USP27X

Chr XXLR

ubiquitin specific peptidase 27 X-linked

Also known as: MRX105, USP22L, USP27, XLID105

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.

Summary from RefSeq, OMIM, UniProt
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Primary Disease Associations & Inheritance

Intellectual developmental disorder, X-linked 105MIM #300984
XLR
0
Active trials
2
Pubs (1 yr)
36
P/LP submissions
3%
P/LP missense
LOEUF
LOF
Mechanism· G2P
Clinical SummaryUSP27X
🧬
Gene-Disease Validity (ClinGen)
X-linked intellectual disability · XLLimited

Limited evidence — not for standalone diagnostic reporting

📋
ClinVar Variants
31 unique Pathogenic / Likely Pathogenic· 62 VUS of 100 total submissions
Some data sources returned errors (1)

gnomad: TimeoutError: The operation was aborted due to timeout

Population Genetics & Constraint

Constraint data not available from gnomAD.

ClinVar Variant Classifications

100 submitted variants in ClinVar

Classification Summary

Pathogenic25
Likely Pathogenic6
VUS62
Likely Benign6
Conflicting1
25
Pathogenic
6
Likely Pathogenic
62
VUS
6
Likely Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
25
0
25
Likely Pathogenic
3
1
2
0
6
VUS
2
50
10
0
62
Likely Benign
0
1
0
5
6
Benign
0
0
0
0
0
Conflicting
1
Total552375100

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

USP27X · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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