SUZ12

Chr 17AD

SUZ12 polycomb repressive complex 2 subunit

Also known as: CHET9, IMMAS, JJAZ1

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.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismADLOEUF 0.131 OMIM phenotype
Clinical SummarySUZ12
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

Dual constrained — LoF & missense intolerant
LoF Constraint
0.13LOEUF
pLI 1.000
Z-score 5.36
OE 0.03 (0.010.13)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint
3.40Z-score
OE missense 0.50 (0.440.56)
178 obs / 359.4 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.03 (0.010.13)
00.351.4
Missense OE0.50 (0.440.56)
00.61.4
Synonymous OE0.87
01.21.6
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
DN
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 tubePMID:19535498

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

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

SUZ12 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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