Jervell and Lange-Nielsen syndrome 2

Summary

Jervell and Lange-Nielsen syndrome 2 (MONDO:0012871) is a disease caused by KCNE1 (GenCC Strong), with 1 cohort gene and 1 clinical trial.

At a glance

• Causal gene: KCNE1 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 127
• Clinical trials: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Jervell and Lange-Nielsen syndrome 2
Mondo ID	MONDO:0012871
MeSH	C567343
OMIM	612347
UMLS	C2676723
MedGen	394108
GARD	0010364
Is cancer (heuristic)	no

Also known as: Jervell and Lange-Nielsen syndrome 2 · Jervell and Lange-Nielsen syndrome caused by mutation in KCNE1 · Jervell and Lange-Nielsen syndrome type 2 · JLNS2 · KCNE1 Jervell and Lange-Nielsen syndrome

Data availability: 127 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › long QT syndrome › familial long QT syndrome › Jervell and Lange-Nielsen syndrome › Jervell and Lange-Nielsen syndrome 2

Related subtypes (1): Jervell and Lange-Nielsen syndrome 1

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, 18 benign, 18 conflicting classifications of pathogenicity, 10 benign/likely benign, 9 likely benign, 5 pathogenic, 1 pathogenic/likely pathogenic, 1 conflicting classifications of pathogenicity; other; risk factor

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
13476	NM_000219.6(KCNE1):c.20C>T (p.Thr7Ile)	KCNE1	Pathogenic	no assertion criteria provided
430060	NM_000219.6(KCNE1):c.12dup (p.Asn5Ter)	KCNE1	Pathogenic	criteria provided, multiple submitters, no conflicts
547162	NM_000219.6(KCNE1):c.138C>A (p.Tyr46Ter)	KCNE1	Pathogenic	criteria provided, single submitter
547163	NM_000219.6(KCNE1):c.50G>A (p.Trp17Ter)	KCNE1	Pathogenic	no assertion criteria provided
547164	NM_000219.6(KCNE1):c.51G>A (p.Trp17Ter)	KCNE1	Pathogenic	criteria provided, multiple submitters, no conflicts
132657	NM_000219.6(KCNE1):c.163G>A (p.Gly55Ser)	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
132677	NM_000219.6(KCNE1):c.29C>T (p.Thr10Met)	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
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
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	Strong	Autosomal recessive	Jervell and Lange-Nielsen syndrome 2	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: 1.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03655223	Not specified	ENROLLING_BY_INVITATION	Early Check: Expanded Screening in Newborns