SUZ12

SUZ12 polycomb repressive complex 2 subunit, the group of Polycomb repressive complex 2|Zinc fingers C2H2-type

Basic information

Region (hg38): 17:31937007-32001045

Links

ENSG00000178691NCBI:23512OMIM:606245HGNC:17101Uniprot:Q15022AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

Phenotypes

GenCC

Source: genCC

  • Imagawa-Matsumoto syndrome (Strong), mode of inheritance: AD
  • Weaver syndrome (Supportive), mode of inheritance: AD
  • Imagawa-Matsumoto syndrome (Moderate), mode of inheritance: AD
  • Imagawa-Matsumoto syndrome (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Imagawa-Matsumoto syndromeADGeneralGenetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testingCraniofacial; Genitourinary; Musculoskeletal; Neurologic; Pulmonary28229514; 30019515; 31736240

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SUZ12 gene.

  • not provided (8 variants)
  • Imagawa-Matsumoto syndrome (5 variants)
  • Inborn genetic diseases (2 variants)
  • not specified (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SUZ12 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type Pathogenic Likely pathogenic VUS Likely benign Benign Sum
synonymous
13
clinvar
1
clinvar
14
missense
1
clinvar
2
clinvar
54
clinvar
11
clinvar
68
nonsense
5
clinvar
4
clinvar
4
clinvar
13
start loss
0
frameshift
5
clinvar
5
clinvar
4
clinvar
14
inframe indel
1
clinvar
1
clinvar
2
splice donor/acceptor (+/-2bp)
3
clinvar
1
clinvar
1
clinvar
5
splice region
5
2
7
non coding
4
clinvar
1
clinvar
5
Total 14 12 64 28 3

Highest pathogenic variant AF is 0.00000658

Variants in SUZ12

This is a list of pathogenic ClinVar variants found in the SUZ12 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position Type Phenotype Significance ClinVar
17-31937262-C-G Uncertain significance (Jul 15, 2022)1878922
17-31937264-C-A Uncertain significance (Feb 15, 2022)1700860
17-31937319-T-C Uncertain significance (Mar 08, 2024)3370578
17-31937331-G-C Inborn genetic diseases Uncertain significance (Jan 03, 2025)3803132
17-31937332-C-T Inborn genetic diseases Uncertain significance (Jan 03, 2025)3803133
17-31937335-C-T Inborn genetic diseases Uncertain significance (Mar 06, 2023)2494468
17-31937344-C-T Likely benign (Mar 01, 2024)3067301
17-31937347-C-G Inborn genetic diseases Likely benign (May 10, 2023)2569160
17-31937356-C-T Inborn genetic diseases Uncertain significance (May 05, 2023)2565332
17-31937365-A-G Inborn genetic diseases Uncertain significance (Mar 05, 2024)3172317
17-31937371-G-A Inborn genetic diseases Uncertain significance (Dec 15, 2024)3803131
17-31937379-A-G Inborn genetic diseases Likely benign (Apr 07, 2023)2569554
17-31937386-G-C Inborn genetic diseases • Imagawa-Matsumoto syndrome Conflicting classifications of pathogenicity (Sep 20, 2024)2231374
17-31937389-G-A Inborn genetic diseases Uncertain significance (Oct 24, 2023)3172320
17-31937392-G-T Uncertain significance (Nov 01, 2024)3390085
17-31937397-A-G Inborn genetic diseases Uncertain significance (Apr 21, 2022)2284559
17-31937402-C-G not specified Pathogenic (Sep 22, 2022)1706550
17-31937406-GCCT-G Benign (Jun 01, 2022)2647644
17-31937416-C-T Inborn genetic diseases Uncertain significance (May 22, 2023)2549425
17-31937438-G-T Likely benign (Dec 31, 2019)781276
17-31937442-G-A Likely benign (Jan 01, 2025)3250500
17-31937457-G-A Benign/Likely benign (Sep 01, 2024)781857
17-31937457-G-T Inborn genetic diseases Uncertain significance (May 14, 2024)3323707
17-31937496-G-A Inborn genetic diseases Uncertain significance (Feb 15, 2023)2463929
17-31937507-C-T Likely benign (Feb 01, 2023)2647645

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
SUZ12protein_codingprotein_codingENST00000322652 1664028
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
1.000.00001631248290981249270.000392
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense3.401783590.4950.00001824886
Missense in Polyphen17108.390.156831436
Synonymous1.111061220.8710.000006241353
Loss of Function5.36135.40.02820.00000189466

