UBR2

protein-coding

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

Gene summary

Enables L-leucine binding activity and ubiquitin protein ligase activity. Involved in several processes, including cellular response to L-leucine; protein K63-linked ubiquitination; and regulation of signal transduction. Predicted to be located in cytosol. Predicted to be part of ubiquitin ligase complex. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Jul 2025]

Previous symbols:

C6orf133

MANE transcript

NM_001363705.2

Inheritance

—

ClinVar variants

U:203B:13

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.14

Max pathogenic AF

—

Genomic locus

chr6:42,564,029-42,693,505

External References & Databases

Ensembl (ENSG00000024048)

Transcript & Mutation Effects

hg38 • Region Span ~129.5 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to UBR2 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 185

not providedTotal: 21

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001363705.2. 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			5 clinvar	5 clinvar	1 clinvar	11
missense			179 clinvar	7 clinvar		186
nonsense			4 clinvar			4
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			14 clinvar			14
Total	0	0	203	12	1	216

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 39 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001363705.2	RefSeq	NP_001350634.1	47	MANE Select
ENST00000372901.2	Ensembl	ENSP00000361992.1	47	MANE Select
NM_001184801.2	RefSeq	NP_001171730.1	12	Standard
NM_015255.3	RefSeq	NP_056070.1	47	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Immune System
Adaptive Immune System
Antigen processing: Ubiquitination & Proteasome degradation
Class I MHC mediated antigen processing & presentation

Biological Process

protein polyubiquitination
chromatin silencing
reciprocal meiotic recombination
male meiotic nuclear division
male meiosis I

Molecular Function

ubiquitin-protein transferase activity
protein binding
zinc ion binding
ubiquitin protein ligase activity
leucine binding

Cellular Component

ubiquitin ligase complex
chromatin
nucleus
cytoplasm
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000372899
Coding exons: 47
Length: 129443
Individuals with no LoFs: 125714
Homozygous LoFs: 0
Heterozygous LoFs: 34
Defined: 125748
p: 0.000135

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	3.15	651	919	0.708	0.0000468	11595
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000063	0.000062	rare
Latino/Admixed American	0.00012	0.00012	rare
Ashkenazi Jewish	0.00020	0.00020	rare
East Asian	0.00011	0.00011	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00022	0.00021	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

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}.;

Recessive Scores

pRec: 0.259

Intolerance Scores

LoFtool: 0.470
RVIS EVS: -1.37
RVIS percentile EVS: 4.52

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.821

Gene Damage Prediction

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