USP27X

Chr XXLR

ubiquitin specific peptidase 27 X-linked

Also known as: MRX105, USP22L, USP27, XLID105

NCBI Gene: 389856 ENSG00000273820 UniProt: A6NNY8 OMIM: 300975

The protein functions as a deubiquitinase that regulates innate antiviral immunity by deubiquitinating CGAS and RIG-I, and stabilizes the pro-apoptotic protein BIM. Mutations cause X-linked intellectual developmental disorder 105 through an X-linked recessive inheritance pattern. The high pLI score (0.92) and low LOEUF score (0.36) indicate strong intolerance to loss-of-function variants, suggesting haploinsufficiency as the likely pathogenic mechanism.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a member of the peptidase protein family. The encoded protein functions as a deubiquitinase that is involved in upregulation of the pro-apoptotic Bim protein. This protein may act as a tumor suppressor by increasing levels of Bim to counteract anti-apoptotic signals in cancer cells. Mutations in this gene have been associated with X-linked cognitive disability. [provided by RefSeq, Dec 2016]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Intellectual developmental disorder, X-linked 105MIM #300984

XLR

Clinical highlights

Gene-disease validity (ClinGen)

X-linked complex neurodevelopmental disorder · XLModerateconsider for supplementary testing

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.36

LOEUF

LOF

Mechanism· G2P