AMBRA1: Autophagy and Beclin 1 Regulator 1
A key regulator of autophagy, cell proliferation, and tumor suppression
Gene Information Card
| Symbol | AMBRA1 |
|---|---|
| Full Name | Autophagy and Beclin 1 Regulator 1 |
| Gene Type | Protein-coding |
| Chromosomal Location | 11p11.2 |
| NCBI Gene ID | 55626 ncbi.nlm.nih.gov/gene/55626 |
| Ensembl ID | ENSG00000110497 |
| UniProt ID | Q9C0C7 |
| OMIM ID | 611359 |
| HGNC ID | 25990 |
| Aliases | WDR94, DCAF3, KIAA1736 |
Description
AMBRA1 (Autophagy and Beclin 1 Regulator 1) encodes a WD40-repeat protein that acts as a positive regulator of autophagy by interacting with the Beclin 1/VPS34 complex. It also functions as a substrate receptor for the CUL4-DDB1 E3 ubiquitin ligase complex, targeting proteins for degradation. AMBRA1 is involved in cell cycle control, neurodevelopment, and tumor suppression. Loss of AMBRA1 leads to increased cell proliferation and genomic instability.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Bladder cancer | AMBRA1 loss-of-function mutations reduce autophagy and promote cell cycle progression via D-type cyclin stabilization | COSMIC, ClinVar |
| Melanoma | Decreased AMBRA1 expression correlates with poor prognosis and increased proliferation | NCBI Gene, PubMed |
| Neurodevelopmental disorders | AMBRA1 mutations impair autophagy and neuronal differentiation, linked to intellectual disability | OMIM, ClinVar |
| Breast cancer | AMBRA1 downregulation associated with aggressive tumor features and reduced patient survival | COSMIC, PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Lung | 8.3 | Low |
| Liver | 6.1 | Low |
| Kidney | 9.7 | Low |
| Testis | 15.2 | Medium |
| Spleen | 7.4 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 14.8 | High expression in embryonic kidney cells |
| HeLa | 11.2 | Moderate expression in cervical cancer cells |
| A549 | 9.5 | Low expression in lung cancer cells |
| MCF7 | 8.1 | Low expression in breast cancer cells |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.187C>T (p.Arg63*) | Nonsense | <1% | Loss of function, truncated protein |
| c.1000_1001del (p.Leu334fs) | Frameshift | <1% | Loss of function, premature stop |
| c.215G>A (p.Arg72Gln) | Missense | <1% | Unknown functional impact |
| c.1234A>G (p.Lys412Glu) | Missense | <1% | Potential loss of function |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations leading to truncated or absent AMBRA1 protein, impairing autophagy and promoting cell proliferation.
Gain of Function (GOF)
No gain-of-function mutations reported in AMBRA1.
Dominant Negative (DN)
No dominant-negative mutations reported in AMBRA1.
View complete mutation data：
Gene Ontology (GO)
| • GO:0006914 - autophagy | • GO:0016236 - macroautophagy |
| • GO:0043161 - proteasome-mediated ubiquitin-dependent protein catabolic process | • GO:0007049 - cell cycle |
| • GO:0005737 - cytoplasm | • GO:0032991 - protein-containing complex |
Pathways
• Autophagy (KEGG hsa04140)
• Ubiquitin mediated proteolysis (KEGG hsa04120)
• Cell cycle (KEGG hsa04110)
Protein Summary
AMBRA1 is a 1302-amino acid protein containing WD40 repeats that mediate protein-protein interactions. It localizes to the cytoplasm and endoplasmic reticulum. As a positive regulator of autophagy, AMBRA1 promotes the formation of autophagosomes by activating the Beclin 1/VPS34 complex. Additionally, AMBRA1 acts as a substrate receptor for the CUL4-DDB1 E3 ubiquitin ligase, targeting D-type cyclins for degradation, thereby controlling cell cycle progression. Loss of AMBRA1 leads to cyclin D accumulation, increased proliferation, and genomic instability, underscoring its tumor suppressor role.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| AMBRA1 Knockout HEK293 Cell Line | EDC07527 | Human | 55626 | Details Get a Quote |
| AMBRA1 Knockout A-549 Cell Line | EDJ-KQ40555 | Human | 55626 | Details Get a Quote |
| AMBRA1 Knockout HCT 116 Cell Line | EDJ-KQ40556 | Human | 55626 | Details Get a Quote |
| AMBRA1 Knockout HeLa Cell Line | EDJ-KQ40557 | Human | 55626 | Details Get a Quote |
Displaying Records 1 To 4 Of 4 Records