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.000.00
Ashkenazi Jewish0.000.00
East Asian0.0005030.000436
Finnish0.000.00
European (Non-Finnish)0.0001460.000141
Middle Eastern0.0005030.000436
South Asian0.002600.00243
Other0.000.00

dbNSFP

Source: dbNSFP

Function
FUNCTION: Polycomb group (PcG) protein. Component of the PRC2/EED- EZH2 complex, which methylates 'Lys-9' (H3K9me) and 'Lys-27' (H3K27me) of histone H3, leading to transcriptional repression of the affected target gene. The PRC2/EED-EZH2 complex may also serve as a recruiting platform for DNA methyltransferases, thereby linking two epigenetic repression systems. Genes repressed by the PRC2/EED-EZH2 complex include HOXC8, HOXA9, MYT1 and CDKN2A. {ECO:0000269|PubMed:15225548, ECO:0000269|PubMed:15231737, ECO:0000269|PubMed:15385962, ECO:0000269|PubMed:16618801, ECO:0000269|PubMed:17344414, ECO:0000269|PubMed:18285464, ECO:0000269|PubMed:28229514}.;
Disease
DISEASE: Note=A chromosomal aberration involving SUZ12 may be a cause of endometrial stromal tumors. Translocation t(7;17)(p15;q21) with JAZF1. The translocation generates the JAZF1-SUZ12 oncogene consisting of the N-terminus part of JAZF1 and the C-terminus part of SUZ12. It is frequently found in all cases of endometrial stromal tumors, except in endometrial stromal sarcomas, where it is rarer. {ECO:0000269|PubMed:11371647}.; DISEASE: Note=Defects in EED are associated with Weaver syndrome (WVS): A syndrome of accelerated growth and osseous maturation, unusual craniofacial appearance, hoarse and low-pitched cry, and hypertonia with camptodactyly. Distinguishing features of Weaver syndrome include broad forehead and face, ocular hypertelorism, prominent wide philtrum, micrognathia, deep horizontal chin groove, and deep-set nails. In addition, carpal bone development is advanced over the rest of the hand. {ECO:0000269|PubMed:28229514}.;
Pathway
Interactome of polycomb repressive complex 2 (PRC2);Oxidative Stress Induced Senescence;Tumor suppressor activity of SMARCB1;EMT transition in Colorectal Cancer;Signal Transduction;Epigenetic regulation of gene expression;Gene expression (Transcription);the prc2 complex sets long-term gene silencing through modification of histone tails;Transcriptional Regulation by E2F6;Generic Transcription Pathway;Oxidative Stress Induced Senescence;Cellular Senescence;SUMOylation of chromatin organization proteins;Cellular responses to stress;Post-translational protein modification;SUMO E3 ligases SUMOylate target proteins;Metabolism of proteins;PKMTs methylate histone lysines;RNA Polymerase II Transcription;Chromatin modifying enzymes;SUMOylation;Cellular responses to external stimuli;Regulation of PTEN gene transcription;PTEN Regulation;PIP3 activates AKT signaling;Chromatin organization;Intracellular signaling by second messengers;PRC2 methylates histones and DNA (Consensus)

Intolerance Scores

loftool
0.410
rvis_EVS
-0.16
rvis_percentile_EVS
41.91

Haploinsufficiency Scores

pHI
0.900
hipred
Y
hipred_score
0.825
ghis
0.650

Essentials

essential_gene_CRISPR
E
essential_gene_CRISPR2
S
essential_gene_gene_trap
E
gene_indispensability_pred
E
gene_indispensability_score
1.00

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

Mouse Genome Informatics

Gene name
Suz12
Phenotype
growth/size/body region phenotype; cellular phenotype; skeleton phenotype; embryo phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); hematopoietic system phenotype; neoplasm; pigmentation phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); immune system phenotype;

Zebrafish Information Network

Gene name
suz12a
Affected structure
blood cell
Phenotype tag
abnormal
Phenotype quality
decreased amount

Gene ontology

Biological process
negative regulation of transcription by RNA polymerase II;positive regulation of cell population proliferation;histone ubiquitination;negative regulation of cell differentiation;negative regulation of gene expression, epigenetic;negative regulation of G0 to G1 transition;histone H3-K27 methylation
Cellular component
sex chromatin;nucleus;nucleoplasm;nucleolus;RSC-type complex;nuclear body;protein-DNA complex;ESC/E(Z) complex
Molecular function
RNA polymerase II proximal promoter sequence-specific DNA binding;RNA binding;protein binding;chromatin DNA binding;methylated histone binding;histone methyltransferase activity;metal ion binding;histone methyltransferase activity (H3-K27 specific);promoter-specific chromatin binding