SCN3B

Summary

SCN3B (sodium voltage-gated channel beta subunit 3, HGNC:20665) is a protein-coding gene on chromosome 11q24.1, encoding Sodium channel regulatory subunit beta-3 (Q9NY72). Regulatory subunit of multiple voltage-gated sodium (Nav) channels directly mediating the depolarization of excitable membranes.

Voltage-gated sodium channels are transmembrane glycoprotein complexes composed of a large alpha subunit and one or more regulatory beta subunits. They are responsible for the generation and propagation of action potentials in neurons and muscle. This gene encodes one member of the sodium channel beta subunit gene family, and influences the inactivation kinetics of the sodium channel. Two alternatively spliced variants, encoding the same protein, have been identified.

Source: NCBI Gene 55800 — RefSeq curated summary.

At a glance

• Gene–disease (curated): familial atrial fibrillation (Supportive, GenCC) — +3 more curated relationships
• GWAS associations: 4
• Clinical variants (ClinVar): 266 total — 3 pathogenic
• Phenotypes (HPO): 29
• MANE Select transcript: NM_001040151

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20665
Approved symbol	SCN3B
Name	sodium voltage-gated channel beta subunit 3
Location	11q24.1
Locus type	gene with protein product
Status	Approved
Aliases	HSA243396, SCNB3
Ensembl gene	ENSG00000166257
Ensembl biotype	protein_coding
OMIM	608214
Entrez	55800

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 13 protein_coding, 2 nonsense_mediated_decay, 1 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000299333, ENST00000392770, ENST00000527125, ENST00000530277, ENST00000655686, ENST00000657123, ENST00000657191, ENST00000659826, ENST00000667790, ENST00000851381, ENST00000851382, ENST00000851383, ENST00000851384, ENST00000851385, ENST00000950698, ENST00000950699, ENST00000950700

RefSeq mRNA: 2 — MANE Select: NM_001040151 NM_001040151, NM_018400

CCDS: CCDS8442

Canonical transcript exons

ENST00000299333 — 7 exons

Exon	Start	End
ENSE00001101487	123642446	123642671
ENSE00001101497	123638186	123638324
ENSE00001101500	123645587	123645750
ENSE00001134092	123653747	123653826
ENSE00003642572	123634121	123634206
ENSE00003910171	123654226	123654624
ENSE00003911323	123629188	123633776

Expression profiles

Bgee: expression breadth ubiquitous, 193 present calls, max score 98.69.

FANTOM5 (CAGE): breadth broad, TPM avg 4.5787 / max 271.1913, expressed in 349 samples.

FANTOM5 promoters (15 alternative TSS)

Promoter ID	TPM avg	Samples expressed
122919	2.9183	271
122918	0.5787	133
122916	0.1972	66
122917	0.1937	72
122920	0.1308	62
122911	0.1112	55
122913	0.0830	38
122906	0.0718	35
122915	0.0661	44
122914	0.0529	29

Top tissues by expression

284 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
middle temporal gyrus	UBERON:0002771	98.69	gold quality
orbitofrontal cortex	UBERON:0004167	97.77	gold quality
cortical plate	UBERON:0005343	97.33	gold quality
Brodmann (1909) area 46	UBERON:0006483	97.32	gold quality
entorhinal cortex	UBERON:0002728	97.26	gold quality
superior frontal gyrus	UBERON:0002661	96.92	gold quality
CA1 field of hippocampus	UBERON:0003881	96.34	gold quality
prefrontal cortex	UBERON:0000451	95.42	gold quality
postcentral gyrus	UBERON:0002581	95.12	gold quality
frontal cortex	UBERON:0001870	95.05	gold quality
frontal lobe	UBERON:0016525	95.05	gold quality
parietal lobe	UBERON:0001872	94.94	gold quality
cerebral cortex	UBERON:0000956	94.30	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	94.27	gold quality
Ammon’s horn	UBERON:0001954	94.10	gold quality
Brodmann (1909) area 23	UBERON:0013554	94.10	gold quality
neocortex	UBERON:0001950	94.08	gold quality
Brodmann (1909) area 9	UBERON:0013540	93.54	gold quality
temporal lobe	UBERON:0001871	93.35	gold quality
right frontal lobe	UBERON:0002810	93.05	gold quality
cingulate cortex	UBERON:0003027	92.71	gold quality
anterior cingulate cortex	UBERON:0009835	92.70	gold quality
endothelial cell	CL:0000115	92.08	gold quality
telencephalon	UBERON:0001893	91.80	gold quality
forebrain	UBERON:0001890	91.21	gold quality
amygdala	UBERON:0001876	90.87	gold quality
pituitary gland	UBERON:0000007	89.43	gold quality
occipital lobe	UBERON:0002021	89.18	gold quality
nucleus accumbens	UBERON:0001882	88.89	gold quality
brain	UBERON:0000955	88.88	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-GEOD-137537	yes	8.08
E-ANND-3	yes	7.30
E-MTAB-7303	no	732.13
E-MTAB-6678	no	3.08

