Preeclampsia/eclampsia 4

Summary

Preeclampsia/eclampsia 4 (MONDO:0012266) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 5

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	preeclampsia/eclampsia 4
Mondo ID	MONDO:0012266
MeSH	C563724
OMIM	609404
UMLS	C1836255
MedGen	322874
GARD	0018392
Is cancer (heuristic)	no

Also known as: PEE4 · preeclampsia caused by mutation in STOX1 · preeclampsia/eclampsia 4 · Preeclampsia/eclampsia type 4 · STOX1 preeclampsia

Data availability: 5 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › preeclampsia › preeclampsia/eclampsia 4

Related subtypes (6): mild pre-eclampsia, severe pre-eclampsia, preeclampsia/eclampsia 2, preeclampsia/eclampsia 3, preeclampsia/eclampsia 5, preeclampsia/eclampsia 1

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

5 retrieved; paginated sample, class counts are floors:

3 uncertain significance, 1 risk factor, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1719	NM_152709.5(STOX1):c.457T>C (p.Tyr153His)	STOX1	risk factor	no assertion criteria provided
3892573	NM_152709.5(STOX1):c.1450G>C (p.Gly484Arg)	STOX1	Uncertain significance	criteria provided, multiple submitters, no conflicts
3892574	NM_152709.5(STOX1):c.1750A>G (p.Ser584Gly)	STOX1	Uncertain significance	criteria provided, single submitter
3892575	NM_152709.5(STOX1):c.2195G>A (p.Cys732Tyr)	STOX1	Uncertain significance	criteria provided, single submitter
1720	NM_152709.5(STOX1):c.1824A>C (p.Glu608Asp)	STOX1	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

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

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
STOX1	Orphanet:275555	Preeclampsia

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
STOX1	HGNC:23508	ENSG00000165730	Q6ZVD7	Storkhead-box protein 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
STOX1	Storkhead-box protein 1	Involved in regulating the levels of reactive oxidative species and reactive nitrogen species and in mitochondrial homeostasis in the placenta.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · 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
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
STOX1	Other/Unknown	no		Storkhead-box_WHD, STOX1/2

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
bronchial epithelial cell	1
bronchus	1
ventricular zone	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
STOX1	195	broad	marker	bronchial epithelial cell, bronchus, ventricular zone

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
STOX1	820

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
STOX1	Q6ZVD7	48.87

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

GO biological processes 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.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
positive regulation of cyclin-dependent protein kinase activity	1	16852.0×	5e-04	STOX1
positive regulation of otic vesicle morphogenesis	1	16852.0×	5e-04	STOX1
regulation of mitochondrial DNA metabolic process	1	8426.0×	5e-04	STOX1
regulation of response to oxidative stress	1	8426.0×	5e-04	STOX1
cellular response to nitrosative stress	1	5617.3×	6e-04	STOX1
positive regulation of peptidyl-threonine phosphorylation	1	1872.4×	0.002	STOX1
regulation of mitochondrion organization	1	842.6×	0.003	STOX1
positive regulation of peptidyl-serine phosphorylation	1	766.0×	0.003	STOX1
positive regulation of G2/M transition of mitotic cell cycle	1	601.9×	0.003	STOX1
regulation of mitochondrial membrane potential	1	543.6×	0.003	STOX1
positive regulation of G1/S transition of mitotic cell cycle	1	401.2×	0.004	STOX1
inner ear development	1	374.5×	0.004	STOX1
regulation of gene expression	1	83.4×	0.016	STOX1
positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	1	78.4×	0.016	STOX1
negative regulation of gene expression	1	69.1×	0.017	STOX1
cell division	1	46.2×	0.024	STOX1
positive regulation of gene expression	1	38.7×	0.027	STOX1
regulation of transcription by RNA polymerase II	1	11.7×	0.086	STOX1

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
STOX1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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	STOX1

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)
STOX1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.