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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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UBXN2A
UBX domain protein 2A
Chromosome 2 · 2p23.3
NCBI Gene: 165324Ensembl: ENSG00000173960.15HGNC: HGNC:27265UniProt: P68543
38PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingpositive regulation of protein catabolic processnegative regulation of proteolysisnegative regulation of ERAD pathwayAbnormality of the skeletal systemsmoking cessationovarian neoplasmmathematical ability
✦AI Summary

UBXN2A (UBX domain protein 2A) is a ubiquitin-like protein that functions as a multifaceted regulator of protein stability and cellular signaling. As a p97 adaptor protein, UBXN2A represses CHIP-mediated ubiquitination and endoplasmic reticulum-associated degradation (ERAD) of the nicotinic acetylcholine receptor subunit CHR2 in cortical neurons, thereby promoting its trafficking to the plasma membrane 1. Conversely, UBXN2A positively mediates proteasomal degradation of RICTOR, a core component of the mTORC2 complex, thereby suppressing this oncogenic signaling pathway 23. UBXN2A also inhibits STUB1-mediated TP53 degradation through interaction with HSPA9, stabilizing the p53 tumor suppressor 4. In cancer biology, UBXN2A functions as a tumor suppressor: it enhances CHIP-dependent degradation of the oncoprotein mortalin-2, suppressing epithelial-mesenchymal transition and chemotherapy resistance 54. UBXN2A expression is often reduced in colorectal cancer tissues, and its pharmacological upregulation via veratridine sensitizes cancer cells to chemotherapy 67. Recent genome-wide association studies identify UBXN2A as a causal gene associated with lung function traits (FEV1 and FVC), suggesting broader physiological relevance beyond cancer 8.

Sources cited
1
UBXN2A acts as a p97 adaptor protein that represses CHIP-mediated ubiquitination and ERAD of CHRNA3, promoting nicotinic receptor trafficking
PMID: 26265139
2
UBXN2A targets RICTOR for proteasomal degradation, suppressing mTORC2 signaling and tumor progression in colorectal cancer
PMID: 37037900
3
UBXN2A decreases RICTOR protein levels and downstream mTORC2 signaling, reducing cancer cell migration and stem cell populations
PMID: 36889268
4
UBXN2A binds mortalin and interferes with CHIP-mediated p53 degradation, stabilizing p53 and enhancing chemotherapy sensitivity
PMID: 26634371
5
UBXN2A enhances CHIP-dependent ubiquitination and proteasomal degradation of mortalin-2 oncoprotein in cancer cells
PMID: 30107089
6
Veratridine upregulates UBXN2A to inhibit mortalin-2, enhance chemotherapy efficacy, and suppress cancer stem cells in colorectal cancer
PMID: 26188124
7
Veratridine induces UBXN2A expression to suppress mortalin and inhibit tumor growth with demonstrated safety in mouse models
PMID: 35347121
8
UBXN2A is identified as a causal gene associated with lung function traits FEV1 and FVC through multi-omics cross-tissue analysis
PMID: 40128644
Disease Associationsⓘ20
Abnormality of the skeletal systemOpen Targets
0.35Weak
smoking cessationOpen Targets
0.33Weak
ovarian neoplasmOpen Targets
0.27Weak
mathematical abilityOpen Targets
0.24Weak
major depressive disorderOpen Targets
0.21Weak
mood disorderOpen Targets
0.21Weak
hemolysisOpen Targets
0.19Weak
alcohol drinkingOpen Targets
0.18Weak
intelligenceOpen Targets
0.16Weak
neurotic disorderOpen Targets
0.14Weak
mental or behavioural disorderOpen Targets
0.13Weak
squamous cell lung carcinomaOpen Targets
0.09Suggestive
neoplasmOpen Targets
0.09Suggestive
health study participationOpen Targets
0.08Suggestive
liver diseaseOpen Targets
0.08Suggestive
type 1 diabetes nephropathyOpen Targets
0.07Suggestive
risk-taking behaviourOpen Targets
0.07Suggestive
COVID-19Open Targets
0.07Suggestive
cancerOpen Targets
0.06Suggestive
colon carcinomaOpen Targets
0.05Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
LACTBProtein interaction99%YOD1Protein interaction99%UBXN10Protein interaction99%PLAAProtein interaction96%UBXN7Protein interaction96%VCPProtein interaction95%
Tissue Expression6 tissues
Heart
100%
Brain
61%
Bone Marrow
40%
Lung
31%
Liver
28%
Ovary
24%
Gene Interaction Network
Click a node to explore
UBXN2ALACTBYOD1UBXN10PLAAUBXN7VCP
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt P68543
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
1.12LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.76 [0.52–1.12]
RankingsWhere UBXN2A stands among ~20K protein-coding genes
  • #10,568of 20,598
    Most Researched38
  • #11,557of 17,882
    Most Constrained (LOEUF)1.12
Genes detectedUBXN2A
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Identifying cross-tissue molecular targets of lung function by multi-omics integration analysis from DNA methylation and gene expression of diverse human tissues.
PMID: 40128644
BMC Genomics · 2025
1.00
2
UBXN2A suppresses the Rictor-mTORC2 signaling pathway, an established tumorigenic pathway in human colorectal cancer.
PMID: 37037900
Oncogene · 2023
0.90
3
Pre-clinical safety and therapeutic efficacy of a plant-based alkaloid in a human colon cancer xenograft model.
PMID: 35347121
Cell Death Discov · 2022
0.80
4
Structural studies of UBXN2A and mortalin interaction and the putative role of silenced UBXN2A in preventing response to chemotherapy.
PMID: 26634371
Cell Stress Chaperones · 2016
0.70
5
UBXN2A enhances CHIP-mediated proteasomal degradation of oncoprotein mortalin-2 in cancer cells.
PMID: 30107089
Mol Oncol · 2018
0.60