Familial temporal lobe epilepsy 5
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Also known as epilepsy, familial temporal lobe, 5epilepsy, familial temporal lobe, type 5ETL5familial temporal lobe epilepsy type 5
Summary
Familial temporal lobe epilepsy 5 (MONDO:0013741) is a disease with 2 cohort genes.
At a glance
- Cohort genes: 2
- ClinVar variants: 72
Clinical features
No curated clinical features (Orphanet) for this disease.
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | familial temporal lobe epilepsy 5 |
| Mondo ID | MONDO:0013741 |
| OMIM | 614417 |
| DOID | DOID:0060752 |
| UMLS | C3280730 |
| MedGen | 482360 |
| GARD | 0018280 |
| Is cancer (heuristic) | no |
Also known as: epilepsy, familial temporal lobe, 5 · epilepsy, familial temporal lobe, type 5 · ETL5 · familial temporal lobe epilepsy type 5
Data availability: 72 ClinVar variants · 2 GenCC gene-disease records.
Disease family
Classification path: 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 › familial mesial temporal lobe epilepsy › familial temporal lobe epilepsy 5
Related subtypes (2): familial temporal lobe epilepsy 3, familial temporal lobe epilepsy 6
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
72 retrieved; paginated sample, class counts are floors:
55 uncertain significance, 9 conflicting classifications of pathogenicity, 3 benign, 2 benign/likely benign, 2 likely benign, 1 no classifications from unflagged records
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 281269 | NM_020361.5(CPA6):c.799G>A (p.Gly267Arg) | ARFGEF1-DT | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 30791 | NM_020361.5(CPA6):c.809C>T (p.Ala270Val) | ARFGEF1-DT | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 363605 | NM_020361.5(CPA6):c.932G>A (p.Arg311Gln) | ARFGEF1-DT | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 472765 | NM_020361.5(CPA6):c.916G>A (p.Val306Ile) | ARFGEF1-DT | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 539979 | NM_020361.5(CPA6):c.759G>A (p.Trp253Ter) | ARFGEF1-DT | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 774243 | NM_020361.5(CPA6):c.920C>T (p.Ala307Val) | ARFGEF1-DT | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 363610 | NM_020361.5(CPA6):c.505T>C (p.Tyr169His) | CPA6 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 363614 | NM_020361.5(CPA6):c.98A>G (p.Tyr33Cys) | CPA6 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 393467 | NM_020361.5(CPA6):c.619C>G (p.Gln207Glu) | CPA6 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1030703 | NM_020361.5(CPA6):c.1096T>C (p.Tyr366His) | ARFGEF1-DT | Uncertain significance | criteria provided, single submitter |
| 1334016 | NM_020361.5(CPA6):c.1294C>A (p.Leu432Met) | ARFGEF1-DT | Uncertain significance | criteria provided, single submitter |
| 2664165 | NM_020361.5(CPA6):c.1007A>G (p.Tyr336Cys) | ARFGEF1-DT | Uncertain significance | criteria provided, single submitter |
| 3065225 | NM_020361.5(CPA6):c.1207G>T (p.Gly403Ter) | ARFGEF1-DT | Uncertain significance | criteria provided, single submitter |
| 3065258 | NM_020361.5(CPA6):c.871A>G (p.Thr291Ala) | ARFGEF1-DT | Uncertain significance | criteria provided, single submitter |
| 3234978 | NM_020361.5(CPA6):c.1205C>A (p.Thr402Asn) | ARFGEF1-DT | Uncertain significance | criteria provided, single submitter |
| 3377700 | NM_020361.5(CPA6):c.1223T>C (p.Leu408Ser) | ARFGEF1-DT | Uncertain significance | criteria provided, single submitter |
| 363597 | NM_020361.5(CPA6):c.*260A>C | ARFGEF1-DT | Uncertain significance | criteria provided, single submitter |
| 363599 | NM_020361.5(CPA6):c.1288A>G (p.Met430Val) | ARFGEF1-DT | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 363602 | NM_020361.5(CPA6):c.1126+13C>T | ARFGEF1-DT | Uncertain significance | criteria provided, single submitter |
| 363604 | NM_020361.5(CPA6):c.1021A>G (p.Ile341Val) | ARFGEF1-DT | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 363606 | NM_020361.5(CPA6):c.797G>T (p.Arg266Leu) | ARFGEF1-DT | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 363607 | NM_020361.5(CPA6):c.791G>A (p.Arg264His) | ARFGEF1-DT | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 363608 | NM_020361.5(CPA6):c.715A>G (p.Asn239Asp) | ARFGEF1-DT | Uncertain significance | criteria provided, single submitter |
