UBR5
protein-codingubiquitin protein ligase E3 component n-recognin 5, the group of HECT domain containing|Ubiquitin protein ligase E3 component n-recognins
Gene summary
This gene encodes a progestin-induced protein, which belongs to the HECT (homology to E6-AP carboxyl terminus) family. The HECT family proteins function as E3 ubiquitin-protein ligases, targeting specific proteins for ubiquitin-mediated proteolysis. This gene is localized to chromosome 8q22 which is disrupted in a variety of cancers. This gene potentially has a role in regulation of cell proliferation or differentiation. [provided by RefSeq, Jul 2008]
- EDD1
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~160.5 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0700092
Submitter: G2P
Inheritance Pattern: AD
Disease ID:MONDO:0700092
Submitter: PanelApp Australia
Inheritance Pattern: AD
Disease ID:MONDO:0700092
Submitter: Ambry Genetics
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to UBR5 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_015902.6. 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 | 10 | 33 | 3 | 46 | ||
| missense | 3 | 258 | 9 | 270 | ||
| nonsense | 1 | 7 | 8 | |||
| start loss | 0 | |||||
| frameshift | 1 | 1 | 10 | 12 | ||
| splice donor/acceptor (+/-2bp) | 18 | 18 | ||||
| Total | 5 | 1 | 303 | 42 | 3 | 354 |
Highest pathogenic variant AF is 7.114936e-7
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_056986.2 | 59 | MANE Select | |
| Ensembl | ENSP00000429084.1 | 59 | MANE Select | |
| RefSeq | NP_001269802.1 | 59 | Standard | |
| Ensembl | ENSP00000220959.4 | 59 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Ubiquitin mediated proteolysis - Homo sapiens (human)
- Mesodermal Commitment Pathway
- Tryptophan metabolism
Biological Process
- protein polyubiquitination
- DNA repair
- ubiquitin-dependent protein catabolic process
- cellular response to DNA damage stimulus
- cell population proliferation
Molecular Function
- RNA binding
- ubiquitin-protein transferase activity
- protein binding
- zinc ion binding
- ubiquitin-ubiquitin ligase activity
Cellular Component
- nucleus
- nucleoplasm
- cytosol
- membrane
- protein-containing complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000520539
- Coding exons
- 59
- Length
- 159830
- Individuals with no LoFs
- 125738
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 8
- Defined
- 125746
- p
- 0.0000318
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 6.21 | 843 | 1.53e+3 | 0.553 | 0.0000834 | 18301 |
| Missense (PolyPhen) | 382 | 813.69 | 0.46947 | 9624 | ||
| Synonymous | 1.01 | 492 | 521 | 0.944 | 0.0000270 | 5466 |
| Loss of Function | 11.3 | 6 | 162 | 0.0371 | 0.0000101 | 1782 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.000093 | 0.000092 | rare |
| European (Non-Finnish) | 0.000044 | 0.000044 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: E3 ubiquitin-protein ligase which is a component of the N-end rule pathway. Recognizes and binds to proteins bearing specific N-terminal residues that are destabilizing according to the N-end rule, leading to their ubiquitination and subsequent degradation (By similarity). Involved in maturation and/or transcriptional regulation of mRNA by activating CDK9 by polyubiquitination. May play a role in control of cell cycle progression. May have tumor suppressor function. Regulates DNA topoisomerase II binding protein (TopBP1) in the DNA damage response. Plays an essential role in extraembryonic development. Ubiquitinates acetylated PCK1. Also acts as a regulator of DNA damage response by acting as a suppressor of RNF168, an E3 ubiquitin-protein ligase that promotes accumulation of 'Lys-63'- linked histone H2A and H2AX at DNA damage sites, thereby acting as a guard against excessive spreading of ubiquitinated chromatin at damaged chromosomes. {ECO:0000250, ECO:0000269|PubMed:21127351, ECO:0000269|PubMed:21726808, ECO:0000269|PubMed:22884692}.;
Recessive Scores
- pRec
- 0.141
Intolerance Scores
- LoFtool
- 0.0612
- RVIS EVS
- -2.92
- RVIS percentile EVS
- 0.57
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- H
- Indispensability pred.
- E
- Indispensability score
- 0.974
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |