Atrial fibrillation, familial, 10

Summary

Atrial fibrillation, familial, 10 (MONDO:0013530) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 253

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	atrial fibrillation, familial, 10
Mondo ID	MONDO:0013530
OMIM	614022
UMLS	C3151464
MedGen	462814
GARD	0015745
Is cancer (heuristic)	no

Also known as: ATFB10 · atrial fibrillation, familial, 10 · atrial fibrillation, familial, type 10 · familial atrial fibrillation caused by mutation in SCN5A · SCN5A familial atrial fibrillation

Data availability: 253 ClinVar variants.

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, 10

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, 9, 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

253 retrieved; paginated sample, class counts are floors:

161 uncertain significance, 54 conflicting classifications of pathogenicity, 16 pathogenic/likely pathogenic, 8 benign/likely benign, 6 likely benign, 6 pathogenic, 2 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
201438	NM_000335.5(SCN5A):c.664C>T (p.Arg222Ter)	SCN5A	Pathogenic	criteria provided, multiple submitters, no conflicts
201508	NM_000335.5(SCN5A):c.4242+1G>C	SCN5A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
201560	NM_000335.5(SCN5A):c.2550_2551dup (p.Phe851fs)	SCN5A	Pathogenic	criteria provided, multiple submitters, no conflicts
201572	NM_000335.5(SCN5A):c.4844TCT[1] (p.Phe1616del)	SCN5A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
39444	NM_000335.5(SCN5A):c.665G>A (p.Arg222Gln)	SCN5A	Pathogenic	criteria provided, multiple submitters, no conflicts
406415	NM_000335.5(SCN5A):c.5414_5417del (p.Thr1805fs)	SCN5A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
67633	NM_000335.5(SCN5A):c.1099C>T (p.Arg367Cys)	SCN5A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
67639	NM_000335.5(SCN5A):c.1127G>A (p.Arg376His)	SCN5A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
67753	NM_000335.5(SCN5A):c.2729C>T (p.Ser910Leu)	SCN5A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
67778	NM_000335.5(SCN5A):c.310C>T (p.Arg104Trp)	SCN5A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
67807	NM_000335.5(SCN5A):c.361C>T (p.Arg121Trp)	SCN5A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
67838	NM_000335.5(SCN5A):c.3953G>T (p.Gly1318Val)	SCN5A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
67932	NM_000335.5(SCN5A):c.4856C>T (p.Thr1619Met)	SCN5A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
67967	NM_000335.5(SCN5A):c.5224G>A (p.Gly1742Arg)	SCN5A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
68032	NM_000335.5(SCN5A):c.673C>T (p.Arg225Trp)	SCN5A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
9374	NM_000335.5(SCN5A):c.4864C>T (p.Arg1622Ter)	SCN5A	Pathogenic	criteria provided, multiple submitters, no conflicts
9377	NM_000335.5(SCN5A):c.5347G>A (p.Glu1783Lys)	SCN5A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
9383	NM_000335.5(SCN5A):c.5126C>T (p.Ser1709Leu)	SCN5A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
9385	NM_000335.5(SCN5A):c.4780G>A (p.Asp1594Asn)	SCN5A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
9395	NM_000335.5(SCN5A):c.4219G>A (p.Gly1407Arg)	SCN5A	Pathogenic	criteria provided, multiple submitters, no conflicts
9401	NM_000335.5(SCN5A):c.3820G>A (p.Asp1274Asn)	SCN5A	Pathogenic	criteria provided, multiple submitters, no conflicts
9406	NM_000335.5(SCN5A):c.4780G>C (p.Asp1594His)	SCN5A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3252218	NM_000335.5(SCN5A):c.2425_2426del (p.Ser809fs)	SCN5A	Likely pathogenic	criteria provided, multiple submitters, no conflicts
3383167	NM_000335.5(SCN5A):c.3741T>G (p.Tyr1247Ter)	SCN5A	Likely pathogenic	criteria provided, single submitter
520458	NM_000335.5(SCN5A):c.3080G>A (p.Arg1027Gln)	LOC110121269	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
532068	NM_000335.5(SCN5A):c.3301G>A (p.Ala1101Thr)	LOC110121269	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
67771	NM_000335.5(SCN5A):c.2989G>A (p.Ala997Thr)	LOC110121269	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
67774	NM_000335.5(SCN5A):c.3047C>T (p.Thr1016Met)	LOC110121269	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
67779	NM_000335.5(SCN5A):c.3118G>A (p.Gly1040Arg)	LOC110121269	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
67782	NM_000335.5(SCN5A):c.3206C>T (p.Thr1069Met)	LOC110121269	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 8 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SCN5A	Orphanet:101016	Romano-Ward syndrome
SCN5A	Orphanet:130	Brugada syndrome
SCN5A	Orphanet:1344	Isolated atrial standstill
SCN5A	Orphanet:154	Familial isolated dilated cardiomyopathy
SCN5A	Orphanet:166282	Hereditary sick sinus syndrome
SCN5A	Orphanet:228140	Idiopathic ventricular fibrillation
SCN5A	Orphanet:334	Hereditary atrial fibrillation
SCN5A	Orphanet:871	Hereditary progressive cardiac conduction defect

