Epilepsy, early-onset, 3, with or without developmental delay

Summary

Epilepsy, early-onset, 3, with or without developmental delay (MONDO:0958196) is a disease caused by ATP6V0C (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: ATP6V0C (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 8

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	epilepsy, early-onset, 3, with or without developmental delay
Mondo ID	MONDO:0958196
OMIM	620465
DOID	DOID:0070472
UMLS	C5882674
MedGen	1847911
Is cancer (heuristic)	no

Data availability: 8 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › epilepsy, early-onset › epilepsy, early-onset, 3, with or without developmental delay

Related subtypes (2): epilepsy, early-onset, vitamin B6-dependent, epilepsy, early-onset, with or without developmental delay

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

8 retrieved; paginated sample, class counts are floors:

3 pathogenic, 3 likely pathogenic, 2 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
2575309	NM_001694.4(ATP6V0C):c.64G>A (p.Ala22Thr)	ATP6V0C	Pathogenic	no assertion criteria provided
2575310	NM_001694.4(ATP6V0C):c.361_373del (p.Thr121fs)	ATP6V0C	Pathogenic	no assertion criteria provided
2575311	NM_001694.4(ATP6V0C):c.260_263+11del	ATP6V0C	Pathogenic	no assertion criteria provided
3358938	NM_001694.4(ATP6V0C):c.376C>T (p.Arg126Ter)	ATP6V0C	Likely pathogenic	criteria provided, single submitter
3772671	NM_001694.4(ATP6V0C):c.263dup (p.Ser89fs)	ATP6V0C	Likely pathogenic	criteria provided, single submitter
4291797	NM_001694.4(ATP6V0C):c.70del (p.Val24fs)	ATP6V0C	Likely pathogenic	criteria provided, single submitter
2671958	NM_001694.4(ATP6V0C):c.377G>C (p.Arg126Pro)	ATP6V0C	Uncertain significance	criteria provided, single submitter
4279566	NM_001694.4(ATP6V0C):c.*136C>T	ATP6V0C	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · Orphanet: 0 · 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
ATP6V0C	Strong	Autosomal dominant	epilepsy, early-onset, 3, with or without developmental delay	3

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
ATP6V0C	HGNC:855	ENSG00000185883	P27449	V-type proton ATPase 16 kDa proteolipid subunit c	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ATP6V0C	V-type proton ATPase 16 kDa proteolipid subunit c	Proton-conducting pore forming 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 translocates protons.

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)
ATP6V0C	Other/Unknown	no		ATPase_proteolipid_csu, ATPase_proteolipid_c-like_dom, ATPase_proteolipid_su_C_euk

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
right frontal lobe	1
right hemisphere of cerebellum	1
superior frontal gyrus	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ATP6V0C	134	ubiquitous	marker	superior frontal gyrus, right frontal lobe, right hemisphere of cerebellum

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ATP6V0C	3,353

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ATP6V0C	P27449	9

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 7. 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×	0.005	ATP6V0C
Insulin receptor recycling	1	380.7×	0.005	ATP6V0C
Transferrin endocytosis and recycling	1	368.4×	0.005	ATP6V0C
ROS and RNS production in phagocytes	1	335.9×	0.005	ATP6V0C
Amino acids regulate mTORC1	1	200.3×	0.007	ATP6V0C
Ion channel transport	1	96.0×	0.012	ATP6V0C
Neutrophil degranulation	1	23.1×	0.043	ATP6V0C

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
Golgi lumen acidification	1	1685.2×	0.002	ATP6V0C
endosomal lumen acidification	1	1203.7×	0.002	ATP6V0C
intracellular pH reduction	1	1203.7×	0.002	ATP6V0C
synaptic vesicle lumen acidification	1	936.2×	0.002	ATP6V0C
vacuolar acidification	1	732.7×	0.002	ATP6V0C
lysosomal lumen acidification	1	674.1×	0.002	ATP6V0C
positive regulation of Wnt signaling pathway	1	383.0×	0.003	ATP6V0C
proton transmembrane transport	1	312.1×	0.003	ATP6V0C
regulation of macroautophagy	1	295.6×	0.003	ATP6V0C

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
ATP6V0C	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
ATP6V0C	1	Binding:1

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	ATP6V0C

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)
ATP6V0C	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.