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): TP53

miRNA regulators (miRDB)

185 targeting SCN3B, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-6748-5P	100.00	65.81	1057
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-3120-5P	100.00	65.56	965
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4745-5P	99.98	65.95	1028
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-6888-3P	99.97	65.95	1170
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-146A-5P	99.96	68.93	988
HSA-MIR-146B-5P	99.96	69.13	977
HSA-MIR-8082	99.95	67.27	1170
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-7153-5P	99.94	68.89	1006
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-205-3P	99.92	69.92	3165

Literature-anchored findings (GeneRIF, showing 15)

• SCN3B mediates a p53-dependent apoptotic pathway and may be a candidate for gene therapy combined with anticancer drugs. (PMID:15334053)
• In patients with temporal lobe epilepsy, Na(v)beta3 levels were dramatically reduced in the hippocampus, but not in the cortex of non-hippocampal sclerosis patients when compared to hippocampal sclerosis patients. (PMID:19385982)
• beta3 does not participate in trans homophilic cell-cell adhesion or associate with contactin. (PMID:19596049)
• Study provides molecular and cellular evidence implicating mutations in SCN3B as a cause of idiopathic ventricular fibrillation. (PMID:20042427)
• The researchers found evidence of an association between SCN3B subunit mutations and sudden infant death syndrome pathogenesis. (PMID:20226894)
• This study identifies the first atrial fibrillation(AF) -associated mutation in SCN3B, and suggests that mutations in SCN3B may be a new pathogenic cause of AF. (PMID:20558140)
• The sodium channel {beta}3-subunit induces multiphasic gating in NaV1.3 and affects fast inactivation via distinct intracellular regions. (PMID:20675377)
• three mutations in SCN3B were investigated electrophysiologically and all led to loss of function in the sodium current, supporting the hypothesis that decreased sodium current enhances atrial fibrillation susceptibility (PMID:21051419)
• the beta3 subunit can mediate trans homophilic-binding via its Ig domain and the beta3-Ig domain can associate heterophilically with the beta1 subunit (PMID:23118027)
• The Val110Ile mutation of SCN3B is a relatively common cause of SCN5A-negative BrS in Japan, which has a reduced sodium current because of the loss of cell surface expression of Nav1.5. (PMID:23257389)
• SCN1-3B the gene that encode respectively a- and b-subunits of the cardiac fast voltage-gated sodium channel, have been linked to atrial fibrillation. (PMID:25443231)
• In a nonreferred nationwide Danish cohort of SIDS cases, up to 5/66 (7.5%) of SIDS cases can be explained by genetic variants in the sodium channel complex genes. (PMID:25757662)
• Contribution of Cardiac Sodium Channel beta-Subunit Variants to Brugada Syndrome. (PMID:26179811)
• rs1783901 may play a potential role of gene regulation and/or epistasis in a complex etiology of vertigo. (PMID:30300896)
• Voltage-gated sodium channels beta3 subunit promotes tumorigenesis in hepatocellular carcinoma by facilitating p53 degradation. (PMID:31626714)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	scn3b	ENSDARG00000062359
mus_musculus	Scn3b	ENSMUSG00000049281
rattus_norvegicus	Scn3b	ENSRNOG00000057221

Paralogs (1): SCN1B (ENSG00000105711)

Protein

Protein identifiers

Sodium channel regulatory subunit beta-3 — Q9NY72 (reviewed: Q9NY72)

All UniProt accessions (3): A0A590UJ13, A0A590UJQ5, Q9NY72

UniProt curated annotations — full annotation on UniProt →

Function. Regulatory subunit of multiple voltage-gated sodium (Nav) channels directly mediating the depolarization of excitable membranes. Navs, also called VGSCs (voltage-gated sodium channels) or VDSCs (voltage-dependent sodium channels), operate by switching between closed and open conformations depending on the voltage difference across the membrane. In the open conformation they allow Na(+) ions to selectively pass through the pore, along their electrochemical gradient. The influx of Na+ ions provokes membrane depolarization, initiating the propagation of electrical signals throughout cells and tissues. The accessory beta subunits participate in localization and functional modulation of the Nav channels. Modulates the activity of SCN2A/Nav1.2, causing a hyperpolarizing shift in the voltage-dependence of inactivation of the channel and increasing the fraction of channels operating in the fast gating mode. Modulates the activity of SCN5A/Nav1.5. Could also regulate the atypical sodium channel SCN7A/Nav2.1. Modulates the activity of SCN10A/Nav1.8, regulating its oligomerization and accelerating the recovery from inactivation.

