Atrial fibrillation, familial, 13

Summary

Atrial fibrillation, familial, 13 (MONDO:0014155) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 34

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	atrial fibrillation, familial, 13
Mondo ID	MONDO:0014155
OMIM	615377
UMLS	C3809311
MedGen	815641
GARD	0015954
Is cancer (heuristic)	no

Also known as: ATFB13 · atrial fibrillation, familial, 13 · atrial fibrillation, familial, type 13 · familial atrial fibrillation caused by mutation in SCN1B · SCN1B familial atrial fibrillation

Data availability: 34 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, 13

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, 10, atrial fibrillation, familial, 11, atrial fibrillation, familial, 12, 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

34 retrieved; paginated sample, class counts are floors:

20 uncertain significance, 8 conflicting classifications of pathogenicity, 3 benign/likely benign, 2 pathogenic/likely pathogenic, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
60767	NM_001037.5(SCN1B):c.254G>A (p.Arg85His)	SCN1B	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
9252	NM_001037.5(SCN1B):c.363C>G (p.Cys121Trp)	SCN1B	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1307910	NM_001037.5(SCN1B):c.448+201C>T	SCN1B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
190847	NM_001037.5(SCN1B):c.448+193G>A	SCN1B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
190860	NM_001037.5(SCN1B):c.266G>A (p.Arg89His)	SCN1B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
190870	NM_001037.5(SCN1B):c.38T>C (p.Leu13Pro)	SCN1B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
190874	NM_001037.5(SCN1B):c.590C>T (p.Ala197Val)	SCN1B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
190881	NM_001037.5(SCN1B):c.374G>A (p.Arg125His)	SCN1B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
375686	NM_001037.5(SCN1B):c.373C>T (p.Arg125Cys)	SCN1B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
9254	NM_001037.5(SCN1B):c.448+88G>A	SCN1B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1410718	NM_001037.5(SCN1B):c.560C>A (p.Ala187Asp)	SCN1B	Uncertain significance	criteria provided, multiple submitters, no conflicts
1677376	NM_001037.5(SCN1B):c.584A>C (p.Glu195Ala)	SCN1B	Uncertain significance	criteria provided, multiple submitters, no conflicts
190857	NM_001037.5(SCN1B):c.134G>A (p.Arg45His)	SCN1B	Uncertain significance	criteria provided, multiple submitters, no conflicts
190880	NM_001037.5(SCN1B):c.82A>G (p.Thr28Ala)	SCN1B	Uncertain significance	criteria provided, multiple submitters, no conflicts
3019895	NM_001037.5(SCN1B):c.77C>T (p.Ser26Leu)	SCN1B	Uncertain significance	criteria provided, multiple submitters, no conflicts
328832	NM_001037.5(SCN1B):c.-88A>C	SCN1B	Uncertain significance	criteria provided, multiple submitters, no conflicts
3382919	NM_001037.5(SCN1B):c.419AGA[1] (p.Lys141del)	SCN1B	Uncertain significance	criteria provided, single submitter
3583635	NM_001037.5(SCN1B):c.463G>T (p.Ala155Ser)	SCN1B	Uncertain significance	criteria provided, multiple submitters, no conflicts
3892361	NM_001037.5(SCN1B):c.448+241C>T	SCN1B	Uncertain significance	criteria provided, single submitter
406503	NM_001037.5(SCN1B):c.448+123C>T	SCN1B	Uncertain significance	criteria provided, multiple submitters, no conflicts
436652	NM_001037.5(SCN1B):c.133C>T (p.Arg45Cys)	SCN1B	Uncertain significance	criteria provided, multiple submitters, no conflicts
450936	NM_001037.5(SCN1B):c.448+103C>T	SCN1B	Uncertain significance	criteria provided, multiple submitters, no conflicts
470182	NM_001037.5(SCN1B):c.448+192C>T	SCN1B	Uncertain significance	criteria provided, multiple submitters, no conflicts
537730	NM_001037.5(SCN1B):c.415G>A (p.Val139Ile)	SCN1B	Uncertain significance	criteria provided, multiple submitters, no conflicts
565664	NM_001037.5(SCN1B):c.158C>A (p.Thr53Asn)	SCN1B	Uncertain significance	criteria provided, multiple submitters, no conflicts
60768	NM_001037.5(SCN1B):c.457G>A (p.Asp153Asn)	SCN1B	Uncertain significance	criteria provided, multiple submitters, no conflicts
619998	NM_001037.5(SCN1B):c.347C>T (p.Ser116Leu)	SCN1B	Uncertain significance	criteria provided, multiple submitters, no conflicts
852686	NM_001037.5(SCN1B):c.250G>A (p.Glu84Lys)	SCN1B	Uncertain significance	criteria provided, multiple submitters, no conflicts
889374	NM_001037.5(SCN1B):c.*305C>T	SCN1B	Uncertain significance	criteria provided, multiple submitters, no conflicts
889376	NM_001037.5(SCN1B):c.*378G>A	SCN1B	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 15 · 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
SCN1B	Limited	Unknown	atrial fibrillation, familial, 13	15