| 3897986 | NM_020361.5(CPA6):c.1009A>G (p.Lys337Glu) | ARFGEF1-DT | Uncertain significance | criteria provided, single submitter |
| 4277841 | NM_020361.5(CPA6):c.1153T>C (p.Trp385Arg) | ARFGEF1-DT | Uncertain significance | criteria provided, single submitter |
| 437415 | NM_020361.5(CPA6):c.994T>C (p.Tyr332His) | ARFGEF1-DT | Uncertain significance | criteria provided, single submitter |
| 444757 | NM_020361.5(CPA6):c.902C>T (p.Pro301Leu) | ARFGEF1-DT | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 472761 | NM_020361.5(CPA6):c.1271C>T (p.Ala424Val) | ARFGEF1-DT | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 472763 | NM_020361.5(CPA6):c.757T>G (p.Trp253Gly) | ARFGEF1-DT | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 657933 | NM_020361.5(CPA6):c.725G>T (p.Gly242Val) | ARFGEF1-DT | Uncertain significance | criteria provided, multiple submitters, no conflicts |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 5 · 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 |
|---|---|---|---|---|
| CPA6 | Supportive | Autosomal dominant | benign familial mesial temporal lobe epilepsy | 5 |
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|---|---|
| CPA6 | Orphanet:163717 | Familial mesial temporal lobe epilepsy |
| CPA6 | Orphanet:36387 | Genetic epilepsy with febrile seizure plus |
Cohort genes → proteins
2 cohort genes, 1 distinct canonical proteins.
Evidence partition
| Subset | Genes |
|---|---|
| multi_evidence | 2 |
Cohort genes (full)
| Symbol | HGNC | Ensembl | UniProt | Name | Evidence |
|---|---|---|---|---|---|
| CPA6 | HGNC:17245 | ENSG00000165078 | Q8N4T0 | Carboxypeptidase A6 | gencc,clinvar |
| ARFGEF1-DT | HGNC:55237 | ENSG00000271966 | ARFGEF1 divergent transcript | clinvar |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| CPA6 | Carboxypeptidase A6 | May be involved in the proteolytic inactivation of enkephalins and neurotensin in some brain areas. |
Protein-family classification
Druggable: 1 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.5
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 |
|---|---|---|---|
| Protease | 1 | 18.3× | 0.108 |
| Other/Unknown | 1 | 0.9× | 0.805 |
Per-gene assignment
| Symbol | Family | Druggable? | EC | InterPro (top 3) |
|---|---|---|---|---|
| CPA6 | Protease | yes | Peptidase_M14, M14A_act_pep, CPAH | |
| ARFGEF1-DT | Other/Unknown | no |
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) | 2 |
| unknown | 0 |
Top tissues across cohort
| Tissue | Cohort genes |
|---|---|
| buccal mucosa cell | 1 |
| mucosa of transverse colon | 1 |
| urethra | 1 |
| bone marrow | 1 |
| bone marrow cell | 1 |
| ganglionic eminence | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| CPA6 | 103 | broad | marker | buccal mucosa cell, mucosa of transverse colon, urethra |
| ARFGEF1-DT | 127 | yes | bone marrow cell, bone marrow, ganglionic eminence |
Protein interactions among cohort
Intra-cohort edges: 0.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| CPA6 | 605 |
| ARFGEF1-DT | 0 |
Structural data
PDB: 0 · AlphaFold-only: 1 · No structure: 1
AlphaFold-only cohort genes (top 30 by pLDDT)
| Symbol | UniProt | pLDDT |
|---|---|---|
| CPA6 | Q8N4T0 | 90.93 |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 2 evidence-associated genes (0 with Reactome annotation).
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 |
|---|---|---|---|---|
| proteolysis | 1 | 34.2× | 0.029 | CPA6 |
Therapeutics
Drug target analysis
Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2
Druggability breadth: 0 of 2 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 |
|---|---|---|
| CPA6 | 0 | 0 |
| ARFGEF1-DT | 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 | 1 | CPA6 |
| E | Difficult family or no structure, no drug | 1 | ARFGEF1-DT |
Undrugged target profiles
2 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).
| Symbol | ChEMBL assays | Drugged partners (top 3) |
|---|---|---|
| CPA6 | 0 | — |
| ARFGEF1-DT | 0 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 0.
Related Atlas pages
- Cohort genes: CPA6, ARFGEF1-DT