Developmental and epileptic encephalopathy 104

disease

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Also known as DEE104

Summary

Developmental and epileptic encephalopathy 104 (MONDO:0031021) is a disease caused by ATP6V0A1 (GenCC Definitive), with 1 cohort gene.

At a glance

Causal gene: ATP6V0A1 (GenCC Definitive)
Cohort genes: 1
ClinVar variants: 22

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	developmental and epileptic encephalopathy 104
Mondo ID	MONDO:0031021
OMIM	619970
DOID	DOID:0070390
UMLS	C5774183
MedGen	1823956
GARD	0025677
Is cancer (heuristic)	no

Also known as: DEE104 · developmental and epileptic encephalopathy 104

Data availability: 22 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 104

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

22 retrieved; paginated sample, class counts are floors:

16 uncertain significance, 3 pathogenic, 2 conflicting classifications of pathogenicity, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1698401	NM_001130021.3(ATP6V0A1):c.1429T>C (p.Ser477Pro)	ATP6V0A1	Pathogenic	no assertion criteria provided
1698402	NM_001130021.3(ATP6V0A1):c.1631G>A (p.Gly544Asp)	ATP6V0A1	Pathogenic	no assertion criteria provided
1698403	NM_001130021.3(ATP6V0A1):c.2411G>A (p.Arg804His)	ATP6V0A1	Pathogenic	no assertion criteria provided
3068292	NM_001130021.3(ATP6V0A1):c.118-2A>G	ATP6V0A1	Likely pathogenic	criteria provided, single submitter
1325812	NM_001130021.3(ATP6V0A1):c.53A>T (p.Gln18Leu)	ATP6V0A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
560227	NM_001130021.3(ATP6V0A1):c.2219G>A (p.Arg740Gln)	ATP6V0A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3065213	NM_001130021.3(ATP6V0A1):c.1949T>C (p.Met650Thr)	ATP6V0A1	Uncertain significance	criteria provided, single submitter
3065920	NM_001130021.3(ATP6V0A1):c.2492G>A (p.Arg831Gln)	ATP6V0A1	Uncertain significance	criteria provided, single submitter
3338276	NM_001130021.3(ATP6V0A1):c.985G>A (p.Asp329Asn)	ATP6V0A1	Uncertain significance	criteria provided, single submitter
3342258	NM_001130021.3(ATP6V0A1):c.287A>T (p.Asp96Val)	ATP6V0A1	Uncertain significance	criteria provided, single submitter
3367110	NM_001130021.3(ATP6V0A1):c.1471G>A (p.Glu491Lys)	ATP6V0A1	Uncertain significance	criteria provided, single submitter
3376171	NM_001130021.3(ATP6V0A1):c.1230C>G (p.Phe410Leu)	ATP6V0A1	Uncertain significance	criteria provided, single submitter
3393266	NM_001130021.3(ATP6V0A1):c.664A>G (p.Ile222Val)	ATP6V0A1	Uncertain significance	criteria provided, single submitter
3393328	NM_001130021.3(ATP6V0A1):c.1160G>A (p.Arg387Gln)	ATP6V0A1	Uncertain significance	criteria provided, multiple submitters, no conflicts
3393484	NM_001130021.3(ATP6V0A1):c.628G>C (p.Val210Leu)	ATP6V0A1	Uncertain significance	criteria provided, single submitter
3731491	NM_001130021.3(ATP6V0A1):c.2471C>G (p.Pro824Arg)	ATP6V0A1	Uncertain significance	criteria provided, single submitter
3780568	NM_001130021.3(ATP6V0A1):c.2004+1512_2004+1521del	ATP6V0A1	Uncertain significance	criteria provided, single submitter
4277230	NM_001130021.3(ATP6V0A1):c.1279G>C (p.Glu427Gln)	ATP6V0A1	Uncertain significance	criteria provided, single submitter
4277770	NM_001130021.3(ATP6V0A1):c.1175-8C>T	ATP6V0A1	Uncertain significance	criteria provided, single submitter
4278289	NM_001130021.3(ATP6V0A1):c.911A>G (p.Tyr304Cys)	ATP6V0A1	Uncertain significance	criteria provided, single submitter
4278340	NM_001130021.3(ATP6V0A1):c.1844T>C (p.Met615Thr)	ATP6V0A1	Uncertain significance	criteria provided, single submitter
4531654	NM_001130021.3(ATP6V0A1):c.1225G>T (p.Asp409Tyr)	ATP6V0A1	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 7 · 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
ATP6V0A1	Definitive	Autosomal dominant	developmental and epileptic encephalopathy 104	7

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ATP6V0A1	Orphanet:528084	Non-specific syndromic intellectual disability

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
ATP6V0A1	HGNC:865	ENSG00000033627	Q93050	V-type proton ATPase 116 kDa subunit a 1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ATP6V0A1	V-type proton ATPase 116 kDa subunit a 1	Subunit of the V0 complex of vacuolar(H+)-ATPase (V-ATPase), a multisubunit enzyme composed of a peripheral complex (V1) that hydrolyzes ATP and a membrane integral complex (V0) that transports protons across cellular membranes.

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)
ATP6V0A1	Other/Unknown	no		V-ATPase_116kDa_su, V-type_ATPase_116kDa_su_euka

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
cerebellar hemisphere	1
right frontal lobe	1
right hemisphere of cerebellum	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ATP6V0A1	287	ubiquitous	marker	right frontal lobe, right hemisphere of cerebellum, cerebellar hemisphere

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ATP6V0A1	2,158

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ATP6V0A1	Q93050	7

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 6. 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
Regulation of MITF-M-dependent genes involved in lysosome biogenesis and autophagy	1	671.8×	0.004	ATP6V0A1
Insulin receptor recycling	1	380.7×	0.004	ATP6V0A1
Transferrin endocytosis and recycling	1	368.4×	0.004	ATP6V0A1
ROS and RNS production in phagocytes	1	335.9×	0.004	ATP6V0A1
Ion channel transport	1	96.0×	0.013	ATP6V0A1
Neutrophil degranulation	1	23.1×	0.043	ATP6V0A1

GO biological processes by enrichment

GO term	Cohort genes	Fold	FDR	Sample cohort genes
endosomal lumen acidification	1	1203.7×	0.002	ATP6V0A1
synaptic vesicle lumen acidification	1	936.2×	0.002	ATP6V0A1
vacuolar acidification	1	732.7×	0.002	ATP6V0A1
lysosomal lumen acidification	1	674.1×	0.002	ATP6V0A1
proton transmembrane transport	1	312.1×	0.003	ATP6V0A1
regulation of macroautophagy	1	295.6×	0.003	ATP6V0A1

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
ATP6V0A1	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	ATP6V0A1

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)
ATP6V0A1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.

Cohort genes: ATP6V0A1