Generalized epilepsy with febrile seizures plus, type 9
disease diseaseOn this page
Also known as GEFSP9generalised epilepsy with febrile seizures plus caused by mutation in STX1Bgeneralized epilepsy with febrile seizures plus caused by mutation in STX1BSTX1B generalised epilepsy with febrile seizures plusSTX1B generalized epilepsy with febrile seizures plus
Summary
Generalized epilepsy with febrile seizures plus, type 9 (MONDO:0014517) is a disease caused by STX1B (GenCC Strong), with 3 cohort genes.
At a glance
- Causal gene: STX1B (GenCC Strong)
- Cohort genes: 3
- ClinVar variants: 370
Clinical features
No curated clinical features (Orphanet) for this disease.
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | generalized epilepsy with febrile seizures plus, type 9 |
| Mondo ID | MONDO:0014517 |
| OMIM | 616172 |
| DOID | DOID:0111301 |
| UMLS | C4015395 |
| MedGen | 863832 |
| GARD | 0018668 |
| Is cancer (heuristic) | no |
Also known as: GEFSP9 · generalised epilepsy with febrile seizures plus caused by mutation in STX1B · generalised epilepsy with febrile seizures plus caused by mutation in STX1b · generalized epilepsy with febrile seizures plus caused by mutation in STX1B · generalized epilepsy with febrile seizures plus caused by mutation in STX1b · generalized epilepsy with febrile seizures plus, type 9 · STX1B generalised epilepsy with febrile seizures plus · STX1b generalised epilepsy with febrile seizures plus · STX1B generalized epilepsy with febrile seizures plus · STX1b generalized epilepsy with febrile seizures plus
Data availability: 370 ClinVar variants · 3 GenCC gene-disease records · 1 cell line.
Disease family
Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › hereditary neurological disease › hereditary generalized epilepsy › generalized epilepsy with febrile seizures plus › generalized epilepsy with febrile seizures plus, type 9
Related subtypes (9): generalized epilepsy with febrile seizures plus, type 1, generalized epilepsy with febrile seizures plus, type 2, febrile seizures, familial, 8, generalized epilepsy with febrile seizures plus, type 4, generalized epilepsy with febrile seizures plus, type 6, generalized epilepsy with febrile seizures plus, type 8, generalized epilepsy with febrile seizures plus, type 7, generalized epilepsy with febrile seizures plus, type 10, generalized epilepsy with febrile seizures plus, type 12
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
370 retrieved; paginated sample, class counts are floors:
153 likely benign, 124 uncertain significance, 34 pathogenic, 27 likely pathogenic, 14 benign, 10 conflicting classifications of pathogenicity, 6 benign/likely benign, 2 pathogenic/likely pathogenic
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 162396 | NM_052874.5(STX1B):c.[133_134insGGATGTGCATTG;135_136delinsGA] | Pathogenic | no assertion criteria provided | |
| 1458547 | NC_000016.9:g.(?30996980)(31021717_?)del | HSD3B7 | Pathogenic | criteria provided, single submitter |
| 475337 | NC_000016.10:g.(?30992801)(31068051_?)del | LOC130058885 | Pathogenic | criteria provided, single submitter |
| 2808202 | NM_052874.5(STX1B):c.340_354+123del | LOC130058887 | Pathogenic | criteria provided, single submitter |
| 3066028 | NC_000016.10:g.30996672_31010406del | LOC130058887 | Pathogenic | no assertion criteria provided |
| 1066204 | NM_052874.5(STX1B):c.537+2T>C | STX1B | Pathogenic | criteria provided, single submitter |
| 1070577 | NM_052874.5(STX1B):c.334del (p.Leu112fs) | STX1B | Pathogenic | criteria provided, single submitter |
| 1308652 | NM_052874.5(STX1B):c.160A>T (p.Lys54Ter) | STX1B | Pathogenic | criteria provided, single submitter |
| 1451994 | NM_052874.5(STX1B):c.205_205+1del | STX1B | Pathogenic | criteria provided, single submitter |
| 1460098 | NM_052874.5(STX1B):c.214C>T (p.Gln72Ter) | STX1B | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1481736 | NM_052874.5(STX1B):c.430T>C (p.Cys144Arg) | STX1B | Pathogenic | criteria provided, single submitter |