Subunit / interactions. A voltage-gated sodium (Nav) channel consists of an ion-conducting pore-forming alpha subunit functional on its own that is regulated by one or more beta subunits. Forms homodimers and homotrimers. SCN3B is non-covalently associated with alpha subunits and induces the formation of alpha subunit oligomers, including trimers. Interacts with SCN5A/Nav1.5; regulatory subunit of SCN5A/Nav1.5. Interacts with SCN7A/Nav2.1; probable regulatory subunit of SCN7A/Nav2.1. Interacts with SCN10A; regulatory subunit of SCN10A/Nav1.8. Interacts with NFASC; probably involved in targeting the sodium channels to the nodes of Ranvier.

Subcellular location. Cell membrane.

Tissue specificity. Expressed in the atrium.

Post-translational modifications. Intramolecular disulfide bonds favor the voltage-gated sodium channel oligomeric complex assembly. N-glycosylated.

Disease relevance. Brugada syndrome 7 (BRGDA7) [MIM:613120] A tachyarrhythmia characterized by right bundle branch block and ST segment elevation on an electrocardiogram (ECG). It can cause the ventricles to beat so fast that the blood is prevented from circulating efficiently in the body. When this situation occurs, the individual will faint and may die in a few minutes if the heart is not reset. The gene represented in this entry may be involved in disease pathogenesis. Atrial fibrillation, familial, 16 (ATFB16) [MIM:613120] A familial form of atrial fibrillation, a common sustained cardiac rhythm disturbance. Atrial fibrillation is characterized by disorganized atrial electrical activity and ineffective atrial contraction promoting blood stasis in the atria and reduces ventricular filling. It can result in palpitations, syncope, thromboembolic stroke, and congestive heart failure. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the sodium channel auxiliary subunit SCN3B (TC 8.A.17) family.

RefSeq proteins (2): NP_001035241, NP_060870 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003599	Ig_sub	Domain
IPR007110	Ig-like_dom	Domain
IPR013106	Ig_V-set	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR027098	Na_channel_b1/b3	Family
IPR036179	Ig-like_dom_sf	Homologous_superfamily

Pfam: PF07686

UniProt features (34 total): strand 10, sequence variant 8, glycosylation site 4, disulfide bond 2, topological domain 2, helix 2, signal peptide 1, chain 1, mutagenesis site 1, turn 1, transmembrane region 1, domain 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
4L1D	X-RAY DIFFRACTION	2.5
7TJ9	ELECTRON MICROSCOPY	2.9
7TJ8	ELECTRON MICROSCOPY	3.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NY72-F1	86.41	0.59

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Disulfide bonds (2): 26–48, 45–120

Glycosylation sites (4): 95, 109, 113, 121

Mutagenesis-validated functional residues (1):

Position	Phenotype
48	decreased voltage-gated sodium channel oligomeric complex assembly.

Function

Pathways and Gene Ontology

Reactome pathways

8 pathways

ID	Pathway
R-HSA-445095	Interaction between L1 and Ankyrins
R-HSA-5576892	Phase 0 - rapid depolarisation
R-HSA-1266738	Developmental Biology
R-HSA-373760	L1CAM interactions
R-HSA-397014	Muscle contraction
R-HSA-422475	Axon guidance
R-HSA-5576891	Cardiac conduction
R-HSA-9675108	Nervous system development

MSigDB gene sets: 282 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_DN, GNF2_RTN1, GOBP_MEMBRANE_DEPOLARIZATION, TGCGCANK_UNKNOWN, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_SODIUM_ION_TRANSMEMBRANE_TRANSPORT, GCANCTGNY_MYOD_Q6, GOBP_MEMBRANE_DEPOLARIZATION_DURING_ACTION_POTENTIAL, AREB6_03, GOBP_REGULATION_OF_MEMBRANE_DEPOLARIZATION, GOBP_POSITIVE_REGULATION_OF_SODIUM_ION_TRANSPORT, GGGTGGRR_PAX4_03, AAAYRNCTG_UNKNOWN, CAGCTG_AP4_Q5, GOBP_PROTEIN_LOCALIZATION_TO_CELL_PERIPHERY

