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25 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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UFD1
ubiquitin recognition factor in ER associated degradation 1
Chromosome 22 · 22q11.21
NCBI Gene: 7353Ensembl: ENSG00000070010.20HGNC: HGNC:12520UniProt: Q541A5
167PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Hub Gene
RESEARCH IMPACT
Trending
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
cellular response to misfolded proteinUFD1-NPL4 complexprotein bindingnucleusdengue diseasealcohol drinkinginfectionacute lymphoblastic leukemia
✦AI Summary

UFD1 (ubiquitin recognition factor in ER associated degradation 1) is an essential component of protein quality control pathways, functioning primarily as part of the VCP-UFD1-NPLOC4 complex. This ternary complex facilitates the extraction and degradation of ubiquitinated proteins through multiple mechanisms 1. UFD1 plays a critical role in ER-associated degradation (ERAD) by promoting the export of misfolded proteins from the ER to the cytoplasm for proteasomal degradation 2. The protein also regulates autophagy processes, with the VCP-UFD1-NPLOC4 complex being required for aggresome disassembly and subsequent piecemeal autophagy 2. Additionally, UFD1 modulates cellular stress responses through a microprotein isoform (UFD1s) that competitively binds E3 ligases to regulate protein ubiquitination dynamics 3. In disease contexts, pathogenic VCP mutations cause aberrant recruitment of the VCP-UFD1-NPLOC4 complex to nuclear pore complexes, leading to inappropriate nucleoporin degradation and disrupted nucleocytoplasmic transport in neurodegenerative diseases 4. The complex also participates in DNA repair by processing DNA-protein crosslinks 5, and UFD1 contributes to anti-tumor immunity regulation through FTO protein degradation 6.

Sources cited
1
UFD1 functions as part of the VCP-UFD1-NPLOC4 ternary complex for protein quality control
PMID: 36087575
2
VCP-UFD1-NPLOC4 complex is required for aggresome disassembly and piecemeal autophagy
PMID: 40335532
3
UFD1s microprotein isoform regulates ubiquitination dynamics and stress responses
PMID: 40691175
4
Pathogenic VCP mutations cause aberrant VCP-UFD1-NPLOC4 recruitment to nuclear pores in neurodegeneration
PMID: 41475349
5
VCP-UFD1-NPLOC4 complex processes DNA-protein crosslinks for DNA repair
PMID: 38744091
6
UFD1 mediates FTO protein degradation affecting tumor immunity
PMID: 39661064
Disease Associationsⓘ20
dengue diseaseOpen Targets
0.37Weak
alcohol drinkingOpen Targets
0.24Weak
infectionOpen Targets
0.08Suggestive
acute lymphoblastic leukemiaOpen Targets
0.08Suggestive
non-alcoholic steatohepatitisOpen Targets
0.06Suggestive
neoplasmOpen Targets
0.05Suggestive
strokeOpen Targets
0.04Suggestive
schizophreniaOpen Targets
0.03Suggestive
viral diseaseOpen Targets
0.02Suggestive
heart diseaseOpen Targets
0.02Suggestive
Ischemic strokeOpen Targets
0.02Suggestive
leukemiaOpen Targets
0.01Suggestive
cancerOpen Targets
0.01Suggestive
retinitis pigmentosa 1Open Targets
0.01Suggestive
Cognitive impairmentOpen Targets
0.01Suggestive
22q11.2 deletion syndromeOpen Targets
0.01Suggestive
transient ischemic attackOpen Targets
0.01Suggestive
adrenal cortex carcinomaOpen Targets
0.01Suggestive
SepsisOpen Targets
0.01Suggestive
metabolic diseaseOpen Targets
0.01Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
OS9Protein interaction100%UBXN10Protein interaction100%IFT74Protein interaction99%SELENOSProtein interaction98%UBE4AProtein interaction97%UBCProtein interaction97%
Tissue Expression6 tissues
Bone Marrow
100%
Liver
88%
Lung
78%
Heart
52%
Brain
49%
Ovary
43%
Gene Interaction Network
Click a node to explore
UFD1OS9UBXN10IFT74SELENOSUBE4AUBC
PROTEIN STRUCTURE
Preparing viewer…
PDB5B6C · 1.55 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.44Moderately Constrained
pLIⓘ
1.00Intolerant
Observed/Expected LoF0.28 [0.18–0.44]
RankingsWhere UFD1 stands among ~20K protein-coding genes
  • #2,680of 20,598
    Most Researched167 · top quartile
  • #2,381of 17,882
    Most Constrained (LOEUF)0.44 · top quartile
Genes detectedUFD1
Sources retrieved25 papers
Response time—
📄 Sources
25▼
1
VCP/p97 UFMylation stabilizes BECN1 and facilitates the initiation of autophagy.
PMID: 38762759
Autophagy · 2024
1.00
2
Targeting DTX2/UFD1-mediated FTO degradation to regulate antitumor immunity.
PMID: 39661064
Proc Natl Acad Sci U S A · 2024
0.90
3
PLAC8 attenuates pulmonary fibrosis and inhibits apoptosis of alveolar epithelial cells via facilitating autophagy.
PMID: 39810019
Commun Biol · 2025
0.80
4
Structural basis for the interaction between human Npl4 and Npl4-binding motif of human Ufd1.
PMID: 36087575
Structure · 2022
0.70
5
Adaptor-Specific Peptide Inhibitors of the Ubiquitin-Chain-Dependent Unfolding Activity of the Human p97(VCP)-UFD1-NPL4 Complex.
PMID: 40421687
J Med Chem · 2025
0.60