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): 8:102252272-102412759

Previous symbols: [ "EDD1" ]

Links

ENSG00000104517 ∙ NCBI:51366 ∙ OMIM:608413 ∙ HGNC:16806 ∙ Uniprot:O95071 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the UBR5 gene.

• Inborn genetic diseases (36 variants)
• not provided (22 variants)
• UBR5-related condition (4 variants)
• - (2 variants)
• UBR5-related diseases (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.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				13	1	14
missense			40	1		41
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			1	1	3	5
non coding					2	2
Total	0	0	40	14	3

Variants in UBR5

This is a list of pathogenic ClinVar variants found in the UBR5 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
8-102254355-G-T		not specified	Uncertain significance (Sep 21, 2023)
8-102254491-T-C			Likely benign (Jul 01, 2022)
8-102259029-T-C		not specified	Uncertain significance (Oct 26, 2022)
8-102259073-C-T		UBR5-related disorder	Likely benign (Aug 01, 2019)
8-102261188-G-A		UBR5-related disorder	Likely benign (Jul 01, 2022)
8-102261956-C-A		not specified	Uncertain significance (Aug 10, 2023)
8-102262068-G-C			Benign (Feb 01, 2023)
8-102264525-T-G		UBR5-related disorder	Benign (Oct 28, 2019)
8-102265200-T-A		not specified	Uncertain significance (Jun 11, 2021)
8-102265239-C-A		UBR5-related disorder	Uncertain significance (Mar 14, 2023)
8-102270047-T-C		not specified	Uncertain significance (Feb 01, 2023)
8-102270190-G-T		UBR5-related disorder	Benign (Oct 28, 2019)
8-102271248-A-G		UBR5-related disorder	Likely benign (Jun 19, 2019)
8-102272596-T-C		UBR5-related disorder	Likely benign (Sep 17, 2019)
8-102275601-C-G		not specified	Uncertain significance (Aug 04, 2023)
8-102275616-G-A			Likely benign (Aug 01, 2022)
8-102275619-T-C		not specified	Uncertain significance (Sep 16, 2021)
8-102275711-T-A			Likely benign (Oct 01, 2022)
8-102275736-A-G		not specified	Uncertain significance (May 25, 2023)
8-102275748-C-G			Uncertain significance (Dec 07, 2017)
8-102275750-G-A		UBR5-related disorder	Likely benign (Feb 01, 2024)
8-102276978-G-A		not specified	Uncertain significance (Oct 20, 2021)
8-102277028-G-A		UBR5-related disorder	Likely benign (Jul 12, 2019)
8-102277140-A-G		UBR5-related disorder	Uncertain significance (Nov 21, 2023)
8-102277147-T-C		not specified	Uncertain significance (May 31, 2022)

GnomAD

Source: gnomAD

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: dbNSFP

• 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