FZR1

Chr 19p13.3

fizzy and cell division cycle 20 related 1

Aliases:: HCDH1, CDH1, HCDH, FZR, FZR2
MANE:: ENST00000441788.7

OMIM: 603619 ↗NCBI: 51343 ↗Ensembl ↗

Annotations refreshed 9 hours ago.

Predicted protein structure

AlphaFold predicted structure

FZR1 · Q9UM11

v62025-08-01

Predicted Aligned Error matrix for FZR1 — diagonal shows residue index, colour shows pairwise prediction confidence (lower is better) — Predicted Aligned Error

Mean pLDDT

82.4/ 100

Confident

496 residues

Confidence breakdown

Very high(≥ 90)58%
Confident(70–90)17%
Low(50–70)10%
Very low(< 50)15%

Open interactive 3D viewer

AlphaFold (Jumper et al., 2021) · CC BY 4.0

Clinical relevance (Genomics England PanelApp)

Diagnostic Grade (Green)

DDG2P
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Early onset or syndromic epilepsy
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Disease associations (Open Targets)

developmental and epileptic encephalopathy 109
0.64
neurodegenerative disease
0.49
undetermined early-onset epileptic encephalopathy
0.37
hereditary disease
0.34
Global developmental delay
0.29
lysosomal storage disease
0.28
cerebellar ataxia
0.12
Hypotonia
0.12
Seizure
0.12
autism
0.12

Score is the Open Targets composite evidence score (0-1). Higher = stronger gene-disease association.

Protein function (UniProt)

Fizzy-related protein homolog

Substrate-specific adapter for the anaphase promoting complex/cyclosome (APC/C) E3 ubiquitin-protein ligase complex. Associates with the APC/C in late mitosis, in replacement of CDC20, and activates the APC/C during anaphase and telophase. The APC/C remains active in degrading substrates to ensure that positive regulators of the cell cycle do not accumulate prematurely. At the G1/S transition FZR1 is phosphorylated, leading to its dissociation from the APC/C. Following DNA damage, it is required for the G2 DNA damage checkpoint: its dephosphorylation and reassociation with the APC/C leads to the ubiquitination of PLK1, preventing entry into mitosis. Acts as an adapter for APC/C to target the DNA-end resection factor RBBP8/CtIP for ubiquitination and subsequent proteasomal degradation. Through the regulation of RBBP8/CtIP protein turnover, may play a role in DNA damage response, favoring DNA double-strand repair through error-prone non-homologous end joining (NHEJ) over error-free, RBBP8-mediated homologous recombination (HR) (PubMed:25349192)