USP27X

Chr X

ubiquitin specific peptidase 27 X-linked

Also known as: MRX105, USP22L, USP27, XLID105

NCBI Gene: 389856 ENSG00000273820 UniProt: A6NNY8

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.

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]

ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.36

Clinical Summary— USP27X

🧬

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.

📋

ClinVar Variants

6 unique Pathogenic / Likely Pathogenic· 56 VUS of 69 total submissions

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Dual constrained — LoF & missense intolerant

LoF Constraint?

0.36LOEUF

pLI 0.924

Z-score 2.66

OE 0.00 (0.00–0.36)

Highly constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

3.18Z-score

OE missense 0.32 (0.26–0.40)

55 obs / 172.5 exp

Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?

LoF OE?0.00 (0.00–0.36)

0≤0.351.4

Missense OE?0.32 (0.26–0.40)

0≤0.61.4

Synonymous OE?0.69

0≤1.21.6

LoF obs/exp: 0 / 8.2Missense obs/exp: 55 / 172.5Syn Z: 2.10

ClinVar Variant Classifications

69 submitted variants in ClinVar

ClinVar

Classification Summary

Likely Pathogenic6

VUS56

Likely Benign6

Conflicting1

Likely Pathogenic

VUS

Likely Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0	0
Likely Pathogenic	5	1	0	0	6
VUS	2	52	2	0	56
Likely Benign	0	1	0	5	6
Benign	0	0	0	0	0
Conflicting	—				1
Total	7	54	2	5	69

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

View in ClinVar →

70 pathogenic / likely-pathogenic (of 77) ClinVar copy-number / structural variants overlap USP27X — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →