HACE1: HECT Domain and Ankyrin Repeat Containing E3 Ubiquitin Protein Ligase 1
A tumor suppressor gene encoding an E3 ubiquitin ligase involved in protein degradation, cell cycle regulation, and neurodevelopment.
Gene Information Card
| Symbol | HACE1 |
|---|---|
| Full Name | HECT Domain and Ankyrin Repeat Containing E3 Ubiquitin Protein Ligase 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 6q21 |
| NCBI Gene ID | 57531 ncbi.nlm.nih.gov/gene/57531 |
| Ensembl ID | ENSG00000112419 |
| UniProt ID | Q8IYU2 |
| OMIM ID | 610876 |
| HGNC ID | 21033 |
| Aliases | KIAA1320, MGC138499 |
Description
HACE1 encodes a HECT domain-containing E3 ubiquitin ligase that targets proteins for proteasomal degradation. It functions as a tumor suppressor by regulating cell proliferation, migration, and apoptosis. HACE1 is frequently inactivated by promoter methylation or deletion in various cancers, including neuroblastoma and Wilms tumor. It also plays a role in neurodevelopment and oxidative stress response.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Neuroblastoma | Loss of HACE1 expression via deletion or methylation leads to increased cell proliferation and tumorigenesis. | PMID: 21725308, PMID: 24469055 |
| Wilms Tumor | Homozygous deletions and mutations in HACE1 are associated with Wilms tumor predisposition. | PMID: 23023333 |
| Hereditary Spastic Paraplegia | Biallelic loss-of-function mutations in HACE1 cause a neurodevelopmental disorder with spastic paraplegia. | PMID: 31981491 |
| Breast Cancer | Reduced HACE1 expression correlates with poor prognosis and metastasis. | PMID: 26030138 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 15.2 | Medium |
| Heart | 8.7 | Low |
| Liver | 6.3 | Low |
| Kidney | 12.1 | Medium |
| Lung | 9.5 | Low |
| Testis | 18.4 | High |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 14.5 | Embryonic kidney cells |
| HeLa | 11.2 | Cervical cancer cells |
| SH-SY5Y | 16.8 | Neuroblastoma cells |
| MCF7 | 7.3 | Breast cancer cells |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.109C>T (p.Arg37*) | Nonsense | Rare | Loss of function; truncation of protein |
| c.1465C>T (p.Arg489*) | Nonsense | Rare | Loss of function; truncation of protein |
| c.1A>G (p.Met1?) | Start loss | Rare | Loss of function; no translation |
| Whole gene deletion | Copy number loss | Variable | Loss of heterozygosity; tumor suppressor inactivation |
Mutation functional classification
Loss of Function (LOF)
Nonsense, frameshift, and start-loss mutations lead to truncated or absent protein, impairing ubiquitin ligase activity and tumor suppression.
Gain of Function (GOF)
No gain-of-function mutations reported.
Dominant Negative (DN)
No dominant-negative mutations reported.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Ubiquitin mediated proteolysis (KEGG: hsa04120)
• p53 signaling pathway (KEGG: hsa04115)
• RAC1 GTPase cycle (Reactome: R-HSA-9013408)
Protein Summary
HACE1 is a 909-amino acid E3 ubiquitin ligase containing an N-terminal ankyrin repeat domain and a C-terminal HECT domain. It ubiquitinates substrates such as RAC1, targeting them for proteasomal degradation. HACE1 regulates cell migration, oxidative stress, and apoptosis. Loss of HACE1 leads to RAC1 accumulation and increased tumorigenesis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| HACE1 Knockout HEK293 Cell Line | EDJ-KQ12977 | Human | 57531 | Details Get a Quote |
| HACE1 Knockout A-549 Cell Line | EDJ-KQ43464 | Human | 57531 | Details Get a Quote |
| HACE1 Knockout HCT 116 Cell Line | EDJ-KQ43466 | Human | 57531 | Details Get a Quote |
| HACE1 Knockout HeLa Cell Line | EDJ-KQ43467 | Human | 57531 | Details Get a Quote |
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