UBE3C

ubiquitin protein ligase E3C, the group of HECT domain containing

Basic information

Region (hg38): 7:157138926-157269370

Links

ENSG00000009335 ∙ NCBI:9690 ∙ OMIM:614454 ∙ HGNC:16803 ∙ Uniprot:Q15386 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• neurodevelopmental disorder with absent speech and movement and behavioral abnormalities (Limited), mode of inheritance: AR
• neurodevelopmental disorder with absent speech and movement and behavioral abnormalities (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Neurodevelopmental disorder with absent speech and movement and behavioral abnormalities	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	36401616

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the UBE3C gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the UBE3C 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				3	2	5
missense			42	1		43
nonsense						0
start loss						0
frameshift		1				1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					1	1
non coding				1		1
Total	0	1	42	5	2

Variants in UBE3C

This is a list of pathogenic ClinVar variants found in the UBE3C region.

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

Position	Type	Phenotype	Significance	ClinVar
7-157169075-A-G		not specified	Uncertain significance (Jan 16, 2024)
7-157170310-A-G		not specified	Uncertain significance (May 23, 2023)
7-157170370-A-G		not specified	Uncertain significance (Jan 31, 2022)
7-157170421-T-C		not specified	Uncertain significance (Oct 20, 2023)
7-157174925-C-G		not specified	Uncertain significance (Jan 10, 2023)
7-157174949-A-G		not specified	Uncertain significance (Feb 17, 2023)
7-157174970-T-A		not specified	Uncertain significance (Aug 22, 2023)
7-157175008-A-G		not specified	Uncertain significance (Jan 31, 2022)
7-157178682-T-C		UBE3C-related disorder	Benign (Feb 04, 2020)
7-157178704-G-A		not specified	Uncertain significance (Jan 26, 2023)
7-157178758-C-T		not specified	Uncertain significance (Oct 10, 2023)
7-157178759-G-C		UBE3C-related disorder	Likely benign (Feb 20, 2019)
7-157181590-G-A		not specified	Uncertain significance (Jul 25, 2023)
7-157181660-G-A		UBE3C-related disorder	Benign (Jan 13, 2020)
7-157182194-C-T		not specified	Uncertain significance (Feb 12, 2024)
7-157182259-T-G		not specified	Uncertain significance (Apr 12, 2022)
7-157183895-G-A		not specified	Uncertain significance (Jan 31, 2024)
7-157184038-C-T		UBE3C-related disorder	Likely benign (Jan 02, 2020)
7-157186836-G-C		not specified	Uncertain significance (Jun 24, 2022)
7-157186873-T-A		not specified	Uncertain significance (Oct 04, 2022)
7-157186964-T-C		Neurodevelopmental disorder with absent speech and movement and behavioral abnormalities	Uncertain significance (Sep 22, 2024)
7-157186982-C-T		not specified	Uncertain significance (May 13, 2024)
7-157187002-A-G		not specified	Uncertain significance (Jul 13, 2021)
7-157201729-A-G		not specified	Uncertain significance (Mar 29, 2023)
7-157201795-G-A		not specified	Uncertain significance (Aug 02, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
UBE3C	protein_coding	protein_coding	ENST00000348165	23	130460

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.00000326	125708	1	38	125747	0.000155

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.54	421	596	0.707	0.0000326	7097
Missense in Polyphen		67	148.43	0.45138		1779
Synonymous	0.797	216	231	0.933	0.0000135	2075
Loss of Function	6.41	5	57.4	0.0871	0.00000316	673

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000310	0.000309
Ashkenazi Jewish	0.000199	0.000198
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000973	0.0000967
Middle Eastern	0.00	0.00
South Asian	0.000827	0.000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: E3 ubiquitin-protein ligase that accepts ubiquitin from the E2 ubiquitin-conjugating enzyme UBE2D1 in the form of a thioester and then directly transfers the ubiquitin to targeted substrates. Can assemble unanchored poly-ubiquitin chains in either 'Lys-29'- or 'Lys-48'-linked polyubiquitin chains. Has preference for 'Lys-48' linkages. It can target itself for ubiquitination in vitro and may promote its own degradation in vivo. {ECO:0000269|PubMed:11278995, ECO:0000269|PubMed:12692129, ECO:0000269|PubMed:16341092, ECO:0000269|PubMed:16601690}.
• 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: 0.229

Intolerance Scores

• loftool: 0.473
• rvis_EVS: -1.06
• rvis_percentile_EVS: 7.54

Haploinsufficiency Scores

• pHI: 0.0768
• hipred: Y
• hipred_score: 0.816
• ghis: 0.600

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.877

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ube3c
• Phenotype: growth/size/body region phenotype; homeostasis/metabolism phenotype; hematopoietic system phenotype; 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); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); immune system phenotype; skeleton phenotype; hearing/vestibular/ear phenotype; limbs/digits/tail phenotype

Gene ontology

• Biological process: protein polyubiquitination;ubiquitin-dependent protein catabolic process
• Cellular component: proteasome complex;nucleus
• Molecular function: ubiquitin-protein transferase activity;protein binding;ubiquitin conjugating enzyme activity