UBXN1
protein-codingUBX domain protein 1, the group of UBX domain containing
Gene summary
Enables several functions, including enzyme binding activity; polyubiquitin modification-dependent protein binding activity; and proteasome regulatory particle binding activity. Involved in negative regulation of protein metabolic process. Located in cytosol and endoplasmic reticulum. Part of VCP-NPL4-UFD1 AAA ATPase complex. [provided by Alliance of Genome Resources, Jun 2026]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~2.6 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to UBXN1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001286077.2. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 2 | 2 | ||||
| missense | 37 | 1 | 38 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 4 | 4 | ||||
| Total | 0 | 0 | 41 | 3 | 0 | 44 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001273006.1 | 9 | MANE Select | |
| Ensembl | ENSP00000303991.5 | 9 | MANE Select | |
| RefSeq | NP_001273007.1 | 7 | Standard | |
| RefSeq | NP_056937.2 | 8 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Post-translational protein modification
- Metabolism of proteins
- Asparagine N-linked glycosylation
- N-glycan trimming in the ER and Calnexin/Calreticulin cycle
Biological Process
- protein folding
- viral process
- negative regulation of protein ubiquitination
- negative regulation of proteasomal ubiquitin-dependent protein catabolic process
- proteasome-mediated ubiquitin-dependent protein catabolic process
Molecular Function
- protein binding
- polyubiquitin modification-dependent protein binding
- ubiquitin protein ligase binding
- K48-linked polyubiquitin modification-dependent protein binding
- ubiquitin binding
Cellular Component
- nucleus
- cytoplasm
- endoplasmic reticulum
- cytosol
- dendrite
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000294119
- Coding exons
- 8
- Length
- 2598
- Individuals with no LoFs
- 125739
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 9
- Defined
- 125748
- p
- 0.0000358
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.838 | 160 | 193 | 0.830 | 0.0000116 | 1983 |
| Missense (PolyPhen) | 55 | 77.16 | 0.7128 | 814 | ||
| Synonymous | -1.25 | 82 | 68.8 | 1.19 | 0.00000352 | 637 |
| Loss of Function | 3.20 | 3 | 17.4 | 0.172 | 8.50e-7 | 194 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.000095 | 0.000092 | rare |
| European (Non-Finnish) | 0.000027 | 0.000026 | rare |
| South Asian | 0.000065 | 0.000065 | rare |
| Other | 0.00033 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Ubiquitin-binding protein that plays a role in the modulation of innate immune response. Blocks both the RIG-I-like receptors (RLR) and NF-kappa-B pathways. Following viral infection, UBXN1 is induced and recruited to the RLR component MAVS. In turn, interferes with MAVS oligomerization, and disrupts the MAVS/TRAF3/TRAF6 signalosome. This function probably serves as a brake to prevent excessive RLR signaling (PubMed:23545497). Interferes with the TNFalpha-triggered NF-kappa-B pathway by interacting with cellular inhibitors of apoptosis proteins (cIAPs) and thereby inhibiting their recruitment to TNFR1 (PubMed:25681446). Prevents also the activation of NF-kappa-B by associating with CUL1 and thus inhibiting NF-kappa-B inhibitor alpha/NFKBIA degradation that remains bound to NF-kappa-B (PubMed:28152074). Interacts with the BRCA1-BARD1 heterodimer and regulates its activity. Specifically binds 'Lys-6'-linked polyubiquitin chains. Interaction with autoubiquitinated BRCA1 leads to the inhibition of the E3 ubiquitin-protein ligase activity of the BRCA1-BARD1 heterodimer (PubMed:20351172). Component of a complex required to couple deglycosylation and proteasome-mediated degradation of misfolded proteins in the endoplasmic reticulum that are retrotranslocated in the cytosol. {ECO:0000269|PubMed:20351172, ECO:0000269|PubMed:23545497, ECO:0000269|PubMed:25681446, ECO:0000269|PubMed:28152074}.;
Recessive Scores
- pRec
- 0.118
Intolerance Scores
- LoFtool
- 0.415
- RVIS EVS
- 0.48
- RVIS percentile EVS
- 79.04
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.567
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |