UBR1

ubiquitin protein ligase E3 component n-recognin 1, the group of Ubiquitin protein ligase E3 component n-recognins

Basic information

Region (hg38): 15:42942897-43106113

Links

ENSG00000159459 ∙ NCBI:197131 ∙ OMIM:605981 ∙ HGNC:16808 ∙ Uniprot:Q8IWV7 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Johanson-Blizzard syndrome (Definitive), mode of inheritance: AR
• Johanson-Blizzard syndrome (Strong), mode of inheritance: AR
• Johanson-Blizzard syndrome (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Johanson-Blizzard syndrome	AR	Audiologic/Otolaryngologic; Cardiovascular; Endocrine; Gastrointestinal; Hematologic	Medical treatment of exocrine pancreatic insufficiency can be beneficial; Awareness of cardiovascular manifestastions (which can include structural malformations as well as cardiomyopathy) can allow early diagnosis and treatment; As the condition can include congenital deafness, early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; Treatment of endocrine manifestations, such as hypothyroidism, growth hormone deficiency, and diabetes mellitus, can be beneficial; Severe anemia requiring transfusions has been described, and awareness may allow prompt diagnosis and treatment	Audiologic/Otolaryngologic; Craniofacial; Dental; Dermatologic; Cardiovascular; Endocrine; Gastrointestinal; Hematologic; Neurologic; Ophthalmologic	5171616; 728568; 474625; 4050852; 2645405; 12535044; 12725595; 14647752; 15379429; 16311597; 16632090; 17378628; 18553553; 19058315; 19006206; 19717322; 20556423; 21931868; 20556422; 21429315; 21711208; 22072859; 23463671; 23778732; 24052374

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the UBR1 gene.

• not_provided (932 variants)
• Inborn_genetic_diseases (159 variants)
• Johanson-Blizzard_syndrome (40 variants)
• UBR1-related_disorder (36 variants)
• not_specified (20 variants)
• Microcephaly (2 variants)
• Intellectual_disability (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the UBR1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000174916.3. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	361	20	382
missense	1	7	205	45	5	263
nonsense	18	2				20
start loss						0
frameshift	14	6				20
splice donor/acceptor (+/-2bp)	4	17	2			23
Total	37	32	208	406	25

Highest pathogenic variant AF is 0.00005763367

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
UBR1	protein_coding	protein_coding	ENST00000290650	47	163217

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00549	0.995	125704	0	44	125748	0.000175

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.40	714	918	0.777	0.0000463	11593
Missense in Polyphen		146	279.14	0.52303		3529
Synonymous	-0.546	319	307	1.04	0.0000155	3135
Loss of Function	7.15	27	107	0.253	0.00000531	1329

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000478	0.000478
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.0000544	0.0000544
Finnish	0.0000925	0.0000924
European (Non-Finnish)	0.000187	0.000185
Middle Eastern	0.0000544	0.0000544
South Asian	0.000229	0.000229
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. May be involved in pancreatic homeostasis. Binds leucine and is a negative regulator of the leucine-mTOR signaling pathway, thereby controlling cell growth. {ECO:0000269|PubMed:15548684, ECO:0000269|PubMed:16311597, ECO:0000269|PubMed:20298436, ECO:0000269|PubMed:20835242}.
• Disease: DISEASE: Johanson-Blizzard syndrome (JBS) [MIM:243800]: This disorder includes congenital exocrine pancreatic insufficiency, multiple malformations such as nasal wing aplasia, and frequent mental retardation. Pancreas of individuals with JBS do not express UBR1 and show intrauterine-onset destructive pancreatitis. {ECO:0000269|PubMed:16311597, ECO:0000269|PubMed:21931868, ECO:0000269|PubMed:22072859, ECO:0000269|PubMed:24599544, ECO:0000269|PubMed:26149651}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: protein ubiquitylation;Immune System;Adaptive Immune System;Antigen processing: Ubiquitination & Proteasome degradation;Class I MHC mediated antigen processing & presentation (Consensus)

Recessive Scores

• pRec: 0.194

Intolerance Scores

• loftool: 0.598
• rvis_EVS: -0.63
• rvis_percentile_EVS: 16.81

Haploinsufficiency Scores

• pHI: 0.655
• hipred: N
• hipred_score: 0.488
• ghis: 0.607

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.775

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ubr1
• Phenotype: growth/size/body region phenotype; endocrine/exocrine gland phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); homeostasis/metabolism phenotype; cellular phenotype; muscle 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); 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); embryo phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); digestive/alimentary phenotype

Gene ontology

• Biological process: protein ubiquitination;negative regulation of TOR signaling;cellular response to leucine;ubiquitin-dependent protein catabolic process via the N-end rule pathway
• Cellular component: ubiquitin ligase complex;proteasome complex;cytoplasm;cytosol
• Molecular function: protein binding;zinc ion binding;ubiquitin protein ligase activity;leucine binding