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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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UBXN4
UBX domain protein 4
Chromosome 2 · 2q21.3
NCBI Gene: 23190Ensembl: ENSG00000144224.18HGNC: HGNC:14860UniProt: Q92575
85PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingERAD pathwayendoplasmic reticulumnuclear envelopeneurodegenerative diseaseessential tremorobesityPrecordial pain
✦AI Summary

UBXN4 (UBX domain protein 4) functions as a critical platform protein in endoplasmic reticulum-associated protein degradation (ERAD), recruiting both UBQLN1 and VCP to the ER during the degradation of misfolded proteins 1. The protein participates in cellular proteostasis regulation, with its dysfunction potentially precipitating inflammatory stress 2. UBXN4 is subject to proteasomal regulation during cellular processes, as demonstrated in sperm capacitation where it becomes less abundant following proteasomal inhibition 3. The gene shows involvement in WNT signaling pathway regulation through interactions with EVI/WLS, linking it to the ubiquitin-proteasome system 4. Genetic studies have identified UBXN4 as a shared susceptibility gene between obesity and metabolic disorders, potentially involving cholesterol metabolism regulation 5. Additionally, UBXN4 expression is influenced by genomic variants in the 2q21.3 chr2 region, particularly in immune cells where it may impact neutrophil and white blood cell counts 6. The gene appears in multiple disease contexts including inflammatory bowel disease, where it functions as a potential mediator of protective microbial effects 2, and serves as a potential prognostic marker in lung cancer 7.

Sources cited
1
UBXN4 acts as a platform to recruit both UBQLN1 and VCP to the ER during ERAD
PMID: 19822669
2
UBXN4 abundance decreases during proteasomal inhibition in sperm capacitation
PMID: 37371576
3
UBXN4 interacts with EVI/WLS in WNT signaling pathway regulation
PMID: 34406391
4
UBXN4 is a shared susceptibility gene for obesity and metabolic disorders, potentially involving cholesterol metabolism
PMID: 39999931
5
UBXN4 expression is affected by 2q21.3 genomic variants and impacts immune cell counts
PMID: 40063818
6
UBXN4 functions as a critical regulator of cellular proteostasis and mediates protective effects in IBD
PMID: 41695715
7
UBXN4 serves as a potential prognostic marker in lung cancer
PMID: 32699134
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.36Weak
essential tremorOpen Targets
0.10Weak
obesityOpen Targets
0.07Suggestive
Precordial painOpen Targets
0.06Suggestive
cutaneous lupus erythematosusOpen Targets
0.05Suggestive
metabolic syndromeOpen Targets
0.05Suggestive
muscle strainOpen Targets
0.04Suggestive
sprainOpen Targets
0.04Suggestive
ovarian carcinomaOpen Targets
0.03Suggestive
nutritional deficiency diseaseOpen Targets
0.02Suggestive
ulcerative colitisOpen Targets
0.01Suggestive
Alzheimer diseaseOpen Targets
0.01Suggestive
ataxia telangiectasiaOpen Targets
0.01Suggestive
hepatocellular carcinomaOpen Targets
0.00Suggestive
hereditary spastic paraplegiaOpen Targets
0.00Suggestive
acute quadriplegic myopathyOpen Targets
0.00Suggestive
neoplasmOpen Targets
0.00Suggestive
lung cancerOpen Targets
0.00Suggestive
Dravet syndromeOpen Targets
0.00Suggestive
metabolic diseaseOpen Targets
0.00Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
RNF175Shared pathway100%TMUB1Shared pathway100%SEL1L2Shared pathway100%FOXRED2Shared pathway100%TMUB2Shared pathway100%RNF121Shared pathway100%
Tissue Expression6 tissues
Bone Marrow
100%
Liver
74%
Brain
63%
Heart
61%
Ovary
55%
Lung
53%
Gene Interaction Network
Click a node to explore
UBXN4RNF175TMUB1SEL1L2FOXRED2TMUB2RNF121
PROTEIN STRUCTURE
Preparing viewer…
PDB2KXJ · NMR
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.78LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.56 [0.41–0.78]
RankingsWhere UBXN4 stands among ~20K protein-coding genes
  • #5,650of 20,598
    Most Researched85
  • #6,320of 17,882
    Most Constrained (LOEUF)0.78
Genes detectedUBXN4
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Spatial Density and Distribution of Tumor-Associated Macrophages Predict Survival in Non-Small Cell Lung Carcinoma.
PMID: 32699134
Cancer Res · 2020
1.00
2
Identifying genetic overlaps in obesity and metabolic disorders unlocking unique and shared mechanistic insights.
PMID: 39999931
Free Radic Biol Med · 2025
0.90
3
Genetic variants at the chromosomal region 2q21.3 underlying inhibitor development in patients with severe haemophilia A.
PMID: 35182444
Haemophilia · 2022
0.80
4
The Ubiquitin-Proteasome System Participates in Sperm Surface Subproteome Remodeling during Boar Sperm Capacitation.
PMID: 37371576
Biomolecules · 2023
0.70
5
EVI/WLS function is regulated by ubiquitylation and is linked to ER-associated degradation by ERLIN2.
PMID: 34406391
J Cell Sci · 2021
0.60