USP7

Chr 16AD

ubiquitin specific peptidase 7

Also known as: C16DELp13.2, DEL16P13.2, HAFOUS, HAUSP, TEF1

NCBI Gene: 7874ENSG00000187555UniProt: Q93009

The protein encoded by this gene belongs to the peptidase C19 family, which includes ubiquitinyl hydrolases. This protein deubiquitinates target proteins such as p53 (a tumor suppressor protein) and WASH (essential for endosomal protein recycling), and regulates their activities by counteracting the opposing ubiquitin ligase activity of proteins such as HDM2 and TRIM27, involved in the respective process. Mutations in this gene have been implicated in a neurodevelopmental disorder. [provided by RefSeq, Mar 2016]

Primary Disease Associations & Inheritance

Hao-Fountain syndromeMIM #616863
AD
535
ClinVar variants
58
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— USP7
🧬
Gene-Disease Validity (ClinGen)
Hao-Fountain syndrome · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
58 Pathogenic / Likely Pathogenic· 230 VUS of 535 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.06LOEUF
pLI 1.000
Z-score 8.04
OE 0.01 (0.00–0.06)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
5.65Z-score
OE missense 0.36 (0.32–0.41)
225 obs / 621.1 exp
Constrained

Extremely missense-constrained (top ~0.01%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.01 (0.00–0.06)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.36 (0.32–0.41)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.20
0≤1.21.6
LoF obs/exp: 1 / 77.2Missense obs/exp: 225 / 621.1Syn Z: -2.44

ClinVar Variant Classifications

535 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic37
Likely Pathogenic21
VUS230
Likely Benign210
Benign33
Conflicting4
37
Pathogenic
21
Likely Pathogenic
230
VUS
210
Likely Benign
33
Benign
4
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
9
1
27
0
37
Likely Pathogenic
9
8
4
0
21
VUS
0
165
60
5
230
Likely Benign
0
10
118
82
210
Benign
0
3
22
8
33
Conflicting
—4
Total1818723195535

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

View in ClinVar →

Protein Context — Lollipop Plot

USP7 · protein map & ClinVar variants

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

Gene2Phenotype Curations

USP7-related developmental disorder

strong
ADLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Hao-Fountain syndrome

MIM #616863

Molecular basis of disorder known

Autosomal dominant
📖
GeneReview available — USP7
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
USP7 - a crucial regulator of cancer hallmarks.
Saha G et al.·Biochim Biophys Acta Rev Cancer
2023Review
CAF secreted miR-522 suppresses ferroptosis and promotes acquired chemo-resistance in gastric cancer.
Zhang H et al.·Mol Cancer
2020
Blocking Ubiquitin-Specific Protease 7 Induces Ferroptosis in Gastric Cancer via Targeting Stearoyl-CoA Desaturase.
Guan X et al.·Adv Sci (Weinh)
2024
Knocking out USP7 attenuates cardiac fibrosis and endothelial-to-mesenchymal transition by destabilizing SMAD3 in mice with heart failure with preserved ejection fraction.
Yuan S et al.·Theranostics
2024
Ubiquitination-directed cytosolic DNA degradation governs cGAS-STING-mediated immune response to DNA damage.
Li L et al.·Cancer Cell
2026
ANXA1-derived peptide for targeting PD-L1 degradation inhibits tumor immune evasion in multiple cancers.
Yu ZZ et al.·J Immunother Cancer
2023
USP7 inhibits the progression of nasopharyngeal carcinoma via promoting SPLUNC1-mediated M1 macrophage polarization through TRIM24.
Liu H et al.·Cell Death Dis
2023
Mitochondrial-Derived Peptide MOTS-c Suppresses Ovarian Cancer Progression by Attenuating USP7-Mediated LARS1 Deubiquitination.
Yin Y et al.·Adv Sci (Weinh)
2024
Therapeutic targeting of the USP2-E2F4 axis inhibits autophagic machinery essential for zinc homeostasis in cancer progression.
Xiao W et al.·Autophagy
2022
CRIP1 involves the pathogenesis of multiple myeloma via dual-regulation of proteasome and autophagy.
Tang P et al.·EBioMedicine
2024
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools