Frontal lobe epilepsy

Summary

Frontal lobe epilepsy (MONDO:0002612) is a disease with 2 cohort genes and 3 clinical trials.

At a glance

• Cohort genes: 2
• Clinical trials: 3

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	frontal lobe epilepsy
Mondo ID	MONDO:0002612
MeSH	D017034
DOID	DOID:3331
SNOMED CT	230394006
UMLS	C0085541
MedGen	39074
Anatomy (UBERON)	UBERON:0016525
Is cancer (heuristic)	no

Also known as: epilepsy of frontal lobe · frontal lobe epilepsy

Data availability: 2 GenCC gene-disease records.

Disease family

An umbrella term covering 2 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › nervous system disorder › central nervous system disorder › brain disorder › epilepsy › focal epilepsy › frontal lobe epilepsy

Related subtypes (8): simple partial epilepsy, complex partial epilepsy, partial motor epilepsy, partial sensory epilepsy, familial partial epilepsy, combined generalized and focal epilepsy, variable-age onset focal epilepsy syndrome, childhood-onset self-limited focal epilepsy syndrome

Subtypes (2): primary motor cortex epilepsy, sleep-related hypermotor epilepsy

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

No tiered GWAS variants or ClinVar records for this disease.

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · 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
CRH	Supportive	Autosomal dominant	autosomal dominant nocturnal frontal lobe epilepsy	3
PRIMA1	Limited	Autosomal recessive	frontal lobe epilepsy

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CRH	Orphanet:98784	Sleep-related hypermotor epilepsy

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
PRIMA1	HGNC:18319	ENSG00000175785	Q86XR5	Proline-rich membrane anchor 1	gencc
CRH	HGNC:2355	ENSG00000147571	P06850	Corticoliberin	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PRIMA1	Proline-rich membrane anchor 1	Required to anchor acetylcholinesterase (ACHE) to the basal lamina of the neuromuscular junction and to the membrane of neuronal synapses in brain.
CRH	Corticoliberin	Hormone regulating the release of corticotropin from pituitary gland.

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)
PRIMA1	Other/Unknown	no		PRIMA1
CRH	Other/Unknown	no		CRF, Urocortin_CRF, Corticotropin-releasing_fac_CS

Expression context

Cohort genes with no expression data: 0.

2 cohort genes 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
C1 segment of cervical spinal cord	1
sural nerve	1
tibial nerve	1
buccal mucosa cell	1
lateral nuclear group of thalamus	1
placenta	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PRIMA1	127	broad	marker	tibial nerve, sural nerve, C1 segment of cervical spinal cord
CRH	97	tissue_specific	marker	lateral nuclear group of thalamus, placenta, buccal mucosa cell

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CRH	2,247
PRIMA1	464

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CRH	P06850	5

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
PRIMA1	Q86XR5	63.74

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. 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
MECP2 regulates transcription of neuronal ligands	1	1427.5×	0.002	CRH
Class B/2 (Secretin family receptors)	1	190.3×	0.008	CRH
G alpha (s) signalling events	1	73.2×	0.014	CRH

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
positive regulation of digestive system process	1	16852.0×	9e-04	CRH
regulation of serotonin secretion	1	8426.0×	9e-04	CRH
diterpenoid metabolic process	1	8426.0×	9e-04	CRH
negative regulation of circadian sleep/wake cycle, REM sleep	1	8426.0×	9e-04	CRH
positive regulation of corticosterone secretion	1	8426.0×	9e-04	CRH
positive regulation of circadian sleep/wake cycle, wakefulness	1	5617.3×	9e-04	CRH
negative regulation of luteinizing hormone secretion	1	5617.3×	9e-04	CRH
response to ether	1	5617.3×	9e-04	CRH
negative regulation of glucagon secretion	1	5617.3×	9e-04	CRH
positive regulation of cortisol secretion	1	4213.0×	0.001	CRH
regulation of NMDA receptor activity	1	4213.0×	0.001	CRH
hormone-mediated apoptotic signaling pathway	1	3370.4×	0.001	CRH
negative regulation of epinephrine secretion	1	3370.4×	0.001	CRH
positive regulation of corticotropin secretion	1	3370.4×	0.001	CRH
negative regulation of norepinephrine secretion	1	2808.7×	0.001	CRH
monoatomic ion homeostasis	1	2407.4×	0.001	CRH
positive regulation of behavioral fear response	1	2407.4×	0.001	CRH
synaptic transmission, dopaminergic	1	2106.5×	0.001	CRH
parturition	1	1872.4×	0.001	CRH
response to aldosterone	1	1685.2×	0.001	CRH
glucocorticoid biosynthetic process	1	1532.0×	0.001	CRH
cellular response to cocaine	1	1296.3×	0.002	CRH
response to corticosterone	1	1123.5×	0.002	CRH
negative regulation of systemic arterial blood pressure	1	1053.2×	0.002	CRH
hypothalamus development	1	1053.2×	0.002	CRH
positive regulation of cAMP/PKA signal transduction	1	1053.2×	0.002	CRH
locomotory exploration behavior	1	991.3×	0.002	CRH
positive regulation of calcium ion import	1	936.2×	0.002	CRH
response to pain	1	887.0×	0.002	CRH
response to immobilization stress	1	732.7×	0.002	CRH

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
PRIMA1	0	0
CRH	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
CRH	1	Binding:1

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; 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	PRIMA1, CRH

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)
PRIMA1	0	—
CRH	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 3.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	3

Top trials by phase / activity

NCT	Phase	Status	Title
NCT06466681	Not specified	RECRUITING	Changes in Attentional Control After a Focal Seizure.
NCT00382707	Not specified	TERMINATED	Transcranial Magnetic Stimulation and Anti-epileptic Effect: Optimization and Evaluation With Electrophysiology.
NCT02441478	Not specified	COMPLETED	Co-operative Behavior and Decision-making in Frontal Lobe Epilepsy