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
SCN5A	HGNC:10593	ENSG00000183873	Q14524	Sodium channel protein type 5 subunit alpha	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SCN5A	Sodium channel protein type 5 subunit alpha	Pore-forming subunit of Nav1.5, a voltage-gated sodium (Nav) channel that directly mediates the depolarizing phase of action potentials in excitable membranes.

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)
SCN5A	Ion channel	yes		Na_channel_asu, Ion_trans_dom, Na_channel_a5su

Expression context

Cohort genes with no expression data: 0.

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
apex of heart	1
cardiac ventricle	1
heart left ventricle	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SCN5A	161	broad	yes	apex of heart, heart left ventricle, cardiac ventricle

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SCN5A	2,090

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SCN5A	Q14524	16

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 8. 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
Interaction between L1 and Ankyrins	1	368.4×	0.012	SCN5A
Phase 0 - rapid depolarisation	1	346.1×	0.012	SCN5A
L1CAM interactions	1	120.2×	0.018	SCN5A
Cardiac conduction	1	108.8×	0.018	SCN5A
Muscle contraction	1	77.2×	0.021	SCN5A
Axon guidance	1	45.1×	0.027	SCN5A
Nervous system development	1	42.9×	0.027	SCN5A
Developmental Biology	1	14.5×	0.069	SCN5A

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
bundle of His cell action potential	1	8426.0×	0.001	SCN5A
AV node cell to bundle of His cell communication	1	8426.0×	0.001	SCN5A
membrane depolarization during Purkinje myocyte cell action potential	1	5617.3×	0.001	SCN5A
membrane depolarization during bundle of His cell action potential	1	5617.3×	0.001	SCN5A
membrane depolarization during atrial cardiac muscle cell action potential	1	5617.3×	0.001	SCN5A
AV node cell action potential	1	4213.0×	0.001	SCN5A
membrane depolarization during AV node cell action potential	1	3370.4×	0.001	SCN5A
membrane depolarization during SA node cell action potential	1	3370.4×	0.001	SCN5A
regulation of ventricular cardiac muscle cell membrane depolarization	1	2808.7×	0.001	SCN5A
SA node cell action potential	1	2808.7×	0.001	SCN5A
cardiac ventricle development	1	2407.4×	0.001	SCN5A
response to denervation involved in regulation of muscle adaptation	1	2407.4×	0.001	SCN5A
regulation of atrial cardiac muscle cell membrane repolarization	1	2407.4×	0.001	SCN5A
brainstem development	1	2106.5×	0.001	SCN5A
positive regulation of action potential	1	2106.5×	0.001	SCN5A
regulation of atrial cardiac muscle cell membrane depolarization	1	1872.4×	0.001	SCN5A
membrane depolarization during action potential	1	1685.2×	0.001	SCN5A
atrial cardiac muscle cell action potential	1	1685.2×	0.001	SCN5A
membrane depolarization during cardiac muscle cell action potential	1	1404.3×	0.001	SCN5A
regulation of cardiac muscle cell contraction	1	1123.5×	0.002	SCN5A
cardiac conduction system development	1	1053.2×	0.002	SCN5A
regulation of sodium ion transmembrane transport	1	1053.2×	0.002	SCN5A
telencephalon development	1	991.3×	0.002	SCN5A
ventricular cardiac muscle cell action potential	1	991.3×	0.002	SCN5A
positive regulation of sodium ion transport	1	842.6×	0.002	SCN5A
regulation of ventricular cardiac muscle cell membrane repolarization	1	842.6×	0.002	SCN5A
cardiac muscle cell action potential involved in contraction	1	702.2×	0.002	SCN5A
membrane depolarization	1	510.7×	0.003	SCN5A
regulation of heart rate	1	468.1×	0.003	SCN5A
cardiac muscle contraction	1	401.2×	0.003	SCN5A