GO Biological Process (20): sodium ion transport (GO:0006814), nervous system development (GO:0007399), positive regulation of heart rate (GO:0010460), positive regulation of sodium ion transport (GO:0010765), sodium ion transmembrane transport (GO:0035725), membrane depolarization (GO:0051899), cardiac muscle contraction (GO:0060048), regulation of atrial cardiac muscle cell membrane depolarization (GO:0060371), regulation of ventricular cardiac muscle cell membrane depolarization (GO:0060373), protein localization to plasma membrane (GO:0072659), cardiac muscle cell action potential involved in contraction (GO:0086002), ventricular cardiac muscle cell action potential (GO:0086005), membrane depolarization during action potential (GO:0086010), membrane depolarization during cardiac muscle cell action potential (GO:0086012), atrial cardiac muscle cell action potential (GO:0086014), SA node cell action potential (GO:0086015), regulation of heart rate by cardiac conduction (GO:0086091), monoatomic ion transport (GO:0006811), monoatomic ion transmembrane transport (GO:0034220), cardiac conduction (GO:0061337)

GO Molecular Function (6): sodium channel regulator activity (GO:0017080), sodium channel inhibitor activity (GO:0019871), transmembrane transporter binding (GO:0044325), voltage-gated sodium channel activity involved in cardiac muscle cell action potential (GO:0086006), sodium channel activity (GO:0005272), protein binding (GO:0005515)

GO Cellular Component (6): voltage-gated sodium channel complex (GO:0001518), cytosol (GO:0005829), plasma membrane (GO:0005886), membrane (GO:0016020), Z disc (GO:0030018), monoatomic ion channel complex (GO:0034702)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
L1CAM interactions	1
Cardiac conduction	1
Axon guidance	1
Nervous system development	1
Muscle contraction	1
Developmental Biology	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cardiac muscle cell action potential	3
cellular anatomical structure	3
regulation of heart rate	2
sodium ion transport	2
regulation of membrane depolarization	2
cardiac muscle cell action potential involved in contraction	2
sodium channel activity	2
metal ion transport	1
system development	1
positive regulation of heart contraction	1
regulation of sodium ion transport	1
positive regulation of monoatomic ion transport	1
monoatomic cation transmembrane transport	1
regulation of membrane potential	1
striated muscle contraction	1
heart contraction	1
protein localization to membrane	1
protein localization to cell periphery	1
cardiac muscle cell contraction	1
action potential	1
membrane depolarization	1
membrane depolarization during action potential	1
atrial cardiac muscle cell to AV node cell signaling	1
SA node cell to atrial cardiac muscle cell signaling	1
cardiac conduction	1
transport	1
monoatomic ion transport	1
transmembrane transport	1
regulation of heart contraction	1
ion channel regulator activity	1
ion channel inhibitor activity	1
sodium channel regulator activity	1
protein binding	1
voltage-gated sodium channel activity	1
membrane depolarization during cardiac muscle cell action potential	1
monoatomic cation channel activity	1
sodium ion transmembrane transporter activity	1
binding	1
sodium channel complex	1
plasma membrane protein complex	1

Protein interactions and networks

STRING

1622 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SCN3B	SCN2B	O60939	976
SCN3B	SCN4B	Q8IWT1	943
SCN3B	GPD1L	Q8N335	901
SCN3B	SCN5A	Q14524	891
SCN3B	KCNE3	Q9Y6H6	890
SCN3B	CACNB2	Q08289	840
SCN3B	SCN4A	P35499	823
SCN3B	SCN2A	Q99250	808
SCN3B	HCN4	Q9Y3Q4	799
SCN3B	CACNA1C	Q13936	787
SCN3B	RANGRF	Q9HD47	771
SCN3B	KCNE2	Q9Y6J6	760
SCN3B	KCNJ8	Q15842	723
SCN3B	KCNE5	Q9UJ90	720
SCN3B	KCNE4	Q8WWG9	715

IntAct

319 interactions, top by confidence:

