Atrial fibrillation, familial, 14

Summary

Atrial fibrillation, familial, 14 (MONDO:0014156) is a disease with 2 cohort genes.

At a glance

• Cohort genes: 2
• ClinVar variants: 161

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	atrial fibrillation, familial, 14
Mondo ID	MONDO:0014156
OMIM	615378
UMLS	C3809312
MedGen	815642
GARD	0015955
Is cancer (heuristic)	no

Also known as: ATFB14 · atrial fibrillation, familial, 14 · atrial fibrillation, familial, type 14 · familial atrial fibrillation caused by mutation in SCN2B · SCN2B familial atrial fibrillation

Data availability: 161 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, 14

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, 13, 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

161 retrieved; paginated sample, class counts are floors:

77 uncertain significance, 66 likely benign, 13 conflicting classifications of pathogenicity, 3 benign/likely benign, 2 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1006173	NM_004588.5(SCN2B):c.5A>G (p.His2Arg)	SCN2B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1427799	NM_004588.5(SCN2B):c.343A>G (p.Arg115Gly)	SCN2B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1730893	NM_004588.5(SCN2B):c.338T>C (p.Met113Thr)	SCN2B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1749641	NM_004588.5(SCN2B):c.578C>T (p.Thr193Ile)	SCN2B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
191493	NM_004588.5(SCN2B):c.629C>T (p.Pro210Leu)	SCN2B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2496755	NM_004588.5(SCN2B):c.191C>T (p.Ser64Phe)	SCN2B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
408874	NM_004588.5(SCN2B):c.578C>G (p.Thr193Arg)	SCN2B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
408875	NM_004588.5(SCN2B):c.140G>A (p.Arg47His)	SCN2B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
422854	NM_004588.5(SCN2B):c.625_626delinsCC (p.Asn209Pro)	SCN2B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
60769	NM_004588.5(SCN2B):c.82C>T (p.Arg28Trp)	SCN2B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
60770	NM_004588.5(SCN2B):c.83G>A (p.Arg28Gln)	SCN2B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
935689	NM_004588.5(SCN2B):c.281G>A (p.Arg94Gln)	SCN2B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
947137	NM_004588.5(SCN2B):c.640G>A (p.Ala214Thr)	SCN2B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3244705	NC_000011.9:g.(?118007742)(119170491_?)dup	BCL9L	Uncertain significance	criteria provided, single submitter
1022738	NM_004588.5(SCN2B):c.237G>C (p.Met79Ile)	SCN2B	Uncertain significance	criteria provided, multiple submitters, no conflicts
1023340	NM_004588.5(SCN2B):c.412G>A (p.Gly138Ser)	SCN2B	Uncertain significance	criteria provided, multiple submitters, no conflicts
1059103	NM_004588.5(SCN2B):c.292C>T (p.Arg98Cys)	SCN2B	Uncertain significance	criteria provided, multiple submitters, no conflicts
1370529	NM_004588.5(SCN2B):c.295G>T (p.Val99Leu)	SCN2B	Uncertain significance	criteria provided, multiple submitters, no conflicts
1378025	NM_004588.5(SCN2B):c.622G>A (p.Gly208Ser)	SCN2B	Uncertain significance	criteria provided, multiple submitters, no conflicts
1396947	NM_004588.5(SCN2B):c.267C>G (p.Asn89Lys)	SCN2B	Uncertain significance	criteria provided, single submitter
1399650	NM_004588.5(SCN2B):c.299A>G (p.Glu100Gly)	SCN2B	Uncertain significance	criteria provided, multiple submitters, no conflicts
1403985	NM_004588.5(SCN2B):c.448+6G>C	SCN2B	Uncertain significance	criteria provided, single submitter
1411255	NC_000011.9:g.(?118047057)(118047146_?)del	SCN2B	Uncertain significance	criteria provided, single submitter
1413325	NM_004588.5(SCN2B):c.109A>G (p.Thr37Ala)	SCN2B	Uncertain significance	criteria provided, single submitter
1414774	NM_004588.5(SCN2B):c.152C>T (p.Thr51Ile)	SCN2B	Uncertain significance	criteria provided, single submitter
1439728	NM_004588.5(SCN2B):c.452C>A (p.Pro151His)	SCN2B	Uncertain significance	criteria provided, multiple submitters, no conflicts
1440200	NM_004588.5(SCN2B):c.344G>A (p.Arg115Lys)	SCN2B	Uncertain significance	criteria provided, single submitter
1445540	NM_004588.5(SCN2B):c.125A>G (p.Asn42Ser)	SCN2B	Uncertain significance	criteria provided, single submitter
1497551	NM_004588.5(SCN2B):c.388A>T (p.Met130Leu)	SCN2B	Uncertain significance	criteria provided, single submitter
1514438	NM_004588.5(SCN2B):c.236T>C (p.Met79Thr)	SCN2B	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 7 · Orphanet: 2 · 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
SCN2B	Moderate	Autosomal dominant	atrial fibrillation, familial, 14	7

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SCN2B	Orphanet:130	Brugada syndrome
SCN2B	Orphanet:334	Hereditary atrial fibrillation

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
SCN2B	HGNC:10589	ENSG00000149575	O60939	Sodium channel regulatory subunit beta-2	gencc,clinvar
BCL9L	HGNC:23688	ENSG00000186174	Q86UU0	B-cell CLL/lymphoma 9-like protein	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SCN2B	Sodium channel regulatory subunit beta-2	Regulatory subunit of multiple voltage-gated sodium (Nav) channels directly mediating the depolarization of excitable membranes.
BCL9L	B-cell CLL/lymphoma 9-like protein	Transcriptional regulator that acts as an activator.

