UBR4

protein-coding

ubiquitin protein ligase E3 component n-recognin 4, the group of Armadillo like helical domain containing|Ubiquitin protein ligase E3 component n-recognins

Gene summary

The protein encoded by this gene is an E3 ubiquitin-protein ligase that interacts with the retinoblastoma-associated protein in the nucleus and with calcium-bound calmodulin in the cytoplasm. The encoded protein appears to be a cytoskeletal component in the cytoplasm and part of the chromatin scaffold in the nucleus. In addition, this protein is a target of the human papillomavirus type 16 E7 oncoprotein. [provided by RefSeq, Aug 2010]

Previous symbols:

ZUBR1

MANE transcript

NM_020765.3

Inheritance

ClinVar variants

P:3U:579B:116

Top phenotype

UBR4-related disorder

gnomAD constraint

pLI —, LoF o/e 0.06

Max pathogenic AF

—

Genomic locus

chr1:19,074,510-19,210,266

External References & Databases

Ensembl (ENSG00000127481)

Transcript & Mutation Effects

hg38 • Region Span ~135.8 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

hereditary episodic ataxiaMODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0016227

Submitter: PanelApp Australia

hereditary ataxiaLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0100309

Submitter: PMGRC

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to UBR4 variants in ClinVar

9 Conditions Cataloged

not specifiedTotal: 519

not providedTotal: 123

UBR4-related disorderTotal: 82

Short statureTotal: 6

Long QT syndromeTotal: 4

UBR4-associated neurodevelopmental syndromeTotal: 2

Neurodevelopmental disorderTotal: 1

Premature ovarian insufficiencyTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_020765.3. 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			9 clinvar	71 clinvar	22 clinvar	102
missense		3 clinvar	549 clinvar	16 clinvar	7 clinvar	575
nonsense			1 clinvar			1
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			19 clinvar			19
Total	0	3	579	87	29	698

Highest pathogenic variant AF is 0.000019826395

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 60 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_020765.3	RefSeq	NP_065816.2	106	MANE Select
ENST00000375254.8	Ensembl	ENSP00000364403.3	106	MANE Select
ENST00000375218.3	Ensembl	ENSP00000364366.3	4	Standard
ENST00000375224.1	Ensembl	ENSP00000364372.1	20	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Viral carcinogenesis - Homo sapiens (human)
Human papillomavirus infection - Homo sapiens (human)
Neutrophil degranulation
Innate Immune System
Immune System

Biological Process

ubiquitin-dependent protein catabolic process
viral process
protein ubiquitination
neutrophil degranulation

Molecular Function

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

Cellular Component

nucleoplasm
centrosome
cytosol
plasma membrane
membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000375254
Coding exons: 106
Length: 135771
Individuals with no LoFs: 125712
Homozygous LoFs: 0
Heterozygous LoFs: 36
Defined: 125748
p: 0.000143

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	5.68	2000	2.85e+3	0.701	0.000166	33939
Missense (PolyPhen)		638	1172.3	0.54421		13707
Synonymous	-0.452	1142	1.12e+3	1.02	0.0000656	10271
Loss of Function	13.9	16	255	0.0628	0.0000129	3054

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00025	0.00012	rare
Latino/Admixed American	0.00012	0.00012	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000054	0.000054	rare
Finnish	0.00028	0.00028	rare
European (Non-Finnish)	0.00018	0.00018	rare
South Asian	0.000098	0.000098	rare
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. Together with clathrin, forms meshwork structures involved in membrane morphogenesis and cytoskeletal organization. Regulates integrin-mediated signaling. May play a role in activation of FAK in response to cell-matrix interactions. Mediates ubiquitination of ACLY, leading to its subsequent degradation. {ECO:0000269|PubMed:16214886, ECO:0000269|PubMed:23932781}.;

Recessive Scores

pRec: 0.127

Intolerance Scores

LoFtool: 0.297
RVIS EVS: -7.5
RVIS percentile EVS: 0.01

Essentials

Essential (CRISPR): E
Essential (CRISPR2): E
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.911

Gene Damage Prediction

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