UBR2

ubiquitin protein ligase E3 component n-recognin 2, the group of Ubiquitin protein ligase E3 component n-recognins

Basic information

Region (hg38): 6:42564029-42693505

Previous symbols: [ "C6orf133" ]

Links

ENSG00000024048 ∙ NCBI:23304 ∙ OMIM:609134 ∙ HGNC:21289 ∙ Uniprot:Q8IWV8 ∙ 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 UBR2 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the UBR2 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				4	2	6
missense			73	2		75
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				1		1
non coding				7		7
Total	0	0	73	13	2

Variants in UBR2

This is a list of pathogenic ClinVar variants found in the UBR2 region.

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

Position	Type	Phenotype	Significance	ClinVar
6-42564319-G-A			Likely benign (Apr 01, 2023)
6-42564343-G-T		not specified	Uncertain significance (Aug 08, 2022)
6-42564367-G-C		not specified	Uncertain significance (Feb 17, 2024)
6-42564388-G-C		not specified	Uncertain significance (Aug 02, 2023)
6-42573754-C-A		not specified	Uncertain significance (Oct 11, 2024)
6-42573783-C-A		not specified	Uncertain significance (Jun 01, 2023)
6-42573783-C-T		not specified	Uncertain significance (Jun 24, 2022)
6-42573812-G-A		not specified	Uncertain significance (Nov 03, 2022)
6-42573813-G-C		not specified	Uncertain significance (May 17, 2023)
6-42573840-A-G		not specified	Uncertain significance (Oct 25, 2023)
6-42573872-A-G		not specified	Uncertain significance (Jun 24, 2022)
6-42573873-T-C		not specified	Uncertain significance (Dec 03, 2021)
6-42573956-C-A		not specified	Uncertain significance (Nov 30, 2021)
6-42573957-G-A		not specified	Uncertain significance (Apr 09, 2024)
6-42592200-G-A		not specified	Uncertain significance (Jan 04, 2024)
6-42594296-G-A		not specified	Uncertain significance (Oct 25, 2023)
6-42603605-A-G			Likely benign (Sep 01, 2022)
6-42603654-C-T		not specified	Uncertain significance (Sep 25, 2024)
6-42603687-G-C		not specified	Uncertain significance (Jul 16, 2024)
6-42605721-A-G			Likely benign (Jul 01, 2022)
6-42605846-C-T		not specified	Uncertain significance (Dec 14, 2023)
6-42605857-G-A		not specified	Uncertain significance (Oct 29, 2024)
6-42606593-G-A		not specified	Uncertain significance (Jan 03, 2024)
6-42606605-G-A		not specified	Uncertain significance (Mar 19, 2024)
6-42606623-A-T		not specified	Uncertain significance (Aug 17, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
UBR2	protein_coding	protein_coding	ENST00000372899	47	129443

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	2.23e-7	125714	0	34	125748	0.000135

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.15	651	919	0.708	0.0000468	11595
Missense in Polyphen		115	215.97	0.53247		2585
Synonymous	0.252	306	312	0.982	0.0000160	3123
Loss of Function	8.33	15	109	0.138	0.00000558	1347

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000180	0.000179
Ashkenazi Jewish	0.000201	0.000198
East Asian	0.000110	0.000109
Finnish	0.0000463	0.0000462
European (Non-Finnish)	0.000223	0.000211
Middle Eastern	0.000110	0.000109
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. Plays a critical role in chromatin inactivation and chromosome-wide transcriptional silencing during meiosis via ubiquitination of histone H2A. Binds leucine and is a negative regulator of the leucine-mTOR signaling pathway, thereby controlling cell growth. Required for spermatogenesis, promotes, with Tex19.1, SPO11-dependent recombination foci to accumulate and drive robust homologous chromosome synapsis (By similarity). Polyubiquitinates LINE-1 retrotransposon encoded, LIRE1, which induces degradation, inhibiting LINE-1 retranstoposon mobilization (By similarity). {ECO:0000250|UniProtKB:Q6WKZ8, ECO:0000269|PubMed:15548684, ECO:0000269|PubMed:20298436, ECO:0000269|PubMed:20835242}.
• Pathway: Immune System;Adaptive Immune System;Antigen processing: Ubiquitination & Proteasome degradation;Class I MHC mediated antigen processing & presentation (Consensus)

Recessive Scores

• pRec: 0.259

Intolerance Scores

• loftool: 0.470
• rvis_EVS: -1.37
• rvis_percentile_EVS: 4.52

Haploinsufficiency Scores

• pHI: 0.728
• hipred: Y
• hipred_score: 0.696
• ghis: 0.577

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.821

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	High
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Ubr2
• 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); reproductive system phenotype; 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); growth/size/body region phenotype; endocrine/exocrine gland phenotype; muscle phenotype; homeostasis/metabolism phenotype; cellular phenotype

Gene ontology

• Biological process: protein polyubiquitination;chromatin silencing;reciprocal meiotic recombination;male meiotic nuclear division;male meiosis I;spermatogenesis;negative regulation of transposition;protein ubiquitination;negative regulation of TOR signaling;histone H2A ubiquitination;cellular response to leucine;ubiquitin-dependent protein catabolic process via the N-end rule pathway
• Cellular component: ubiquitin ligase complex;chromatin;nucleus;cytoplasm;cytosol
• Molecular function: ubiquitin-protein transferase activity;protein binding;zinc ion binding;ubiquitin protein ligase activity;leucine binding