| 162395 | NM_052874.5(STX1B):c.166C>T (p.Gln56Ter) | STX1B | Pathogenic | no assertion criteria provided |
| 162397 | NM_052874.5(STX1B):c.140C>A (p.Ser47Ter) | STX1B | Pathogenic | criteria provided, single submitter |
| 162398 | NM_052874.5(STX1B):c.647T>A (p.Val216Glu) | STX1B | Pathogenic | no assertion criteria provided |
| 162399 | NM_052874.5(STX1B):c.676G>C (p.Gly226Arg) | STX1B | Pathogenic | no assertion criteria provided |
| 2576582 | NM_052874.5(STX1B):c.354+1G>C | STX1B | Pathogenic | criteria provided, single submitter |
| 2693031 | NM_052874.5(STX1B):c.786+1G>A | STX1B | Pathogenic | criteria provided, single submitter |
| 2748620 | NM_052874.5(STX1B):c.815del (p.Val272fs) | STX1B | Pathogenic | criteria provided, single submitter |
| 2811860 | NM_052874.5(STX1B):c.786+1G>T | STX1B | Pathogenic | criteria provided, single submitter |
| 2813188 | NM_052874.5(STX1B):c.39del (p.Asp13fs) | STX1B | Pathogenic | criteria provided, single submitter |
| 2849088 | NM_052874.5(STX1B):c.338_354+15del | STX1B | Pathogenic | criteria provided, single submitter |
| 2864828 | NM_052874.5(STX1B):c.366del (p.Ser123fs) | STX1B | Pathogenic | criteria provided, single submitter |
| 3650187 | NM_052874.5(STX1B):c.565C>T (p.Gln189Ter) | STX1B | Pathogenic | criteria provided, single submitter |
| 3663941 | NM_052874.5(STX1B):c.2T>A (p.Met1Lys) | STX1B | Pathogenic | criteria provided, single submitter |
| 4726056 | NM_052874.5(STX1B):c.725dup (p.Tyr242Ter) | STX1B | Pathogenic | criteria provided, single submitter |
| 4732781 | NM_052874.5(STX1B):c.846dup (p.Gly283fs) | STX1B | Pathogenic | criteria provided, single submitter |
| 4735231 | NM_052874.5(STX1B):c.613G>T (p.Glu205Ter) | STX1B | Pathogenic | criteria provided, single submitter |
| 567167 | NM_052874.5(STX1B):c.35_36dup (p.Asp13fs) | STX1B | Pathogenic | criteria provided, single submitter |
| 590057 | NM_052874.5(STX1B):c.733C>T (p.Arg245Ter) | STX1B | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 620559 | NM_052874.5(STX1B):c.394G>T (p.Glu132Ter) | STX1B | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 4 · Orphanet: 2 · 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 |
|---|---|---|---|---|
| STX1B | Strong | Autosomal dominant | generalized epilepsy with febrile seizures plus, type 9 | 4 |
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|---|---|
| STX1B | Orphanet:36387 | Genetic epilepsy with febrile seizure plus |
| HSD3B7 | Orphanet:79301 | Congenital bile acid synthesis defect type 1 |
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 |
|---|---|---|---|---|---|
| STX1B | HGNC:18539 | ENSG00000099365 | P61266 | Syntaxin-1B | gencc,clinvar |
| HSD3B7 | HGNC:18324 | ENSG00000099377 | Q9H2F3 | 3 beta-hydroxysteroid dehydrogenase type 7 | clinvar |
| CFAP119 | HGNC:28078 | ENSG00000196118 | A1A4V9 | Cilia- and flagella-associated protein 119 | clinvar |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| STX1B | Syntaxin-1B | Potentially involved in docking of synaptic vesicles at presynaptic active zones. |
| HSD3B7 | 3 beta-hydroxysteroid dehydrogenase type 7 | The 3-beta-HSD enzymatic system plays a crucial role in the biosynthesis of all classes of hormonal steroids. |
Protein-family classification
Druggable: 0 · Difficult: 0 · Unknown: 3 · 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 | 3 | 1.8× | 0.174 |
Per-gene assignment
| Symbol | Family | Druggable? | EC | InterPro (top 3) |
|---|---|---|---|---|
| STX1B | Other/Unknown | no | T_SNARE_dom, Syntaxin_N, Syntaxin/epimorphin_CS | |
| HSD3B7 | Other/Unknown | no | 3Beta_OHSteriod_DH/Estase, NAD(P)-bd_dom_sf, NAD(P)_dehydrat-like | |
| CFAP119 | Other/Unknown | no | CLAMP |
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 |
|---|---|
| cerebellar cortex | 1 |
| cerebellar hemisphere | 1 |
| right hemisphere of cerebellum | 1 |
| left adrenal gland | 1 |
| liver | 1 |
| right lobe of liver | 1 |
| bronchial epithelial cell | 1 |
| bronchus | 1 |
| right uterine tube | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| STX1B | 176 | ubiquitous | marker | right hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex |
