Epilepsy, familial adult myoclonic, 6

Summary

Epilepsy, familial adult myoclonic, 6 (MONDO:0054846) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 10

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	epilepsy, familial adult myoclonic, 6
Mondo ID	MONDO:0054846
OMIM	618074
DOID	DOID:0111696
UMLS	C4748079
MedGen	1648448
GARD	0025986
Is cancer (heuristic)	no

Also known as: FAME6

Data availability: 10 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 › hereditary neurological disease › epilepsy, familial adult myoclonic › epilepsy, familial adult myoclonic, 6

Related subtypes (7): epilepsy, familial adult myoclonic, 1, epilepsy, familial adult myoclonic, 2, epilepsy, familial adult myoclonic, 3, epilepsy, familial adult myoclonic, 4, epilepsy, familial adult myoclonic, 5, benign adult familial myoclonic epilepsy, 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

10 retrieved; paginated sample, class counts are floors:

6 benign, 3 uncertain significance, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
559390	TNRC6A, 5-BP INS, TTTCA(n) REPEAT EXPANSION	TNRC6A	Pathogenic	no assertion criteria provided
1696478	NM_014494.4(TNRC6A):c.3838-10G>T	TNRC6A	Uncertain significance	criteria provided, single submitter
1701693	NM_014494.4(TNRC6A):c.136AAG[1] (p.Lys47del)	TNRC6A	Uncertain significance	criteria provided, single submitter
3180706	NM_014494.4(TNRC6A):c.5779A>G (p.Ser1927Gly)	TNRC6A	Uncertain significance	criteria provided, multiple submitters, no conflicts
1279086	NM_014494.4(TNRC6A):c.555T>A (p.Asn185Lys)	TNRC6A	Benign	criteria provided, multiple submitters, no conflicts
1342237	NM_014494.4(TNRC6A):c.1774G>A (p.Ala592Thr)	TNRC6A	Benign	criteria provided, multiple submitters, no conflicts
1342238	NM_014494.4(TNRC6A):c.2016C>T (p.Ser672=)	TNRC6A	Benign	criteria provided, multiple submitters, no conflicts
1342239	NM_014494.4(TNRC6A):c.2362C>T (p.Pro788Ser)	TNRC6A	Benign	criteria provided, multiple submitters, no conflicts
1342240	NM_014494.4(TNRC6A):c.4122+20A>G	TNRC6A	Benign	criteria provided, multiple submitters, no conflicts
769896	NM_014494.4(TNRC6A):c.339_350del (p.113_114PQ[1])	TNRC6A	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
TNRC6A	Limited	Unknown	epilepsy, familial adult myoclonic, 6	2

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TNRC6A	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
TNRC6A	HGNC:11969	ENSG00000090905	Q8NDV7	Trinucleotide repeat-containing gene 6A protein	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TNRC6A	Trinucleotide repeat-containing gene 6A protein	Plays a role in RNA-mediated gene silencing by both micro-RNAs (miRNAs) and short interfering RNAs (siRNAs).

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)
TNRC6A	Other/Unknown	no		Nucleotide-bd_a/b_plait_sf, Argonaute_hook_dom, TNRC6_PABC-bd

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
calcaneal tendon	1
corpus callosum	1
sural nerve	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TNRC6A	143	ubiquitous	marker	corpus callosum, calcaneal tendon, sural nerve

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TNRC6A	2,123

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TNRC6A	Q8NDV7	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 24. 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
Post-transcriptional silencing by small RNAs	1	1631.4×	0.003	TNRC6A
Competing endogenous RNAs (ceRNAs) regulate PTEN translation	1	1427.5×	0.003	TNRC6A
Regulation of CDH11 mRNA translation by microRNAs	1	1268.9×	0.003	TNRC6A
Regulation of NPAS4 mRNA translation	1	1268.9×	0.003	TNRC6A
Regulation of PD-L1(CD274) translation	1	1268.9×	0.003	TNRC6A
Regulation of PTEN mRNA translation	1	1142.0×	0.003	TNRC6A
Regulation of CDH1 mRNA translation by microRNAs	1	1038.2×	0.003	TNRC6A
Regulation of RUNX1 Expression and Activity	1	671.8×	0.004	TNRC6A
Regulation of MITF-M-dependent genes involved in apoptosis	1	634.4×	0.004	TNRC6A
TGFBR3 expression	1	456.8×	0.005	TNRC6A
Regulation of MECP2 expression and activity	1	368.4×	0.006	TNRC6A
Oncogene Induced Senescence	1	335.9×	0.006	TNRC6A
Transcriptional Regulation by MECP2	1	317.2×	0.006	TNRC6A
NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflux	1	308.6×	0.006	TNRC6A
MTOR signalling	1	265.6×	0.006	TNRC6A
Transcriptional Regulation by VENTX	1	265.6×	0.006	TNRC6A
Ca2+ pathway	1	178.4×	0.008	TNRC6A
Transcriptional regulation by small RNAs	1	144.6×	0.009	TNRC6A
MAPK6/MAPK4 signaling	1	135.9×	0.009	TNRC6A
TP53 Regulates Metabolic Genes	1	129.8×	0.009	TNRC6A
Pre-NOTCH Transcription and Translation	1	122.8×	0.009	TNRC6A
RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function	1	120.2×	0.009	TNRC6A
Oxidative Stress Induced Senescence	1	90.6×	0.012	TNRC6A
Estrogen-dependent gene expression	1	75.6×	0.013	TNRC6A

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
miRNA-mediated post-transcriptional gene silencing	1	1296.3×	0.002	TNRC6A
positive regulation of nuclear-transcribed mRNA poly(A) tail shortening	1	1296.3×	0.002	TNRC6A
P-body assembly	1	1053.2×	0.002	TNRC6A
miRNA-mediated gene silencing by inhibition of translation	1	887.0×	0.002	TNRC6A
endoderm development	1	624.1×	0.002	TNRC6A
cellular response to starvation	1	193.7×	0.005	TNRC6A

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
TNRC6A	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	TNRC6A

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)
TNRC6A	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.