancer cell line	Female
CVCL_C8T1	CUTO-27	Cancer cell line
CVCL_C8T3	CUTO-37	Cancer cell line
CVCL_C8T4	CUTO-38	Cancer cell line

Clinical trials (associated diseases)

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