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SCN1B	Orphanet:130	Brugada syndrome
SCN1B	Orphanet:1934	Early infantile developmental and epileptic encephalopathy
SCN1B	Orphanet:33069	Dravet syndrome
SCN1B	Orphanet:334	Hereditary atrial fibrillation
SCN1B	Orphanet:36387	Genetic epilepsy with febrile seizure plus
SCN1B	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
SCN1B	HGNC:10586	ENSG00000105711	Q07699	Sodium channel regulatory subunit beta-1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SCN1B	Sodium channel regulatory subunit beta-1	Regulatory subunit of multiple voltage-gated sodium (Nav) channels directly mediating the depolarization of 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
Antibody/Immunoglobulin	1	29.2×	0.034

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SCN1B	Antibody/Immunoglobulin	yes		Ig_V-set, Ig-like_fold, Na_channel_b1/b3

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
cerebellum	1
primary visual cortex	1
right hemisphere of cerebellum	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SCN1B	133	ubiquitous	marker	primary visual cortex, right hemisphere of cerebellum, cerebellum

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SCN1B	1,328

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SCN1B	Q07699	39

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
Interaction between L1 and Ankyrins	1	368.4×	0.010	SCN1B
Phase 0 - rapid depolarisation	1	346.1×	0.010	SCN1B
Sensory perception of taste	1	335.9×	0.010	SCN1B
Sensory perception of sweet, bitter, and umami (glutamate) taste	1	278.5×	0.010	SCN1B
L1CAM interactions	1	120.2×	0.017	SCN1B
Cardiac conduction	1	108.8×	0.017	SCN1B
Sensory Perception	1	95.2×	0.017	SCN1B
Muscle contraction	1	77.2×	0.018	SCN1B
Axon guidance	1	45.1×	0.026	SCN1B
Nervous system development	1	42.9×	0.026	SCN1B
Developmental Biology	1	14.5×	0.069	SCN1B

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
corticospinal neuron axon guidance	1	16852.0×	0.001	SCN1B
membrane depolarization during Purkinje myocyte cell action potential	1	5617.3×	0.001	SCN1B
positive regulation of voltage-gated sodium channel activity	1	5617.3×	0.001	SCN1B
regulation of atrial cardiac muscle cell membrane depolarization	1	1872.4×	0.002	SCN1B
cardiac conduction	1	1685.2×	0.002	SCN1B
membrane depolarization during action potential	1	1685.2×	0.002	SCN1B
locomotion	1	1532.0×	0.002	SCN1B
neuronal action potential propagation	1	1404.3×	0.002	SCN1B
membrane depolarization during cardiac muscle cell action potential	1	1404.3×	0.002	SCN1B
regulation of sodium ion transmembrane transport	1	1053.2×	0.002	SCN1B
positive regulation of sodium ion transport	1	842.6×	0.002	SCN1B
regulation of ventricular cardiac muscle cell membrane repolarization	1	842.6×	0.002	SCN1B
cardiac muscle cell action potential involved in contraction	1	702.2×	0.002	SCN1B
membrane depolarization	1	510.7×	0.003	SCN1B
cardiac muscle contraction	1	401.2×	0.003	SCN1B
regulation of heart rate by cardiac conduction	1	374.5×	0.003	SCN1B
sodium ion transmembrane transport	1	203.0×	0.006	SCN1B
positive regulation of neuron projection development	1	137.0×	0.008	SCN1B
axon guidance	1	90.6×	0.012	SCN1B
cell adhesion	1	37.5×	0.027	SCN1B

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · 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).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SCN1B	2	2

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
DS-1971	2	SCN1B
PF-05089771	2	SCN1B

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
SCN1B	15	Binding:7, ADMET:6, Toxicity:2

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

2 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)
DS-1971	2	SCN1B
PF-05089771	2	SCN1B

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	1	SCN1B
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.