A	B	Type	Score
TUSC5	SCN3B	psi-mi:“MI:0915”(physical association)	0.560
VAMP2	SCN3B	psi-mi:“MI:0915”(physical association)	0.560
ORMDL2	SCN3B	psi-mi:“MI:0915”(physical association)	0.560
PLP2	SCN3B	psi-mi:“MI:0915”(physical association)	0.560
LEMD1	SCN3B	psi-mi:“MI:0915”(physical association)	0.560
GIMAP1	SCN3B	psi-mi:“MI:0915”(physical association)	0.560
LPAR3	SCN3B	psi-mi:“MI:0915”(physical association)	0.560
TSPAN2	SCN3B	psi-mi:“MI:0915”(physical association)	0.560
TMEM120A	SCN3B	psi-mi:“MI:0915”(physical association)	0.560
SCD	SCN3B	psi-mi:“MI:0915”(physical association)	0.560
BNIP3	SCN3B	psi-mi:“MI:0915”(physical association)	0.560
SMCO4	SCN3B	psi-mi:“MI:0915”(physical association)	0.560
YIF1A	SCN3B	psi-mi:“MI:0915”(physical association)	0.560
UBIAD1	SCN3B	psi-mi:“MI:0915”(physical association)	0.560
AGPAT4	SCN3B	psi-mi:“MI:0915”(physical association)	0.560
PLBD2	SCN3B	psi-mi:“MI:0915”(physical association)	0.560
TMEM239	SCN3B	psi-mi:“MI:0915”(physical association)	0.560
FKBP8	SCN3B	psi-mi:“MI:0915”(physical association)	0.560
SEC22A	SCN3B	psi-mi:“MI:0915”(physical association)	0.560
SERP2	SCN3B	psi-mi:“MI:0915”(physical association)	0.560
TMEM65	SCN3B	psi-mi:“MI:0915”(physical association)	0.560
VAMP1	SCN3B	psi-mi:“MI:0915”(physical association)	0.560
	SCN3B	psi-mi:“MI:0915”(physical association)	0.560
TMEM128	SCN3B	psi-mi:“MI:0915”(physical association)	0.560
SLC30A8	SCN3B	psi-mi:“MI:0915”(physical association)	0.560
LEPROTL1	SCN3B	psi-mi:“MI:0915”(physical association)	0.560
STX8	SCN3B	psi-mi:“MI:0915”(physical association)	0.560
AGPAT5	SCN3B	psi-mi:“MI:0915”(physical association)	0.560
ANKRD46	SCN3B	psi-mi:“MI:0915”(physical association)	0.560
TMEM86A	SCN3B	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (278): SOGA3 (Affinity Capture-MS), DHRS7 (Affinity Capture-MS), TARBP1 (Affinity Capture-MS), DPY19L1 (Affinity Capture-MS), CENPL (Affinity Capture-MS), UTP20 (Affinity Capture-MS), CENPN (Affinity Capture-MS), ABCC5 (Affinity Capture-MS), BCAP29 (Affinity Capture-MS), TMTC4 (Affinity Capture-MS), TMED4 (Affinity Capture-MS), HSDL1 (Affinity Capture-MS), PEX10 (Affinity Capture-MS), ATR (Affinity Capture-MS), TUSC3 (Affinity Capture-MS)

ESM2 similar proteins: A5D7H1, A8MXK1, O76036, P01134, P01135, P08887, P14745, P35790, P48030, P48061, P55244, P98135, Q01134, Q05078, Q06922, Q08334, Q08DW9, Q08E08, Q0V881, Q12841, Q28284, Q29423, Q2KI11, Q3SXP7, Q3UHH2, Q58D84, Q5M7U7, Q5R9Y1, Q5SQ64, Q62356, Q62632, Q6AZB0, Q6MG56, Q6UXG2, Q7M729, Q7M730, Q7TPB4, Q86XW9, Q8BHK2, Q8BZI6

Diamond homologs: A5A6L6, P53788, P97952, Q00954, Q07699, Q17QN4, Q2KI11, Q4PPC4, Q8BHK2, Q8HXJ7, Q9JK00, Q9NY72, A0JM41, A2VD98, A5D7C3, O60487, O60939, O70255, O95297, P06907, P10522, P20938, P25189, P27573, P37301, P54900, Q08E08, Q32PI9, Q3TEW6, Q3V3F6, Q4KLY3, Q56A07, Q5EAB0, Q5R804, Q6AYT8, Q6UWV2, Q6WEB5, Q7M729, Q7M730, Q864L3

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
SCN3B	“form complex”	“Nax cation channel complex SCN2B-SCN3B variant”	binding
SCN3B	“form complex”	“Nax cation channel complex, SCN3B-SCN4B variant”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 103 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

GO biological processes:

GO term	Partners	Fold	FDR
vesicle fusion	6	43.5×	2e-06
endoplasmic reticulum to Golgi vesicle-mediated transport	6	9.8×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

