Infantile-onset mesial temporal lobe epilepsy with severe cognitive regression

Summary

Infantile-onset mesial temporal lobe epilepsy with severe cognitive regression (MONDO:0018314) is a disease with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 1

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		3	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	infantile-onset mesial temporal lobe epilepsy with severe cognitive regression
Mondo ID	MONDO:0018314
Orphanet	391316
UMLS	C4750853
MedGen	1654958
GARD	0021619
Is cancer (heuristic)	no

Data availability: 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › central nervous system disorder › brain disorder › epilepsy › monogenic epilepsy › infantile-onset mesial temporal lobe epilepsy with severe cognitive regression

Related subtypes (17): Mowat-Wilson syndrome, developmental and epileptic encephalopathy, 2, severe neonatal-onset encephalopathy with microcephaly, familial infantile myoclonic epilepsy, neuronal ceroid lipofuscinosis 8 northern epilepsy variant, polyhydramnios, megalencephaly, and symptomatic epilepsy, neonatal-onset encephalopathy with rigidity and seizures, developmental and epileptic encephalopathy, 23, spastic paraplegia-severe developmental delay-epilepsy syndrome, X-linked intellectual disability-epilepsy syndrome, focal epilepsy-intellectual disability-cerebro-cerebellar malformation, autosomal recessive cerebellar ataxia - epilepsy - intellectual disability syndrome, developmental and epileptic encephalopathy, 73, neurodevelopmental disorder with epilepsy, cataracts, feeding difficulties, and delayed brain myelination, intellectual developmental disorder with dysmorphic facies, seizures, and distal limb anomalies, epilepsy, X-linked, with or without impaired intellectual development and dysmorphic features, neurodevelopmental disorder with motor abnormalities, seizures, and facial dysmorphism

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: 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
TNK2	Supportive	Autosomal recessive	infantile-onset mesial temporal lobe epilepsy with severe cognitive regression	2

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TNK2	Orphanet:391316	Infantile-onset mesial temporal lobe epilepsy with severe cognitive regression

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
TNK2	HGNC:19297	ENSG00000061938	Q07912	Activated CDC42 kinase 1	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TNK2	Activated CDC42 kinase 1	Non-receptor tyrosine-protein and serine/threonine-protein kinase that is implicated in cell spreading and migration, cell survival, cell growth and proliferation.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
Kinase	1	27.7×	0.036

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TNK2	Kinase	yes	2.7.10.2	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, SH3_domain

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
cerebellar hemisphere	1
right frontal lobe	1
right hemisphere of cerebellum	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TNK2	276	ubiquitous	marker	right hemisphere of cerebellum, right frontal lobe, cerebellar hemisphere

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TNK2	1,450

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TNK2	Q07912	18

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. 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
Signaling by LTK	1	878.5×	0.003	TNK2
Signaling by Receptor Tyrosine Kinases	1	51.7×	0.029	TNK2
Signal Transduction	1	10.2×	0.098	TNK2

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 clathrin-dependent endocytosis	1	1685.2×	0.002	TNK2
phosphorylation	1	1296.3×	0.002	TNK2
positive regulation of peptidyl-tyrosine phosphorylation	1	802.5×	0.002	TNK2
small GTPase-mediated signal transduction	1	183.2×	0.008	TNK2
endocytosis	1	95.2×	0.013	TNK2
cell surface receptor signaling pathway	1	64.1×	0.016	TNK2

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
TNK2	VEMURAFENIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TNK2	51	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
VEMURAFENIB	4	TNK2
FEDRATINIB	4	TNK2
AXITINIB	4	TNK2
RUXOLITINIB	4	TNK2
NERATINIB	4	TNK2
ENTRECTINIB	4	TNK2
PACRITINIB	4	TNK2
TOFACITINIB	4	TNK2
CERITINIB	4	TNK2
BOSUTINIB	4	TNK2
LORLATINIB	4	TNK2
GILTERITINIB	4	TNK2
OSIMERTINIB	4	TNK2
UPADACITINIB	4	TNK2
LAROTRECTINIB	4	TNK2
PAZOPANIB	4	TNK2
NINTEDANIB	4	TNK2
SUNITINIB	4	TNK2
DASATINIB	4	TNK2
CRIZOTINIB	4	TNK2
MIDOSTAURIN	4	TNK2
GEFITINIB	4	TNK2
SARACATINIB	3	TNK2
ALISERTIB	3	TNK2
LESTAURTINIB	3	TNK2
FORETINIB	2	TNK2
AZD-1480	2	TNK2
SU-014813	2	TNK2
CENISERTIB	2	TNK2
ADAVOSERTIB	2	TNK2

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
TNK2	348	Binding:346, Functional:2

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
TNK2	2.7.10.2	non-specific protein-tyrosine kinase

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
TNK2	348

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

30 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.

Compound	Max phase	Cohort target (bioactivity)
VEMURAFENIB	4	TNK2
FEDRATINIB	4	TNK2
AXITINIB	4	TNK2
RUXOLITINIB	4	TNK2
NERATINIB	4	TNK2
ENTRECTINIB	4	TNK2
PACRITINIB	4	TNK2
TOFACITINIB	4	TNK2
CERITINIB	4	TNK2
BOSUTINIB	4	TNK2
LORLATINIB	4	TNK2
GILTERITINIB	4	TNK2
OSIMERTINIB	4	TNK2
UPADACITINIB	4	TNK2
LAROTRECTINIB	4	TNK2
PAZOPANIB	4	TNK2
NINTEDANIB	4	TNK2
SUNITINIB	4	TNK2
DASATINIB	4	TNK2
CRIZOTINIB	4	TNK2
MIDOSTAURIN	4	TNK2
GEFITINIB	4	TNK2
SARACATINIB	3	TNK2
ALISERTIB	3	TNK2
LESTAURTINIB	3	TNK2
FORETINIB	2	TNK2
AZD-1480	2	TNK2
SU-014813	2	TNK2
CENISERTIB	2	TNK2
ADAVOSERTIB	2	TNK2

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	TNK2
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	0

Undrugged target profiles

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

Clinical trials & evidence

Clinical trials

Clinical trials: 0.