UBR5
ubiquitin protein ligase E3 component n-recognin 5, the group of HECT domain containing|Ubiquitin protein ligase E3 component n-recognins
Basic information
Region (hg38): 8:102252273-102412759
Previous symbols: [ "EDD1" ]
Links
Phenotypes
GenCC
Source:
- neurodevelopmental disorder (Moderate), mode of inheritance: AD
- neurodevelopmental disorder (Definitive), mode of inheritance: AD
ClinVar
This is a list of variants' phenotypes submitted to
- not_specified (141 variants)
- not_provided (80 variants)
- UBR5-related_disorder (31 variants)
- NEURODEVELOPMENTAL_DISORDER_WITH_SPEECH_DELAY_AND_BEHAVIORAL_ABNORMALITIES (6 variants)
- Neurodevelopmental_disorder (1 variants)
- Long_QT_syndrome (1 variants)
- UBR5-associated_neurodevelopmental_condition (1 variants)
- UBR5-associated_neurodevelopmental_disorder (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the UBR5 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000015902.6. Only rare variants are included in the table.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 26 | 29 | ||||
| missense | 183 | 192 | ||||
| nonsense | 4 | |||||
| start loss | 0 | |||||
| frameshift | 10 | 10 | ||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 3 | 0 | 198 | 32 | 2 |
Highest pathogenic variant AF is 7.11494e-7
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| UBR5 | protein_coding | protein_coding | ENST00000520539 | 59 | 159830 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 1.00 | 2.03e-22 | 125738 | 0 | 8 | 125746 | 0.0000318 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 6.21 | 843 | 1.53e+3 | 0.553 | 0.0000834 | 18301 |
| Missense in 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 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000617 | 0.0000615 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.0000932 | 0.0000924 |
| European (Non-Finnish) | 0.0000441 | 0.0000440 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
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}.;
- Pathway
- Ubiquitin mediated proteolysis - Homo sapiens (human);Mesodermal Commitment Pathway;Tryptophan metabolism
(Consensus)
Recessive Scores
- pRec
- 0.141
Intolerance Scores
- loftool
- 0.0612
- rvis_EVS
- -2.92
- rvis_percentile_EVS
- 0.57
Haploinsufficiency Scores
- pHI
- 0.819
- hipred
- Y
- hipred_score
- 0.786
- ghis
- 0.711
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- H
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.974
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Ubr5
- Phenotype
- embryo phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); cellular phenotype; growth/size/body region phenotype; craniofacial phenotype; homeostasis/metabolism phenotype;
Gene ontology
- Biological process
- protein polyubiquitination;DNA repair;ubiquitin-dependent protein catabolic process;cellular response to DNA damage stimulus;cell population proliferation;positive regulation of gene expression;viral process;obsolete positive regulation of protein import into nucleus, translocation;progesterone receptor signaling pathway;protein K48-linked ubiquitination;positive regulation of canonical Wnt signaling pathway;negative regulation of histone H2A K63-linked ubiquitination;negative regulation of double-strand break repair
- Cellular component
- nucleus;nucleoplasm;cytosol;membrane;protein-containing complex;perinuclear region of cytoplasm
- Molecular function
- RNA binding;ubiquitin-protein transferase activity;protein binding;zinc ion binding;ubiquitin-ubiquitin ligase activity;ubiquitin binding;ubiquitin protein ligase activity