266 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	0
Uncertain significance	125
Likely benign	87
Benign	24

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
140598	NM_001040151.2(SCN3B):c.482T>C (p.Met161Thr)	Pathogenic
140599	NM_001040151.2(SCN3B):c.17G>A (p.Arg6Lys)	Pathogenic
151354	GRCh38/hg38 11q23.3-24.2(chr11:120080142-125829106)x1	Pathogenic

SpliceAI

1425 predictions. Top by Δscore:

Variant	Effect	Δscore
11:123638184:A:AC	donor_gain	1.0000
11:123638184:ACG:A	donor_gain	1.0000
11:123638185:C:CC	donor_gain	1.0000
11:123638185:CG:C	donor_gain	1.0000
11:123638185:CGC:C	donor_gain	1.0000
11:123638185:CGCG:C	donor_gain	1.0000
11:123638320:TCCAG:T	acceptor_gain	1.0000
11:123638321:CCAG:C	acceptor_gain	1.0000
11:123638321:CCAGC:C	acceptor_gain	1.0000
11:123638322:CAG:C	acceptor_gain	1.0000
11:123638322:CAGC:C	acceptor_gain	1.0000
11:123638323:AG:A	acceptor_gain	1.0000
11:123638323:AGC:A	acceptor_loss	1.0000
11:123638324:GCTGA:G	acceptor_loss	1.0000
11:123638325:C:CC	acceptor_gain	1.0000
11:123638325:C:T	acceptor_loss	1.0000
11:123642438:AG:A	donor_gain	1.0000
11:123642444:AC:A	donor_gain	1.0000
11:123642444:ACCCT:A	donor_gain	1.0000
11:123642445:CC:C	donor_gain	1.0000
11:123642445:CCCTC:C	donor_gain	1.0000
11:123642448:T:A	donor_gain	1.0000
11:123642518:C:CA	donor_gain	1.0000
11:123638185:CGCGT:C	donor_gain	0.9900
11:123638323:A:T	acceptor_gain	0.9900
11:123642445:CCCT:C	donor_gain	0.9900
11:123642513:AAACT:A	donor_gain	0.9900
11:123645585:A:AC	donor_gain	0.9900
11:123645586:C:CC	donor_gain	0.9900
11:123645595:CTTTA:C	donor_loss	0.9900

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000071497 (11:123634252 G>A), RS1000312586 (11:123645614 G>A), RS1000343866 (11:123645832 G>C), RS1000570801 (11:123640340 T>G), RS1000604095 (11:123632439 C>G), RS1000661579 (11:123654652 C>A,G,T), RS1000680095 (11:123644489 C>T), RS1001043771 (11:123656139 A>G), RS1001082354 (11:123637894 G>A,T), RS1001280576 (11:123629716 G>A), RS1001374084 (11:123654723 A>C,G), RS1001494439 (11:123654923 T>C,G), RS1001532028 (11:123638281 G>A), RS1001612517 (11:123654884 A>C), RS1002072090 (11:123631141 G>C)

Disease associations

OMIM: gene MIM:608214 | disease phenotypes: MIM:613120, MIM:601144

GenCC curated gene-disease

Disease	Classification	Inheritance
familial atrial fibrillation	Supportive	Autosomal dominant
Brugada syndrome 7	Limited	Autosomal dominant

ClinGen Gene-Disease Validity (2)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
atrial fibrillation	Disputed	AD
Brugada syndrome	Refuted	AD

Mondo (7): Brugada syndrome 7 (MONDO:0013146), atrial fibrillation, familial, 16 (MONDO:0800349), cardiomyopathy (MONDO:0004994), cardiac rhythm disease (MONDO:0007263), Brugada syndrome (MONDO:0015263), long QT syndrome (MONDO:0002442), familial atrial fibrillation (MONDO:0018054)

Orphanet (2): Brugada syndrome (Orphanet:130), Rare cardiomyopathy (Orphanet:167848)

