SMURF2
Chr 17SMAD specific E3 ubiquitin protein ligase 2
Enables SMAD binding activity; identical protein binding activity; and ubiquitin protein ligase activity. Involved in negative regulation of transforming growth factor beta receptor signaling pathway; positive regulation of trophoblast cell migration; and ubiquitin-dependent protein catabolic process. Located in nuclear speck. Part of ubiquitin ligase complex. [provided by Alliance of Genome Resources, Jul 2025]
Clinical Summary— SMURF2
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Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.87) — some intolerance to loss-of-function variants.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
LoF intolerant — likely haploinsufficient
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.
0.33LOEUF
pLI 0.872
Z-score 5.30
OE 0.20 (0.12–0.33)
Highly LoF-intolerant (top ~10% 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.
2.90Z-score
OE missense 0.59 (0.53–0.66)
238 obs / 401.6 exp
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.0.20 (0.12–0.33)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.59 (0.53–0.66)
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.0.90
0≤1.21.6
LoF obs/exp: 10 / 50.8Missense obs/exp: 238 / 401.6Syn Z: 0.91
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
SMURF2 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →Clinical Literature
Landmark / reviewRecent case evidence
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
Development and characterisation of SMURF2-targeting modifiers
Manikoth Ayyathan D et al.·J Enzyme Inhib Med Chem
2021
Smurf2 suppresses the metastasis of hepatocellular carcinoma via ubiquitin degradation of Smad2
Song D et al.·Open Med (Wars)
2022
SMAD-specific E3 ubiquitin ligase 2 promotes angiogenesis by facilitating PTX3 degradation in MSCs from patients with ankylosing spondylitis
Ma M et al.·Stem Cells
2021Cohort
MALAT1 Knockdown Inhibits the Proliferation, Migration, and Collagen Deposition of Human Hypertrophic Scar Fibroblasts via Targeting miR-29a-3p/Smurf2 Axis
Guo C et al.·Clin Cosmet Investig Dermatol
2024
CBX3 Regulated By YBX1 Promotes Smoking-induced Pancreatic Cancer Progression via Inhibiting SMURF2 Expression
Zhang H et al.·Int J Biol Sci
2022
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
FOXO1 regulates RUNX2 ubiquitination through SMURF2 in calcific aortic valve disease.
Jiang C et al.·Redox Biol
2024
Smurf1 and Smurf2 mediated polyubiquitination and degradation of RNF220 suppresses Shh-group medulloblastoma.
Li Y et al.·Cell Death Dis
2023
Curcumin inhibits the activity of ubiquitin ligase Smurf2 to promote NLRP3‑dependent pyroptosis in non‑small cell lung cancer cells.
Xi Y et al.·Int J Oncol
2025
SMURF2 Facilitates GAP17 Isoform 1 Membrane Displacement to Promote Mutant p53-KRAS Oncogenic Synergy.
Ray P et al.·Mol Cancer Res
2025
Smurf2 inhibition enhances chemotherapy and radiation sensitivity in non-small-cell lung cancer.
Chaudhary KR et al.·Sci Rep
2022
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Retinol saturase promotes tubulointerstitial fibrosis in diabetic kidney disease by inhibiting ChREBP ubiquitination via Smurf2 suppression.
Huang H et al.·Front Endocrinol (Lausanne)
2026Open Access
SMURF2 in Anticancer Therapy: Dual Role in Carcinogenesis and Theranostics.
Eom J et al.·Int J Mol Sci
2026Open Access
Uridine-Cytidine Kinase 2 (UCK2)/Uridine-Cytidine Kinase Like 1 (UCKL1) complex exacerbates the differentiation of myocardial fibroblasts via TRIM21/Smurf2/Smad3 pathway after myocardial infarction.
Zhou X et al.·Mol Biomed
2025Open Access
Tip60-HDAC8-SMURF2-mediated β-TrCP1 degradation is a key mechanism for hypoxia-induced cell death and tissue injury.
Li S et al.·Cell Mol Life Sci
2025Open AccessFunctional
MiR-486-5p-modified DPSC-derived sEVs encapsulated in GelMA hydrogel promote wound healing by enhancing angiogenesis via Smurf2/TGF-β1 pathways.
Wang S et al.·Int J Biol Macromol
2026
Top 5 resultsSearch Europe PMC ↗
External Resources
Links to major genomics databases and tools