| HSD3B7 | 177 | ubiquitous | marker | right lobe of liver, liver, left adrenal gland |
| CFAP119 | 184 | ubiquitous | marker | right uterine tube, bronchial epithelial cell, bronchus |
Protein interactions among cohort
Intra-cohort edges: 0.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| HSD3B7 | 3,327 |
| STX1B | 2,130 |
| CFAP119 | 884 |
Structural data
PDB: 0 · AlphaFold-only: 3 · No structure: 0
AlphaFold-only cohort genes (top 30 by pLDDT)
| Symbol | UniProt | pLDDT |
|---|---|---|
| HSD3B7 | Q9H2F3 | 94.01 |
| STX1B | P61266 | 84.17 |
| CFAP119 | A1A4V9 | 74.17 |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 16. 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 |
|---|---|---|---|---|
| Toxicity of botulinum toxin type C (botC) | 1 | 1903.3× | 0.007 | STX1B |
| Neurotoxicity of clostridium toxins | 1 | 713.8× | 0.007 | STX1B |
| Synthesis of bile acids and bile salts via 24-hydroxycholesterol | 1 | 439.2× | 0.007 | HSD3B7 |
| Uptake and actions of bacterial toxins | 1 | 407.9× | 0.007 | STX1B |
| LGI-ADAM interactions | 1 | 407.9× | 0.007 | STX1B |
| Synthesis of bile acids and bile salts via 27-hydroxycholesterol | 1 | 380.7× | 0.007 | HSD3B7 |
| Bile acid and bile salt metabolism | 1 | 248.3× | 0.009 | HSD3B7 |
| Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol | 1 | 228.4× | 0.009 | HSD3B7 |
| Synthesis of bile acids and bile salts | 1 | 203.9× | 0.009 | HSD3B7 |
| Bacterial Infection Pathways | 1 | 167.9× | 0.010 | STX1B |
| Metabolism of steroids | 1 | 68.8× | 0.021 | HSD3B7 |
| Metabolism of lipids | 1 | 15.8× | 0.083 | HSD3B7 |
| Infectious disease | 1 | 12.4× | 0.097 | STX1B |
| Developmental Biology | 1 | 7.2× | 0.153 | STX1B |
| Disease | 1 | 6.5× | 0.157 | STX1B |
| Metabolism | 1 | 5.8× | 0.165 | HSD3B7 |
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 |
|---|---|---|---|---|
| negative regulation of synaptic vesicle recycling | 1 | 5617.3× | 0.001 | STX1B |
| positive regulation of spontaneous neurotransmitter secretion | 1 | 5617.3× | 0.001 | STX1B |
| negative regulation of macropinocytosis | 1 | 5617.3× | 0.001 | STX1B |
| calcium ion-regulated exocytosis of neurotransmitter | 1 | 1404.3× | 0.003 | STX1B |
| regulation of synaptic activity | 1 | 1404.3× | 0.003 | STX1B |
| B cell chemotaxis | 1 | 936.2× | 0.004 | HSD3B7 |
| spontaneous neurotransmitter secretion | 1 | 936.2× | 0.004 | STX1B |
| positive regulation of neurotransmitter secretion | 1 | 624.1× | 0.004 | STX1B |
| regulation of synaptic vesicle priming | 1 | 561.7× | 0.004 | STX1B |
| synaptic vesicle fusion to presynaptic active zone membrane | 1 | 561.7× | 0.004 | STX1B |
| obsolete synaptic vesicle docking | 1 | 432.1× | 0.005 | STX1B |
| obsolete vesicle docking | 1 | 255.3× | 0.007 | STX1B |
| obsolete vesicle docking involved in exocytosis | 1 | 224.7× | 0.007 | STX1B |
| sperm flagellum assembly | 1 | 224.7× | 0.007 | CFAP119 |
| bile acid biosynthetic process | 1 | 208.1× | 0.007 | HSD3B7 |
| steroid biosynthetic process | 1 | 200.6× | 0.007 | HSD3B7 |
| positive regulation of excitatory postsynaptic potential | 1 | 175.5× | 0.008 | STX1B |
| negative regulation of neuron projection development | 1 | 79.1× | 0.016 | STX1B |
| single fertilization | 1 | 61.1× | 0.020 | CFAP119 |
| exocytosis | 1 | 50.6× | 0.023 | STX1B |
| regulation of gene expression | 1 | 27.8× | 0.039 | STX1B |
| gene expression | 1 | 26.6× | 0.039 | CFAP119 |
| intracellular protein transport | 1 | 21.6× | 0.046 | STX1B |
Therapeutics
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 |
|---|---|---|
| STX1B | 0 | 0 |
| HSD3B7 | 0 | 0 |
| CFAP119 | 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 | 0 | |
| D | Druggable family + AlphaFold only, no drug | 0 | |
| E | Difficult family or no structure, no drug | 3 | STX1B, HSD3B7, CFAP119 |
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) |
|---|---|---|
| STX1B | 0 | — |
| HSD3B7 | 0 | — |
| CFAP119 | 0 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 0.