FZR1

Chr 19AD

fizzy and cell division cycle 20 related 1

Also known as: CDC20C, CDH1, DEE109, FZR, FZR2, HCDH, HCDH1

The FZR1 protein functions as a substrate-specific adapter for the anaphase promoting complex (APC/C), regulating cell cycle progression by controlling protein degradation during mitosis and DNA damage checkpoints. Mutations cause developmental and epileptic encephalopathy 109, inherited in an autosomal dominant pattern. This gene is highly constrained against loss-of-function variants, reflecting its critical role in cellular function.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismADLOEUF 0.171 OMIM phenotype
Clinical SummaryFZR1
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.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Dual constrained — LoF & missense intolerant
LoF Constraint
0.17LOEUF
pLI 1.000
Z-score 4.69
OE 0.04 (0.010.17)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
3.64Z-score
OE missense 0.43 (0.380.50)
143 obs / 328.8 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.04 (0.010.17)
00.351.4
Missense OE0.43 (0.380.50)
00.61.4
Synonymous OE1.06
01.21.6
LoF obs/exp: 1 / 27.6Missense obs/exp: 143 / 328.8Syn Z: -0.60
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongFZR1-related intellectual disability and epilepsyOTHERAD
DN
0.3395th %ile
GOF
0.1999th %ile
LOF
0.85top 5%

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

LOFprediction above median · LOEUF 0.17

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

FZR1 · 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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