UBE3C

protein-coding

ubiquitin protein ligase E3C, the group of HECT domain containing

Gene summary

Enables ubiquitin protein ligase activity. Involved in protein K29-linked ubiquitination; protein K48-linked ubiquitination; and ubiquitin-dependent protein catabolic process. Predicted to be part of proteasome complex. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_014671.3

Inheritance

ClinVar variants

P:1U:124B:11

Top phenotype

Neurodevelopmental disorder with absent speech and movement and behavioral abnormalities

gnomAD constraint

pLI —, LoF o/e 0.09

Max pathogenic AF

—

Genomic locus

chr7:157,138,926-157,269,370

External References & Databases

Ensembl (ENSG00000009335)

Transcript & Mutation Effects

hg38 • Region Span ~130.4 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

neurodevelopmental disorder with absent speech and movement and behavioral abnormalitiesSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0859519

Submitter: Labcorp Genetics (formerly Invitae)

neurodevelopmental disorder with absent speech and movement and behavioral abnormalitiesLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0859519

Submitter: Ambry Genetics

neurodevelopmental disorder with absent speech and movement and behavioral abnormalitiesSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0859519

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Neurodevelopmental disorder with absent speech and movement and behavioral abnormalitiesAR

Manifestation: Craniofacial; Neurologic

Intervention: General

Rationale: 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

Refs: 36401616

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to UBE3C variants in ClinVar

5 Conditions Cataloged

not specifiedTotal: 109

UBE3C-related disorderTotal: 7

not providedTotal: 6

Neurodevelopmental disorder with absent speech and movement and behavioral abnormalitiesTotal: 3

See casesTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_014671.3. 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			2 clinvar	8 clinvar		10
missense			116 clinvar	3 clinvar		119
nonsense			2 clinvar			2
start loss						0
frameshift		1 clinvar	1 clinvar			2
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	0	1	124	11	0	136

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 56 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_014671.3	RefSeq	NP_055486.2	23	MANE Select
ENST00000348165.10	Ensembl	ENSP00000309198.8	23	MANE Select
ENST00000389103.4	Ensembl	ENSP00000373755.4	9	Standard
ENST00000389103.5	Ensembl	ENSP00000373755.4	9	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Ubiquitin mediated proteolysis - Homo sapiens (human)
Immune System
Adaptive Immune System
Antigen processing: Ubiquitination & Proteasome degradation
Class I MHC mediated antigen processing & presentation

Biological Process

protein polyubiquitination
ubiquitin-dependent protein catabolic process

Molecular Function

ubiquitin-protein transferase activity
protein binding
ubiquitin conjugating enzyme activity

Cellular Component

proteasome complex
nucleus

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000348165
Coding exons: 23
Length: 130460
Individuals with no LoFs: 125708
Homozygous LoFs: 1
Heterozygous LoFs: 38
Defined: 125747
p: 0.000155

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.54	421	596	0.707	0.0000326	7097
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00025	0.00025	rare
Latino/Admixed American	0.000062	0.000058	rare
Ashkenazi Jewish	0.00020	0.00020	rare
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000097	0.000097	rare
South Asian	0.00083	0.00065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

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}.;

Recessive Scores

pRec: 0.229

Intolerance Scores

LoFtool: 0.473
RVIS EVS: -1.06
RVIS percentile EVS: 7.54

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.877

Gene Damage Prediction

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