ULK1 Gene: Autophagy Kinase and Disease Implications
Unc-51 Like Autophagy Activating Kinase 1: Structure, Function, and Clinical Relevance
Gene Information Card
| Symbol | ULK1 |
|---|---|
| Full Name | Unc-51 Like Autophagy Activating Kinase 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 12q24.33 |
| NCBI Gene ID | 8408 ncbi.nlm.nih.gov/gene/8408 |
| Ensembl ID | ENSG00000177169 |
| UniProt ID | O75385 |
| OMIM ID | 603168 |
| HGNC ID | 12558 |
| Aliases | ATG1, Unc51.1, KIAA0722 |
Description
ULK1 (Unc-51 Like Autophagy Activating Kinase 1) encodes a serine/threonine kinase that is a key initiator of autophagy. It forms a complex with ATG13, RB1CC1 (FIP200), and ATG101, which is essential for autophagosome formation. ULK1 is regulated by MTOR and AMPK, linking nutrient and energy status to autophagy. It also plays roles in mitophagy, cell survival, and neuronal development. Aberrant ULK1 expression or mutations are implicated in various cancers, neurodegenerative diseases, and metabolic disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (various types) | ULK1 overexpression or activation promotes tumor cell survival under stress; inhibition may enhance chemotherapy sensitivity. | COSMIC; multiple studies (e.g., PubMed) show altered expression in gastric, colorectal, and lung cancers. |
| Neurodegenerative diseases (e.g., Alzheimer's, Parkinson's) | Impaired autophagy due to ULK1 dysfunction leads to accumulation of toxic protein aggregates. | ClinVar; studies indicate reduced ULK1 activity in affected neurons. |
| Crohn's disease | ULK1 variants may affect autophagy in intestinal epithelium, influencing inflammation. | ClinVar; genome-wide association studies (GWAS) link ULK1 locus to IBD susceptibility. |
| Myopathy (e.g., X-linked myopathy with excessive autophagy) | Mutations in ULK1 can disrupt autophagy in muscle tissue, causing abnormal autophagic vacuoles. | OMIM; rare case reports. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Skeletal muscle | 12.3 | Medium |
| Brain (cerebellum) | 9.8 | Medium |
| Heart | 8.5 | Medium |
| Liver | 6.2 | Low |
| Lung | 5.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa (cervical cancer) | 15.2 | High expression; commonly used for autophagy studies. |
| A549 (lung carcinoma) | 10.4 | Moderate expression. |
| MCF7 (breast cancer) | 8.9 | Moderate expression. |
| HEK293 (embryonic kidney) | 7.3 | Low-moderate expression. |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.164A>G (p.Asn55Ser) | Missense | Rare (<0.01%) | Potential loss of kinase activity; observed in cancer samples (COSMIC). |
| c.557C>T (p.Thr186Met) | Missense | Rare (<0.01%) | May affect protein stability; reported in ClinVar as variant of uncertain significance. |
| c.1003G>A (p.Val335Ile) | Missense | Rare (<0.01%) | No functional data; found in population databases. |
| c.2146C>T (p.Arg716Ter) | Nonsense | Very rare | Predicted to truncate protein, likely loss of function; not observed in large cohorts. |
Mutation functional classification
Loss of Function (LOF)
Mutations that impair kinase activity or disrupt complex formation (e.g., with ATG13) reduce autophagy initiation, leading to accumulation of damaged organelles and proteins.
Gain of Function (GOF)
Amplification or overexpression of ULK1 (not point mutations) can enhance autophagy, promoting tumor cell survival under metabolic stress.
Dominant Negative (DN)
Some missense mutations in the kinase domain may act as dominant-negative by binding to ATG13 but failing to phosphorylate downstream targets, blocking autophagy.
View complete mutation data：
Gene Ontology (GO)
| • autophagy | • protein serine/threonine kinase activity |
| • ATP binding | • signal transduction |
| • response to starvation | • mitophagy |
| • protein phosphorylation | • regulation of autophagy |
Pathways
• Autophagy - animal
• mTOR signaling pathway
• AMPK signaling pathway
• Mitophagy
• Regulation of autophagy
Protein Summary
ULK1 is a 112 kDa serine/threonine kinase with an N-terminal kinase domain, a central proline/serine-rich region, and a C-terminal domain that mediates interactions with ATG13 and RB1CC1. It is the mammalian ortholog of yeast Atg1. Under nutrient-rich conditions, MTOR phosphorylates ULK1, inhibiting its activity. Upon starvation or energy stress, AMPK phosphorylates ULK1, activating it to initiate autophagosome formation. ULK1 also phosphorylates ATG13 and FIP200, coordinating the autophagic cascade. Beyond autophagy, ULK1 is involved in vesicle trafficking, neuronal axon guidance, and cell death regulation. Its activity is tightly controlled by post-translational modifications, including phosphorylation and ubiquitination.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ULK1 Knockout HEK293 Cell Line | EDJ-KQ1175 | Human | 8408 | Details Get a Quote |
| ULK1 Knockout A-549 Cell Line | EDJ-KQ18276 | Human | 8408 | Details Get a Quote |
| ULK1 Knockout HCT 116 Cell Line | EDJ-KQ18277 | Human | 8408 | Details Get a Quote |
| ULK1 Knockout HeLa Cell Line | EDJ-KQ20444 | Human | 8408 | Details Get a Quote |
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