GeneBe

SUZ12

protein-coding

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

Gene summary

This zinc finger gene has been identified at the breakpoints of a recurrent chromosomal translocation reported in endometrial stromal sarcoma. Recombination of these breakpoints results in the fusion of this gene and JAZF1. The protein encoded by this gene contains a zinc finger domain in the C terminus of the coding region. [provided by RefSeq, Jul 2009]

MANE transcript

NM_015355.4

Inheritance

AD

ClinVar variants

P:41U:125B:35

Top phenotype

Imagawa-Matsumoto syndrome

gnomAD constraint

pLI —, LoF o/e 0.03

Max pathogenic AF

—

Genomic locus

chr17:31,937,007-32,001,045

External References & Databases

Ensembl (ENSG00000178691)NCBI Gene (23512)OMIM (606245)HGNC:17101GenCCUniProt (Q15022)AlphaFoldClinVar (SUZ12)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~64.0 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

Imagawa-Matsumoto syndromeSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0032916

Submitter: PanelApp Australia

Imagawa-Matsumoto syndromeDEFINITIVE

Inheritance Pattern: AD

Disease ID:MONDO:0032916

Submitter: G2P

Imagawa-Matsumoto syndromeDEFINITIVE

Inheritance Pattern: AD

Disease ID:MONDO:0032916

Submitter: Illumina

Weaver syndromeSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0010193

Submitter: Orphanet

Imagawa-Matsumoto syndromeMODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0032916

Submitter: Ambry Genetics

Imagawa-Matsumoto syndromeSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0032916

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Imagawa-Matsumoto syndromeAD

Manifestation: Craniofacial; Genitourinary; Musculoskeletal; Neurologic; Pulmonary

Intervention: General

Rationale: 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

Refs: 28229514; 30019515; 31736240Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SUZ12 variants in ClinVar

12 Conditions Cataloged
not providedTotal: 100
Inborn genetic diseasesTotal: 70
Imagawa-Matsumoto syndromeTotal: 34
not specifiedTotal: 17
SUZ12-related disorderTotal: 16
Neurodevelopmental disorderTotal: 1
TeratomaTotal: 1
Weaver syndromeTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_015355.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
1
clinvar
18
clinvar
2
clinvar
 21
missense
3
clinvar
3
clinvar
106
clinvar
14
clinvar
1
clinvar
 127
nonsense
4
clinvar
8
clinvar
4
clinvar
 16
start loss
0
frameshift
7
clinvar
9
clinvar
8
clinvar
 24
splice donor/acceptor (+/-2bp)
2
clinvar
5
clinvar
6
clinvar
 13
Total1625125323201

Highest pathogenic variant AF is 0.000006583192

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 41 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_015355.4RefSeqNP_056170.216MANE Select
ENST00000322652.10EnsemblENSP00000316578.516MANE Select
NM_001321207.2RefSeqNP_001308136.115Standard
ENST00000580398.1EnsemblENSP00000463936.115Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / ModelOrganismObserved Phenotype
suz12aDanio rerio

Structure: blood cell

Quality: decreased amount

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Interactome of polycomb repressive complex 2 (PRC2)
  • Oxidative Stress Induced Senescence
  • Tumor suppressor activity of SMARCB1
  • EMT transition in Colorectal Cancer
  • Signal Transduction

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

Molecular Function

  • RNA polymerase II proximal promoter sequence-specific DNA binding
  • RNA binding
  • protein binding
  • chromatin DNA binding
  • methylated histone binding

Cellular Component

  • sex chromatin
  • nucleus
  • nucleoplasm
  • nucleolus
  • RSC-type complex

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000322652
Coding exons
16
Length
64028
Individuals with no LoFs
124829
Homozygous LoFs
0
Heterozygous LoFs
98
Defined
124927
p
0.000392
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense3.401783590.4950.00001824886
Missense (PolyPhen)17108.390.156831436
Synonymous1.111061220.8710.000006241353
Loss of Function5.36135.40.02820.00000189466

Population LoF Frequency

PopulationCAFp-valueStatus
African00.0absent
Latino/Admixed American00.0absent
Ashkenazi Jewish00.0absent
East Asian0.000500.00044rare
Finnish00.0absent
European (Non-Finnish)0.000150.00014rare
South Asian0.00260.0024notable
Other00.0absent

dbNSFP Gene Annotations

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}.;

Intolerance Scores

LoFtool
0.410
RVIS EVS
-0.16
RVIS percentile EVS
41.91

Essentials

Essential (CRISPR)
E
Essential (CRISPR2)
S
Essential (gene trap)
E
Indispensability pred.
E
Indispensability score
1.00

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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