HPO phenotypes

29 total (29 of 29 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0001279	Syncope
HP:0001649	Tachycardia
HP:0001658	Myocardial infarction
HP:0001663	Ventricular fibrillation
HP:0001695	Cardiac arrest
HP:0001727	Thromboembolic stroke
HP:0001907	Thromboembolism
HP:0001962	Palpitations
HP:0002094	Dyspnea
HP:0002321	Vertigo
HP:0003546	Exercise intolerance
HP:0003596	Middle age onset
HP:0004308	Ventricular arrhythmia
HP:0004749	Atrial flutter
HP:0004751	Paroxysmal ventricular tachycardia
HP:0004754	Permanent atrial fibrillation
HP:0004755	Supraventricular tachycardia
HP:0004757	Paroxysmal atrial fibrillation
HP:0005110	Atrial fibrillation
HP:0011704	Sick sinus syndrome
HP:0011705	First degree atrioventricular block
HP:0011712	Complete right bundle branch block
HP:0011715	Trifascicular block
HP:0012251	ST segment elevation
HP:0012378	Fatigue
HP:0025710	Late young adult onset
HP:0034308	Prolonged P wave
HP:0100749	Chest pain

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST002073_18	Chronic lymphocytic leukemia	4.000000e-39
GCST002299_15	Chronic lymphocytic leukemia	4.000000e-24
GCST003802_5	Response to citalopram or escitalopram in depression	7.000000e-07
GCST004146_16	Chronic lymphocytic leukemia	4.000000e-58

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D053840	Brugada Syndrome	C14.280.067.322; C14.280.123.250; C16.320.100
D009202	Cardiomyopathies	C14.280.238
D008133	Long QT Syndrome	C14.280.067.565; C14.280.123.625; C16.131.240.400.715; C23.550.073.547
C567734	Brugada Syndrome 7 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases expression	3
Benzo(a)pyrene	increases expression, increases methylation	2
Cisplatin	affects cotreatment, increases expression	2
Valproic Acid	affects expression, increases expression	2
butyraldehyde	increases expression	1
manganese chloride	increases expression	1
CGP 52608	affects binding, increases reaction	1
nutlin 3	affects cotreatment, increases expression	1
abrine	increases expression	1
licochalcone B	decreases expression	1
jinfukang	decreases expression, affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Fulvestrant	decreases methylation	1
Acetaminophen	increases expression	1
Air Pollutants	increases abundance, increases expression	1
Camptothecin	increases expression	1
Dactinomycin	affects cotreatment, increases expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Doxorubicin	decreases expression	1
Folic Acid	decreases expression	1
Lead	affects expression	1
Manganese	increases expression	1
Methylcholanthrene	affects binding, increases reaction	1
Silicon Dioxide	increases expression	1
Tretinoin	increases expression	1
Triclosan	increases expression	1
Cyclosporine	increases expression	1
Aflatoxin B1	affects expression	1
Particulate Matter	increases abundance, increases expression	1

Cellosaurus cell lines

1 cell lines: 1 spontaneously immortalized cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_C0YD	B’SYS CHO Nav1.8/beta3	Spontaneously immortalized cell line	Female

Clinical trials (associated diseases)

