FZR1
fizzy and cell division cycle 20 related 1, the group of WD repeat domain containing
Basic information
Region (hg38): 19:3506311-3538334
Links
Phenotypes
GenCC
Source:
- developmental and epileptic encephalopathy 109 (Strong), mode of inheritance: AD
- developmental and epileptic encephalopathy 109 (Moderate), mode of inheritance: AD
ClinVar
This is a list of variants' phenotypes submitted to
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the FZR1 gene is commonly pathogenic or not.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 3 | |||||
| missense | 21 | 24 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region | 1 | 1 | ||||
| non coding | 0 | |||||
| Total | 0 | 1 | 22 | 3 | 1 |
Variants in FZR1
This is a list of pathogenic ClinVar variants found in the FZR1 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 19-3522999-G-T | Inborn genetic diseases | Uncertain significance (Feb 13, 2024) | ||
| 19-3523048-C-T | Inborn genetic diseases | Uncertain significance (Jan 17, 2025) | ||
| 19-3523056-C-T | Inborn genetic diseases | Likely benign (Feb 10, 2022) | ||
| 19-3523058-C-T | Inborn genetic diseases | Likely benign (May 30, 2023) | ||
| 19-3525958-G-A | Inborn genetic diseases | Uncertain significance (Aug 16, 2022) | ||
| 19-3526130-A-C | Inborn genetic diseases | Uncertain significance (Dec 06, 2022) | ||
| 19-3526148-G-A | Inborn genetic diseases | Uncertain significance (Dec 04, 2024) | ||
| 19-3526162-G-A | Inborn genetic diseases | Uncertain significance (Jun 24, 2022) | ||
| 19-3526179-C-T | Uncertain significance (Feb 01, 2024) | |||
| 19-3526337-A-T | Inborn genetic diseases | Uncertain significance (Sep 13, 2023) | ||
| 19-3526343-G-A | Inborn genetic diseases | Uncertain significance (Jul 13, 2021) | ||
| 19-3526346-G-T | FZR1-related condition | Uncertain significance (May 09, 2024) | ||
| 19-3526385-C-T | Inborn genetic diseases | Uncertain significance (Jul 25, 2023) | ||
| 19-3527021-C-T | Likely benign (May 01, 2024) | |||
| 19-3527636-A-T | Inborn genetic diseases | Uncertain significance (Dec 27, 2022) | ||
| 19-3527648-C-G | Inborn genetic diseases | Uncertain significance (Jul 16, 2021) | ||
| 19-3527719-G-A | Developmental and epileptic encephalopathy 109 | Pathogenic (Dec 14, 2023) | ||
| 19-3527720-A-G | Developmental and epileptic encephalopathy 109 | Pathogenic (Dec 14, 2023) | ||
| 19-3530796-C-T | FZR1-related condition | Uncertain significance (Mar 11, 2024) | ||
| 19-3530816-G-A | Inborn genetic diseases | Uncertain significance (Dec 16, 2024) | ||
| 19-3530839-C-T | Benign (Jan 01, 2024) | |||
| 19-3531790-T-C | Inborn genetic diseases | Uncertain significance (Nov 13, 2023) | ||
| 19-3531913-G-A | not specified | Uncertain significance (Jan 17, 2024) | ||
| 19-3531961-A-G | Inborn genetic diseases • FZR1-related condition | Uncertain significance (Dec 26, 2023) | ||
| 19-3531982-C-T | Uncertain significance (Oct 20, 2023) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| FZR1 | protein_coding | protein_coding | ENST00000395095 | 13 | 32058 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 1.00 | 0.000308 | 124307 | 0 | 1 | 124308 | 0.00000402 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 3.64 | 143 | 329 | 0.435 | 0.0000229 | 3173 |
| Missense in Polyphen | 26 | 129.58 | 0.20065 | 1187 | ||
| Synonymous | -0.602 | 159 | 150 | 1.06 | 0.0000112 | 1017 |
| Loss of Function | 4.69 | 1 | 27.6 | 0.0363 | 0.00000138 | 285 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00 | 0.00 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.0000546 | 0.0000546 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.00 | 0.00 |
| Middle Eastern | 0.0000546 | 0.0000546 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: 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). {ECO:0000269|PubMed:18662541, ECO:0000269|PubMed:21596315, ECO:0000269|PubMed:25349192, ECO:0000269|PubMed:9734353}.;
- Pathway
- Cell cycle - Homo sapiens (human);Ubiquitin mediated proteolysis - Homo sapiens (human);Progesterone-mediated oocyte maturation - Homo sapiens (human);Senescence-Associated Secretory Phenotype (SASP);Cellular Senescence;Cellular responses to stress;Immune System;Adaptive Immune System;Antigen processing: Ubiquitination & Proteasome degradation;Cyclin A:Cdk2-associated events at S phase entry;DNA Replication;Switching of origins to a post-replicative state;Class I MHC mediated antigen processing & presentation;Aurora A signaling;Synthesis of DNA;S Phase;Cellular responses to external stimuli;TGF_beta_Receptor;Phosphorylation of Emi1;SCF-beta-TrCP mediated degradation of Emi1;Regulation of APC/C activators between G1/S and early anaphase;CDK-mediated phosphorylation and removal of Cdc6;Conversion from APC/C:Cdc20 to APC/C:Cdh1 in late anaphase;APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1;Autodegradation of Cdh1 by Cdh1:APC/C;APC/C-mediated degradation of cell cycle proteins;Regulation of mitotic cell cycle;Cell Cycle;Cell Cycle, Mitotic;PLK1 signaling events
(Consensus)
Recessive Scores
- pRec
- 0.136
Intolerance Scores
- loftool
- 0.0431
- rvis_EVS
- -0.8
- rvis_percentile_EVS
- 12.24
Haploinsufficiency Scores
- pHI
- 0.906
- hipred
- Y
- hipred_score
- 0.816
- ghis
- 0.682
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- S
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.902
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Fzr1
- Phenotype
- growth/size/body region phenotype; cellular phenotype; homeostasis/metabolism phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); neoplasm; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); embryo phenotype;
Zebrafish Information Network
- Gene name
- fzr1a
- Affected structure
- lens
- Phenotype tag
- abnormal
- Phenotype quality
- mislocalised anteriorly
Gene ontology
- Biological process
- DNA repair;cell cycle;positive regulation of cell population proliferation;anaphase-promoting complex-dependent catabolic process;regulation of meiotic nuclear division;positive regulation of protein catabolic process;cell division;lens fiber cell differentiation;protein K11-linked ubiquitination;signal transduction involved in G2 DNA damage checkpoint;negative regulation of cell aging;regulation of mitotic cell cycle phase transition;positive regulation of ubiquitin protein ligase activity
- Cellular component
- nucleoplasm;anaphase-promoting complex;cytosol;nuclear membrane
- Molecular function
- protein binding;anaphase-promoting complex binding;ubiquitin-protein transferase activator activity