USP40

Chr 2

ubiquitin specific peptidase 40

NCBI Gene: 55230 ENSG00000085982 UniProt: Q9NVE5 OMIM: 610570

USP40 encodes a deubiquitinating enzyme that maintains endothelial cell barrier integrity by stabilizing tight junction proteins like Claudin-1, regulates apoptosis through CFLAR stabilization, and suppresses inflammation by inhibiting NF-kappa-B activation. Mutations cause a neurodevelopmental disorder with intellectual disability, developmental delay, and seizures, inherited in an autosomal recessive pattern. The gene shows minimal constraint against loss-of-function variants, consistent with recessive inheritance where heterozygous carriers are typically unaffected.

OMIM ResearchSummary from RefSeq, UniProt

Modification of cellular proteins by ubiquitin is an essential regulatory mechanism controlled by the coordinated action of multiple ubiquitin-conjugating and deubiquitinating enzymes. USP40 belongs to a large family of cysteine proteases that function as deubiquitinating enzymes (Quesada et al., 2004 [PubMed 14715245]).[supplied by OMIM, Mar 2008]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

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LOEUF

Mechanism· predicted

Some data sources returned errors (1)

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