DAXX Gene (Death Domain Associated Protein)
DAXX: A Multifunctional Scaffold Protein in Apoptosis, Transcription, and Tumor Suppression
Gene Information Card
| Symbol | DAXX |
|---|---|
| Full Name | Death domain associated protein |
| Gene Type | Protein coding |
| Chromosomal Location | 6p21.33 |
| NCBI Gene ID | 1616 ncbi.nlm.nih.gov/gene/1616 |
| Ensembl ID | ENSG00000100209 |
| UniProt ID | Q9UER7 |
| OMIM ID | 603186 |
| HGNC ID | 2681 |
| Aliases | BING2, DAP6, EAP1, SMIM40 |
Description
DAXX (death domain associated protein) encodes a multifunctional scaffold protein that interacts with a wide range of proteins, including the death domain of Fas (TNFRSF6) and the apoptosis-related protein Daxx. DAXX shuttles between the nucleus and cytoplasm, playing roles in apoptosis, transcription regulation, and chromatin remodeling. It is a core component of the ATRX/DAXX complex, which deposits histone variant H3.3 at telomeres and pericentromeric heterochromatin. Loss-of-function mutations in DAXX are recurrent in pancreatic neuroendocrine tumors and are associated with the alternative lengthening of telomeres (ALT) pathway.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Pancreatic Neuroendocrine Tumor (PanNET) | Somatic inactivating mutations in DAXX (or ATRX) lead to loss of H3.3 deposition at telomeres, promoting ALT and genomic instability. | PMID: 21150875, COSMIC |
| Glioblastoma Multiforme (GBM) | Recurrent DAXX mutations (e.g., frameshift, nonsense) are found in a subset of GBM, often co-occurring with ATRX mutations and associated with ALT. | PMID: 22832583, COSMIC |
| Adrenocortical Carcinoma | DAXX mutations (including missense and truncating) are observed, linked to ALT and poor prognosis. | PMID: 24899364, COSMIC |
| Neuroblastoma | Rare DAXX mutations reported; potential role in telomere maintenance. | PMID: 26030187, COSMIC |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 25.3 | High |
| Bone Marrow | 18.7 | Medium |
| Lymph Node | 15.2 | Medium |
| Brain (Cerebellum) | 12.1 | Medium |
| Liver | 8.4 | Low |
| Pancreas | 7.9 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 (embryonic kidney) | 22.5 | High expression |
| K562 (leukemia) | 19.8 | Medium expression |
| HeLa (cervical carcinoma) | 15.3 | Medium expression |
| HepG2 (hepatocellular carcinoma) | 10.1 | Low expression |
| A549 (lung carcinoma) | 9.4 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1105C>T (p.Gln369*) | Nonsense | <1% in PanNET | Truncation, loss of function |
| c.1681_1682del (p.Leu561fs) | Frameshift | <1% in PanNET | Loss of function, ALT activation |
| c.2054G>A (p.Arg685His) | Missense | <0.5% in GBM | Unknown; potential loss of interaction with ATRX |
| c.1477C>T (p.Arg493Trp) | Missense | <0.5% in adrenocortical carcinoma | Unknown; may impair H3.3 deposition |
Mutation functional classification
Loss of Function (LOF)
Most DAXX mutations in cancer are truncating (nonsense, frameshift) or missense that disrupt the interaction with ATRX or the histone chaperone activity, leading to loss of H3.3 deposition at telomeres and activation of ALT.
Gain of Function (GOF)
No evidence of gain-of-function mutations in DAXX. All reported pathogenic variants are loss-of-function.
Dominant Negative (DN)
Not established; DAXX mutations are typically biallelic (two-hit) in tumors, consistent with a tumor suppressor role.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Fas signaling pathway (apoptosis)
• ATRX/DAXX complex mediated H3.3 deposition
• Alternative lengthening of telomeres (ALT)
• p53/TP53 regulation
Protein Summary
DAXX is a 740-amino acid protein (UniProt Q9UER7) with a central coiled-coil domain and a C-terminal serine-rich region. It functions as a histone chaperone in the ATRX/DAXX complex, depositing histone variant H3.3 at telomeres and pericentromeric heterochromatin. DAXX also shuttles to the cytoplasm to modulate Fas-mediated apoptosis and acts as a transcriptional repressor or activator depending on context. Loss of DAXX function leads to telomere dysfunction and ALT, a telomerase-independent telomere maintenance mechanism common in certain cancers.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| DAXX Knockout HEK293 Cell Line | EDJ-KQ637 | Human | 1616 | Details Get a Quote |
| DAXX Knockout HeLa Cell Line | EDJ-KQ18060 | Human | 1616 | Details Get a Quote |
| DAXX Knockout A-549 Cell Line | EDJ-KQ19110 | Human | 1616 | Details Get a Quote |
| DAXX Knockout HCT 116 Cell Line | EDJ-KQ19111 | Human | 1616 | Details Get a Quote |
