Encephalopathy, acute, infection-induced

Summary

Encephalopathy, acute, infection-induced (MONDO:0000166) is a disease with 1 cohort gene (2 GWAS associations across 1 studies).

At a glance

• Cohort genes: 1
• GWAS associations: 2

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	encephalopathy, acute, infection-induced
Mondo ID	MONDO:0000166
OMIM	610551
Is cancer (heuristic)	no

Data availability: 2 GWAS associations (1 study) · 1 GenCC gene-disease record.

Disease family

An umbrella term covering 1 Mondo subtype.

Classification path: disease › human disease › disease by body system or component › nervous system disorder › central nervous system disorder › brain disorder › encephalopathy, acute, infection-induced

Related subtypes (70): leukoencephalopathy, megalencephalic, diabetic encephalopathy, complex cortical dysplasia with other brain malformations, hydrocephalus, brain compression, cerebral sarcoidosis, hepatic encephalopathy, visual pathway disorder, central nervous system origin vertigo, cerebellar disorder, cerebritis, olfactory nerve disorder, thalamic disorder, pituitary gland disorder, disorder of optic chiasm, basal ganglia disorder, epilepsy, mental disorder, central nervous system cyst, migraine disorder, multiple sclerosis, prion disease, carbon monoxide-induced delayed encephalopathy, cerebral malaria, akinetic mutism, bulbar polio, Reye syndrome, brain edema, encephalomalacia, intracranial hypertension, intracranial hypotension, Wernicke encephalopathy, encephalopathy, recurrent, of childhood, XK aprosencephaly, progressive bulbar palsy, cerebrovascular disorder, glycine encephalopathy, autosomal recessive frontotemporal pachygyria, occipital pachygyria and polymicrogyria, insomnia, narcolepsy-cataplexy syndrome, megalencephaly, meningoencephalocele, cerebral cortical dysplasia, encephaloclastic disorder, bilirubin encephalopathy, autoimmune encephalopathy with parasomnia and obstructive sleep apnea, narcolepsy without cataplexy, hypothalamic hamartomas with gelastic seizures, encephalitis, cerebral lipidosis with dementia, brain neoplasm, colpocephaly, corpus callosum agenesis of blepharophimosis robin type, corpus callosum dysgenesis X-linked recessive, corpus callosum dysgenesis cleft spasm, corpus callosum dysgenesis hypopituitarism, cerebral degeneration, acute bilirubin encephalopathy, chronic bilirubin encephalopathy, atelencephaly, aprosencephaly, brain injury, traumatic encephalopathy, cluster headache syndrome, cerebral cortex disorder, midbrain disorder, encephalopathy due to mitochondrial and peroxisomal fission defect, brain malformations with or without urinary tract defects, encephalopathy, acute transient

Subtypes (1): familial acute necrotizing encephalopathy

Genetics & variants

GWAS landscape

2 GWAS associations across 1 studies. Top hits map to 3 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs12656207	4e-07	MARCOL, FBXO38-DT	G	1.6
rs9349362	1e-06	RCAN2	T	1.54

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90102509	Kasai M	2022	252	0	GWAS identifies candidate susceptibility loci and microRNA biomarkers for acute encephalopathy with biphasic seizures and late reduced diffusion.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	0
Tier 2: splice/UTR	0
Tier 3: regulatory	0
Tier 4: intronic/intergenic	2

MAF distribution

Bucket	Variants
common (>=0.05)	2
low_freq (0.01-0.05)	0
rare (<0.01)	0
unknown	0

Functional consequences

Consequence	Count
intron_variant	2

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs12656207	5	148226499	C>A,G,T	0.28	intron_variant	MARCOL, FBXO38-DT	4e-07	Tier 4: intronic/intergenic
rs9349362	6	46488799	C>G,T	0.39	intron_variant	RCAN2	1e-06	Tier 4: intronic/intergenic

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 20 · Orphanet: 4 · 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
ATP1A3	Strong	Autosomal dominant	developmental and epileptic encephalopathy 99	20

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ATP1A3	Orphanet:1171	Cerebellar ataxia-areflexia-pes cavus-optic atrophy-sensorineural hearing loss syndrome
ATP1A3	Orphanet:2131	Alternating hemiplegia of childhood
ATP1A3	Orphanet:442835	Non-specific early-onset epileptic encephalopathy
ATP1A3	Orphanet:71517	Rapid-onset dystonia-parkinsonism

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
ATP1A3	HGNC:801	ENSG00000105409	P13637	Sodium/potassium-transporting ATPase subunit alpha-3	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ATP1A3	Sodium/potassium-transporting ATPase subunit alpha-3	This is the catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of sodium and potassium ions across the plasma membrane.

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
Transcription factor	1	8.3×	0.121

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ATP1A3	Transcription factor	no		P_typ_ATPase, ATPase_P-typ_cation-transptr_N, P-type_ATPase_IIC

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
cortical plate	1
primary visual cortex	1
superior frontal gyrus	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ATP1A3	129	broad	marker	superior frontal gyrus, primary visual cortex, cortical plate

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ATP1A3	3,876

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ATP1A3	P13637	5

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 11. 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
Ion transport by P-type ATPases	1	207.6×	0.023	ATP1A3
Ion homeostasis	1	203.9×	0.023	ATP1A3
Potential therapeutics for SARS	1	114.2×	0.023	ATP1A3
Cardiac conduction	1	108.8×	0.023	ATP1A3
Ion channel transport	1	96.0×	0.023	ATP1A3
Muscle contraction	1	77.2×	0.024	ATP1A3
SARS-CoV Infections	1	55.4×	0.028	ATP1A3
Viral Infection Pathways	1	30.8×	0.044	ATP1A3
Transport of small molecules	1	25.1×	0.044	ATP1A3
Infectious disease	1	24.8×	0.044	ATP1A3
Disease	1	13.1×	0.076	ATP1A3

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
response to glycoside	1	2407.4×	0.002	ATP1A3
cell communication by electrical coupling involved in cardiac conduction	1	1404.3×	0.002	ATP1A3
regulation of resting membrane potential	1	1296.3×	0.002	ATP1A3
neuron projection maintenance	1	1123.5×	0.002	ATP1A3
sodium ion export across plasma membrane	1	1053.2×	0.002	ATP1A3
cellular response to steroid hormone stimulus	1	1053.2×	0.002	ATP1A3
intracellular potassium ion homeostasis	1	991.3×	0.002	ATP1A3
intracellular sodium ion homeostasis	1	766.0×	0.002	ATP1A3
cellular response to amyloid-beta	1	391.9×	0.003	ATP1A3
potassium ion import across plasma membrane	1	366.4×	0.003	ATP1A3
proton transmembrane transport	1	312.1×	0.003	ATP1A3

Therapeutics

Drug target analysis

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

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

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
ATP1A3	OMEPRAZOLE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ATP1A3	5	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
OMEPRAZOLE	4	ATP1A3
DIGOXIN	4	ATP1A3
DIGITOXIN	4	ATP1A3
LANSOPRAZOLE	4	ATP1A3
ROSTAFUROXIN	2	ATP1A3

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
ATP1A3	45	Binding:45

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

5 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.

Compound	Max phase	Cohort target (bioactivity)
OMEPRAZOLE	4	ATP1A3
DIGOXIN	4	ATP1A3
DIGITOXIN	4	ATP1A3
LANSOPRAZOLE	4	ATP1A3
ROSTAFUROXIN	2	ATP1A3

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	ATP1A3
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	0

Undrugged target profiles

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

Clinical trials & evidence

Clinical trials

Clinical trials: 0.