Developmental and epileptic encephalopathy 109

disease

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Summary

Developmental and epileptic encephalopathy 109 (MONDO:0859325) is a disease caused by FZR1 (GenCC Strong), with 1 cohort gene.

At a glance

Causal gene: FZR1 (GenCC Strong)
Cohort genes: 1
ClinVar variants: 7

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	developmental and epileptic encephalopathy 109
Mondo ID	MONDO:0859325
OMIM	620145
DOID	DOID:0070378
UMLS	C5774263
MedGen	1824036
GARD	0026699
Is cancer (heuristic)	no

Data availability: 7 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › hereditary neurological disease › Mendelian neurodevelopmental disorder › genetic developmental and epileptic encephalopathy › developmental and epileptic encephalopathy 109

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

7 retrieved; paginated sample, class counts are floors:

3 pathogenic, 3 uncertain significance, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
1802183	NM_016263.4(FZR1):c.560A>G (p.Asp187Gly)	FZR1	Pathogenic	no assertion criteria provided
1802185	NM_016263.4(FZR1):c.999C>G (p.Asn333Lys)	FZR1	Pathogenic	no assertion criteria provided
1802186	NM_016263.4(FZR1):c.999C>A (p.Asn333Lys)	FZR1	Pathogenic	criteria provided, single submitter
1330275	NM_016263.4(FZR1):c.1126G>A (p.Gly376Ser)	FZR1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1802184	NM_016263.4(FZR1):c.559G>A (p.Asp187Asn)	FZR1	Uncertain significance	criteria provided, single submitter
4531716	NM_016263.4(FZR1):c.818G>A (p.Arg273His)	FZR1	Uncertain significance	criteria provided, single submitter
4813516	NM_016263.4(FZR1):c.1013T>G (p.Leu338Arg)	FZR1	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
FZR1	Strong	Autosomal dominant	developmental and epileptic encephalopathy 109	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
FZR1	Orphanet:442835	Non-specific early-onset epileptic encephalopathy

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
FZR1	HGNC:24824	ENSG00000105325	Q9UM11	Fizzy-related protein homolog	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
FZR1	Fizzy-related protein homolog	Substrate-specific adapter for the anaphase promoting complex/cyclosome (APC/C) E3 ubiquitin-protein ligase complex.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 0 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Scaffold/PPI	1	17.3×	0.058

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
FZR1	Scaffold/PPI	no		WD40_rpt, WD40/YVTN_repeat-like_dom_sf, WD40_repeat_CS

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
left testis	1
right testis	1
ventricular zone	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
FZR1	254	ubiquitous	marker	ventricular zone, left testis, right testis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
FZR1	5,895

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
FZR1	Q9UM11	6

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 14. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Phosphorylation of Emi1	1	1427.5×	0.007	FZR1
Conversion from APC/C:Cdc20 to APC/C:Cdh1 in late anaphase	1	519.1×	0.007	FZR1
Aberrant regulation of mitotic exit in cancer due to RB1 defects	1	519.1×	0.007	FZR1
Regulation of APC/C activators between G1/S and early anaphase	1	308.6×	0.007	FZR1
Cyclin A/B1/B2 associated events during G2/M transition	1	308.6×	0.007	FZR1
Cyclin A:Cdk2-associated events at S phase entry	1	265.6×	0.007	FZR1
Transcriptional Regulation by VENTX	1	265.6×	0.007	FZR1
SCF-beta-TrCP mediated degradation of Emi1	1	237.9×	0.007	FZR1
Autodegradation of Cdh1 by Cdh1:APC/C	1	190.3×	0.007	FZR1
APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1	1	170.4×	0.007	FZR1
CDK-mediated phosphorylation and removal of Cdc6	1	170.4×	0.007	FZR1
Assembly of the pre-replicative complex	1	139.3×	0.008	FZR1
Senescence-Associated Secretory Phenotype (SASP)	1	99.3×	0.011	FZR1
Antigen processing: Ubiquitination & Proteasome degradation	1	37.2×	0.027	FZR1

GO biological processes by enrichment

GO term	Cohort genes	Fold	FDR	Sample cohort genes
positive regulation of anaphase-promoting complex-dependent catabolic process	1	3370.4×	0.002	FZR1
positive regulation of ubiquitin protein ligase activity	1	2808.7×	0.002	FZR1
regulation of meiotic nuclear division	1	2407.4×	0.002	FZR1
lens fiber cell differentiation	1	1053.2×	0.003	FZR1
regulation of meiotic cell cycle	1	766.0×	0.003	FZR1
anaphase-promoting complex-dependent catabolic process	1	702.2×	0.003	FZR1
negative regulation of cellular senescence	1	648.1×	0.003	FZR1
mitotic G2 DNA damage checkpoint signaling	1	443.5×	0.004	FZR1
protein K11-linked ubiquitination	1	391.9×	0.004	FZR1
regulation of mitotic cell cycle	1	240.7×	0.005	FZR1
DNA repair	1	63.8×	0.019	FZR1
cell division	1	46.2×	0.023	FZR1
positive regulation of cell population proliferation	1	33.6×	0.030	FZR1

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
FZR1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
FZR1	2	Binding:2

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	FZR1

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
FZR1	2	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.

Cohort genes: FZR1