CDC37
protein-codingcell division cycle 37, HSP90 cochaperone, the group of MicroRNA protein coding host genes
Gene summary
The protein encoded by this gene is highly similar to Cdc 37, a cell division cycle control protein of Sacchromyces cerevisiae. This protein is a molecular chaperone with specific function in cell signal transduction. It has been shown to form complex with Hsp90 and a variety of protein kinases including CDK4, CDK6, SRC, RAF-1, MOK, as well as eIF2 alpha kinases. It is thought to play a critical role in directing Hsp90 to its target kinases. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~29.0 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to CDC37 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_007065.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 2 | 2 | 4 | |||
| missense | 40 | 1 | 41 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 42 | 0 | 3 | 45 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_008996.1 | 8 | MANE Select | |
| Ensembl | ENSP00000222005.1 | 8 | MANE Select | |
| Ensembl | ENSP00000464971.1 | 2 | Standard | |
| Ensembl | ENSP00000464889.1 | 2 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| cdc37 | Danio rerio | Structure: trunk Quality: necrotic abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- PI3K-Akt signaling pathway - Homo sapiens (human)
- TNF alpha Signaling Pathway
- Aryl Hydrocarbon Receptor
- Aryl Hydrocarbon Receptor Pathway
- Nuclear Receptors Meta-Pathway
Biological Process
- regulation of cyclin-dependent protein serine/threonine kinase activity
- protein folding
- protein targeting
- posttranscriptional regulation of gene expression
- peptidyl-tyrosine phosphorylation
Molecular Function
- protein tyrosine kinase activity
- protein binding
- protein kinase regulator activity
- kinase binding
- protein kinase binding
Cellular Component
- cytoplasm
- cytosol
- extracellular exosome
- chaperone complex
- HSP90-CDC37 chaperone complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000222005
- Coding exons
- 8
- Length
- 28988
- Individuals with no LoFs
- 125713
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 15
- Defined
- 125728
- p
- 0.0000597
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.68 | 175 | 250 | 0.701 | 0.0000166 | 2531 |
| Missense (PolyPhen) | 39 | 82.888 | 0.47051 | 867 | ||
| Synonymous | 0.566 | 92 | 99.2 | 0.928 | 0.00000713 | 656 |
| Loss of Function | 3.63 | 3 | 20.9 | 0.143 | 0.00000100 | 232 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.00049 | 0.00046 | rare |
| European (Non-Finnish) | 0.000027 | 0.000026 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Co-chaperone that binds to numerous kinases and promotes their interaction with the Hsp90 complex, resulting in stabilization and promotion of their activity (PubMed:8666233). Inhibits HSP90AA1 ATPase activity (PubMed:23569206). {ECO:0000269|PubMed:23569206, ECO:0000269|PubMed:8666233}.;
Recessive Scores
- pRec
- 0.221
Intolerance Scores
- LoFtool
- 0.302
- RVIS EVS
- -0.34
- RVIS percentile EVS
- 30.56
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- E
- Essential (gene trap)
- E
- Indispensability pred.
- E
- Indispensability score
- 0.933
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |