Atrial fibrillation, familial, 17

Summary

Atrial fibrillation, familial, 17 (MONDO:0800345) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 2

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	atrial fibrillation, familial, 17
Mondo ID	MONDO:0800345
UMLS	C4013560
MedGen	861997
GARD	0026510
Is cancer (heuristic)	no

Also known as: ATFB17

Data availability: 2 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, 17

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, 14, atrial fibrillation, familial, 15, atrial fibrillation, familial, 18, 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

2 retrieved; paginated sample, class counts are floors:

2 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
140600	NM_174934.4(SCN4B):c.485T>G (p.Val162Gly)	SCN4B	Pathogenic	no assertion criteria provided
140601	NM_174934.4(SCN4B):c.496A>C (p.Ile166Leu)	SCN4B	Pathogenic	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SCN4B	Orphanet:101016	Romano-Ward syndrome
SCN4B	Orphanet:334	Hereditary atrial fibrillation

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
SCN4B	HGNC:10592	ENSG00000177098	Q8IWT1	Sodium channel regulatory subunit beta-4	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SCN4B	Sodium channel regulatory subunit beta-4	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)
SCN4B	Antibody/Immunoglobulin	yes		Myelin_P0-rel, Ig_sub, Ig-like_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)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
dorsal root ganglion	1
lateral globus pallidus	1
putamen	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SCN4B	223	broad	marker	lateral globus pallidus, dorsal root ganglion, putamen

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SCN4B	1,551

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SCN4B	Q8IWT1	5

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	SCN4B
Phase 0 - rapid depolarisation	1	346.1×	0.010	SCN4B
Sensory perception of taste	1	335.9×	0.010	SCN4B
Sensory perception of sweet, bitter, and umami (glutamate) taste	1	278.5×	0.010	SCN4B
L1CAM interactions	1	120.2×	0.017	SCN4B
Cardiac conduction	1	108.8×	0.017	SCN4B
Sensory Perception	1	95.2×	0.017	SCN4B
Muscle contraction	1	77.2×	0.018	SCN4B
Axon guidance	1	45.1×	0.026	SCN4B
Nervous system development	1	42.9×	0.026	SCN4B
Developmental Biology	1	14.5×	0.069	SCN4B

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
AV node cell action potential	1	4213.0×	0.003	SCN4B
cardiac conduction	1	1685.2×	0.003	SCN4B
membrane depolarization during cardiac muscle cell action potential	1	1404.3×	0.003	SCN4B
positive regulation of sodium ion transport	1	842.6×	0.003	SCN4B
regulation of ventricular cardiac muscle cell membrane repolarization	1	842.6×	0.003	SCN4B
cardiac muscle cell action potential involved in contraction	1	702.2×	0.003	SCN4B
neuronal action potential	1	481.5×	0.004	SCN4B
cardiac muscle contraction	1	401.2×	0.004	SCN4B
regulation of heart rate by cardiac conduction	1	374.5×	0.004	SCN4B
sodium ion transport	1	271.8×	0.004	SCN4B
sodium ion transmembrane transport	1	203.0×	0.005	SCN4B
establishment of localization in cell	1	160.5×	0.006	SCN4B

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SCN4B	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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	SCN4B
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)
SCN4B	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.