HomeAboutRankingsData Sources
Β© 2026 GeneE
🧬
GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
ULK2
unc-51 like autophagy activating kinase 2
Chromosome 17 Β· 17p11.2
NCBI Gene: 9706Ensembl: ENSG00000083290.21HGNC: HGNC:13480UniProt: Q8IYT8
55PubMed Papers
20Diseases
0Drugs
1Pathogenic Variants
FUNCTIONAL ROLE
Kinase
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
protein serine/threonine kinase activityprotein autophosphorylationprotein bindingphagophore assembly site membraneAbnormal brain morphologyprostate cancerFamilial prostate cancerovarian cancer
✦AI Summary

ULK2 (unc-51 like autophagy activating kinase 2) is a serine/threonine protein kinase that plays a crucial role in regulating autophagy and cellular energy homeostasis. As a key component of the autophagy machinery, ULK2 functions alongside ULK1 to initiate autophagosome formation and is essential for mitochondrial quality control through mitophagy 1. The kinase is regulated by AMPK phosphorylation, which connects cellular energy sensing to autophagy activation during starvation conditions 1. ULK2 participates in regulatory feedback loops with mTORC1, acting both as a downstream effector and negative regulator 2. Recent evidence indicates ULK2 functions as a copper-dependent signaling kinase, expanding beyond its traditional role as a metabolic cofactor 3. The protein's expression is regulated at the post-transcriptional level through alternative polyadenylation, where Nudt21-mediated 3'UTR shortening affects ULK2 mRNA stability in activated macrophages, ultimately modulating autophagic activity and inflammatory responses 4. ULK2 is transcriptionally activated by E2F4, contributing to cancer cell survival through autophagy-mediated zinc homeostasis 5. Mutations in ULK2 have been identified in malignant pleural mesothelioma, suggesting potential tumor suppressor functions 6.

Sources cited
1
ULK2 is required for autophagy and mitophagy, and AMPK phosphorylation of ULK1/ULK2 connects energy sensing to autophagy
PMID: 21205641
2
ULK2 functions as a copper-dependent signaling kinase in autophagy
PMID: 34764459
3
ULK2 participates in AMPK/mTOR pathway regulation and autophagy initiation
PMID: 37438882
4
ULK2 mRNA stability is regulated by Nudt21-mediated alternative polyadenylation in macrophages
PMID: 39537902
5
E2F4 transcriptionally activates ULK2 for autophagy-mediated zinc homeostasis in cancer
PMID: 35253629
6
ULK2 is significantly mutated in malignant pleural mesothelioma
PMID: 26928227
Disease Associationsβ“˜20
Abnormal brain morphologyOpen Targets
0.27Weak
prostate cancerOpen Targets
0.11Weak
Familial prostate cancerOpen Targets
0.11Weak
ovarian cancerOpen Targets
0.08Suggestive
schizophreniaOpen Targets
0.07Suggestive
major depressive disorderOpen Targets
0.06Suggestive
attention deficit hyperactivity disorderOpen Targets
0.06Suggestive
obsessive-compulsive disorderOpen Targets
0.06Suggestive
neoplasmOpen Targets
0.05Suggestive
gliomaOpen Targets
0.04Suggestive
non-small cell lung carcinomaOpen Targets
0.04Suggestive
acute myeloid leukemiaOpen Targets
0.03Suggestive
psoriasisOpen Targets
0.03Suggestive
Alzheimer diseaseOpen Targets
0.02Suggestive
colorectal carcinomaOpen Targets
0.02Suggestive
gastric cancerOpen Targets
0.01Suggestive
breast cancerOpen Targets
0.01Suggestive
cancerOpen Targets
0.01Suggestive
chronic myelogenous leukemiaOpen Targets
0.01Suggestive
urinary bladder carcinomaOpen Targets
0.01Suggestive
Pathogenic Variants1
NM_014683.4(ULK2):c.1733A>G (p.His578Arg)Likely pathogenic
Abnormal brain morphology
β˜…β˜†β˜†β˜†β†’ Residue 578
View on ClinVar β†—
Related Genes
MTORProtein interaction100%PIK3C3Protein interaction100%UVRAGProtein interaction100%BECN1Protein interaction100%ATG12Protein interaction100%ATG5Protein interaction100%
Tissue Expression6 tissues
Brain
100%
Ovary
66%
Heart
59%
Lung
37%
Bone Marrow
37%
Liver
16%
Gene Interaction Network
Click a node to explore
ULK2MTORPIK3C3UVRAGBECN1ATG12ATG5
PROTEIN STRUCTURE
Preparing viewer…
PDB6QAV Β· 2.05 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.77LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.62 [0.51–0.77]
RankingsWhere ULK2 stands among ~20K protein-coding genes
  • #8,266of 20,598
    Most Researched55
  • #5,073of 5,498
    Most Pathogenic Variants1
  • #6,185of 17,882
    Most Constrained (LOEUF)0.77
Genes detectedULK2
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Copper metabolism in cell death and autophagy.
PMID: 37055935
Autophagy Β· 2023
1.00
2
Connecting copper and cancer: from transition metal signalling to metalloplasia.
PMID: 34764459
Nat Rev Cancer Β· 2022
0.90
3
Mitochondrial respiratory chain deficiency inhibits lysosomal hydrolysis.
PMID: 30917721
Autophagy Β· 2019
0.80
4
Comprehensive genomic analysis of malignant pleural mesothelioma identifies recurrent mutations, gene fusions and splicing alterations.
PMID: 26928227
Nat Genet Β· 2016
0.70
5
Alternative mRNA polyadenylation regulates macrophage hyperactivation via the autophagy pathway.
PMID: 39537902
Cell Mol Immunol Β· 2024
0.60