UBR3

protein-coding

ubiquitin protein ligase E3 component n-recognin 3, the group of Ubiquitin protein ligase E3 component n-recognins

Gene summary

Predicted to enable ubiquitin protein ligase activity. Predicted to be involved in several processes, including sensory perception of smell; suckling behavior; and ubiquitin-dependent protein catabolic process via the N-end rule pathway. Predicted to act upstream of or within in utero embryonic development and olfactory behavior. Predicted to be located in membrane. Predicted to be part of ubiquitin ligase complex. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Jul 2025]

Previous symbols:

ZNF650

MANE transcript

NM_172070.4

Inheritance

—

ClinVar variants

U:169B:18

Top phenotype

UBR3-related disorder

gnomAD constraint

pLI —, LoF o/e 0.07

Max pathogenic AF

—

Genomic locus

chr2:169,827,454-170,084,131

External References & Databases

Ensembl (ENSG00000144357)

Transcript & Mutation Effects

hg38 • Region Span ~256.7 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 UBR3 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 159

UBR3-related disorderTotal: 18

not providedTotal: 7

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_172070.4. 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			1 clinvar	8 clinvar	3 clinvar	12
missense			162 clinvar	6 clinvar		168
nonsense						0
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			5 clinvar	1 clinvar		6
Total	0	0	169	15	3	187

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 26 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_172070.4	RefSeq	NP_742067.3	39	MANE Select
ENST00000272793.11	Ensembl	ENSP00000272793.5	39	MANE Select
ENST00000392632.6	Ensembl	ENSP00000376409.2	19	Standard
ENST00000430321.5	Ensembl	ENSP00000415982.1	8	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
ubr3	Danio rerio	Structure: whole organism Quality: has extra parts of type abnormal

Gene / Model

Organism

Observed Phenotype

ubr3

Danio rerio

Structure: whole organism

Quality: has extra parts of type

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

in utero embryonic development
suckling behavior
ubiquitin-dependent protein catabolic process
sensory perception of smell
embryo development ending in birth or egg hatching

Molecular Function

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

Cellular Component

ubiquitin ligase complex
cytoplasm
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000418381
Coding exons: 39
Length: 256674
Individuals with no LoFs: 125731
Homozygous LoFs: 0
Heterozygous LoFs: 13
Defined: 125744
p: 0.0000517

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	4.43	468	826	0.566	0.0000410	12375
Missense (PolyPhen)		159	375.34	0.42362		5576
Synonymous	2.02	244	288	0.848	0.0000149	3446
Loss of Function	8.25	6	90.9	0.0660	0.00000452	1296

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.000063	0.000058	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000054	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000072	0.000070	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 (By similarity). Does not bind 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). May play a role in Shh signaling by mediating the ubiquitination of Kif7 (By similarity). May be important for MYH9 function in certain tissues, possibly by regulating the ubiquitination of MYH9 and consequently affecting its interaction with MYO7A (PubMed:27331610). {ECO:0000250|UniProtKB:Q5U430, ECO:0000269|PubMed:27331610}.;

Intolerance Scores

LoFtool: 0.401
RVIS EVS: -1.04
RVIS percentile EVS: 7.71

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Indispensability pred.: E
Indispensability score: 0.859

Gene Damage Prediction

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