Developmental and epileptic encephalopathy 98

disease

On this page

Also known as DEE98

Summary

Developmental and epileptic encephalopathy 98 (MONDO:0030472) is a disease caused by ATP1A2 (GenCC Strong), with 1 cohort gene.

At a glance

Causal gene: ATP1A2 (GenCC Strong)
Cohort genes: 1
ClinVar variants: 103

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	developmental and epileptic encephalopathy 98
Mondo ID	MONDO:0030472
OMIM	619605
DOID	DOID:0070384
UMLS	C5562017
MedGen	1794227
GARD	0025571
Is cancer (heuristic)	no

Also known as: DEE98

Data availability: 103 ClinVar variants · 4 GenCC gene-disease records · 1 cell line.

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 98

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

103 retrieved; paginated sample, class counts are floors:

36 benign, 31 benign/likely benign, 15 uncertain significance, 6 pathogenic/likely pathogenic, 5 conflicting classifications of pathogenicity, 5 likely pathogenic, 4 pathogenic, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1216390	NM_000702.4(ATP1A2):c.2723G>A (p.Arg908Gln)	ATP1A2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
12926	NM_000702.4(ATP1A2):c.1643G>A (p.Arg548His)	ATP1A2	Pathogenic	criteria provided, multiple submitters, no conflicts
204884	NM_000702.4(ATP1A2):c.1091C>T (p.Thr364Met)	ATP1A2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
204898	NM_000702.4(ATP1A2):c.2438T>A (p.Met813Lys)	ATP1A2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3598996	NM_000702.4(ATP1A2):c.36dup (p.Ala13fs)	ATP1A2	Pathogenic	criteria provided, single submitter
383452	NM_000702.4(ATP1A2):c.1022G>T (p.Cys341Phe)	ATP1A2	Pathogenic	criteria provided, single submitter
430293	NM_000702.4(ATP1A2):c.889G>A (p.Ala297Thr)	ATP1A2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
446871	NM_000702.4(ATP1A2):c.2563G>A (p.Gly855Arg)	ATP1A2	Pathogenic	criteria provided, multiple submitters, no conflicts
493055	NM_000702.4(ATP1A2):c.1096G>A (p.Gly366Ser)	ATP1A2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
585463	NM_000702.4(ATP1A2):c.788C>T (p.Thr263Met)	ATP1A2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2430257	NM_000702.4(ATP1A2):c.1022G>A (p.Cys341Tyr)	ATP1A2	Likely pathogenic	criteria provided, multiple submitters, no conflicts
3068468	NM_000702.4(ATP1A2):c.1021T>C (p.Cys341Arg)	ATP1A2	Likely pathogenic	criteria provided, single submitter
3382567	NM_000702.4(ATP1A2):c.2444C>G (p.Pro815Arg)	ATP1A2	Likely pathogenic	criteria provided, single submitter
3598997	NM_000702.4(ATP1A2):c.2935_2936delinsAA (p.Pro979Lys)	ATP1A2	Likely pathogenic	criteria provided, single submitter
4279597	NM_000702.4(ATP1A2):c.1132A>C (p.Thr378Pro)	ATP1A2	Likely pathogenic	criteria provided, single submitter
197162	NM_000702.4(ATP1A2):c.194G>T (p.Arg65Leu)	ATP1A2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
204881	NM_000702.4(ATP1A2):c.25T>A (p.Tyr9Asn)	ATP1A2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
406194	NM_000702.4(ATP1A2):c.1262G>A (p.Arg421Gln)	ATP1A2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
570135	NM_000702.4(ATP1A2):c.1550C>A (p.Thr517Asn)	ATP1A2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
655259	NM_000702.4(ATP1A2):c.970G>A (p.Gly324Ser)	ATP1A2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1052245	NM_000702.4(ATP1A2):c.2120C>A (p.Ala707Asp)	ATP1A2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1486680	NM_000702.4(ATP1A2):c.215G>A (p.Arg72Gln)	ATP1A2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1526131	NM_000702.4(ATP1A2):c.2387C>T (p.Pro796Leu)	ATP1A2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1705641	NM_000702.4(ATP1A2):c.1408_1409del (p.Asp470fs)	ATP1A2	Uncertain significance	criteria provided, single submitter
204894	NM_000702.4(ATP1A2):c.1931G>A (p.Arg644Gln)	ATP1A2	Uncertain significance	criteria provided, multiple submitters, no conflicts
204910	NM_000702.4(ATP1A2):c.192G>T (p.Gln64His)	ATP1A2	Uncertain significance	criteria provided, multiple submitters, no conflicts
2482939	NM_000702.4(ATP1A2):c.2750C>T (p.Thr917Met)	ATP1A2	Uncertain significance	criteria provided, multiple submitters, no conflicts
2779651	NM_000702.4(ATP1A2):c.160C>A (p.Gln54Lys)	ATP1A2	Uncertain significance	criteria provided, multiple submitters, no conflicts
3234873	NM_000702.4(ATP1A2):c.2942+7G>C	ATP1A2	Uncertain significance	criteria provided, single submitter
3234965	NM_000702.4(ATP1A2):c.589G>T (p.Val197Phe)	ATP1A2	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 19 · Orphanet: 3 · 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
ATP1A2	Strong	Autosomal dominant	developmental and epileptic encephalopathy 98	19

