Generalized epilepsy with febrile seizures plus, type 10
disease diseaseOn this page
Also known as GEFSP10
Summary
Generalized epilepsy with febrile seizures plus, type 10 (MONDO:0032777) is a disease caused by HCN1 (GenCC Strong), with 1 cohort gene.
At a glance
- Causal gene: HCN1 (GenCC Strong)
- Cohort genes: 1
- ClinVar variants: 42
Clinical features
No curated clinical features (Orphanet) for this disease.
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | generalized epilepsy with febrile seizures plus, type 10 |
| Mondo ID | MONDO:0032777 |
| OMIM | 618482 |
| DOID | DOID:0111296 |
| UMLS | C5193120 |
| MedGen | 1676426 |
| GARD | 0018671 |
| Is cancer (heuristic) | no |
Also known as: GEFSP10
Data availability: 42 ClinVar variants · 2 GenCC gene-disease records.
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 10
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 9, 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
42 retrieved; paginated sample, class counts are floors:
18 uncertain significance, 9 pathogenic, 8 conflicting classifications of pathogenicity, 4 likely pathogenic, 2 benign/likely benign, 1 pathogenic/likely pathogenic
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 1342978 | NM_021072.4(HCN1):c.1184C>G (p.Ala395Gly) | HCN1 | Pathogenic | no assertion criteria provided |
| 1342979 | NM_021072.4(HCN1):c.1138A>T (p.Ile380Phe) | HCN1 | Pathogenic | criteria provided, single submitter |
| 1342980 | NM_021072.4(HCN1):c.1169T>C (p.Val390Ala) | HCN1 | Pathogenic | no assertion criteria provided |
| 139572 | NM_021072.4(HCN1):c.299C>T (p.Ser100Phe) | HCN1 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 635188 | NM_021072.4(HCN1):c.728T>G (p.Met243Arg) | HCN1 | Pathogenic | no assertion criteria provided |
| 635189 | NM_021072.4(HCN1):c.1171G>A (p.Gly391Ser) | HCN1 | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 635190 | NM_021072.4(HCN1):c.1769G>A (p.Arg590Gln) | HCN1 | Pathogenic | no assertion criteria provided |
| 635191 | NM_021072.4(HCN1):c.986G>C (p.Cys329Ser) | HCN1 | Pathogenic | no assertion criteria provided |
| 635192 | NM_021072.4(HCN1):c.1240G>A (p.Val414Met) | HCN1 | Pathogenic | no assertion criteria provided |
| 635193 | NM_021072.4(HCN1):c.469C>G (p.Leu157Val) | HCN1 | Pathogenic | no assertion criteria provided |
| 1308642 | NM_021072.4(HCN1):c.628C>T (p.Pro210Ser) | HCN1 | Likely pathogenic | criteria provided, single submitter |
| 1342977 | NM_021072.4(HCN1):c.2128_2129dup (p.Ser710fs) | HCN1 | Likely pathogenic | no assertion criteria provided |
| 3382566 | NM_021072.4(HCN1):c.499T>C (p.Phe167Leu) | HCN1 | Likely pathogenic | criteria provided, single submitter |
| 3897806 | NM_021072.4(HCN1):c.1136T>G (p.Met379Arg) | HCN1 | Likely pathogenic | criteria provided, single submitter |
| 1004454 | NM_021072.4(HCN1):c.763C>T (p.Arg255Cys) | HCN1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 2963474 | NM_021072.4(HCN1):c.2246A>C (p.Gln749Pro) | HCN1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 3366984 | NM_021072.4(HCN1):c.701A>G (p.Tyr234Cys) | HCN1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 3367042 | NM_021072.4(HCN1):c.1917C>G (p.Ile639Met) | HCN1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 530453 | NM_021072.4(HCN1):c.1522G>A (p.Val508Met) | HCN1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 573431 | NM_021072.4(HCN1):c.192_206dup (p.Gly70_Gly74dup) | HCN1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 581499 | NM_021072.4(HCN1):c.203GCG[6] (p.Gly74del) | HCN1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 857604 | NM_021072.4(HCN1):c.1777C>G (p.Arg593Gly) | HCN1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1184324 | Single allele | HCN1 | Uncertain significance | criteria provided, single submitter |
| 1208904 | NM_021072.4(HCN1):c.808C>T (p.Arg270Ter) | HCN1 | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 1319936 | NM_021072.4(HCN1):c.1429G>A (p.Ala477Thr) | HCN1 | Uncertain significance | no assertion criteria provided |
| 1325609 | NM_021072.4(HCN1):c.2165C>T (p.Pro722Leu) | HCN1 | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 1342975 | NM_021072.4(HCN1):c.719A>G (p.Glu240Gly) | HCN1 | Uncertain significance | no assertion criteria provided |
