UBD
protein-codingubiquitin D
Gene summary
This gene encodes a protein which contains two ubiquitin-like domains and appears to have similar function to ubiquitin. Through covalent attachment, the encoded protein targets other proteins for 26S proteasome degradation. This protein has been implicated to function in many cellular processes, including caspase-dependent apoptosis, formation of aggresomes, mitotic regulation, and dendritic cell maturation. Upregulation of this gene may promote inflammation in chronic kidney disease and has been observed in many cancer types. [provided by RefSeq, Aug 2017]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~4.2 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 UBD variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_006398.4. 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 | 0 | |||||
| missense | 21 | 4 | 1 | 26 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 22 | 4 | 1 | 27 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_006389.2 | 2 | MANE Select | |
| Ensembl | ENSP00000366249.4 | 2 | MANE Select | |
| Ensembl | ENSP00000536199.1 | 3 | Standard | |
| Ensembl | ENSP00000536199.1 | 3 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Post-translational protein modification
- Metabolism of proteins
- Neddylation
Biological Process
- proteolysis
- ubiquitin-dependent protein catabolic process
- protein ubiquitination
- protein modification by small protein conjugation
- response to interferon-gamma
Molecular Function
- protein binding
- proteasome binding
Cellular Component
- fibrillar center
- nucleus
- cytoplasm
- cytosol
- aggresome
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000377050
- Coding exons
- 2
- Length
- 4411
- Individuals with no LoFs
- 123379
- Homozygous LoFs
- 1
- Heterozygous LoFs
- 54
- Defined
- 123434
- p
- 0.000223
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.236 | 85 | 91.3 | 0.931 | 0.00000489 | 1066 |
| Missense (PolyPhen) | 23 | 23.841 | 0.96471 | 331 | ||
| Synonymous | 0.418 | 33 | 36.2 | 0.912 | 0.00000200 | 326 |
| Loss of Function | 0.0758 | 3 | 3.15 | 0.954 | 1.31e-7 | 48 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000066 | 0.000066 | rare |
| Latino/Admixed American | 0.0013 | 0.0012 | notable |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000090 | 0.000090 | rare |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Ubiquitin-like protein modifier which can be covalently attached to target protein and subsequently leads to their degradation by the 26S proteasome, in a NUB1-dependent manner. Probably functions as a survival factor. Conjugation ability activated by UBA6. Promotes the expression of the proteasome subunit beta type-9 (PSMB9/LMP2). Regulates TNF-alpha-induced and LPS-mediated activation of the central mediator of innate immunity NF-kappa-B by promoting TNF-alpha-mediated proteasomal degradation of ubiquitinated-I-kappa-B-alpha. Required for TNF-alpha-induced p65 nuclear translocation in renal tubular epithelial cells (RTECs). May be involved in dendritic cell (DC) maturation, the process by which immature dendritic cells differentiate into fully competent antigen-presenting cells that initiate T-cell responses. Mediates mitotic non-disjunction and chromosome instability, in long-term in vitro culture and cancers, by abbreviating mitotic phase and impairing the kinetochore localization of MAD2L1 during the prometaphase stage of the cell cycle. May be involved in the formation of aggresomes when proteasome is saturated or impaired. Mediates apoptosis in a caspase-dependent manner, especially in renal epithelium and tubular cells during renal diseases such as polycystic kidney disease and Human immunodeficiency virus (HIV)- associated nephropathy (HIVAN). {ECO:0000269|PubMed:15831455, ECO:0000269|PubMed:16495226, ECO:0000269|PubMed:16495380, ECO:0000269|PubMed:17889673, ECO:0000269|PubMed:18574467, ECO:0000269|PubMed:19028597, ECO:0000269|PubMed:19033385, ECO:0000269|PubMed:19166848, ECO:0000269|PubMed:19726511, ECO:0000269|PubMed:19959714}.;
Intolerance Scores
- LoFtool
- 0.501
- RVIS EVS
- 1.66
- RVIS percentile EVS
- 96.23
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.543
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | High |
| Cancer | Medium | Medium | Medium |