Developmental and epileptic encephalopathy, 16

Summary

Developmental and epileptic encephalopathy, 16 (MONDO:0014133) is a disease caused by TBC1D24 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: TBC1D24 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 54

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	developmental and epileptic encephalopathy, 16
Mondo ID	MONDO:0014133
OMIM	615338
DOID	DOID:0080449
UMLS	C3809173
MedGen	815503
GARD	0015945
Is cancer (heuristic)	no

Also known as: DEE16 · developmental and epileptic encephalopathy 16 · EIEE16 · epileptic encephalopathy, early infantile, 16 · epileptic encephalopathy, early infantile, type 16

Data availability: 54 ClinVar variants · 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 › epilepsy syndrome › neonatal epilepsy syndrome › malignant migrating partial seizures of infancy › developmental and epileptic encephalopathy, 16

Related subtypes (2): developmental and epileptic encephalopathy, 12, developmental and epileptic encephalopathy, 34

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

54 retrieved; paginated sample, class counts are floors:

24 uncertain significance, 9 pathogenic, 8 conflicting classifications of pathogenicity, 5 pathogenic/likely pathogenic, 4 benign/likely benign, 4 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1029242	NM_001199107.2(TBC1D24):c.965+2T>C	TBC1D24	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1071941	NM_001199107.2(TBC1D24):c.642_793del (p.Trp215fs)	TBC1D24	Pathogenic	criteria provided, multiple submitters, no conflicts
1456664	NM_001199107.2(TBC1D24):c.752del (p.Phe251fs)	TBC1D24	Pathogenic	criteria provided, multiple submitters, no conflicts
207499	NM_001199107.2(TBC1D24):c.457G>A (p.Glu153Lys)	TBC1D24	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
207505	NM_001199107.2(TBC1D24):c.845C>G (p.Pro282Arg)	TBC1D24	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
421795	NM_001199107.2(TBC1D24):c.1360_1363dup (p.Pro455fs)	TBC1D24	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
430018	NM_001199107.2(TBC1D24):c.557del (p.Leu186fs)	TBC1D24	Pathogenic	criteria provided, multiple submitters, no conflicts
474302	NM_001199107.2(TBC1D24):c.116C>T (p.Ala39Val)	TBC1D24	Pathogenic	criteria provided, multiple submitters, no conflicts
523796	NM_001199107.2(TBC1D24):c.619C>T (p.Gln207Ter)	TBC1D24	Pathogenic	criteria provided, multiple submitters, no conflicts
56845	NM_001199107.1(TBC1D24):c.969_970delGT	TBC1D24	Pathogenic	no assertion criteria provided
56846	NM_001199107.2(TBC1D24):c.686T>C (p.Phe229Ser)	TBC1D24	Pathogenic	criteria provided, multiple submitters, no conflicts
56847	NM_001199107.2(TBC1D24):c.468C>A (p.Cys156Ter)	TBC1D24	Pathogenic	criteria provided, single submitter
91395	NM_001199107.2(TBC1D24):c.724C>T (p.Arg242Cys)	TBC1D24	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
91398	NM_001199107.2(TBC1D24):c.1008del (p.His336fs)	TBC1D24	Pathogenic	criteria provided, multiple submitters, no conflicts
424803	NM_020705.2(TBC1D24):c.[1218G>C];[1270T>C]		Likely pathogenic	criteria provided, single submitter
1339566	NM_001199107.2(TBC1D24):c.1652G>A (p.Trp551Ter)	TBC1D24	Likely pathogenic	no assertion criteria provided
3252044	NM_001199107.2(TBC1D24):c.2T>C (p.Met1Thr)	TBC1D24	Likely pathogenic	criteria provided, single submitter
436948	NM_001199107.2(TBC1D24):c.866C>T (p.Ala289Val)	TBC1D24	Likely pathogenic	criteria provided, multiple submitters, no conflicts
130541	NM_001199107.2(TBC1D24):c.1015A>G (p.Asn339Asp)	TBC1D24	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
183157	NM_001199107.2(TBC1D24):c.1079G>T (p.Arg360Leu)	TBC1D24	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
207484	NM_001199107.2(TBC1D24):c.493G>A (p.Gly165Ser)	TBC1D24	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
208413	NM_001199107.2(TBC1D24):c.1327G>A (p.Glu443Lys)	TBC1D24	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
375707	NM_001199107.2(TBC1D24):c.1078C>T (p.Arg360Cys)	TBC1D24	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
418692	NM_001199107.2(TBC1D24):c.229ATCGTGGGCAAG[1] (p.77IVGK[1])	TBC1D24	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
425091	NM_001199107.2(TBC1D24):c.1525G>A (p.Gly509Arg)	TBC1D24	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
807960	NM_001199107.2(TBC1D24):c.442G>A (p.Glu148Lys)	TBC1D24	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1060035	NM_001199107.2(TBC1D24):c.820_822del (p.Arg274del)	TBC1D24	Uncertain significance	criteria provided, multiple submitters, no conflicts
1213711	NM_001199107.2(TBC1D24):c.1142+272T>C	TBC1D24	Uncertain significance	criteria provided, single submitter
1333213	NM_001199107.2(TBC1D24):c.844C>T (p.Pro282Ser)	TBC1D24	Uncertain significance	criteria provided, single submitter
1696584	NM_001199107.2(TBC1D24):c.-116+125A>C	TBC1D24	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 21 · Orphanet: 8 · 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
TBC1D24	Strong	Autosomal recessive	developmental and epileptic encephalopathy, 16	21

