SUZ12 Gene: Polycomb Repressive Complex 2 Subunit
A core component of PRC2 involved in transcriptional repression and frequently mutated in cancer and overgrowth syndromes.
Gene Information Card
| Symbol | SUZ12 |
|---|---|
| Full Name | SUZ12 polycomb repressive complex 2 subunit |
| Gene Type | Protein coding |
| Chromosomal Location | 17q11.2 |
| NCBI Gene ID | 23512 ncbi.nlm.nih.gov/gene/23512 |
| Ensembl ID | ENSG00000178691 |
| UniProt ID | Q15022 |
| OMIM ID | 606245 |
| HGNC ID | 17101 |
| Aliases | CHET9, JJAZ1, KMT11F, SUZ12P1 |
Description
SUZ12 (SUZ12 polycomb repressive complex 2 subunit) encodes a zinc finger protein that is a core component of the Polycomb Repressive Complex 2 (PRC2). PRC2 catalyzes the di- and trimethylation of histone H3 at lysine 27 (H3K27me2/me3), a repressive histone mark essential for maintaining gene silencing during development and differentiation. SUZ12 is required for the integrity and catalytic activity of PRC2. Loss-of-function mutations in SUZ12 are recurrent in malignant peripheral nerve sheath tumors (MPNST) and other cancers, and germline mutations cause Weaver syndrome and related overgrowth disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Malignant peripheral nerve sheath tumor (MPNST) | Biallelic loss-of-function mutations in SUZ12 lead to loss of PRC2 activity, global reduction of H3K27me3, and aberrant gene expression promoting tumorigenesis. | COSMIC, ClinVar, PMID: 24316981 |
| Weaver syndrome | Heterozygous germline loss-of-function mutations in SUZ12 cause overgrowth, intellectual disability, and characteristic facial features due to haploinsufficiency of PRC2. | OMIM #606245, PMID: 25612909 |
| Endometrial stromal sarcoma | Recurrent SUZ12 rearrangements (e.g., SUZ12-PHF1 fusion) drive oncogenesis through aberrant PRC2 function. | COSMIC, PMID: 17200668 |
| Colorectal cancer | Somatic SUZ12 mutations contribute to tumor progression via epigenetic dysregulation. | COSMIC, PMID: 22980975 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 18.5 | Medium |
| Bone marrow | 15.2 | Medium |
| Lymph node | 14.8 | Medium |
| Brain | 12.1 | Medium |
| Liver | 8.3 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| K562 (leukemia) | 22.4 | High expression |
| HeLa (cervical cancer) | 19.7 | High expression |
| HepG2 (liver cancer) | 14.2 | Medium expression |
| A549 (lung cancer) | 11.5 | Medium expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1579C>T (p.Arg527*) | Nonsense | ~5% in MPNST | Loss of function; truncation of C-terminal VEFS domain |
| c.1099_1100del (p.Glu367fs) | Frameshift | ~3% in MPNST | Loss of function; premature termination |
| c.1A>G (p.Met1?) | Start loss | Rare | Loss of function; no protein production |
| SUZ12-PHF1 fusion | Structural variant | Recurrent in endometrial stromal sarcoma | Oncogenic fusion; aberrant PRC2 targeting |
Mutation functional classification
Loss of Function (LOF)
The majority of SUZ12 mutations in cancer and overgrowth syndromes are loss-of-function (nonsense, frameshift, splice site, deletions), leading to PRC2 inactivation and global reduction of H3K27me3.
Gain of Function (GOF)
No well-characterized gain-of-function mutations reported for SUZ12.
Dominant Negative (DN)
Some missense mutations in the VEFS domain may exert dominant-negative effects by disrupting PRC2 assembly, but evidence is limited.
View complete mutation data：
Gene Ontology (GO)
| • protein binding (GO:0005515) | • nucleus (GO:0005634) |
| • chromatin organization (GO:0006325) | • regulation of transcription (GO:0006355) |
| • regulation of gene expression (GO:0010468) | • histone H3-K27 trimethylation (GO:0016573) |
| • ESC/E(Z) complex (GO:0035098) | • protein heterodimerization activity (GO:0046982) |
Pathways
• hsa04110: Cell cycle
• hsa05202: Transcriptional misregulation in cancer
• hsa05205: Proteoglycans in cancer
• hsa05212: Pancreatic cancer
• hsa05222: Small cell lung cancer
• hsa05226: Gastric cancer
• hsa05235: PD-L1 expression and PD-1 checkpoint pathway in cancer
Protein Summary
SUZ12 is a 739-amino-acid protein (UniProt Q15022) containing a zinc finger domain and a VEFS (VRN2-EMF2-FIS2-SUZ12) domain. It is a core structural component of PRC2, directly interacting with EED and EZH2 to form the catalytically active complex. SUZ12 is essential for the methyltransferase activity of PRC2 and for the recruitment of the complex to target genes. Loss of SUZ12 leads to global loss of H3K27me3 and derepression of PRC2 target genes, contributing to tumorigenesis and developmental disorders.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SUZ12 Knockout HEK293 Cell Line | EDJ-KQ2999 | Human | 23512 | Details Get a Quote |
| SUZ12 Knockout HCT 116 Cell Line | EDJ-KQ24196 | Human | 23512 | Details Get a Quote |
| SUZ12 Knockout HeLa Cell Line | EDJ-KQ24197 | Human | 23512 | Details Get a Quote |
| SUZ12 Knockout A-549 Cell Line | EDJ-KQ22823 | Human | 23512 | Details Get a Quote |
