Temporal lobe epilepsy

Summary

Temporal lobe epilepsy (MONDO:0005115) is a disease (an umbrella term covering 6 Mondo subtypes) with 3 cohort genes and 21 clinical trials. Top therapeutic interventions include escitalopram, florbetaben f18, and lovastatin.

At a glance

• Umbrella term: 6 Mondo subtypes
• Cohort genes: 3
• ClinVar variants: 1
• Clinical trials: 21

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	temporal lobe epilepsy
Mondo ID	MONDO:0005115
EFO	EFO:0000773
MeSH	D004833
OMIM	600512
Orphanet	98819
DOID	DOID:3328
NCIT	C177244
SNOMED CT	193000002, 783739005
UMLS	C0014556
MedGen	4990
GARD	0005135
Anatomy (UBERON)	UBERON:0001871
Is cancer (heuristic)	no

Also known as: epilepsy of temporal lobe · epilepsy, familial temporal lobe · familial temporal lobe epilepsy syndrome · temporal lobe epilepsy

Data availability: 1 ClinVar variant · 2 GenCC gene-disease records · 12 cell lines.

Disease family

An umbrella term covering 6 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 › familial partial epilepsy › temporal lobe epilepsy

Related subtypes (6): familial sleep-related hypermotor epilepsy, self-limited epilepsy with centrotemporal spikes, autosomal dominant epilepsy with auditory features, generalized epilepsy-paroxysmal dyskinesia syndrome, familial focal epilepsy with variable foci, mesial temporal lobe epilepsy with hippocampal sclerosis

Subtypes (6): familial temporal lobe epilepsy 2, familial temporal lobe epilepsy 4, familial temporal lobe epilepsy 7, familial temporal lobe epilepsy 8, epilepsy, familial temporal lobe, 1, familial mesial temporal lobe 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

ClinVar germline variants

1 retrieved; paginated sample, class counts are floors:

1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
3068501	NM_001286615.2(ANO4):c.2174T>C (p.Ile725Thr)	ANO4	Likely pathogenic	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 13 · Orphanet: 5 · 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
NALCN	Limited	Autosomal dominant	temporal lobe epilepsy	11
SUCO	Limited	Autosomal dominant	temporal lobe epilepsy	2

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
NALCN	Orphanet:1146	Distal arthrogryposis type 1
NALCN	Orphanet:1147	Sheldon-Hall syndrome
NALCN	Orphanet:2053	Freeman-Sheldon syndrome
NALCN	Orphanet:562528	Congenital limbs-face contractures-hypotonia-developmental delay syndrome
NALCN	Orphanet:700336	Hypotonia-speech impairment-severe cognitive delay syndrome due to NALCN deficiency

Cohort genes → proteins

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SUCO	HGNC:1240	ENSG00000094975	Q9UBS9	SUN domain-containing ossification factor	gencc
NALCN	HGNC:19082	ENSG00000102452	Q8IZF0	Sodium leak channel NALCN	gencc
ANO4	HGNC:23837	ENSG00000151572	Q32M45	Anoctamin-4	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SUCO	SUN domain-containing ossification factor	Required for bone modeling during late embryogenesis.
NALCN	Sodium leak channel NALCN	Voltage-gated ion channel responsible for the resting Na(+) permeability that controls neuronal excitability.
ANO4	Anoctamin-4	Has calcium-dependent phospholipid scramblase activity; scrambles phosphatidylserine, phosphatidylcholine and galactosylceramide.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 2 · Druggable fraction: 0.33

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
Ion channel	1	37.2×	0.053
Other/Unknown	2	1.2×	0.587

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SUCO	Other/Unknown	no		Galactose-bd-like_sf, SUN_dom, Suco/Slp1-like
NALCN	Ion channel	yes		Ion_trans_dom, Volt_channel_dom_sf, NALCN
ANO4	Other/Unknown	no		Anoctamin, Anoct_dimer, Anoctamin_TM

Expression context

Cohort genes with no expression data: 0.

3 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)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
corpus callosum	2
corpus epididymis	1
jejunal mucosa	1
seminal vesicle	1
Brodmann (1909) area 23	1
middle temporal gyrus	1
cortical plate	1
male germ line stem cell (sensu Vertebrata) in testis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SUCO	297	ubiquitous	marker	corpus epididymis, seminal vesicle, jejunal mucosa
NALCN	201	ubiquitous	marker	middle temporal gyrus, Brodmann (1909) area 23, corpus callosum
ANO4	126	broad	marker	corpus callosum, cortical plate, male germ line stem cell (sensu Vertebrata) in testis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
NALCN	1,860
SUCO	1,264
ANO4	673

Structural data

PDB: 1 · AlphaFold-only: 2 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
NALCN	Q8IZF0	5

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ANO4	Q32M45	79.27
SUCO	Q9UBS9	53.03