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ATP1A2	Orphanet:2131	Alternating hemiplegia of childhood
ATP1A2	Orphanet:442835	Non-specific early-onset epileptic encephalopathy
ATP1A2	Orphanet:569	Familial or sporadic hemiplegic migraine

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
ATP1A2	HGNC:800	ENSG00000018625	P50993	Sodium/potassium-transporting ATPase subunit alpha-2	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ATP1A2	Sodium/potassium-transporting ATPase subunit alpha-2	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)
ATP1A2	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
lateral globus pallidus	1
superior vestibular nucleus	1
trigeminal ganglion	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ATP1A2	262	broad	marker	lateral globus pallidus, trigeminal ganglion, superior vestibular nucleus

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ATP1A2	2,679

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ATP1A2	P50993	88.25

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	ATP1A2
Ion homeostasis	1	203.9×	0.023	ATP1A2
Potential therapeutics for SARS	1	114.2×	0.023	ATP1A2
Cardiac conduction	1	108.8×	0.023	ATP1A2
Ion channel transport	1	96.0×	0.023	ATP1A2
Muscle contraction	1	77.2×	0.024	ATP1A2
SARS-CoV Infections	1	55.4×	0.028	ATP1A2
Viral Infection Pathways	1	30.8×	0.044	ATP1A2
Transport of small molecules	1	25.1×	0.044	ATP1A2
Infectious disease	1	24.8×	0.044	ATP1A2
Disease	1	13.1×	0.076	ATP1A2

GO biological processes by enrichment

GO term	Cohort genes	Fold	FDR	Sample cohort genes
olfactory cortex development	1	16852.0×	0.002	ATP1A2
regulation of glutamate uptake involved in transmission of nerve impulse	1	8426.0×	0.002	ATP1A2
negative regulation of calcium ion transmembrane transport	1	8426.0×	0.002	ATP1A2
negative regulation of striated muscle contraction	1	5617.3×	0.002	ATP1A2
negative regulation of heart contraction	1	4213.0×	0.002	ATP1A2
amygdala development	1	2808.7×	0.002	ATP1A2
response to glycoside	1	2407.4×	0.002	ATP1A2
regulation of striated muscle contraction	1	2106.5×	0.002	ATP1A2
response to potassium ion	1	2106.5×	0.002	ATP1A2
positive regulation of heart contraction	1	2106.5×	0.002	ATP1A2
regulation of muscle contraction	1	1685.2×	0.002	ATP1A2
L-ascorbic acid metabolic process	1	1532.0×	0.002	ATP1A2
locomotion	1	1532.0×	0.002	ATP1A2
neurotransmitter uptake	1	1404.3×	0.002	ATP1A2
neuronal action potential propagation	1	1404.3×	0.002	ATP1A2
membrane depolarization during cardiac muscle cell action potential	1	1404.3×	0.002	ATP1A2
cell communication by electrical coupling involved in cardiac conduction	1	1404.3×	0.002	ATP1A2
regulation of respiratory gaseous exchange by nervous system process	1	1296.3×	0.002	ATP1A2
negative regulation of cytosolic calcium ion concentration	1	1296.3×	0.002	ATP1A2
relaxation of cardiac muscle	1	1296.3×	0.002	ATP1A2
membrane repolarization	1	1296.3×	0.002	ATP1A2
regulation of smooth muscle contraction	1	1203.7×	0.002	ATP1A2
regulation of cardiac muscle cell contraction	1	1123.5×	0.002	ATP1A2
sodium ion export across plasma membrane	1	1053.2×	0.002	ATP1A2
cellular response to steroid hormone stimulus	1	1053.2×	0.002	ATP1A2
regulation of the force of heart contraction	1	991.3×	0.002	ATP1A2
intracellular potassium ion homeostasis	1	991.3×	0.002	ATP1A2
locomotory exploration behavior	1	991.3×	0.002	ATP1A2
regulation of vasoconstriction	1	802.5×	0.002	ATP1A2
intracellular sodium ion homeostasis	1	766.0×	0.002	ATP1A2

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
ATP1A2	OMEPRAZOLE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ATP1A2	5	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
OMEPRAZOLE	4	ATP1A2
DIGOXIN	4	ATP1A2
DIGITOXIN	4	ATP1A2
LANSOPRAZOLE	4	ATP1A2
ROSTAFUROXIN	2	ATP1A2

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
ATP1A2	49	Binding:49

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	ATP1A2
DIGOXIN	4	ATP1A2
DIGITOXIN	4	ATP1A2
LANSOPRAZOLE	4	ATP1A2
ROSTAFUROXIN	2	ATP1A2

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	ATP1A2
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.

Cohort genes: ATP1A2