302 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00348530	PHASE4	UNKNOWN	Carvedilol Versus Verapamil in Chronic Heart Failure Secondary to Non-Ischemic Cardiomyopathy
NCT00371891	PHASE4	COMPLETED	Ontario Multidetector Computed Tomographic (MDCT) Coronary Angiography Study (OMCAS)
NCT00401856	PHASE4	COMPLETED	CMR to Assess Fibrosis in Cardiomyopathy Using Eplerenone
NCT00559338	PHASE4	COMPLETED	Impact of Nesiritide Infusion for Decompensated Heart Failure in the Emergency Department
NCT00606775	PHASE4	UNKNOWN	The Preventive Efficacy of Carvedilol on Cardiac Dysfunction in Duchenne Muscular Dystrophy
NCT00658203	PHASE4	COMPLETED	Clinical Evaluation on Advanced Resynchronization
NCT00701220	PHASE4	COMPLETED	Statin Therapy for Ischemic and Nonischemic Cardiomyopathy
NCT00800761	PHASE4	COMPLETED	Intensive Combined Chelation Therapy for Iron-Induced Cardiac Disease in Patients With Thalassemia Major
NCT00806390	PHASE4	TERMINATED	Prevention of Anthracycline or Trastuzumab Induced Cardiomyopathy by Metoprolol
NCT01006473	PHASE4	COMPLETED	Exercise Training in Chagas Cardiomyopathy
NCT01261065	PHASE4	COMPLETED	Mechanisms of Improvement With Beta-Blocker Treatment in Heart Failure
NCT01345188	PHASE4	COMPLETED	Ranolazine in Ischemic Cardiomyopathy
NCT01868841	PHASE4	COMPLETED	123-I mIBG (AdreView) Heart-to-Mediastinal (H/M) Ratio and SPECT Imaging on a Small Field of View-High Efficiency Cardiac SPECT System
NCT02640846	PHASE4	UNKNOWN	Effects of Levosimendan, Milrinone and Norepinephrine on Left and Right Ventricular Function in Septic Shock
NCT03228823	PHASE4	UNKNOWN	Prospective Assessment of Premature Ventricular Contractions Suppression in Cardiomyopathy(PAPS)
NCT04323852	PHASE4	COMPLETED	Can Vitamin D Reduce Heart Muscle Damage After Bypass Surgery?
NCT05034432	PHASE4	RECRUITING	The PIVATAL Study -Study of Ventricular Arrhythmia (VTA) Ablation in Left Ventricular Assist Device (LVAD) Patients
NCT05718128	PHASE4	RECRUITING	Clinical Study of Endocardial Myocardial Biopsy
NCT06964464	PHASE4	RECRUITING	Comparative Effectiveness of Carvedilol Versus Metoprolol Succinate in Heart Failure Patients With an Implantable Cardioverter Defibrillator
NCT00170183	PHASE3	COMPLETED	Brain Natriuretic Peptide (BNP) to Preserve Renal Function in Hospitalized Patients With Heart Failure
NCT00270387	PHASE3	COMPLETED	A Study of Short-Term Outcomes and Economic Impact For Patients With Worsening Congestive Heart Failure When Natrecor (Nesiritide) is Added to Standard-Care Therapy, Compared to Administration of Placebo With Standard-Care Therapy
NCT00321295	PHASE3	COMPLETED	Biventricular Pacing In Patients With Left Ventricular Dysfunction After Cardiovascular Surgery
NCT00483197	PHASE3	UNKNOWN	VentrAssistTM LVAD as a Bridge to Cardiac Transplantation - Pivotal Trial
NCT00490321	PHASE3	UNKNOWN	VentrAssistTM LVAD for the Treatment of Advanced Heart Failure - Destination Therapy
NCT00626028	PHASE3	COMPLETED	Comparison of Inhaled Nitric Oxide and Oxygen in Participants Reactivity During Acute Pulmonary Vasodilator Testing
NCT01013714	PHASE3	UNKNOWN	Cardiac Sympathetic Denervation for Prevention of Ventricular Tachyarrhythmias
NCT01217827	PHASE3	COMPLETED	Implantable Cardioverter-Defibrillator Use in the VA System
NCT01648634	PHASE3	COMPLETED	Nebivolol for the Prevention of Left Ventricular Systolic Dysfunction in Patients With Duchenne Muscular Dystrophy
NCT02924285	PHASE3	COMPLETED	Catheter Ablation Versus Amiodarone for Therapy of Premature Ventricular Contractions in Patients With Structural Heart Disease
NCT03860935	PHASE3	COMPLETED	Efficacy and Safety of AG10 in Subjects With Transthyretin Amyloid Cardiomyopathy
NCT04166331	PHASE3	COMPLETED	Adjunctive DobutAmine in sePtic Cardiomyopathy With Tissue Hypoperfusion
NCT05175066	PHASE3	COMPLETED	Bisoprolol Administration to Prevent Anthracycline-induced Cardiotoxicity
NCT05237323	PHASE3	COMPLETED	Micophenolate Mofetil Versus Azathioprine in Myocarditis
NCT06158698	PHASE3	RECRUITING	CMP-MYTHiC Trial and Registry - CardioMyoPathy With MYocarditis THerapy With Colchicine
NCT06563895	PHASE3	RECRUITING	Acoramidis Transthyretin Amyloidosis Prevention Trial in the Young (ACT-EARLY) Study in Asymptomatic Carriers of a Pathogenic TTR Variant
NCT06846086	PHASE3	RECRUITING	Cardioprotective Effects of Melatonin in Patients With Cardiomyopathy
NCT07116473	PHASE3	NOT_YET_RECRUITING	To Evaluate the Long-term Safety and Tolerability of Acoramidis in Participants With Newly Diagnosed ATTR-CM (ACT-EARLY OLE)
NCT00185250	PHASE2	COMPLETED	Betaferon/ Betaseron (Interferon Beta-1b) in Patients With Chronic Viral Cardiomyopathy
NCT00490347	PHASE2	COMPLETED	VentrAssistTM LVAD as a Bridge to Cardiac Transplantation - Feasibility Trial
NCT00694161	PHASE2	COMPLETED	The Effects Of Fx-1006A On Transthyretin Stabilization And Clinical Outcome Measures In Patients With V122I Or Wild-Type TTR Amyloid Cardiomyopathy