long QT syndrome 5
diseaseOn this page
Also known as KCNE1 long QT syndromelong QT syndrome caused by mutation in KCNE1long QT syndrome type 5LQT5
Summary
long QT syndrome 5 (MONDO:0013372) is a disease caused by KCNE1 (GenCC Definitive), with 1 cohort gene.
At a glance
- Causal gene: KCNE1 (GenCC Definitive)
- Cohort genes: 1
- ClinVar variants: 127
Clinical features
No curated clinical features (Orphanet) for this disease.
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | long QT syndrome 5 |
| Mondo ID | MONDO:0013372 |
| MeSH | C566766 |
| OMIM | 613695 |
| DOID | DOID:0110647 |
| NCIT | C172094 |
| UMLS | C1867904 |
| MedGen | 358092 |
| GARD | 0010433 |
| Is cancer (heuristic) | no |
Also known as: KCNE1 long QT syndrome · long QT syndrome 5 · long QT syndrome caused by mutation in KCNE1 · long QT syndrome type 5 · LQT5
Data availability: 127 ClinVar variants · 3 GenCC gene-disease records · 3 cell lines.
Disease family
An umbrella term covering 1 Mondo subtype.
Classification path: disease › human disease › disease by body system or component › syndromic disease › long QT syndrome › familial long QT syndrome › long QT syndrome 5
Related subtypes (18): Jervell and Lange-Nielsen syndrome, Andersen-Tawil syndrome, cardiac arrhythmia, ankyrin-B-related, Timothy syndrome, long QT syndrome 3, long QT syndrome 9, long QT syndrome 10, long QT syndrome 11, long QT syndrome 12, long QT syndrome 13, long QT syndrome 2, long QT syndrome 6, long QT syndrome 14, long QT syndrome 15, long QT syndrome 8, long QT syndrome 16, long QT syndrome 1, long QT syndrome 4
Subtypes (1): Jervell and Lange-Nielsen syndrome 2
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
127 retrieved; paginated sample, class counts are floors:
65 uncertain significance, 22 conflicting classifications of pathogenicity, 18 benign, 10 benign/likely benign, 9 likely benign, 1 pathogenic/likely pathogenic, 1 conflicting classifications of pathogenicity; other; risk factor, 1 pathogenic
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 13475 | NG_009091.1(KCNE1):g.[66853A>C;66857T>C] | KCNE1 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 430060 | NM_000219.6(KCNE1):c.12dup (p.Asn5Ter) | KCNE1 | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 1202620 | NM_000219.6(KCNE1):c.31_118del (p.Pro11fs) | KCNE1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 132657 | NM_000219.6(KCNE1):c.163G>A (p.Gly55Ser) | KCNE1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 132660 | NM_000219.6(KCNE1):c.199C>T (p.Arg67Cys) | KCNE1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 132661 | NM_000219.6(KCNE1):c.200G>A (p.Arg67His) | KCNE1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 132676 | NM_000219.6(KCNE1):c.292C>T (p.Arg98Trp) | KCNE1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 132678 | NM_000219.6(KCNE1):c.325G>A (p.Val109Ile) | KCNE1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 132679 | NM_000219.6(KCNE1):c.374C>T (p.Thr125Met) | KCNE1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 13477 | NM_000219.6(KCNE1):c.226G>A (p.Asp76Asn) | KCNE1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 13478 | NM_000219.6(KCNE1):c.221C>T (p.Ser74Leu) | KCNE1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 13479 | NM_000219.6(KCNE1):c.253G>A (p.Asp85Asn) | KCNE1 | Conflicting classifications of pathogenicity; other; risk factor | criteria provided, conflicting classifications |
