Gene Function

E3 ubiquitin-protein ligase that specifically catalyzes 'Lys-29'- and 'Lys-48'-linked polyubiquitin chains. Accepts ubiquitin from the E2 ubiquitin-conjugating enzyme UBE2D1 in the form of a thioester and then directly transfers the ubiquitin to targeted substrates. Associates with the proteasome and promotes elongation of ubiquitin chains on substrates bound to the 26S proteasome. Also catalyzes 'Lys-29'- and 'Lys-48'-linked ubiquitination of 26S proteasome subunit ADRM1/RPN13 in response to proteotoxic stress, impairing the ability of the proteasome to bind and degrade ubiquitin-conjugated proteins. Acts as a negative regulator of autophagy by mediating 'Lys-29'- and 'Lys-48'-linked ubiquitination of PIK3C3/VPS34, promoting its degradation. Can assemble unanchored poly-ubiquitin chains in either 'Lys-29'- or 'Lys-48'-linked polyubiquitin chains; with some preference for 'Lys-48' linkages. Acts as a negative regulator of type I interferon by mediating 'Lys-48'-linked ubiquitination of IRF3 and IRF7, leading to their degradation by the proteasome. Catalyzes ubiquitination and degradation of CAND2 Source: UniProt

Relationship to CMT

dHMN/HMN AD
1 subtype
7q36.3

First described 2023

Subtype	Inheritance	Class	OMIM	Sentinel Publication
SubtypedHMN1-UBE3C	Inheritanceautosomal dominant	ClassdHMN/HMN	OMIMn/a	Sentinel Publication Novel Gene-Intergenic Fusion Involving Ubiquitin E3 Ligase UBE3C Causes Distal Hereditary Motor Neuropathy 2023 · 10.1093/brain/awac424

Stored Identifiers

HGNC Aliases: KIAA0010

hgnc_idHGNC:16803

ensembl_gene_idENSG00000009335

coords_grch38chr7:157138908-157269372

coords_grch37chr7:156931607-157062066

entrez_id9690

omim_gene614454

uniprot_idsQ15386

refseq_accessionNM_014671

mane_refseqNM_014671.3

mane_ensemblENST00000348165.10

External recordsHGNC:16803OMIM 614454gnomADUniProt Q15386ClinVar P/LPMANE NM_014671.3

ClinVar Variants

Pathogenic and likely pathogenic variants in UBE3C, as classified in ClinVar, are read live from NCBI. Only aggregate germline records are shown. Uncertain and conflicting classifications are not. Experts in CMT makes no claim to the accuracy of ClinVar data. This index is provided for informational purposes only.

Review stars are ClinVar’s measure of how well a classification is supported: four for a practice guideline, three for an expert panel review, two for agreement among multiple submitters, one for a single submitter with criteria provided, and none where no criteria were provided.

Reported in CMT

Reported in Other Diseases

Reported in a disease other than CMT. Listed apart rather than counted as CMT variants.

Variants w/o a Recorded Disease

Pathogenic or likely pathogenic in ClinVar, submitted without a disease recorded.

The Dorsal Root

A Name That Does Too Much Work

Jean-Martin Charcot's name appears throughout medicine, but nowhere does it create more confusion than in the foot. Learn why the CMT foot and Charcot neuroarthropathy, also known as Charcot foot, share a name yet differ in how they develop, appear, and are managed.

When Medicine Lost Its Compass

Evidence failed not because it was wrong, but because it was weaponized. I lived the downstream effects of that failure for more than a decade. This is what happens when medicine forgets that data always ends in a human being.

Error 404: Gene Not Found

CMT genetic testing often fails to identify the cause of the disease, even when comprehensive panels are used. Here, we discuss why this happens, what genetic tests can and cannot do, and why a negative result still matters.