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 10. Enrichment computed across 3 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Stimuli-sensing channels	2	135.9×	5e-04	NALCN, ANO4
Ion channel transport	2	96.0×	5e-04	NALCN, ANO4
Transport of small molecules	2	25.1×	0.005	NALCN, ANO4
Induction of Cell-Cell Fusion	1	439.2×	0.006	ANO4
Late SARS-CoV-2 Infection Events	1	146.4×	0.014	ANO4
SARS-CoV-2 Infection	1	40.2×	0.041	ANO4
SARS-CoV Infections	1	27.7×	0.051	ANO4
Viral Infection Pathways	1	15.4×	0.080	ANO4
Infectious disease	1	12.4×	0.088	ANO4
Disease	1	6.5×	0.147	ANO4

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
monoatomic ion transmembrane transport	2	138.7×	0.001	NALCN, ANO4
calcium activated galactosylceramide scrambling	1	1872.4×	0.003	ANO4
calcium activated phosphatidylserine scrambling	1	1404.3×	0.003	ANO4
positive regulation of synaptic transmission, cholinergic	1	1123.5×	0.003	NALCN
calcium activated phosphatidylcholine scrambling	1	1123.5×	0.003	ANO4
regulation of bone remodeling	1	936.2×	0.003	SUCO
regulation of resting membrane potential	1	432.1×	0.005	NALCN
positive regulation of synaptic transmission, GABAergic	1	330.4×	0.006	NALCN
positive regulation of collagen biosynthetic process	1	216.1×	0.008	SUCO
chloride transmembrane transport	1	79.1×	0.017	ANO4
ossification	1	75.9×	0.017	SUCO
positive regulation of osteoblast differentiation	1	74.9×	0.017	SUCO
calcium ion transmembrane transport	1	70.2×	0.017	NALCN
sodium ion transmembrane transport	1	67.7×	0.017	NALCN
establishment of localization in cell	1	53.5×	0.020	ANO4
potassium ion transmembrane transport	1	45.3×	0.022	NALCN

Therapeutics

Drugs indicated for this disease

No approved or late-stage (phase ≥3) drug is indicated for this disease; the following are in earlier-phase trials only.

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Ferumoxytol, Naluzotan.

Drug target analysis

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

Druggability breadth: 0 of 3 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
SUCO	0	0
NALCN	0	0
ANO4	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 3; 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	1	NALCN
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	2	SUCO, ANO4

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
SUCO	0	—
NALCN	0	—
ANO4	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 21.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	18
PHASE4	1
PHASE3	1
PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00595699	PHASE4	COMPLETED	Escitalopram Treatment of Major Depression in Patients With Temporal Lobe Epilepsy
NCT00717431	PHASE3	TERMINATED	A Multicenter Study of Hippocampal Electrical Stimulation (HS, in Mesial Temporal Lobe Epilepsy
NCT05179083	PHASE1	UNKNOWN	Exercise for Brain Regeneration in Epilepsy
NCT05609084	Not specified	RECRUITING	Intensive Preoperative Speech Rehabilitation in Drug-Resistant Temporal Epilepsy
NCT06466681	Not specified	RECRUITING	Changes in Attentional Control After a Focal Seizure.
NCT06720922	Not specified	RECRUITING	MRgLITT for mTLE: A PROBE Trial
NCT07202494	Not specified	RECRUITING	Integrating Metabolism, Connectivity, and Mesoscale Imaging at Ultra-high Field to Decipher Mechanisms of Resilience and Neurodegeneration in Neurological Diseases and Healthy Aging
NCT07384351	Not specified	NOT_YET_RECRUITING	MRI Volumetry and Diffusion Tensor Imaging in Temporal Lobe Epilepsy
NCT07434986	Not specified	NOT_YET_RECRUITING	Overnight TI in TLE
NCT07580183	Not specified	RECRUITING	Spatial Scene Recognition Memory in Epilepsy Surgery
NCT00344877	Not specified	COMPLETED	Electrical Brain Stimulation to Reduce Epileptic Seizures
NCT02590419	Not specified	UNKNOWN	Application of Diffusion Tensor Imaging and Tractography in Epilepsy Surgery
NCT02844465	Not specified	COMPLETED	Stereotactic Laser Ablation for Temporal Lobe Epilepsy (Slate)
NCT02946151	Not specified	COMPLETED	Subcutaneous EEG in Epilepsy
NCT03643471	Not specified	UNKNOWN	Advanced Magnetic Resonance Imaging in Temporal Lobe Epilepsy
NCT04055532	Not specified	WITHDRAWN	Biomarkers in Neurodegenerative Diseases
NCT05019404	Not specified	UNKNOWN	Minimally Invasive Surgical Epilepsy Trial for Temporal Lobe Epilepsy
NCT05159609	Not specified	COMPLETED	Closed Loop Auditory Stimulus in Sleep and epilepsY
NCT06269822	Not specified	COMPLETED	Autonomic Dysfunction in Temporal Lobe Epilepsy and SUDEP
NCT06558890	Not specified	UNKNOWN	Transcranial Electrical Stimulation Targeting the Cerebellum for the Treatment of Refractory Temporal Lobe Epilepsy
NCT06789497	Not specified	COMPLETED	The GABAergic Inhibitory System in Drug Resistant Epilepsy

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
ESCITALOPRAM	4	1
FLORBETABEN F18	4	1
LOVASTATIN	4	1