| 1705696 | NM_000219.6(KCNE1):c.106dup (p.Arg36fs) | KCNE1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 3230646 | NM_000219.6(KCNE1):c.61G>A (p.Val21Ile) | KCNE1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 339748 | NM_000219.6(KCNE1):c.*1338C>T | KCNE1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 339760 | NM_000219.6(KCNE1):c.*553A>G | KCNE1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 339767 | NM_000219.6(KCNE1):c.*196C>G | KCNE1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 339771 | NM_000219.6(KCNE1):c.*30C>G | KCNE1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 339772 | NM_000219.6(KCNE1):c.54G>A (p.Gln18=) | KCNE1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 339783 | NM_000219.6(KCNE1):c.-377+13G>A | KCNE1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 504745 | NM_000219.6(KCNE1):c.-5C>A | KCNE1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 506395 | NM_000219.6(KCNE1):c.111C>T (p.Ser37=) | KCNE1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 598781 | NM_000219.6(KCNE1):c.166_180del (p.Phe56_Gly60del) | KCNE1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 644369 | NM_000219.6(KCNE1):c.199C>G (p.Arg67Gly) | KCNE1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 963591 | NM_000219.6(KCNE1):c.120C>T (p.Gly40=) | KCNE1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1056763 | NM_000219.6(KCNE1):c.80T>C (p.Met27Thr) | KCNE1 | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 1060040 | NM_000219.6(KCNE1):c.142C>T (p.Leu48Phe) | KCNE1 | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 1193618 | NM_000219.6(KCNE1):c.199C>A (p.Arg67Ser) | KCNE1 | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 132670 | NM_000219.6(KCNE1):c.23C>T (p.Ala8Val) | KCNE1 | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 132673 | NM_000219.6(KCNE1):c.247G>A (p.Glu83Lys) | KCNE1 | Uncertain significance | criteria provided, multiple submitters, no conflicts |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 7 · Orphanet: 3 · 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 |
|---|---|---|---|---|
| KCNE1 | Definitive | Autosomal dominant | long QT syndrome 5 | 7 |
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|---|---|
| KCNE1 | Orphanet:101016 | Romano-Ward syndrome |
| KCNE1 | Orphanet:334 | Hereditary atrial fibrillation |
| KCNE1 | Orphanet:90647 | Jervell and Lange-Nielsen syndrome |
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 |
|---|---|---|---|---|---|
| KCNE1 | HGNC:6240 | ENSG00000180509 | P15382 | Potassium voltage-gated channel subfamily E member 1 | gencc,clinvar |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| KCNE1 | Potassium voltage-gated channel subfamily E member 1 | Ancillary protein that functions as a regulatory subunit of the voltage-gated potassium (Kv) channel complex composed of pore-forming and potassium-conducting alpha subunits and of regulatory beta subunits. |
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) |
|---|---|---|---|---|
| KCNE1 | Ion channel | yes | K_chnl_KCNE, KCNE1 |
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 |
|---|---|
| blood | 1 |
| leukocyte | 1 |
| monocyte | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| KCNE1 | 121 | broad | marker | blood, monocyte, leukocyte |
Protein interactions among cohort
Intra-cohort edges: 0.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| KCNE1 | 1,005 |
Structural data
PDB: 1 · AlphaFold-only: 0 · No structure: 0
Cohort genes with PDB structures (top 30)
| Symbol | UniProt | PDB entries |
|---|---|---|
| KCNE1 | P15382 | 5 |
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 |
|---|---|---|---|---|
| Phase 3 - rapid repolarisation | 1 | 1142.0× | 0.003 | KCNE1 |
| Phase 2 - plateau phase | 1 | 761.3× | 0.003 | KCNE1 |
| Cardiac conduction | 1 | 108.8× | 0.012 | KCNE1 |
| Muscle contraction | 1 | 77.2× | 0.013 | KCNE1 |
