UBB
protein-codingubiquitin B
Gene summary
This gene encodes ubiquitin, one of the most conserved proteins known. Ubiquitin has a major role in targeting cellular proteins for degradation by the 26S proteosome. It is also involved in the maintenance of chromatin structure, the regulation of gene expression, and the stress response. Ubiquitin is synthesized as a precursor protein consisting of either polyubiquitin chains or a single ubiquitin moiety fused to an unrelated protein. This gene consists of three direct repeats of the ubiquitin coding sequence with no spacer sequence. Consequently, the protein is expressed as a polyubiquitin precursor with a final amino acid after the last repeat. An aberrant form of this protein has been detected in patients with Alzheimer's disease and Down syndrome. Pseudogenes of this gene are located on chromosomes 1, 2, 13, and 17. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~1.9 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0007336
Submitter: Labcorp Genetics (formerly Invitae)
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to UBB variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_018955.4. 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 | 8 | 1 | 9 | |||
| missense | 5 | 5 | ||||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 6 | 8 | 1 | 15 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_061828.1 | 1 | MANE Select | |
| Ensembl | ENSP00000304697.3 | 1 | MANE Select | |
| RefSeq | NP_001268645.1 | 1 | Standard | |
| RefSeq | NP_001268646.1 | 1 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Kaposi,s sarcoma-associated herpesvirus infection - Homo sapiens (human)
- Endocytosis - Homo sapiens (human)
- Mitophagy - animal - Homo sapiens (human)
- Parkinson,s disease - Homo sapiens (human)
- Proteasome Degradation
Biological Process
- negative regulation of transcription by RNA polymerase II
- activation of MAPK activity
- protein polyubiquitination
- nucleotide-excision repair, DNA damage recognition
- MyD88-dependent toll-like receptor signaling pathway
Molecular Function
- protein binding
- protein tag
- ubiquitin protein ligase binding
Cellular Component
- extracellular space
- nucleus
- nucleoplasm
- cytoplasm
- mitochondrion
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000302182
- Coding exons
- 1
- Length
- 1948
- Individuals with no LoFs
- 125730
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 16
- Defined
- 125746
- p
- 0.0000636
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.73 | 40 | 127 | 0.316 | 0.00000756 | 1494 |
| Missense (PolyPhen) | 6 | 17.044 | 0.35203 | 265 | ||
| Synonymous | -6.61 | 114 | 52.8 | 2.16 | 0.00000331 | 458 |
| Loss of Function | 0.733 | 3 | 4.72 | 0.636 | 2.12e-7 | 62 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00012 | 0.00012 | rare |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.000092 | 0.000092 | rare |
| European (Non-Finnish) | 0.000053 | 0.000053 | rare |
| South Asian | 0.00016 | 0.00016 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Ubiquitin: Exists either covalently attached to another protein, or free (unanchored). When covalently bound, it is conjugated to target proteins via an isopeptide bond either as a monomer (monoubiquitin), a polymer linked via different Lys residues of the ubiquitin (polyubiquitin chains) or a linear polymer linked via the initiator Met of the ubiquitin (linear polyubiquitin chains). Polyubiquitin chains, when attached to a target protein, have different functions depending on the Lys residue of the ubiquitin that is linked: Lys-6-linked may be involved in DNA repair; Lys-11-linked is involved in ERAD (endoplasmic reticulum-associated degradation) and in cell-cycle regulation; Lys-29-linked is involved in lysosomal degradation; Lys-33-linked is involved in kinase modification; Lys-48-linked is involved in protein degradation via the proteasome; Lys-63-linked is involved in endocytosis, DNA-damage responses as well as in signaling processes leading to activation of the transcription factor NF-kappa-B. Linear polymer chains formed via attachment by the initiator Met lead to cell signaling. Ubiquitin is usually conjugated to Lys residues of target proteins, however, in rare cases, conjugation to Cys or Ser residues has been observed. When polyubiquitin is free (unanchored-polyubiquitin), it also has distinct roles, such as in activation of protein kinases, and in signaling. {ECO:0000269|PubMed:16543144, ECO:0000269|PubMed:19754430}.;
Recessive Scores
- pRec
- 0.194
Intolerance Scores
- LoFtool
- 0.370
- RVIS EVS
- -0.16
- RVIS percentile EVS
- 41.25
Essentials
- Essential (CRISPR)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.995