SENP3

Chr 17

SUMO specific peptidase 3

Also known as: SMT3IP1, SSP3, Ulp1

NCBI Gene: 26168ENSG00000161956UniProt: Q9H4L4

The reversible posttranslational modification of proteins by the addition of small ubiquitin-like SUMO proteins (see SUMO1; MIM 601912) is required for numerous biologic processes. SUMO-specific proteases, such as SENP3, are responsible for the initial processing of SUMO precursors to generate a C-terminal diglycine motif required for the conjugation reaction. They also have isopeptidase activity for the removal of SUMO from high molecular mass SUMO conjugates (Di Bacco et al., 2006 [PubMed 16738315]).[supplied by OMIM, Jun 2009]

0
ClinVar variants
0
Pathogenic / LP
0.85
pLI score
0
Active trials
Clinical Summary— SENP3
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.85) — some intolerance to loss-of-function variants.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
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.
0.36LOEUF
pLI 0.848
Z-score 4.32
OE 0.18 (0.10–0.36)
Moderately constrained

More LoF-intolerant than ~75% of genes

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.
2.56Z-score
OE missense 0.61 (0.54–0.68)
204 obs / 336.2 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

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.0.18 (0.10–0.36)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.61 (0.54–0.68)
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.0.97
0≤1.21.6
LoF obs/exp: 6 / 32.6Missense obs/exp: 204 / 336.2Syn Z: 0.30

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

SENP3 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
METTL16-SENP3-LTF axis confers ferroptosis resistance and facilitates tumorigenesis in hepatocellular carcinoma.
Wang J et al.·J Hematol Oncol
2024
SENP3 loss promotes M2 macrophage polarization and breast cancer progression.
Xiao M et al.·Mol Oncol
2022
SENP3 inhibition suppresses hepatocellular carcinoma progression and improves the efficacy of anti-PD-1 immunotherapy.
Wang P et al.·Cell Death Differ
2025
Sentrin-specific protease 3 (SENP3)-mediated Krüppel-like factor 4 (KLF4) deSUMOylation regulates vascular smooth muscle cell phenotypic switching in atherosclerosis.
Wang Z et al.·Mol Biomed
2025
SENP3 mediates the deSUMOylation and degradation of YAP1 to regulate the progression of triple-negative breast cancer.
Chen X et al.·J Biol Chem
2024
Hypoxia-induced SENP3 promotes chemosensitivity and mitochondrial fission via deSUMOylation of Drp1.
Mao Y et al.·Head Neck
2024
SERPINH1 secretion by cancer-associated fibroblasts promotes hepatocellular carcinoma malignancy through SENP3-mediated SP1/SQLE pathway.
Xiao H et al.·Int Immunopharmacol
2025
Targeted deprivation of STAT6 sensitizes acute lymphoblastic leukemia cells to cytarabine in vivo and in vitro: clinical implications.
Sun S et al.·Cell Death Dis
2025
Arf-induced turnover of the nucleolar nucleophosmin-associated SUMO-2/3 protease Senp3.
Kuo ML et al.·Cell Cycle
2008
Increased Small Ubiquitin-like Modifier-Activating Enzyme SAE1 Promotes Hepatocellular Carcinoma by Enhancing mTOR SUMOylation.
Chen Y et al.·Lab Invest
2023
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.

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External Resources

Links to major genomics databases and tools