Atrial fibrillation, familial, 9

Summary

Atrial fibrillation, familial, 9 (MONDO:0013513) is a disease caused by KCNJ2 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: KCNJ2 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 125

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	atrial fibrillation, familial, 9
Mondo ID	MONDO:0013513
OMIM	613980
UMLS	C3151431
MedGen	462781
GARD	0015737
Is cancer (heuristic)	no

Also known as: ATFB9 · atrial fibrillation, familial, 9 · atrial fibrillation, familial, type 9 · familial atrial fibrillation caused by mutation in KCNJ2 · KCNJ2 familial atrial fibrillation

Data availability: 125 ClinVar variants · 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by body system or component › cardiovascular disorder › heart disorder › cardiac rhythm disease › atrial fibrillation › familial atrial fibrillation › atrial fibrillation, familial, 9

Related subtypes (17): atrial fibrillation, familial, 3, atrial fibrillation, familial, 1, atrial fibrillation, familial, 2, atrial fibrillation, familial, 4, atrial fibrillation, familial, 5, atrial fibrillation, familial, 6, atrial fibrillation, familial, 7, atrial fibrillation, familial, 8, atrial fibrillation, familial, 10, atrial fibrillation, familial, 11, atrial fibrillation, familial, 12, atrial fibrillation, familial, 13, atrial fibrillation, familial, 14, atrial fibrillation, familial, 15, atrial fibrillation, familial, 18, atrial fibrillation, familial, 17, atrial fibrillation, familial, 16

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

125 retrieved; paginated sample, class counts are floors:

61 uncertain significance, 39 conflicting classifications of pathogenicity, 14 benign, 6 benign/likely benign, 3 pathogenic, 1 likely pathogenic, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
67574	NM_000891.3(KCNJ2):c.431G>A (p.Gly144Asp)	KCNJ2	Pathogenic	criteria provided, multiple submitters, no conflicts
67585	NM_000891.3(KCNJ2):c.653G>A (p.Arg218Gln)	KCNJ2	Pathogenic	criteria provided, multiple submitters, no conflicts
8919	NM_000891.3(KCNJ2):c.652C>T (p.Arg218Trp)	KCNJ2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
8923	NM_000891.3(KCNJ2):c.199C>T (p.Arg67Trp)	KCNJ2	Pathogenic	criteria provided, multiple submitters, no conflicts
689769	NM_000891.3(KCNJ2):c.896A>G (p.Glu299Gly)	KCNJ2	Likely pathogenic	criteria provided, single submitter
1230618	NM_000891.3(KCNJ2):c.*10del	KCNJ2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
190804	NM_000891.3(KCNJ2):c.1229A>G (p.Asn410Ser)	KCNJ2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
190818	NM_000891.3(KCNJ2):c.1045G>A (p.Glu349Lys)	KCNJ2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
190819	NM_000891.3(KCNJ2):c.1244C>T (p.Pro415Leu)	KCNJ2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
281601	NM_000891.3(KCNJ2):c.616G>A (p.Gly206Ser)	KCNJ2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
30121	NM_000891.3(KCNJ2):c.277G>A (p.Val93Ile)	KCNJ2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
324822	NM_000891.3(KCNJ2):c.-349C>A	KCNJ2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
324823	NM_000891.3(KCNJ2):c.-314T>C	KCNJ2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
324825	NM_000891.3(KCNJ2):c.-228C>T	KCNJ2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
324826	NM_000891.3(KCNJ2):c.-195C>G	KCNJ2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
324830	NM_000891.3(KCNJ2):c.119G>A (p.Arg40Gln)	KCNJ2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
324832	NM_000891.3(KCNJ2):c.531C>T (p.Gly177=)	KCNJ2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
324833	NM_000891.3(KCNJ2):c.*79C>T	KCNJ2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
324837	NM_000891.3(KCNJ2):c.*211T>C	KCNJ2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
324845	NM_000891.3(KCNJ2):c.*732T>G	KCNJ2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
324846	NM_000891.3(KCNJ2):c.*766C>T	KCNJ2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
324848	NM_000891.3(KCNJ2):c.*996C>T	KCNJ2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
324869	NM_000891.3(KCNJ2):c.*1815G>A	KCNJ2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
324871	NM_000891.3(KCNJ2):c.*2262C>T	KCNJ2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
324884	NM_000891.3(KCNJ2):c.*2754T>C	KCNJ2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
324888	NM_000891.3(KCNJ2):c.*2893C>T	KCNJ2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
324890	NM_000891.3(KCNJ2):c.*3163T>A	KCNJ2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
324891	NM_000891.3(KCNJ2):c.*3208A>G	KCNJ2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
378005	NM_000891.3(KCNJ2):c.867C>T (p.Asn289=)	KCNJ2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
378007	NM_000891.3(KCNJ2):c.1254C>G (p.Pro418=)	KCNJ2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 15 · 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
KCNJ2	Strong	Autosomal dominant	atrial fibrillation, familial, 9	15

