FZR1

fizzy and cell division cycle 20 related 1, the group of WD repeat domain containing

Basic information

Region (hg38): 19:3506310-3538334

Links

ENSG00000105325 ∙ NCBI:51343 ∙ OMIM:603619 ∙ HGNC:24824 ∙ Uniprot:Q9UM11 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• developmental and epileptic encephalopathy 109 (Moderate), mode of inheritance: AD
• developmental and epileptic encephalopathy 109 (Strong), mode of inheritance: AD

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the FZR1 gene.

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			1	1	1	3
missense		1	18	1		20
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	19	2	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)
19-3523056-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)
19-3526162-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)
19-3526385-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)
19-3530839-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	Uncertain significance (Dec 26, 2023)
19-3531982-C-T			Uncertain significance (Oct 20, 2023)
19-3532010-G-A		Inborn genetic diseases	Uncertain significance (Sep 26, 2022)
19-3532025-G-A		Inborn genetic diseases	Uncertain significance (Jan 09, 2023)
19-3532033-G-C		Inborn genetic diseases	Likely pathogenic (Sep 29, 2023)
19-3532086-C-A		Developmental and epileptic encephalopathy 109	Pathogenic (Dec 14, 2023)
19-3532086-C-G		Developmental and epileptic encephalopathy 109	Pathogenic (Dec 14, 2023)

GnomAD

Source: gnomAD

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: dbNSFP

• 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