Epilepsy, familial adult myoclonic, 4

Summary

Epilepsy, familial adult myoclonic, 4 (MONDO:0014055) is a disease with 2 cohort genes.

At a glance

• Cohort genes: 2
• ClinVar variants: 19

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	epilepsy, familial adult myoclonic, 4
Mondo ID	MONDO:0014055
OMIM	615127
DOID	DOID:0111693
UMLS	C3554560
MedGen	767474
GARD	0018085
Is cancer (heuristic)	no

Also known as: epilepsy, myoclonic, familial adult, 4 · FAME4

Data availability: 19 ClinVar variants · 1 GenCC gene-disease record.

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, 4

Related subtypes (7): epilepsy, familial adult myoclonic, 1, epilepsy, familial adult myoclonic, 2, epilepsy, familial adult myoclonic, 3, 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

19 retrieved; paginated sample, class counts are floors:

9 uncertain significance, 5 benign, 2 benign/likely benign, 1 conflicting classifications of pathogenicity, 1 likely benign, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
694503	NG_054747.1:g.(19392_19426)TTTTA[(7_?)]TTTCA[(n)]	YEATS2	Pathogenic	no assertion criteria provided
2264943	NM_018023.5(YEATS2):c.3960C>G (p.Phe1320Leu)	YEATS2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1701735	NM_018023.5(YEATS2):c.444C>G (p.Asp148Glu)	YEATS2	Uncertain significance	criteria provided, single submitter
1701748	NM_018023.5(YEATS2):c.4087G>A (p.Ala1363Thr)	YEATS2	Uncertain significance	criteria provided, single submitter
2665022	NM_018023.5(YEATS2):c.1671G>C (p.Leu557Phe)	YEATS2	Uncertain significance	criteria provided, single submitter
3191453	NM_018023.5(YEATS2):c.34G>A (p.Asp12Asn)	YEATS2	Uncertain significance	criteria provided, multiple submitters, no conflicts
3191455	NM_018023.5(YEATS2):c.3647A>G (p.His1216Arg)	YEATS2	Uncertain significance	criteria provided, multiple submitters, no conflicts
3588973	NM_018023.5(YEATS2):c.3587A>G (p.Gln1196Arg)	YEATS2	Uncertain significance	criteria provided, single submitter
4277814	NM_018023.5(YEATS2):c.1747C>G (p.Leu583Val)	YEATS2	Uncertain significance	criteria provided, single submitter
4278004	NM_018023.5(YEATS2):c.3758T>C (p.Val1253Ala)	YEATS2	Uncertain significance	criteria provided, single submitter
3892905	NM_018023.5(YEATS2):c.3994G>A (p.Gly1332Arg)	YEATS2-AS1	Uncertain significance	criteria provided, single submitter
1684242	NM_018023.5(YEATS2):c.292-27T>C	YEATS2	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
1684243	NM_018023.5(YEATS2):c.537+48_537+49insG	YEATS2	Benign	criteria provided, single submitter
1684244	NM_018023.5(YEATS2):c.1588G>A (p.Val530Ile)	YEATS2	Benign	criteria provided, multiple submitters, no conflicts
1684245	NM_018023.5(YEATS2):c.1947+46_1947+48del	YEATS2	Benign	criteria provided, single submitter
1684246	NM_018023.5(YEATS2):c.2412AGG[8] (p.Gly814del)	YEATS2	Benign	criteria provided, single submitter
1684247	NM_018023.5(YEATS2):c.3582+10A>G	YEATS2	Benign	criteria provided, multiple submitters, no conflicts
3393227	NM_018023.5(YEATS2):c.3764C>T (p.Thr1255Ile)	YEATS2	Likely benign	criteria provided, single submitter
783410	NM_018023.5(YEATS2):c.1601C>A (p.Thr534Lys)	YEATS2	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 2 · 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
YEATS2	Supportive	Autosomal dominant	benign adult familial myoclonic epilepsy	2

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
YEATS2	Orphanet:86814	Familial adult myoclonic epilepsy

Cohort genes → proteins

2 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
YEATS2	HGNC:25489	ENSG00000163872	Q9ULM3	YEATS domain-containing protein 2	gencc,clinvar
YEATS2-AS1	HGNC:41101	ENSG00000233885		YEATS2 antisense RNA 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
YEATS2	YEATS domain-containing protein 2	Chromatin reader component of the ATAC complex, a complex with histone acetyltransferase activity on histones H3 and H4.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 2 · 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	2	1.8×	0.312

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
YEATS2	Other/Unknown	no		YEATS, YEAST_sf, YEATS2_3HBD
YEATS2-AS1	Other/Unknown	no

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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
buccal mucosa cell	1
endothelial cell	1
ganglionic eminence	1
cerebellar cortex	1
cerebellar hemisphere	1
cerebellum	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
YEATS2	283	ubiquitous	marker	buccal mucosa cell, endothelial cell, ganglionic eminence
YEATS2-AS1	131		yes	cerebellar cortex, cerebellar hemisphere, cerebellum

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
YEATS2	2,548
YEATS2-AS1	0

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
YEATS2	Q9ULM3	5

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. Enrichment computed across 2 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
Formation of WDR5-containing histone-modifying complexes	1	265.6×	0.008	YEATS2
HATs acetylate histones	1	79.3×	0.013	YEATS2

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
regulation of cell division	1	766.0×	0.009	YEATS2
regulation of embryonic development	1	330.4×	0.011	YEATS2
regulation of cell cycle	1	74.6×	0.024	YEATS2
chromatin remodeling	1	73.0×	0.024	YEATS2
regulation of DNA-templated transcription	1	31.6×	0.044	YEATS2
negative regulation of transcription by RNA polymerase II	1	17.7×	0.066	YEATS2
regulation of transcription by RNA polymerase II	1	11.7×	0.086	YEATS2

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
YEATS2	0	0
YEATS2-AS1	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
YEATS2	11	Binding:11

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	2	YEATS2, YEATS2-AS1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
YEATS2	11	—
YEATS2-AS1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.