SUZ12

Chr 17AD

SUZ12 polycomb repressive complex 2 subunit

Also known as: CHET9, IMMAS, JJAZ1

NCBI Gene: 23512 ENSG00000178691 UniProt: Q15022 OMIM: 606245

The SUZ12 protein is a component of the PRC2 complex that methylates histones H3K9 and H3K27, leading to transcriptional repression of target genes including HOX genes and cell cycle regulators. Mutations cause Imagawa-Matsumoto syndrome with autosomal dominant inheritance. This gene is highly constrained against loss-of-function variants (pLI = 1.0, LOEUF = 0.13), indicating strong selective pressure against damaging mutations.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

GeneReviews OMIM ResearchGenerating clinical summary…

LOFmechanismADLOEUF 0.131 OMIM phenotype

Clinical Summary— SUZ12

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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.

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GeneReview available — SUZ12

Authoritative clinical overview · Recommended first read

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Dual constrained — LoF & missense intolerant

LoF Constraint?

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?

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?

LoF OE?0.03 (0.01–0.13)

0≤0.351.4

Missense OE?0.50 (0.44–0.56)

0≤0.61.4

Synonymous OE?0.87

0≤1.21.6

LoF obs/exp: 1 / 35.4Missense obs/exp: 178 / 359.4Syn Z: 1.11

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveSUZ12-related Weaver-like overgrowth syndromeLOFAD

This gene — mechanism propensity

0.2299th %ile

GOF

0.2497th %ile

LOF

0.90top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · 1 literature citation · LOEUF 0.13

Literature Evidence

LOFHaploinsufficiency of the murine polycomb gene Suz12 results in diverse malformations of the brain and neural tube1

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

References