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26 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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CDC37
cell division cycle 37, HSP90 cochaperone
Chromosome 19 · 19p13.2
NCBI Gene: 11140Ensembl: ENSG00000105401.11HGNC: HGNC:1735UniProt: Q16543
311PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Highly ConstrainedHub Gene
RESEARCH IMPACT
Trending
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
regulation of type II interferon-mediated signaling pathwaycytoplasmprotein maturationprotein bindingcancerresponse to xenobiotic stimulushypothyroidismMiyoshi myopathy
✦AI Summary

CDC37 is a cochaperone that functions as a critical regulator of protein kinase stability and activity. As a Hsp90-binding partner, CDC37 provides kinase-family recognition within the HSP90-CDC37 chaperone complex, facilitating interaction between Hsp90 and client kinases while stabilizing intrinsically unstable kinases 1. The complex supports approximately 60% of the human kinome and allows kinases to respond rapidly to cellular signals while protecting them from degradation 2. CDC37 inhibits HSP90 ATPase activity and works with Hsp90 to regulate protein folding, maturation, and signal transduction 3. Beyond canonical kinase chaperoning, CDC37 displays Hsp90-independent functions and interacts with non-kinase substrates 4, including roles in GSDMD-mediated IL-1β secretion during intestinal inflammation 5. In disease contexts, aberrant HSP90-CDC37 interactions destabilize oncogenic kinases in cancer pathways, including RAF in RAS/RAF/MEK signaling 6. Clinically, CDC37 serves as a prognostic biomarker in gastric carcinoma 7 and represents an attractive therapeutic target due to selective expression in certain cancers and its control of multiple growth-signaling pathways 8. Blocking HSP90-CDC37 protein-protein interactions offers higher selectivity with fewer toxic effects than direct Hsp90 inhibition.

Sources cited
1
CDC37 interacts with kinases but not transcription factors; provides kinase-family recognition while HSP90 binding depends on thermodynamic parameters of client stability
PMID: 22939624
2
HSP90/CDC37 interacts with ~60% of human kinome and supports kinase response to signals while protecting from degradation
PMID: 28784328
3
CDC37-HSP90 complex regulates kinase and non-kinase client stability; blocking their interaction offers better selectivity and fewer side effects than Hsp90 inhibition
PMID: 35400341
4
CDC37 functions independently of Hsp90 with non-kinase substrates and displays Hsp90-independent molecular chaperone activities
PMID: 14627196
5
CDC37/Hsp90 chaperoning of GSDMD is required for IL-1β-containing extracellular vesicle release during intestinal inflammation
PMID: 32597834
6
HSP90-CDC37 chaperone complexes regulate RAF kinase engagement in RAS/RAF/MEK signaling pathway
PMID: 38316136
7
CDC37 identified as prognostic biomarker and therapeutic target in gastric carcinoma through mitophagy-related gene analysis
PMID: 37413850
8
CDC37 controls folding of large proportion of kinases at hub of intracellular signaling; elevated expression in some cancers makes it attractive cancer therapeutic target
PMID: 25487018
Disease Associationsⓘ20
cancerOpen Targets
0.61Moderate
response to xenobiotic stimulusOpen Targets
0.12Weak
hypothyroidismOpen Targets
0.10Weak
Miyoshi myopathyOpen Targets
0.08Suggestive
prostate cancerOpen Targets
0.08Suggestive
colorectal carcinomaOpen Targets
0.08Suggestive
gastrointestinal stromal tumorOpen Targets
0.07Suggestive
nonpapillary renal cell carcinomaOpen Targets
0.07Suggestive
inflammatory bowel diseaseOpen Targets
0.07Suggestive
hepatocellular carcinomaOpen Targets
0.07Suggestive
Crohn's diseaseOpen Targets
0.06Suggestive
ulcerative colitisOpen Targets
0.06Suggestive
attention deficit hyperactivity disorderOpen Targets
0.05Suggestive
breast cancerOpen Targets
0.05Suggestive
hereditary attention deficit-hyperactivity disorderOpen Targets
0.04Suggestive
schizophrenia 15Open Targets
0.04Suggestive
intellectual developmental disorder, autosomal dominant 69Open Targets
0.04Suggestive
neoplasmOpen Targets
0.04Suggestive
ankylosing spondylitisOpen Targets
0.03Suggestive
Phelan-McDermid syndromeOpen Targets
0.03Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
CDK4Protein interaction100%ARAFProtein interaction100%BRAFProtein interaction100%CCT6AProtein interaction100%PPP5CProtein interaction100%SDF2Protein interaction100%
Tissue Expression6 tissues
Lung
100%
Heart
75%
Ovary
74%
Bone Marrow
70%
Liver
65%
Brain
36%
Gene Interaction Network
Click a node to explore
CDC37CDK4ARAFBRAFCCT6APPP5CSDF2
PROTEIN STRUCTURE
Preparing viewer…
PDB2W0G · 1.88 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.32Highly Constrained
pLIⓘ
1.00Intolerant
Observed/Expected LoF0.18 [0.11–0.32]
RankingsWhere CDC37 stands among ~20K protein-coding genes
  • #1,098of 20,598
    Most Researched311 · top 10%
  • #1,298of 17,882
    Most Constrained (LOEUF)0.32 · top 10%
Genes detectedCDC37
Sources retrieved26 papers
Response time—
📄 Sources
26▼
1
Signaling from RAS to RAF: The Molecules and Their Mechanisms.
PMID: 38316136
Annu Rev Biochem · 2024
1.00
2
PARP1 Promotes Heart Regeneration and Cardiomyocyte Proliferation.
PMID: 38481797
Int J Biol Sci · 2024
0.92
3
Quantitative analysis of HSP90-client interactions reveals principles of substrate recognition.
PMID: 22939624
Cell · 2012
0.90
4
Identifying mitophagy-related genes as prognostic biomarkers and therapeutic targets of gastric carcinoma by integrated analysis of single-cell and bulk-RNA sequencing data.
PMID: 37413850
Comput Biol Med · 2023
0.80
5
Intracellular hyaluronan: Importance for cellular functions.
PMID: 31276783
Semin Cancer Biol · 2020
0.80