long QT syndrome 13

Summary

long QT syndrome 13 (MONDO:0013279) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 86

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	long QT syndrome 13
Mondo ID	MONDO:0013279
OMIM	613485
DOID	DOID:0110654
UMLS	C3150733
MedGen	462083
GARD	0015666
Is cancer (heuristic)	no

Also known as: KCNJ5 long QT syndrome · long QT syndrome 13 · long QT syndrome caused by mutation in KCNJ5 · long QT syndrome type 13 · LQT13

Data availability: 86 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 › long QT syndrome 13

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 2, long QT syndrome 6, long QT syndrome 5, long QT syndrome 14, long QT syndrome 15, long QT syndrome 8, long QT syndrome 16, long QT syndrome 1, long QT syndrome 4

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

86 retrieved; paginated sample, class counts are floors:

55 uncertain significance, 10 conflicting classifications of pathogenicity, 10 likely benign, 6 benign/likely benign, 5 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1010966	NM_000890.5(KCNJ5):c.119C>T (p.Thr40Met)	KCNJ5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1761254	NM_000890.5(KCNJ5):c.1253C>T (p.Ser418Leu)	KCNJ5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
238195	NM_000890.5(KCNJ5):c.1124G>A (p.Arg375Gln)	KCNJ5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2856410	NM_000890.5(KCNJ5):c.659G>A (p.Arg220Gln)	KCNJ5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
303628	NM_000890.5(KCNJ5):c.430A>G (p.Ile144Val)	KCNJ5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3599191	NM_000890.5(KCNJ5):c.91G>A (p.Asp31Asn)	KCNJ5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
432222	NM_000890.5(KCNJ5):c.439G>A (p.Glu147Lys)	KCNJ5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
560690	NM_000890.5(KCNJ5):c.864G>T (p.Glu288Asp)	KCNJ5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
843194	NM_000890.5(KCNJ5):c.1220A>G (p.Lys407Arg)	KCNJ5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
941579	NM_000890.5(KCNJ5):c.214C>T (p.Arg72Trp)	KCNJ5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1007137	NM_000890.5(KCNJ5):c.155G>A (p.Arg52His)	KCNJ5	Uncertain significance	criteria provided, multiple submitters, no conflicts
1014195	NM_000890.5(KCNJ5):c.148C>T (p.Arg50Cys)	KCNJ5	Uncertain significance	criteria provided, multiple submitters, no conflicts
1019977	NM_000890.5(KCNJ5):c.902T>A (p.Val301Asp)	KCNJ5	Uncertain significance	criteria provided, multiple submitters, no conflicts
1040985	NM_000890.5(KCNJ5):c.274G>A (p.Val92Ile)	KCNJ5	Uncertain significance	criteria provided, multiple submitters, no conflicts
1045677	NM_000890.5(KCNJ5):c.532G>A (p.Val178Ile)	KCNJ5	Uncertain significance	criteria provided, multiple submitters, no conflicts
1050347	NM_000890.5(KCNJ5):c.1248G>C (p.Arg416Ser)	KCNJ5	Uncertain significance	criteria provided, multiple submitters, no conflicts
1054696	NM_000890.5(KCNJ5):c.994C>T (p.Arg332Ter)	KCNJ5	Uncertain significance	criteria provided, multiple submitters, no conflicts
1058806	NM_000890.5(KCNJ5):c.631C>T (p.Arg211Trp)	KCNJ5	Uncertain significance	criteria provided, multiple submitters, no conflicts
1306130	NM_000890.5(KCNJ5):c.704G>A (p.Arg235Gln)	KCNJ5	Uncertain significance	criteria provided, multiple submitters, no conflicts
1326808	NM_000890.5(KCNJ5):c.955C>T (p.Arg319Trp)	KCNJ5	Uncertain significance	criteria provided, multiple submitters, no conflicts
1396809	NM_000890.5(KCNJ5):c.259C>T (p.Arg87Cys)	KCNJ5	Uncertain significance	criteria provided, multiple submitters, no conflicts
1476591	NM_000890.5(KCNJ5):c.224G>A (p.Ser75Asn)	KCNJ5	Uncertain significance	criteria provided, multiple submitters, no conflicts
1496865	NM_000890.5(KCNJ5):c.149G>A (p.Arg50His)	KCNJ5	Uncertain significance	criteria provided, multiple submitters, no conflicts
1503522	NM_000890.5(KCNJ5):c.834T>A (p.His278Gln)	KCNJ5	Uncertain significance	criteria provided, multiple submitters, no conflicts
1677568	NM_000890.5(KCNJ5):c.835G>A (p.Glu279Lys)	KCNJ5	Uncertain significance	criteria provided, multiple submitters, no conflicts
1739206	NM_000890.5(KCNJ5):c.116G>A (p.Arg39His)	KCNJ5	Uncertain significance	criteria provided, multiple submitters, no conflicts
1768728	NM_000890.5(KCNJ5):c.995G>A (p.Arg332Gln)	KCNJ5	Uncertain significance	criteria provided, multiple submitters, no conflicts
1782286	NM_000890.5(KCNJ5):c.18G>T (p.Arg6Ser)	KCNJ5	Uncertain significance	criteria provided, multiple submitters, no conflicts
2047120	NM_000890.5(KCNJ5):c.628A>T (p.Met210Leu)	KCNJ5	Uncertain significance	criteria provided, multiple submitters, no conflicts
2163554	NM_000890.5(KCNJ5):c.796G>A (p.Asp266Asn)	KCNJ5	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 8 · Orphanet: 4 · 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
KCNJ5	Limited	Autosomal dominant	long QT syndrome 13	8

