SUMO2

Chr 17

small ubiquitin like modifier 2

Also known as: HSMT3, SMT3B, SMT3H2

NCBI Gene: 6613UniProt: P61956

This gene encodes a protein that is a member of the SUMO (small ubiquitin-like modifier) protein family. It functions in a manner similar to ubiquitin in that it is bound to target proteins as part of a post-translational modification system. However, unlike ubiquitin which targets proteins for degradation, this protein is involved in a variety of cellular processes, such as nuclear transport, transcriptional regulation, apoptosis, and protein stability. It is not active until the last two amino acids of the carboxy-terminus have been cleaved off. Numerous pseudogenes have been reported for this gene. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]

0
Active trials
12
Pathogenic / LP
22
ClinVar variants
8
Pubs (1 yr)
2.2
Missense Z
0.45
LOEUF
Clinical Summary— SUMO2
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.87) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
12 Pathogenic / Likely Pathogenic· 9 VUS of 22 total submissions
Some data sources returned errors (1)

ensembl: TimeoutError: The operation was aborted due to timeout

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.
0.45LOEUF
pLI 0.869
Z-score 2.39
OE 0.00 (0.00–0.45)
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.
2.20Z-score
OE missense 0.12 (0.07–0.24)
6 obs / 49.7 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.0.00 (0.00–0.45)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.12 (0.07–0.24)
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.1.02
0≤1.21.6
LoF obs/exp: 0 / 6.7Missense obs/exp: 6 / 49.7Syn Z: -0.07

ClinVar Variant Classifications

22 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic11
Likely Pathogenic1
VUS9
Benign1
11
Pathogenic
1
Likely Pathogenic
9
VUS
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories· variant type breakdown unavailable

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
————11
Likely Pathogenic
————1
VUS
————9
Likely Benign
————0
Benign
————1
Total—22

Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

SUMO2 · 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 Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
SUMOylation-triggered ALIX activation modulates extracellular vesicles circTLCD4-RWDD3 to promote lymphatic metastasis of non-small cell lung cancer.
Diao X et al.·Signal Transduct Target Ther
2023
Paralogue-Specific Roles of SUMO1 and SUMO2/3 in Protein Quality Control and Associated Diseases.
Wang W et al.·Cells
2023Review
Dynamic SUMOylation of MORC2 orchestrates chromatin remodelling and DNA repair in response to DNA damage and drives chemoresistance in breast cancer.
Zhang FL et al.·Theranostics
2023Functional
ROS-mediated up-regulation of SAE1 by Helicobacter pylori promotes human gastric tumor genesis and progression.
Shi L et al.·J Transl Med
2024
Targeting SUMO2 reverses aberrant epigenetic rewiring driven by SS18::SSX fusion oncoproteins and impairs sarcomagenesis.
Iyer R et al.·EMBO J
2025
SUMO2/3 promotes the progression and oxaliplatin resistance of colorectal cancer through facilitating the SUMOylation at Ku80-K307.
Feng D et al.·Biofactors
2023
Exploration of SUMO2/3 Expression Levels and Autophagy Process in Fragile X-Associated Tremor/Ataxia Syndrome: Addressing Study Limitations and Insights for Future Research.
Alvarez-Mora MI et al.·Cells
2023
Exportin-5 SUMOylation promotes hepatocellular carcinoma progression.
Lin D et al.·Exp Cell Res
2020
Circular RNA circRNF13 inhibits proliferation and metastasis of nasopharyngeal carcinoma via SUMO2.
Mo Y et al.·Mol Cancer
2021
SUMO operates from a unique long tandem repeat to keep innate immunity in check.
Goffeney A et al.·Nucleic Acids Res
2025
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Upregulation of Small Ubiquitin-Like Modifier 2 and Protein SUMOylation as a Cardioprotective Mechanism Against Myocardial Ischemia-Reperfusion Injury
Zhao W et al.·Front Pharmacol
2021Functional
SUMO2 inhibits ACSL3 protein degradation to antagonize erastin-induced ferroptosis in hepatocellular carcinoma
Shen Y et al.·Discov Oncol
2025
Proteo-transcriptomics meta-analysis identifies SUMO2 as a promising target in glioblastoma multiforme therapeutics
Krishna AP et al.·Cancer Cell Int
2021
SUMO paralogue-specific functions revealed through systematic analysis of human knockout cell lines and gene expression data
Bouchard D et al.·Mol Biol Cell
2021
Chemical protein synthesis combined with protein cell delivery reveals new insights on the maturation process of SUMO2
Shkolnik D et al.·Chem Sci
2024
SUMOylation Is Associated with Aggressive Behavior in Chondrosarcoma of Bone
Kroonen JS et al.·Cancers (Basel)
2021
SUMOylation of Nuclear gamma-Actin by SUMO2 supports DNA Damage Repair against Myocardial Ischemia-Reperfusion Injury
Zhao W et al.·Int J Biol Sci
2022
Assessment of SENP3-interacting proteins in hepatocytes treated with diethylnitrosamine by BioID assay
Chen F et al.·Acta Biochim Biophys Sin (Shanghai)
2021
SUMO-LMNet: Lossless mapping network for predicting SUMOylation sites in SUMO1 and SUMO2 using high-dimensional features
Ho CH et al.·Comput Struct Biotechnol J
2025
Top 9 full-text resultsSearch PubTator3 ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients