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.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismXLRLOEUF 0.361 OMIM phenotype
Clinical SummaryUSP27X
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Gene-Disease Validity (ClinGen)
X-linked intellectual disability · XLLimited

Limited evidence — not for standalone diagnostic reporting

Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.92). One damaged copy is likely sufficient to cause disease.
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ClinVar Variants
76 unique Pathogenic / Likely Pathogenic· 63 VUS of 146 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Dual constrained — LoF & missense intolerant
LoF Constraint
0.36LOEUF
pLI 0.924
Z-score 2.66
OE 0.00 (0.000.36)
Highly constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
3.18Z-score
OE missense 0.32 (0.260.40)
55 obs / 172.5 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.00 (0.000.36)
00.351.4
Missense OE0.32 (0.260.40)
00.61.4
Synonymous OE0.69
01.21.6
LoF obs/exp: 0 / 8.2Missense obs/exp: 55 / 172.5Syn Z: 2.10

ClinVar Variant Classifications

146 submitted variants in ClinVar

Classification Summary

Pathogenic69
Likely Pathogenic7
VUS63
Likely Benign6
Conflicting1
69
Pathogenic
7
Likely Pathogenic
63
VUS
6
Likely Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
69
0
69
Likely Pathogenic
5
1
1
0
7
VUS
2
52
9
0
63
Likely Benign
0
1
0
5
6
Benign
0
0
0
0
0
Conflicting
1
Total754795146

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.

3D Protein StructureAlphaFold

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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