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
SCN5A	BEPRIDIL

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SCN5A	108	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
BEPRIDIL	4	SCN5A
CANDESARTAN CILEXETIL	4	SCN5A
TELMISARTAN	4	SCN5A
CARBAMAZEPINE	4	SCN5A
DIBUCAINE	4	SCN5A
IMIPRAMINE	4	SCN5A
DROPERIDOL	4	SCN5A
PONATINIB	4	SCN5A
DULOXETINE	4	SCN5A
PALONOSETRON	4	SCN5A
VILANTEROL	4	SCN5A
MEXILETINE HYDROCHLORIDE	4	SCN5A
UNOPROSTONE ISOPROPYL	4	SCN5A
LURASIDONE	4	SCN5A
LETERMOVIR	4	SCN5A
SERTINDOLE	4	SCN5A
FEDRATINIB	4	SCN5A
QUINIDINE	4	SCN5A
DARUNAVIR	4	SCN5A
DARIFENACIN	4	SCN5A
BENZONATATE	4	SCN5A
TOLTERODINE	4	SCN5A
RANOLAZINE	4	SCN5A
PIMOZIDE	4	SCN5A
NIMODIPINE	4	SCN5A
FELODIPINE	4	SCN5A
NICARDIPINE	4	SCN5A
AMLODIPINE	4	SCN5A
PHENYTOIN	4	SCN5A
PALIPERIDONE	4	SCN5A

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
SCN5A	594	Binding:380, Functional:98, ADMET:72, Toxicity:43, Unclassified:1

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
SCN5A	594

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

30 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)
BEPRIDIL	4	SCN5A
CANDESARTAN CILEXETIL	4	SCN5A
TELMISARTAN	4	SCN5A
CARBAMAZEPINE	4	SCN5A
DIBUCAINE	4	SCN5A
IMIPRAMINE	4	SCN5A
DROPERIDOL	4	SCN5A
PONATINIB	4	SCN5A
DULOXETINE	4	SCN5A
PALONOSETRON	4	SCN5A
VILANTEROL	4	SCN5A
MEXILETINE HYDROCHLORIDE	4	SCN5A
UNOPROSTONE ISOPROPYL	4	SCN5A
LURASIDONE	4	SCN5A
LETERMOVIR	4	SCN5A
SERTINDOLE	4	SCN5A
FEDRATINIB	4	SCN5A
QUINIDINE	4	SCN5A
DARUNAVIR	4	SCN5A
DARIFENACIN	4	SCN5A
BENZONATATE	4	SCN5A
TOLTERODINE	4	SCN5A
RANOLAZINE	4	SCN5A
PIMOZIDE	4	SCN5A
NIMODIPINE	4	SCN5A
FELODIPINE	4	SCN5A
NICARDIPINE	4	SCN5A
AMLODIPINE	4	SCN5A
PHENYTOIN	4	SCN5A
PALIPERIDONE	4	SCN5A

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	SCN5A
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.