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TBC1D24	Orphanet:163727	Rolandic epilepsy-paroxysmal exercise-induced dystonia-writer’s cramp syndrome
TBC1D24	Orphanet:293181	Epilepsy of infancy with migrating focal seizures
TBC1D24	Orphanet:352582	Familial infantile myoclonic epilepsy
TBC1D24	Orphanet:352587	Focal epilepsy-intellectual disability-cerebro-cerebellar malformation
TBC1D24	Orphanet:352596	Progressive myoclonic epilepsy with dystonia
TBC1D24	Orphanet:79500	DOORS syndrome
TBC1D24	Orphanet:90635	Rare autosomal dominant non-syndromic sensorineural deafness type DFNA
TBC1D24	Orphanet:90636	Rare autosomal recessive non-syndromic sensorineural deafness type DFNB

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
TBC1D24	HGNC:29203	ENSG00000162065	Q9ULP9	TBC1 domain family member 24	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TBC1D24	TBC1 domain family member 24	May act as a GTPase-activating protein for Rab family protein(s).

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)
TBC1D24	Other/Unknown	no		Rab-GAP-TBC_dom, TLDc_dom, Rab-GAP_TBC_sf

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
Brodmann (1909) area 23	1
middle temporal gyrus	1
parotid gland	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TBC1D24	227	ubiquitous	marker	parotid gland, Brodmann (1909) area 23, middle temporal gyrus

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TBC1D24	1,016

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
TBC1D24	Q9ULP9	84.46

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 4. 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
Rab regulation of trafficking	1	368.4×	0.008	TBC1D24
TBC/RABGAPs	1	259.6×	0.008	TBC1D24
Membrane Trafficking	1	37.1×	0.029	TBC1D24
Vesicle-mediated transport	1	34.8×	0.029	TBC1D24

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
negative regulation of cellular response to oxidative stress	1	4213.0×	0.002	TBC1D24
positive regulation of neuron migration	1	991.3×	0.003	TBC1D24
positive regulation of dendrite morphogenesis	1	887.0×	0.003	TBC1D24
positive regulation of excitatory postsynaptic potential	1	526.6×	0.003	TBC1D24
axon development	1	455.5×	0.003	TBC1D24
synaptic vesicle endocytosis	1	432.1×	0.003	TBC1D24
dendrite development	1	391.9×	0.003	TBC1D24
cellular response to oxidative stress	1	154.6×	0.007	TBC1D24
neuron projection development	1	122.1×	0.008	TBC1D24

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
TBC1D24	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	TBC1D24

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)
TBC1D24	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.