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
KCNJ2	Orphanet:334	Hereditary atrial fibrillation
KCNJ2	Orphanet:37553	Andersen-Tawil syndrome
KCNJ2	Orphanet:51083	Congenital short QT 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
KCNJ2	HGNC:6263	ENSG00000123700	P63252	Inward rectifier potassium channel 2	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
KCNJ2	Inward rectifier potassium channel 2	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)
KCNJ2	Ion channel	yes		K_chnl_inward-rec_Kir2.1, K_chnl_inward-rec_Kir_cyto, K_chnl_inward-rec_Kir_N

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
dorsal motor nucleus of vagus nerve	1
inferior vagus X ganglion	1
skeletal muscle tissue of rectus abdominis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
KCNJ2	256	ubiquitous	marker	inferior vagus X ganglion, skeletal muscle tissue of rectus abdominis, dorsal motor nucleus of vagus nerve

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
KCNJ2	65

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
KCNJ2	P63252	3

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 18. 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
Sensory perception of sour taste	1	5710.0×	0.003	KCNJ2
Classical Kir channels	1	2855.0×	0.003	KCNJ2
G protein gated Potassium channels	1	1142.0×	0.005	KCNJ2
Inwardly rectifying K+ channels	1	713.8×	0.005	KCNJ2
Phase 4 - resting membrane potential	1	601.0×	0.005	KCNJ2
Activation of GABAB receptors	1	601.0×	0.005	KCNJ2
GABA B receptor activation	1	543.8×	0.005	KCNJ2
Activation of G protein gated Potassium channels	1	393.8×	0.005	KCNJ2
Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits	1	393.8×	0.005	KCNJ2
Sensory perception of taste	1	335.9×	0.005	KCNJ2
GABA receptor activation	1	317.2×	0.005	KCNJ2
Potassium Channels	1	134.3×	0.011	KCNJ2
Cardiac conduction	1	108.8×	0.013	KCNJ2
Neurotransmitter receptors and postsynaptic signal transmission	1	100.2×	0.013	KCNJ2
Sensory Perception	1	95.2×	0.013	KCNJ2
Muscle contraction	1	77.2×	0.014	KCNJ2
Transmission across Chemical Synapses	1	76.1×	0.014	KCNJ2
Neuronal System	1	44.3×	0.023	KCNJ2

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
regulation of skeletal muscle contraction via regulation of action potential	1	16852.0×	0.001	KCNJ2
relaxation of skeletal muscle	1	5617.3×	0.002	KCNJ2
membrane repolarization during action potential	1	1685.2×	0.002	KCNJ2
membrane repolarization during cardiac muscle cell action potential	1	1685.2×	0.002	KCNJ2
membrane depolarization during cardiac muscle cell action potential	1	1404.3×	0.002	KCNJ2
relaxation of cardiac muscle	1	1296.3×	0.002	KCNJ2
regulation of resting membrane potential	1	1296.3×	0.002	KCNJ2
regulation of membrane repolarization	1	1296.3×	0.002	KCNJ2
magnesium ion transport	1	1203.7×	0.002	KCNJ2
regulation of cardiac muscle cell contraction	1	1123.5×	0.002	KCNJ2
intracellular potassium ion homeostasis	1	991.3×	0.002	KCNJ2
positive regulation of potassium ion transmembrane transport	1	991.3×	0.002	KCNJ2
regulation of monoatomic ion transmembrane transport	1	732.7×	0.002	KCNJ2
cardiac muscle cell action potential involved in contraction	1	702.2×	0.002	KCNJ2
regulation of heart rate by cardiac conduction	1	374.5×	0.003	KCNJ2
potassium ion import across plasma membrane	1	366.4×	0.003	KCNJ2
protein homotetramerization	1	237.3×	0.005	KCNJ2
cellular response to mechanical stimulus	1	216.1×	0.005	KCNJ2
potassium ion transport	1	191.5×	0.005	KCNJ2
potassium ion transmembrane transport	1	135.9×	0.007	KCNJ2

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
KCNJ2	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
KCNJ2	31	Binding:23, ADMET:8

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	KCNJ2
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)
KCNJ2	31	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.