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
KCNJ5	Orphanet:101016	Romano-Ward syndrome
KCNJ5	Orphanet:251274	Familial hyperaldosteronism type III
KCNJ5	Orphanet:334	Hereditary atrial fibrillation
KCNJ5	Orphanet:37553	Andersen-Tawil 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
KCNJ5	HGNC:6266	ENSG00000120457	P48544	G protein-activated inward rectifier potassium channel 4	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
KCNJ5	G protein-activated inward rectifier potassium channel 4	Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow into the cell rather than out of it.

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)
KCNJ5	Ion channel	yes		K_chnl_inward-rec_Kir3.4, K_chnl_inward-rec_Kir_cyto, Ig_E-set

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
adrenal cortex	1
buccal mucosa cell	1
endothelial cell	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
KCNJ5	175	broad	marker	buccal mucosa cell, endothelial cell, adrenal cortex

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
KCNJ5	1,147

Structural data

PDB: 0 · AlphaFold-only: 1 · No structure: 0

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
KCNJ5	P48544	82.01

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 11. 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
G protein gated Potassium channels	1	1142.0×	0.005	KCNJ5
Inwardly rectifying K+ channels	1	713.8×	0.005	KCNJ5
Activation of GABAB receptors	1	601.0×	0.005	KCNJ5
GABA B receptor activation	1	543.8×	0.005	KCNJ5
Activation of G protein gated Potassium channels	1	393.8×	0.005	KCNJ5
Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits	1	393.8×	0.005	KCNJ5
GABA receptor activation	1	317.2×	0.005	KCNJ5
Potassium Channels	1	134.3×	0.010	KCNJ5
Neurotransmitter receptors and postsynaptic signal transmission	1	100.2×	0.012	KCNJ5
Transmission across Chemical Synapses	1	76.1×	0.014	KCNJ5
Neuronal System	1	44.3×	0.023	KCNJ5

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
ventricular cardiac muscle cell membrane repolarization	1	5617.3×	0.001	KCNJ5
membrane repolarization during atrial cardiac muscle cell action potential	1	2808.7×	0.001	KCNJ5
regulation of monoatomic ion transmembrane transport	1	732.7×	0.003	KCNJ5
regulation of heart rate by cardiac conduction	1	374.5×	0.004	KCNJ5
potassium ion import across plasma membrane	1	366.4×	0.004	KCNJ5
potassium ion transport	1	191.5×	0.006	KCNJ5
potassium ion transmembrane transport	1	135.9×	0.007	KCNJ5

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
KCNJ5	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
KCNJ5	32	Binding:32

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	KCNJ5
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)
KCNJ5	32	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.