FZR1 (Fizzy/Cell Cycle Regulator 1)
Key regulator of the anaphase-promoting complex/cyclosome (APC/C) controlling mitotic exit and G1 phase stability.
Gene Information Card
| Symbol | FZR1 |
|---|---|
| Full Name | Fizzy and cell division cycle 20 related 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 19p13.3 |
| NCBI Gene ID | 51343 ncbi.nlm.nih.gov/gene/51343 |
| Ensembl ID | ENSG00000105325 |
| UniProt ID | Q9Y6D9 |
| OMIM ID | 603277 |
| HGNC ID | 4036 |
| Aliases | CDC20C, FZR, HCDH, KIAA1242, CDC20 homolog 1 |
Description
FZR1 (Fizzy-related protein 1) is a substrate-specific activator of the anaphase-promoting complex/cyclosome (APC/C), a ubiquitin ligase essential for cell cycle progression. FZR1 targets key mitotic regulators (e.g., cyclin B1, securin) for degradation during mitotic exit and G1 phase, ensuring proper chromosome segregation and genomic stability. It also plays roles in neuronal development and synaptic plasticity.
Disease Associations
| Disease Name | Disease Description |
|---|---|
| Colorectal cancer | Loss of FZR1 expression leads to APC/C dysregulation, genomic instability, and tumor progression. |
| Breast cancer | Reduced FZR1 levels correlate with poor prognosis and aneuploidy. |
| Prostate cancer | FZR1 downregulation promotes cell proliferation and invasion. |
| Neurodevelopmental disorders | FZR1 mutations impair APC/C activity, affecting neuronal migration and differentiation. |
| Endometrial cancer | FZR1 alterations associated with microsatellite instability. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 28.5 | High |
| Lymph node | 18.2 | Medium |
| Brain (cerebellum) | 15.1 | Medium |
| Bone marrow | 12.3 | Medium |
| Liver | 6.7 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 22.4 | High expression |
| HeLa | 18.9 | Moderate expression |
| MCF7 | 14.2 | Moderate expression |
| K562 | 11.5 | Low expression |
| HepG2 | 8.1 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Mutation site | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1072C>T (p.Arg358Trp) | Missense | <0.1% | Reduced APC/C binding and activity; associated with neurodevelopmental delay. |
| c.1456G>A (p.Glu486Lys) | Missense | <0.1% | Impaired substrate recognition; linked to intellectual disability. |
| c.1685_1686del (p.Glu562Glyfs*13) | Frameshift | <0.1% | Loss of function; truncation of C-terminal domain. |
| c.1A>G (p.Met1Val) | Start loss | <0.1% | Complete loss of protein expression. |
Mutation functional classification
Loss of Function (LOF)
Missense and truncating mutations that disrupt APC/C binding or catalytic activity, leading to mitotic arrest and genomic instability.
Gain of Function (GOF)
Not reported in literature or curated databases.
Dominant Negative (DN)
Some missense variants (e.g., p.Arg358Trp) may interfere with wild-type FZR1 function by competing for APC/C binding.
View complete mutation data：ClinVar: https://www.clinvar.com/gene/51343 COSMIC: https://cancer.sanger.ac.uk/cosmic/gene/analysis?ln=FZR1
Gene Ontology (GO)
| • GO:0005680 – anaphase-promoting complex | • GO:0016567 – protein ubiquitination |
| • GO:0051301 – cell division | • GO:0007094 – mitotic spindle assembly checkpoint |
| • GO:0043161 – proteasome-mediated ubiquitin-dependent protein catabolic process | • GO:0005515 – protein binding |
Pathways
• Cell Cycle
• Mitotic (Reactome: R-HSA-69278)
• APC/C-mediated degradation of cell cycle proteins (Reactome: R-HSA-174178)
• Regulation of APC/C activators between G1/S and early anaphase (Reactome: R-HSA-176408)
Protein Summary
FZR1 is a 55 kDa protein containing a C-terminal WD40 domain that mediates substrate recognition and binding to the APC/C core. It is essential for timely degradation of cyclins and securin, thereby controlling mitotic exit and G1 phase maintenance. FZR1 also regulates post-mitotic processes such as neuronal differentiation and synaptic function. Its expression is tightly regulated during the cell cycle, peaking in G1.
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| FZR1 Knockout HEK293 Cell Line | EDJ-KQ3137 | Human | 51343 | Details Get a Quote |
| FZR1 Knockout A-549 Cell Line | EDJ-KQ23131 | Human | 51343 | Details Get a Quote |
| FZR1 Knockout HCT 116 Cell Line | EDJ-KQ24517 | Human | 51343 | Details Get a Quote |
| FZR1 Knockout HeLa Cell Line | EDJ-KQ24518 | Human | 51343 | Details Get a Quote |
| FZR1 (c.1450-97C>T )Point Mutation in HAP1 Cell Line | EDC03495 | Human | 51343 | Details Get a Quote |
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