UBR4

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

Basic information

Region (hg38): 1:19074509-19210266

Previous symbols: [ "ZUBR1" ]

Links

ENSG00000127481 ∙ NCBI:23352 ∙ OMIM:609890 ∙ HGNC:30313 ∙ Uniprot:Q5T4S7 ∙ 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 UBR4 gene.

• Inborn genetic diseases (143 variants)
• not provided (121 variants)
• UBR4-related condition (3 variants)
• Short stature (3 variants)
• UBR4-associated neurodevelopmental syndrome (2 variants)
• Developmental disorder (1 variants)
• Neurodevelopmental disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the UBR4 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				41	22	63
missense			154	10	5	169
nonsense			1			1
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)			1			1
splice region			1	15	5	21
non coding					10	10
Total	0	0	156	51	37

Variants in UBR4

This is a list of pathogenic ClinVar variants found in the UBR4 region.

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

Position	Type	Phenotype	Significance	ClinVar
1-19074837-G-T		not specified	Uncertain significance (Feb 12, 2024)
1-19074873-G-C		not specified	Uncertain significance (Feb 12, 2024)
1-19074877-G-A		UBR4-related disorder	Likely benign (Jul 30, 2019)
1-19076793-A-G		not specified	Uncertain significance (Jun 05, 2023)
1-19076803-G-C		not specified	Uncertain significance (Feb 28, 2023)
1-19076827-T-C		not specified	Uncertain significance (Jan 17, 2024)
1-19076858-G-A		UBR4-related disorder	Benign (Jan 29, 2020)
1-19076883-G-A		not specified	Uncertain significance (Nov 07, 2022)
1-19076890-T-C		not specified	Uncertain significance (Nov 09, 2021)
1-19076896-G-A		not specified	Uncertain significance (Mar 17, 2023)
1-19076906-C-A		UBR4-related disorder	Benign (Sep 17, 2019)
1-19078028-C-T			Uncertain significance (Apr 01, 2023)
1-19078034-G-A		not specified	Uncertain significance (Oct 26, 2022)
1-19078035-C-T		not specified	Uncertain significance (Feb 15, 2023)
1-19078036-G-A			Likely benign (Jun 15, 2018)
1-19078075-G-C		UBR4-related disorder	Benign (Jun 03, 2019)
1-19081341-G-A		UBR4-related disorder	Likely benign (Jun 10, 2019)
1-19081374-C-T		not specified	Uncertain significance (Mar 01, 2023)
1-19081376-C-T		not specified	Uncertain significance (Jun 24, 2022)
1-19081403-C-T		not specified	Uncertain significance (Dec 13, 2023)
1-19081412-T-C		not specified	Uncertain significance (Feb 03, 2022)
1-19081412-T-G		not specified	Uncertain significance (Apr 20, 2023)
1-19081419-G-A		not specified	Uncertain significance (Nov 03, 2022)
1-19081422-T-C		not specified	Uncertain significance (Nov 29, 2021)
1-19081520-G-A			Likely benign (Mar 01, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
UBR4	protein_coding	protein_coding	ENST00000375254	106	135771

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	2.04e-30	125712	0	36	125748	0.000143

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	5.68	2000	2.85e+3	0.701	0.000166	33939
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000362	0.000239
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.000277	0.000277
European (Non-Finnish)	0.000177	0.000176
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000981	0.0000980
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. 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}.
• Pathway: Viral carcinogenesis - Homo sapiens (human);Human papillomavirus infection - Homo sapiens (human);Neutrophil degranulation;Innate Immune System;Immune System;Adaptive Immune System;Antigen processing: Ubiquitination & Proteasome degradation;Class I MHC mediated antigen processing & presentation (Consensus)

Recessive Scores

• pRec: 0.127

Intolerance Scores

• loftool: 0.297
• rvis_EVS: -7.5
• rvis_percentile_EVS: 0.01

Haploinsufficiency Scores

• pHI: 0.257
• hipred: Y
• hipred_score: 0.625
• ghis: 0.643

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.911

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ubr4
• Phenotype: growth/size/body region phenotype; cellular phenotype; embryo phenotype; liver/biliary system phenotype; 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); 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); 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)

Gene ontology

• Biological process: ubiquitin-dependent protein catabolic process;viral process;protein ubiquitination;neutrophil degranulation
• Cellular component: nucleoplasm;centrosome;cytosol;plasma membrane;membrane;integral component of membrane;specific granule membrane;tertiary granule membrane;ficolin-1-rich granule membrane
• Molecular function: ubiquitin-protein transferase activity;protein binding;calmodulin binding;zinc ion binding