UBE3B

ubiquitin protein ligase E3B, the group of HECT domain containing

Basic information

Region (hg38): 12:109477401-109536705

Links

ENSG00000151148 ∙ NCBI:89910 ∙ OMIM:608047 ∙ HGNC:13478 ∙ Uniprot:Q7Z3V4 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• oculocerebrofacial syndrome, Kaufman type (Strong), mode of inheritance: AR
• oculocerebrofacial syndrome, Kaufman type (Definitive), mode of inheritance: AR
• oculocerebrofacial syndrome, Kaufman type (Supportive), mode of inheritance: AR
• oculocerebrofacial syndrome, Kaufman type (Definitive), mode of inheritance: AR
• blepharophimosis - intellectual disability syndrome due to UBE3B deficiency (Definitive), mode of inheritance: AR
• oculocerebrofacial syndrome, Kaufman type (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Kaufman oculocerebrofacial syndrome (Blepharophimosis-ptosis-intellectual disability syndrome)	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Craniofacial; Neurologic; Ophthalmologic	23200864

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the UBE3B gene.

• not provided (264 variants)
• Inborn genetic diseases (54 variants)
• Oculocerebrofacial syndrome, Kaufman type (33 variants)
• not specified (2 variants)
• - (2 variants)
• Blepharophimosis - intellectual disability syndrome (1 variants)
• Optic nerve hypoplasia (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the UBE3B 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				66	14	80
missense		3	126	2	3	134
nonsense	4	3		1		8
start loss						0
frameshift	12	4				16
inframe indel		1	1			2
splice donor/acceptor (+/-2bp)	8	3				11
splice region			2	9	4	15
non coding			1	37	15	53
Total	24	14	128	106	32

Highest pathogenic variant AF is 0.0000263

Variants in UBE3B

This is a list of pathogenic ClinVar variants found in the UBE3B region.

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

Position	Type	Phenotype	Significance	ClinVar
12-109481675-C-T			Benign (Jan 20, 2020)
12-109483552-A-G		-	no classification for the single variant (-)
12-109483563-G-C			Likely benign (Jan 04, 2024)
12-109483575-G-A			Likely benign (Nov 15, 2022)
12-109483576-A-G			Uncertain significance (Sep 12, 2022)
12-109483581-A-G			Likely benign (Jul 01, 2022)
12-109483590-C-T			Likely benign (Jul 30, 2022)
12-109483591-G-A			Uncertain significance (Jul 06, 2022)
12-109483600-C-T		Inborn genetic diseases	Uncertain significance (May 03, 2023)
12-109483609-C-T			Pathogenic (Jun 04, 2022)
12-109483612-G-T		Inborn genetic diseases • Oculocerebrofacial syndrome, Kaufman type	Pathogenic (Jan 25, 2024)
12-109483636-C-T			Uncertain significance (Sep 12, 2022)
12-109483637-G-A		Inborn genetic diseases	Uncertain significance (Apr 19, 2022)
12-109483643-G-A			Uncertain significance (Jan 24, 2024)
12-109483663-G-T			Uncertain significance (Jun 16, 2022)
12-109483673-G-A			Likely benign (Dec 30, 2023)
12-109483687-C-T			Uncertain significance (Jul 29, 2022)
12-109483694-G-A			Uncertain significance (Jul 12, 2022)
12-109483707-T-G			Uncertain significance (Aug 02, 2022)
12-109483709-T-C			Uncertain significance (Mar 01, 2022)
12-109483725-A-T			Likely benign (Sep 23, 2022)
12-109483730-C-T			Likely benign (Nov 04, 2022)
12-109483853-T-C			Likely benign (Jul 29, 2022)
12-109483875-A-G		Inborn genetic diseases	Uncertain significance (Sep 22, 2023)
12-109483888-A-T			Likely benign (Jul 17, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
UBE3B	protein_coding	protein_coding	ENST00000342494	26	59301

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
4.19e-8	1.00	125673	0	75	125748	0.000298

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.36	539	635	0.848	0.0000392	6997
Missense in Polyphen		130	186.44	0.69726		2048
Synonymous	0.861	232	249	0.931	0.0000153	2101
Loss of Function	4.47	24	62.0	0.387	0.00000352	661

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000901	0.000901
Ashkenazi Jewish	0.0000993	0.0000992
East Asian	0.000328	0.000326
Finnish	0.000139	0.000139
European (Non-Finnish)	0.000329	0.000325
Middle Eastern	0.000328	0.000326
South Asian	0.000164	0.000163
Other	0.000164	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: E3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates. {ECO:0000250}.
• Pathway: Ubiquitin mediated proteolysis - Homo sapiens (human);Immune System;Adaptive Immune System;Antigen processing: Ubiquitination & Proteasome degradation;Class I MHC mediated antigen processing & presentation (Consensus)

Recessive Scores

• pRec: 0.0934

Intolerance Scores

• loftool: 0.874
• rvis_EVS: -2.23
• rvis_percentile_EVS: 1.32

Haploinsufficiency Scores

• pHI: 0.194
• hipred: Y
• hipred_score: 0.528
• ghis: 0.648

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.531

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ube3b
• Phenotype: growth/size/body region phenotype; homeostasis/metabolism phenotype; vision/eye 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); reproductive system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); immune system 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); hearing/vestibular/ear phenotype

Gene ontology

• Biological process: protein polyubiquitination;ubiquitin-dependent protein catabolic process
• Molecular function: ubiquitin conjugating enzyme activity