CHD5 Gene - Chromodomain Helicase DNA Binding Protein 5
A chromatin remodeling gene with tumor suppressor activity, frequently altered in neuroblastoma and other cancers.
Gene Information Card
| Symbol | CHD5 |
|---|---|
| Full Name | Chromodomain Helicase DNA Binding Protein 5 |
| Gene Type | Protein coding |
| Chromosomal Location | 1p36.31 |
| NCBI Gene ID | 26038 ncbi.nlm.nih.gov/gene/26038 |
| Ensembl ID | ENSG00000116254 |
| UniProt ID | Q8TDI0 |
| OMIM ID | 610913 |
| HGNC ID | 16816 |
| Aliases | CHD-5, KIAA1444 |
Description
The CHD5 gene encodes a protein belonging to the chromodomain helicase DNA-binding (CHD) family. CHD5 is an ATP-dependent chromatin remodeling enzyme that plays a critical role in chromatin assembly, nucleosome mobilization, and transcriptional regulation. It is considered a tumor suppressor gene, with its expression frequently lost or reduced in various cancers, particularly neuroblastoma. CHD5 is involved in the p19(Arf)/p53 pathway and regulates the expression of genes controlling cell cycle progression, apoptosis, and senescence.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Neuroblastoma | Loss of CHD5 expression due to deletion or promoter hypermethylation is common. It acts as a tumor suppressor by regulating p53 pathway and cell cycle genes. | Multiple studies show CHD5 deletion/methylation in neuroblastoma cell lines and primary tumors, correlating with poor prognosis. |
| Breast Cancer | Reduced CHD5 expression is associated with tumor progression and metastasis. It may regulate epithelial-mesenchymal transition (EMT). | Immunohistochemistry and expression analysis show downregulation in invasive breast cancer tissues. |
| Colorectal Cancer | CHD5 promoter methylation and subsequent gene silencing contribute to tumorigenesis. | Methylation-specific PCR and expression studies in colorectal cancer cell lines and tissues. |
| Lung Cancer | CHD5 acts as a tumor suppressor; its loss promotes cell proliferation and invasion. | Functional studies in lung cancer cell lines show that CHD5 overexpression inhibits growth. |
| Ovarian Cancer | Decreased CHD5 expression is linked to aggressive tumor features and poor survival. | Expression profiling and clinical correlation studies. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 14.2 | Medium |
| Testis | 9.8 | Low |
| Adrenal Gland | 8.1 | Low |
| Lung | 5.3 | Low |
| Kidney | 4.1 | Low |
| Liver | 1.2 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (Neuroblastoma) | 0.1 | Very low expression due to promoter methylation. |
| SK-N-BE(2) (Neuroblastoma) | 0.0 | No expression; homozygous deletion. |
| MCF7 (Breast Cancer) | 3.5 | Reduced expression compared to normal breast tissue. |
| A549 (Lung Cancer) | 2.8 | Low expression; associated with promoter methylation. |
| HCT116 (Colorectal Cancer) | 1.5 | Low expression due to methylation. |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.2071C>T (p.Arg691Ter) | Nonsense | Rare | Introduces a premature stop codon, leading to a truncated non-functional protein. Loss of tumor suppressor function. |
| c.1129G>A (p.Gly377Ser) | Missense | Rare | Substitution in the chromodomain, potentially affecting chromatin binding and remodeling activity. |
| c.2542_2543del (p.Leu848ValfsTer3) | Frameshift | Rare | Causes a frameshift and premature termination, resulting in a non-functional protein. |
| Promoter Hypermethylation | Epigenetic | Frequent | Silences CHD5 gene expression without altering the DNA sequence. A major mechanism of CHD5 inactivation in cancers. |
| 1p36 Deletion | Copy Number Loss | Frequent | Hemizygous or homozygous deletion of the chromosomal region containing CHD5, leading to loss of expression. |
Mutation functional classification
Loss of Function (LOF)
The majority of CHD5 mutations are loss-of-function, including nonsense, frameshift, and splice-site mutations, as well as epigenetic silencing via promoter methylation and genomic deletions. These alterations result in reduced or absent CHD5 protein, leading to uncontrolled cell proliferation and tumor development.
Gain of Function (GOF)
No gain-of-function mutations have been described for CHD5. It is primarily characterized as a tumor suppressor, and its activity is lost in cancer.
Dominant Negative (DN)
While not definitively established, some missense mutations in the ATPase or chromodomain regions could potentially exert a dominant-negative effect by competing with the wild-type protein for binding partners or chromatin substrates, thereby inhibiting the function of the remaining wild-type allele.
View complete mutation data：
Gene Ontology (GO)
| • ATP binding | • DNA binding |
| • Chromatin binding | • Helicase activity |
| • Nucleosome binding | • Chromatin remodeling |
| • Regulation of transcription by RNA polymerase II | • Cell cycle arrest |
| • Apoptotic process | • Cellular response to DNA damage stimulus |
Pathways
• p53 pathway
• p19(Arf)/MDM2/p53 pathway
• Chromatin organization
• Transcriptional regulation by CHD5
Protein Summary
The CHD5 protein is a 205 kDa ATP-dependent chromatin remodeler. It contains two N-terminal chromodomains, a SNF2-like ATPase domain, and a C-terminal DNA-binding domain. CHD5 is a core component of the nucleosome remodeling and deacetylation (NuRD) complex, where it helps regulate gene expression by altering chromatin structure. It functions as a tumor suppressor by promoting the expression of tumor suppressor genes and repressing oncogenes, particularly through the p19(Arf)/p53 pathway. CHD5 is critical for normal development and its loss is a key event in the pathogenesis of several cancers.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CHD5 Knockout HEK293 Cell Line | EDJ-KQ8372 | Human | 26038 | Details Get a Quote |
| CHD5 Knockout HCT 116 Cell Line | EDJ-KQ33080 | Human | 26038 | Details Get a Quote |
| CHD5 Knockout HeLa Cell Line | EDJ-KQ55872 | Human | 26038 | Details Get a Quote |
| CHD5 Knockout A-549 Cell Line | EDJ-KQ64362 | Human | 26038 | Details Get a Quote |