| 1342976 | NM_021072.4(HCN1):c.1214G>A (p.Arg405Gln) | HCN1 | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 1675984 | NM_021072.4(HCN1):c.1283G>A (p.Arg428His) | HCN1 | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 1679655 | NM_021072.4(HCN1):c.1377+19834C>T | HCN1 | Uncertain significance | criteria provided, single submitter |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 7 · 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 |
|---|---|---|---|---|
| HCN1 | Strong | Autosomal dominant | generalized epilepsy with febrile seizures plus, type 10 | 7 |
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|---|---|
| HCN1 | Orphanet:36387 | Genetic epilepsy with febrile seizure plus |
| HCN1 | Orphanet:442835 | Non-specific early-onset epileptic encephalopathy |
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 |
|---|---|---|---|---|---|
| HCN1 | HGNC:4845 | ENSG00000164588 | O60741 | Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 1 | gencc,clinvar |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| HCN1 | Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 1 | Hyperpolarization-activated ion channel that are permeable to sodium and potassium ions. |
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 |
|---|---|---|---|
| Ion channel | 1 | 111.5× | 0.009 |
Per-gene assignment
| Symbol | Family | Druggable? | EC | InterPro (top 3) |
|---|---|---|---|---|
| HCN1 | Ion channel | yes | cNMP-bd_dom, K_chnl_volt-dep_EAG/ELK/ERG, Ion_trans_dom |
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 |
| endothelial cell | 1 |
| primary visual cortex | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| HCN1 | 147 | broad | marker | endothelial cell, Brodmann (1909) area 23, primary visual cortex |
Protein interactions among cohort
Intra-cohort edges: 0.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| HCN1 | 726 |
Structural data
PDB: 1 · AlphaFold-only: 0 · No structure: 0
Cohort genes with PDB structures (top 30)
| Symbol | UniProt | PDB entries |
|---|---|---|
| HCN1 | O60741 | 17 |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 1. 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 |
|---|---|---|---|---|
| HCN channels | 1 | 2855.0× | 4e-04 | HCN1 |
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 membrane hyperpolarization | 1 | 16852.0× | 0.001 | HCN1 |
| negative regulation of action potential | 1 | 4213.0× | 0.002 | HCN1 |
| general adaptation syndrome, behavioral process | 1 | 3370.4× | 0.002 | HCN1 |
| regulation of SA node cell action potential | 1 | 2808.7× | 0.002 | HCN1 |
| regulation of membrane depolarization | 1 | 1872.4× | 0.002 | HCN1 |
| negative regulation of synaptic transmission, glutamatergic | 1 | 1685.2× | 0.002 | HCN1 |
| response to L-glutamate | 1 | 1685.2× | 0.002 | HCN1 |
| retinal cone cell development | 1 | 1404.3× | 0.002 | HCN1 |
| maternal behavior | 1 | 1123.5× | 0.002 | HCN1 |
| apical protein localization | 1 | 991.3× | 0.002 | HCN1 |
| sodium ion import across plasma membrane | 1 | 624.1× | 0.003 | HCN1 |
| cellular response to interferon-beta | 1 | 526.6× | 0.003 | HCN1 |
| neuronal action potential | 1 | 481.5× | 0.003 | HCN1 |
| regulation of heart rate by cardiac conduction | 1 | 374.5× | 0.004 | HCN1 |
| potassium ion import across plasma membrane | 1 | 366.4× | 0.004 | HCN1 |
| response to calcium ion | 1 | 318.0× | 0.004 | HCN1 |
| cellular response to cAMP | 1 | 290.6× | 0.004 | HCN1 |
| protein homotetramerization | 1 | 237.3× | 0.005 | HCN1 |
| regulation of membrane potential | 1 | 230.8× | 0.005 | HCN1 |
| sodium ion transmembrane transport | 1 | 203.0× | 0.005 | HCN1 |
| potassium ion transmembrane transport | 1 | 135.9× | 0.007 | HCN1 |
Therapeutics
Drug target analysis
Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1
Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).
Top cohort targets by molecule count
| Symbol | Molecules | Max phase |
|---|---|---|
| HCN1 | 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 |
|---|---|---|
| HCN1 | 21 | Binding:12, Functional:8, ADMET:1 |
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 | 1 | HCN1 |
| D | Druggable family + AlphaFold only, no drug | 0 | |
| E | Difficult family or no structure, no drug | 0 |
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) |
|---|---|---|
| HCN1 | 21 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 0.
Related Atlas pages
- Cohort genes: HCN1