Epilepsy, familial adult myoclonic, 3

Summary

Epilepsy, familial adult myoclonic, 3 (MONDO:0013322) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 6

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	epilepsy, familial adult myoclonic, 3
Mondo ID	MONDO:0013322
MeSH	C567098
OMIM	613608
DOID	DOID:0111695
UMLS	C3150860
MedGen	462210
GARD	0018084
Is cancer (heuristic)	no

Also known as: FAME3

Data availability: 6 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › hereditary neurological disease › epilepsy, familial adult myoclonic › epilepsy, familial adult myoclonic, 3

Related subtypes (7): epilepsy, familial adult myoclonic, 1, epilepsy, familial adult myoclonic, 2, epilepsy, familial adult myoclonic, 4, epilepsy, familial adult myoclonic, 5, benign adult familial myoclonic epilepsy, epilepsy, familial adult myoclonic, 6, epilepsy, familial adult myoclonic, 7

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

6 retrieved; paginated sample, class counts are floors:

4 uncertain significance, 2 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
635281	NM_005885.4(MARCHF6):c.19+2427TTTAT[641]	MARCHF6	Pathogenic	no assertion criteria provided
694446	NC_000005.10:g.10356348_10356407TTTTA[(9_?)]TTTCA[(791_1035)]	MARCHF6	Pathogenic	no assertion criteria provided
1696602	NM_005885.4(MARCHF6):c.914-8C>G	MARCHF6	Uncertain significance	criteria provided, single submitter
3065753	NM_005885.4(MARCHF6):c.674A>G (p.Gln225Arg)	MARCHF6	Uncertain significance	criteria provided, single submitter
4079244	NM_005885.4(MARCHF6):c.190A>G (p.Ile64Val)	MARCHF6	Uncertain significance	criteria provided, single submitter
4278169	NM_005885.4(MARCHF6):c.559G>C (p.Gly187Arg)	MARCHF6	Uncertain significance	criteria provided, single submitter

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
MARCHF6	Orphanet:86814	Familial adult myoclonic epilepsy

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
MARCHF6	HGNC:30550	ENSG00000145495	O60337	E3 ubiquitin-protein ligase MARCHF6	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
MARCHF6	E3 ubiquitin-protein ligase MARCHF6	Endoplasmic reticulum membrane-associated E3 ubiquitin ligase that plays a critical role in mitigating endoplasmic reticulum stress, the regulation of cholesterol and lipid homeostasis, and ferroptosis.

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)
MARCHF6	Transcription factor	no	2.3.2.27	Znf_RING-CH, Znf_RING/FYVE/PHD, MARCHF6-like_C

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
Brodmann (1909) area 23	1
endothelial cell	1
gluteal muscle	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MARCHF6	302	ubiquitous	marker	Brodmann (1909) area 23, endothelial cell, gluteal muscle

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MARCHF6	1,609

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
MARCHF6	O60337	78.23

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
Calnexin/calreticulin cycle	1	713.8×	0.005	MARCHF6
ER Quality Control Compartment (ERQC)	1	543.8×	0.005	MARCHF6
N-glycan trimming in the ER and Calnexin/Calreticulin cycle	1	423.0×	0.005	MARCHF6
Asparagine N-linked glycosylation	1	60.1×	0.025	MARCHF6
Post-translational protein modification	1	19.2×	0.063	MARCHF6
Metabolism of proteins	1	12.4×	0.081	MARCHF6

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
negative regulation of cholesterol biosynthetic process	1	2407.4×	0.003	MARCHF6
endoplasmic reticulum mannose trimming	1	1203.7×	0.003	MARCHF6
proteasomal protein catabolic process	1	766.0×	0.003	MARCHF6
ERAD pathway	1	181.2×	0.008	MARCHF6
protein K48-linked ubiquitination	1	168.5×	0.008	MARCHF6
proteasome-mediated ubiquitin-dependent protein catabolic process	1	52.2×	0.022	MARCHF6
protein ubiquitination	1	41.4×	0.024	MARCHF6

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
MARCHF6	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
MARCHF6	2.3.2.27	RING-type E3 ubiquitin transferase

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	MARCHF6

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)
MARCHF6	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.