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 |
|---|---|---|---|---|
| vestibular nucleus development | 1 | 8426.0× | 0.001 | KCNE1 |
| secretory granule organization | 1 | 3370.4× | 0.001 | KCNE1 |
| negative regulation of protein targeting to membrane | 1 | 2808.7× | 0.001 | KCNE1 |
| negative regulation of delayed rectifier potassium channel activity | 1 | 2808.7× | 0.001 | KCNE1 |
| regulation of potassium ion transport | 1 | 1872.4× | 0.001 | KCNE1 |
| cardiac muscle cell contraction | 1 | 1685.2× | 0.001 | KCNE1 |
| membrane repolarization during action potential | 1 | 1685.2× | 0.001 | KCNE1 |
| membrane repolarization during cardiac muscle cell action potential | 1 | 1685.2× | 0.001 | KCNE1 |
| membrane repolarization during ventricular cardiac muscle cell action potential | 1 | 1685.2× | 0.001 | KCNE1 |
| epithelial cell maturation | 1 | 1532.0× | 0.001 | KCNE1 |
| membrane repolarization | 1 | 1296.3× | 0.002 | KCNE1 |
| potassium ion export across plasma membrane | 1 | 1053.2× | 0.002 | KCNE1 |
| ventricular cardiac muscle cell action potential | 1 | 991.3× | 0.002 | KCNE1 |
| positive regulation of potassium ion transmembrane transport | 1 | 991.3× | 0.002 | KCNE1 |
| regulation of ventricular cardiac muscle cell membrane repolarization | 1 | 842.6× | 0.002 | KCNE1 |
| cardiac muscle cell action potential involved in contraction | 1 | 702.2× | 0.002 | KCNE1 |
| regulation of potassium ion transmembrane transport | 1 | 624.1× | 0.002 | KCNE1 |
| regulation of heart rate by cardiac conduction | 1 | 374.5× | 0.003 | KCNE1 |
| cellular response to cAMP | 1 | 290.6× | 0.004 | KCNE1 |
| regulation of membrane potential | 1 | 230.8× | 0.005 | KCNE1 |
| potassium ion transmembrane transport | 1 | 135.9× | 0.008 | KCNE1 |
| sensory perception of sound | 1 | 100.9× | 0.010 | KCNE1 |
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 |
|---|---|
| KCNE1 | AMBRISENTAN |
Top cohort targets by molecule count
| Symbol | Molecules | Max phase |
|---|---|---|
| KCNE1 | 14 | 4 |
Drugs targeting cohort genes (top 30)
| Molecule | Max phase | Targets in cohort |
|---|---|---|
| AMBRISENTAN | 4 | KCNE1 |
| DULOXETINE | 4 | KCNE1 |
| PALONOSETRON | 4 | KCNE1 |
| DARUNAVIR | 4 | KCNE1 |
| DARIFENACIN | 4 | KCNE1 |
| TOLTERODINE | 4 | KCNE1 |
| SOLIFENACIN | 4 | KCNE1 |
| EVEROLIMUS | 4 | KCNE1 |
| RALTEGRAVIR | 4 | KCNE1 |
| MARAVIROC | 4 | KCNE1 |
| ALVIMOPAN | 4 | KCNE1 |
| NEBIVOLOL | 4 | KCNE1 |
| SUNITINIB | 4 | KCNE1 |
| NELFINAVIR | 4 | KCNE1 |
Bioactivity and enzyme data
Enzyme cohort genes (≥1 EC): 0.
Cohort genes with ChEMBL bioactivity (full, sorted by assay count)
| Symbol | Assays | Type breakdown |
|---|---|---|
| KCNE1 | 117 | Functional:63, Binding:47, ADMET:6, Toxicity:1 |
Cohort genes with high screening signal
≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.
| Symbol | ChEMBL assays |
|---|---|
| KCNE1 | 117 |
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
14 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) |
|---|---|---|
| AMBRISENTAN | 4 | KCNE1 |
| DULOXETINE | 4 | KCNE1 |
| PALONOSETRON | 4 | KCNE1 |
| DARUNAVIR | 4 | KCNE1 |
| DARIFENACIN | 4 | KCNE1 |
| TOLTERODINE | 4 | KCNE1 |
| SOLIFENACIN | 4 | KCNE1 |
| EVEROLIMUS | 4 | KCNE1 |
| RALTEGRAVIR | 4 | KCNE1 |
| MARAVIROC | 4 | KCNE1 |
| ALVIMOPAN | 4 | KCNE1 |
| NEBIVOLOL | 4 | KCNE1 |
| SUNITINIB | 4 | KCNE1 |
| NELFINAVIR | 4 | KCNE1 |
Druggability pyramid
Cohort genes binned by druggability tier (high → low):
| Tier | Definition | Genes | Symbols |
|---|---|---|---|
| A | Approved (phase 4 drug) | 1 | KCNE1 |
| 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.
Related Atlas pages
- Cohort genes: KCNE1