OTUD5

Chr X

OTU deubiquitinase 5

Also known as: DUBA, MCAND

NCBI Gene: 55593 ENSG00000068308 UniProt: Q96G74

The protein functions as a deubiquitinase that suppresses type I interferon-dependent innate immune responses by cleaving polyubiquitin chains from essential interferon adaptor proteins, disrupting downstream signaling cascades. Loss-of-function mutations cause X-linked recessive multiple congenital anomalies-neurodevelopmental syndrome. The mechanism involves haploinsufficiency leading to dysregulated innate immune signaling and abnormal neurodevelopment.

ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

This gene encodes a member of the OTU (ovarian tumor) domain-containing cysteine protease superfamily. The OTU domain confers deubiquitinase activity and the encoded protein has been shown to suppress the type I interferon-dependent innate immune response by cleaving the polyubiquitin chain from an essential type I interferon adaptor protein. Cleavage results in disassociation of the adaptor protein from a downstream signaling complex and disruption of the type I interferon signaling cascade. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Oct 2008]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtMultiple congenital anomalies-neurodevelopmental syndrome, X-linked

Clinical highlights

Gene-disease validity (ClinGen)

multiple congenital anomalies-neurodevelopmental syndrome, X-linked · XLModerateconsider for supplementary testing

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

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P/LP missense

0.17

LOEUF· LoF intol.

LOF

Mechanism· predicted

Some data sources returned errors (1)

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