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

ENSG00000178691 ∙ NCBI:23512 ∙ OMIM:606245 ∙ HGNC:17101 ∙ Uniprot:Q15022 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

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

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Imagawa-Matsumoto syndrome	AD	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Craniofacial; Genitourinary; Musculoskeletal; Neurologic; Pulmonary	28229514; 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	1	14
missense	1	2	54	11		68
nonsense	5	4	4			13
start loss						0
frameshift	5	5	4			14
inframe indel			1		1	2
splice donor/acceptor (+/-2bp)	3	1	1			5
splice region			5	2		7
non coding				4	1	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)
17-31937264-C-A			Uncertain significance (Feb 15, 2022)
17-31937319-T-C			Uncertain significance (Mar 08, 2024)
17-31937331-G-C		Inborn genetic diseases	Uncertain significance (Jan 03, 2025)
17-31937332-C-T		Inborn genetic diseases	Uncertain significance (Jan 03, 2025)
17-31937335-C-T		Inborn genetic diseases	Uncertain significance (Mar 06, 2023)
17-31937344-C-T			Likely benign (Mar 01, 2024)
17-31937347-C-G		Inborn genetic diseases	Likely benign (May 10, 2023)
17-31937356-C-T		Inborn genetic diseases	Uncertain significance (May 05, 2023)
17-31937365-A-G		Inborn genetic diseases	Uncertain significance (Mar 05, 2024)
17-31937371-G-A		Inborn genetic diseases	Uncertain significance (Dec 15, 2024)
17-31937379-A-G		Inborn genetic diseases	Likely benign (Apr 07, 2023)
17-31937386-G-C		Inborn genetic diseases • Imagawa-Matsumoto syndrome	Conflicting classifications of pathogenicity (Sep 20, 2024)
17-31937389-G-A		Inborn genetic diseases	Uncertain significance (Oct 24, 2023)
17-31937392-G-T			Uncertain significance (Nov 01, 2024)
17-31937397-A-G		Inborn genetic diseases	Uncertain significance (Apr 21, 2022)
17-31937402-C-G		not specified	Pathogenic (Sep 22, 2022)
17-31937406-GCCT-G			Benign (Jun 01, 2022)
17-31937416-C-T		Inborn genetic diseases	Uncertain significance (May 22, 2023)
17-31937438-G-T			Likely benign (Dec 31, 2019)
17-31937442-G-A			Likely benign (Jan 01, 2025)
17-31937457-G-A			Benign/Likely benign (Sep 01, 2024)
17-31937457-G-T		Inborn genetic diseases	Uncertain significance (May 14, 2024)
17-31937496-G-A		Inborn genetic diseases	Uncertain significance (Feb 15, 2023)
17-31937507-C-T			Likely benign (Feb 01, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SUZ12	protein_coding	protein_coding	ENST00000322652	16	64028

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.0000163	124829	0	98	124927	0.000392

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.40	178	359	0.495	0.0000182	4886
Missense in Polyphen		17	108.39	0.15683		1436
Synonymous	1.11	106	122	0.871	0.00000624	1353
Loss of Function	5.36	1	35.4	0.0282	0.00000189	466

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.000503	0.000436
Finnish	0.00	0.00
European (Non-Finnish)	0.000146	0.000141
Middle Eastern	0.000503	0.000436
South Asian	0.00260	0.00243
Other	0.00	0.00

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

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

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