Atrial fibrillation, familial, 7

Summary

Atrial fibrillation, familial, 7 (MONDO:0012828) is a disease with 2 cohort genes.

At a glance

• Cohort genes: 2
• ClinVar variants: 524

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	atrial fibrillation, familial, 7
Mondo ID	MONDO:0012828
MeSH	C567389
OMIM	612240
UMLS	C2677106
MedGen	393658
GARD	0015545
Is cancer (heuristic)	no

Also known as: ATFB7 · atrial fibrillation, familial, 7 · atrial fibrillation, familial, type 7 · familial atrial fibrillation caused by mutation in KCNA5 · KCNA5 familial atrial fibrillation

Data availability: 524 ClinVar variants · 3 GenCC gene-disease records.

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, 7

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, 8, atrial fibrillation, familial, 9, 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

524 retrieved; paginated sample, class counts are floors:

365 uncertain significance, 108 likely benign, 29 conflicting classifications of pathogenicity, 11 benign, 8 benign/likely benign, 3 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
127137	NM_002234.4(KCNA5):c.143A>G (p.Glu48Gly)	KCNA5	Pathogenic	no assertion criteria provided
13469	NM_002234.4(KCNA5):c.1123G>T (p.Glu375Ter)	KCNA5	Pathogenic	no assertion criteria provided
13472	NM_002234.4(KCNA5):c.1828G>A (p.Glu610Lys)	KCNA5	Pathogenic	no assertion criteria provided
1275636	NM_002234.4(KCNA5):c.309C>T (p.Gly103=)	KCNA5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
13471	NM_002234.4(KCNA5):c.1727C>T (p.Ala576Val)	KCNA5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
191456	NM_002234.4(KCNA5):c.251A>C (p.Glu84Ala)	KCNA5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
191457	NM_002234.4(KCNA5):c.464A>G (p.Tyr155Cys)	KCNA5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
191459	NM_002234.4(KCNA5):c.633G>C (p.Glu211Asp)	KCNA5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
191460	NM_002234.4(KCNA5):c.634C>T (p.Arg212Cys)	KCNA5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
191462	NM_002234.4(KCNA5):c.898G>A (p.Gly300Ser)	KCNA5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
191463	NM_002234.4(KCNA5):c.919C>T (p.Pro307Ser)	KCNA5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
191573	NM_002234.4(KCNA5):c.1733G>A (p.Arg578Lys)	KCNA5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2515752	NM_002234.4(KCNA5):c.521G>C (p.Gly174Ala)	KCNA5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
309331	NM_002234.4(KCNA5):c.36T>C (p.Gly12=)	KCNA5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
309338	NM_002234.4(KCNA5):c.1210C>T (p.Leu404=)	KCNA5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
309339	NM_002234.4(KCNA5):c.1329C>T (p.Ile443=)	KCNA5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
469583	NM_002234.4(KCNA5):c.1327A>G (p.Ile443Val)	KCNA5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
469585	NM_002234.4(KCNA5):c.1539C>T (p.Pro513=)	KCNA5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
469586	NM_002234.4(KCNA5):c.1595C>T (p.Pro532Leu)	KCNA5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
469587	NM_002234.4(KCNA5):c.1672G>A (p.Gly558Arg)	KCNA5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
469594	NM_002234.4(KCNA5):c.544G>A (p.Gly182Arg)	KCNA5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
469595	NM_002234.4(KCNA5):c.570C>T (p.Asn190=)	KCNA5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
469596	NM_002234.4(KCNA5):c.615G>C (p.Leu205=)	KCNA5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
469598	NM_002234.4(KCNA5):c.79G>A (p.Gly27Ser)	KCNA5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
537308	NM_002234.4(KCNA5):c.1790G>A (p.Arg597Gln)	KCNA5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
537316	NM_002234.4(KCNA5):c.213_245del (p.Asp72_Pro82del)	KCNA5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
579528	NM_002234.4(KCNA5):c.797C>T (p.Thr266Ile)	KCNA5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
596455	NM_002234.4(KCNA5):c.859_860delinsTT (p.Ala287Leu)	KCNA5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
657442	NM_002234.4(KCNA5):c.622G>T (p.Glu208Ter)	KCNA5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
723488	NM_002234.4(KCNA5):c.859G>T (p.Ala287Ser)	KCNA5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · Orphanet: 6 · 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
KCNA5	Moderate	Autosomal dominant	atrial fibrillation, familial, 7	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
KCNA5	Orphanet:334	Hereditary atrial fibrillation
KCNA1	Orphanet:1934	Early infantile developmental and epileptic encephalopathy
KCNA1	Orphanet:199326	Isolated autosomal dominant hypomagnesemia, Glaudemans type
KCNA1	Orphanet:37612	Episodic ataxia type 1
KCNA1	Orphanet:972	Hereditary continuous muscle fiber activity
KCNA1	Orphanet:98809	Paroxysmal kinesigenic dyskinesia

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
KCNA5	HGNC:6224	ENSG00000130037	P22460	Potassium voltage-gated channel subfamily A member 5	gencc,clinvar
KCNA1	HGNC:6218	ENSG00000111262	Q09470	Potassium voltage-gated channel subfamily A member 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
KCNA5	Potassium voltage-gated channel subfamily A member 5	Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes.
KCNA1	Potassium voltage-gated channel subfamily A member 1	Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes, primarily in the brain and the central nervous system, but also in the kidney.