Protein-family classification

Druggable: 1 · Difficult: 1 · Unknown: 0 · Druggable fraction: 0.5

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	14.6×	0.135
Transcription factor	1	4.1×	0.228

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SCN2B	Antibody/Immunoglobulin	yes		Myelin_P0-rel, Ig_sub, Ig-like_dom
BCL9L	Transcription factor	no		Znf_RING/FYVE/PHD, Bcl-9/Bcl-9l, BCL9_beta-catenin-bd_dom

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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
cerebellar cortex	1
lateral nuclear group of thalamus	1
middle temporal gyrus	1
granulocyte	1
right coronary artery	1
stromal cell of endometrium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SCN2B	182	broad	yes	middle temporal gyrus, lateral nuclear group of thalamus, cerebellar cortex
BCL9L	238	ubiquitous	marker	granulocyte, right coronary artery, stromal cell of endometrium

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SCN2B	1,808
BCL9L	879

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SCN2B	O60939	35
BCL9L	Q86UU0	3

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 16. 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
Interaction between L1 and Ankyrins	1	184.2×	0.027	SCN2B
Phase 0 - rapid depolarisation	1	173.0×	0.027	SCN2B
Sensory perception of taste	1	167.9×	0.027	SCN2B
Sensory perception of sweet, bitter, and umami (glutamate) taste	1	139.3×	0.027	SCN2B
Deactivation of the beta-catenin transactivating complex	1	116.5×	0.027	BCL9L
Formation of the beta-catenin:TCF transactivating complex	1	60.1×	0.029	BCL9L
L1CAM interactions	1	60.1×	0.029	SCN2B
TCF dependent signaling in response to WNT	1	58.9×	0.029	BCL9L
Signaling by WNT	1	56.0×	0.029	BCL9L
Cardiac conduction	1	54.4×	0.029	SCN2B
Sensory Perception	1	47.6×	0.030	SCN2B
Muscle contraction	1	38.6×	0.034	SCN2B
Axon guidance	1	22.6×	0.053	SCN2B
Nervous system development	1	21.5×	0.053	SCN2B
Developmental Biology	1	7.2×	0.142	SCN2B
Signal Transduction	1	5.1×	0.187	BCL9L

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
response to pyrethroid	1	8426.0×	0.003	SCN2B
regulation of atrial cardiac muscle cell membrane depolarization	1	936.2×	0.006	SCN2B
cardiac conduction	1	842.6×	0.006	SCN2B
membrane depolarization during action potential	1	842.6×	0.006	SCN2B
membrane depolarization during cardiac muscle cell action potential	1	702.2×	0.006	SCN2B
positive regulation of sodium ion transport	1	421.3×	0.007	SCN2B
myoblast differentiation	1	421.3×	0.007	BCL9L
cardiac muscle cell action potential involved in contraction	1	351.1×	0.008	SCN2B
regulation of cell morphogenesis	1	312.1×	0.008	BCL9L
response to heat	1	210.7×	0.010	SCN2B
cardiac muscle contraction	1	200.6×	0.010	SCN2B
regulation of heart rate by cardiac conduction	1	187.2×	0.010	SCN2B
skeletal muscle cell differentiation	1	172.0×	0.010	BCL9L
positive regulation of epithelial to mesenchymal transition	1	159.0×	0.010	BCL9L
somatic stem cell population maintenance	1	123.9×	0.012	BCL9L
negative regulation of transforming growth factor beta receptor signaling pathway	1	86.9×	0.016	BCL9L
canonical Wnt signaling pathway	1	76.6×	0.017	BCL9L
gene expression	1	39.9×	0.030	SCN2B
chemical synaptic transmission	1	38.6×	0.030	SCN2B
transcription by RNA polymerase II	1	35.3×	0.031	BCL9L
nervous system development	1	23.0×	0.045	SCN2B
positive regulation of transcription by RNA polymerase II	1	7.4×	0.130	BCL9L

Therapeutics

Drug target analysis

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

Druggability breadth: 2 of 2 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
SCN2B	2	2
BCL9L	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
DS-1971	2	SCN2B
PF-05089771	2	SCN2B

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
SCN2B	9	ADMET:4, Binding:3, Toxicity:2
BCL9L	1	Binding:1

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

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	SCN2B
PF-05089771	2	SCN2B

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	SCN2B
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	BCL9L

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)
BCL9L	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.