SUZ12

Chr 17AD

SUZ12 polycomb repressive complex 2 subunit

NCBI Gene: 23512ENSG00000178691UniProt: Q15022

Polycomb group (PcG) protein. Component of the PRC2 complex, which methylates 'Lys-9' (H3K9me) and 'Lys-27' (H3K27me) of histone H3, leading to transcriptional repression of the affected target gene (PubMed:15225548, PubMed:15231737, PubMed:15385962, PubMed:16618801, PubMed:17344414, PubMed:18285464, PubMed:28229514, PubMed:29499137, PubMed:31959557). The PRC2 complex may also serve as a recruiting platform for DNA methyltransferases, thereby linking two epigenetic repression systems (PubMed:12351676, PubMed:12435631, PubMed:15099518, PubMed:15225548, PubMed:15385962, PubMed:15684044, PubMed:16431907, PubMed:18086877, PubMed:18285464). Genes repressed by the PRC2 complex include HOXC8, HOXA9, MYT1 and CDKN2A (PubMed:15231737, PubMed:16618801, PubMed:17200670, PubMed:31959557)

Primary Disease Associations & Inheritance

Imagawa-Matsumoto syndromeMIM #618786
AD
238
ClinVar variants
76
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— SUZ12
⚡
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
76 Pathogenic / Likely Pathogenic· 116 VUS of 238 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.
0.13LOEUF
pLI 1.000
Z-score 5.36
OE 0.03 (0.01–0.13)
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.
3.40Z-score
OE missense 0.50 (0.44–0.56)
178 obs / 359.4 exp
Constrained

Highly missense-constrained (top ~0.1%)

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.0.03 (0.01–0.13)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.50 (0.44–0.56)
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.0.87
0≤1.21.6
LoF obs/exp: 1 / 35.4Missense obs/exp: 178 / 359.4Syn Z: 1.11

ClinVar Variant Classifications

238 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic58
Likely Pathogenic18
VUS116
Likely Benign36
Benign8
Conflicting2
58
Pathogenic
18
Likely Pathogenic
116
VUS
36
Likely Benign
8
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
9
3
46
0
58
Likely Pathogenic
8
2
8
0
18
VUS
8
90
18
0
116
Likely Benign
0
13
7
16
36
Benign
0
0
7
1
8
Conflicting
—2
Total251088617238

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

View in ClinVar →

Protein Context — Lollipop Plot

SUZ12 · protein map & ClinVar variants

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

Gene2Phenotype Curations

SUZ12-related Weaver-like overgrowth syndrome

definitive
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

Imagawa-Matsumoto syndrome

MIM #618786

Molecular basis of disorder known

Autosomal dominant
📖
GeneReview available — SUZ12
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Endometrial stromal tumors of the uterus: Epidemiology, pathological and biological features, treatment options and clinical outcomes.
Gadducci A et al.·Gynecol Oncol
2023Review
Imagawa-Matsumoto syndrome: SUZ12-related overgrowth disorder.
Imagawa E et al.·Clin Genet
2023Review
Identification and prioritization of myeloid malignancy germline variants in a large cohort of adult patients with AML.
Yang F et al.·Blood
2022Clinical trial
EIF4A3-mediated biogenesis of circSTX6 promotes bladder cancer metastasis and cisplatin resistance.
Wei W et al.·J Exp Clin Cancer Res
2024
MARCKSL1-2 reverses docetaxel-resistance of lung adenocarcinoma cells by recruiting SUZ12 to suppress HDAC1 and elevate miR-200b.
Jiang M et al.·Mol Cancer
2022
PRC2-complex related dysfunction in overgrowth syndromes: A review of EZH2, EED, and SUZ12 and their syndromic phenotypes.
Cyrus S et al.·Am J Med Genet C Semin Med Genet
2019Review
Genomic imbalance analysis provides new insight into prognostic factors in adult and pediatric T-ALL.
Balducci E et al.·Blood
2024Clinical trial
Designing Myeloid Gene Panels.
Zhao F et al.·Arch Pathol Lab Med
2022
EZH2 function in immune cell development.
Nutt SL et al.·Biol Chem
2020Review
Proof of Concept for Genome Profiling of the Neurofibroma/Sarcoma Sequence in Neurofibromatosis Type 1.
Cannizzaro IR et al.·Int J Mol Sci
2024
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
SUZ12 promotes pancreatic ductal adenocarcinoma progression and chemoresistance by epigenetically silencing NCOA4-induced ferroptosis.
Yin L et al.·Acta Biochim Biophys Sin (Shanghai)
2026
Exosomal miR-140-3p produced by bone marrow stromal cells affects acute myeloid leukemia cell growth and apoptosis by targeting SUZ12.
Li J et al.·Leuk Res
2025
SUZ12 knockdown restrains the proliferation, migration, and invasion of oral tongue squamous cell carcinoma through inhibiting DNMT1-mediated ZNF582 promoter methylation.
Kong X et al.·World J Surg Oncol
2025🔓 Open Access
Genome-wide CRISPR screen identifies Menin and SUZ12 as regulators of human developmental timing.
Xu N et al.·Nat Cell Biol
2025🔓 Open Access
MIB2-Mediated SUZ12 Ubiquitination Regulates Clonal Proliferation in Patients With Paroxysmal Nocturnal Haemoglobinuria.
Liu H et al.·J Cell Mol Med
2025🔓 Open AccessCohort
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