Protein-family classification

Druggable: 2 · 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	2	111.5×	8e-05

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
KCNA5	Ion channel	yes		BTB/POZ_dom, T1-type_BTB, K_chnl_volt-dep_Kv
KCNA1	Ion channel	yes		BTB/POZ_dom, T1-type_BTB, K_chnl_volt-dep_Kv

Expression context

Cohort genes with no expression data: 0.

2 cohort genes 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
blood vessel layer	1
cardiac atrium	1
cardiac muscle of right atrium	1
Brodmann (1909) area 23	1
endothelial cell	1
middle temporal gyrus	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
KCNA5	179	broad	marker	cardiac muscle of right atrium, blood vessel layer, cardiac atrium
KCNA1	151	broad	marker	endothelial cell, Brodmann (1909) area 23, middle temporal gyrus

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
KCNA1	3,157
KCNA5	2,288

Structural data

PDB: 0 · AlphaFold-only: 2 · No structure: 0

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
KCNA1	Q09470	78.74
KCNA5	P22460	72.64

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 6. Enrichment computed across 2 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Voltage gated Potassium channels	2	243.0×	1e-04	KCNA5, KCNA1
Potassium Channels	2	134.3×	2e-04	KCNA5, KCNA1
Neuronal System	2	44.3×	0.001	KCNA5, KCNA1
Phase 3 - rapid repolarisation	1	571.0×	0.003	KCNA5
Cardiac conduction	1	54.4×	0.022	KCNA5
Muscle contraction	1	38.6×	0.026	KCNA5

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
action potential	2	358.6×	3e-04	KCNA5, KCNA1
regulation of membrane potential	2	230.8×	3e-04	KCNA5, KCNA1
potassium ion transmembrane transport	2	135.9×	6e-04	KCNA5, KCNA1
protein homooligomerization	2	122.1×	6e-04	KCNA5, KCNA1
membrane repolarization during bundle of His cell action potential	1	4213.0×	0.001	KCNA5
membrane repolarization during SA node cell action potential	1	4213.0×	0.001	KCNA5
cell communication by electrical coupling	1	2106.5×	0.002	KCNA1
detection of mechanical stimulus involved in sensory perception of touch	1	2106.5×	0.002	KCNA1
membrane repolarization during atrial cardiac muscle cell action potential	1	1404.3×	0.003	KCNA5
neuronal signal transduction	1	1203.7×	0.003	KCNA1
regulation of atrial cardiac muscle cell membrane repolarization	1	1203.7×	0.003	KCNA5
cellular response to magnesium ion	1	1203.7×	0.003	KCNA1
magnesium ion homeostasis	1	936.2×	0.003	KCNA1
membrane hyperpolarization	1	936.2×	0.003	KCNA5
regulation of muscle contraction	1	842.6×	0.003	KCNA1
membrane repolarization during action potential	1	842.6×	0.003	KCNA1
atrial cardiac muscle cell action potential	1	842.6×	0.003	KCNA5
positive regulation of myoblast proliferation	1	702.2×	0.003	KCNA5
negative regulation of cytosolic calcium ion concentration	1	648.1×	0.003	KCNA5
startle response	1	561.7×	0.003	KCNA1
detection of mechanical stimulus involved in sensory perception of pain	1	561.7×	0.003	KCNA1
response to hyperoxia	1	561.7×	0.003	KCNA5
potassium ion export across plasma membrane	1	526.6×	0.003	KCNA5
regulation of vasoconstriction	1	401.2×	0.004	KCNA5
potassium ion homeostasis	1	383.0×	0.004	KCNA5
neuromuscular process	1	263.3×	0.005	KCNA1
neuronal action potential	1	240.7×	0.006	KCNA1
response to hydrogen peroxide	1	234.1×	0.006	KCNA5
positive regulation of G1/S transition of mitotic cell cycle	1	200.6×	0.006	KCNA5
regulation of insulin secretion	1	195.9×	0.006	KCNA5

Therapeutics

Drug target analysis

Approved (phase 4): 2 · Phase ≥3: 2 · Phased (≥1): 2 · Undrugged: 0

Druggability breadth: 2 of 2 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
KCNA5	DRONEDARONE HYDROCHLORIDE
KCNA1	NIFEDIPINE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
KCNA5	8	4
KCNA1	5	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
DRONEDARONE HYDROCHLORIDE	4	KCNA5
SERTINDOLE	4	KCNA5
QUINIDINE	4	KCNA5
NIFEDIPINE	4	KCNA1, KCNA5
VERNAKALANT HYDROCHLORIDE	4	KCNA5
FLECAINIDE	4	KCNA5
DALFAMPRIDINE	4	KCNA1
CAPSAICIN	4	KCNA1
CORTISONE	3	KCNA1
BMS-919373	2	KCNA5
TETRYLAMMONIUM	2	KCNA1
BMS-394136	1	KCNA5

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
KCNA5	152	Binding:130, Functional:14, ADMET:5, Toxicity:3
KCNA1	59	Binding:52, Functional: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
KCNA5	152

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

12 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)
DRONEDARONE HYDROCHLORIDE	4	KCNA5
SERTINDOLE	4	KCNA5
QUINIDINE	4	KCNA5
NIFEDIPINE	4	KCNA1, KCNA5
VERNAKALANT HYDROCHLORIDE	4	KCNA5
FLECAINIDE	4	KCNA5
DALFAMPRIDINE	4	KCNA1
CAPSAICIN	4	KCNA1
CORTISONE	3	KCNA1
BMS-919373	2	KCNA5
TETRYLAMMONIUM	2	KCNA1
BMS-394136	1	KCNA5

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	2	KCNA5, KCNA1
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.