SCN7A

Summary

SCN7A (sodium voltage-gated channel alpha subunit 7, HGNC:10594) is a protein-coding gene on chromosome 2q24.3, encoding Sodium channel protein type 7 subunit alpha (Q01118). Sodium leak channel functioning as an osmosensor regulating sodium ion levels in various tissues and organs.

This gene encodes one of the many voltage-gated sodium channel proteins. For proper functioning of neurons and muscles during action potentials, voltage-gated sodium channels direct sodium ion diffusion for membrane depolarization. This sodium channel protein has some atypical characteristics; the similarity between the human and mouse proteins is lower compared to other orthologous sodium channel pairs. Also, the S4 segments, which sense voltage changes, have fewer positive charged residues that in other sodium channels; domain 4 has fewer arginine and lysine residues compared to other sodium channel proteins. Several alternatively spliced transcript variants exist, but the full-length natures of all of them remain unknown.

Source: NCBI Gene 6332 — RefSeq curated summary.

At a glance

• Gene–disease (curated): holoprosencephaly (Limited, GenCC)
• GWAS associations: 6
• Clinical variants (ClinVar): 284 total — 1 pathogenic, 1 likely-pathogenic
• Druggable target: yes — 20 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_002976

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10594
Approved symbol	SCN7A
Name	sodium voltage-gated channel alpha subunit 7
Location	2q24.3
Locus type	gene with protein product
Status	Approved
Aliases	Nav2.1, Nav2.2, NaG
Ensembl gene	ENSG00000136546
Ensembl biotype	protein_coding
OMIM	182392
Entrez	6332

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 7 protein_coding, 1 nonsense_mediated_decay, 1 retained_intron

ENST00000419992, ENST00000424326, ENST00000441411, ENST00000497562, ENST00000643258, ENST00000650747, ENST00000961721, ENST00000961722, ENST00000961723

RefSeq mRNA: 1 — MANE Select: NM_002976 NM_002976

CCDS: CCDS46442

Canonical transcript exons

ENST00000643258 — 26 exons

Exon	Start	End
ENSE00001009842	166447612	166447708
ENSE00001071470	166462389	166462530
ENSE00001071474	166470615	166470706
ENSE00001071478	166465781	166465987
ENSE00001071480	166441396	166441752
ENSE00001071484	166443503	166443676
ENSE00001071485	166456870	166457076
ENSE00001071488	166477463	166477710
ENSE00001071491	166444762	166445000
ENSE00001071495	166465462	166465531
ENSE00001071496	166472317	166472445
ENSE00001332555	166486856	166486968
ENSE00001583680	166473799	166473888
ENSE00001587896	166474226	166474344
ENSE00001589709	166403573	166406646
ENSE00001723065	166493968	166494249
ENSE00003461170	166423259	166423432
ENSE00003480272	166432318	166432752
ENSE00003483657	166412530	166412667
ENSE00003492975	166409665	166409935
ENSE00003537578	166410220	166410324
ENSE00003547563	166427788	166427942
ENSE00003549318	166421190	166421297
ENSE00003564156	166413068	166413121
ENSE00003602601	166416707	166416985
ENSE00003628695	166429169	166429274

Expression profiles

Bgee: expression breadth ubiquitous, 226 present calls, max score 96.95.

FANTOM5 (CAGE): breadth broad, TPM avg 2.4465 / max 650.4434, expressed in 230 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
31691	0.9720	143
31694	0.5971	125
31693	0.4628	132
31690	0.1833	69
31692	0.1453	69
31689	0.0444	24
31695	0.0416	23

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
trigeminal ganglion	UBERON:0001675	96.95	gold quality
sural nerve	UBERON:0015488	96.80	gold quality
right lung	UBERON:0002167	96.16	gold quality
tibial nerve	UBERON:0001323	95.85	gold quality
dorsal root ganglion	UBERON:0000044	95.57	gold quality
lower lobe of lung	UBERON:0008949	95.09	gold quality
seminal vesicle	UBERON:0000998	93.55	gold quality
heart right ventricle	UBERON:0002080	92.66	gold quality
left ovary	UBERON:0002119	92.60	gold quality
visceral pleura	UBERON:0002401	92.27	gold quality
muscle layer of sigmoid colon	UBERON:0035805	91.48	gold quality
right ovary	UBERON:0002118	91.40	gold quality
upper lobe of lung	UBERON:0008948	90.27	gold quality
lower esophagus muscularis layer	UBERON:0035833	90.12	gold quality
upper lobe of left lung	UBERON:0008952	90.07	gold quality
lower esophagus	UBERON:0013473	90.06	gold quality
ovary	UBERON:0000992	89.78	gold quality
cauda epididymis	UBERON:0004360	88.89	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	88.67	gold quality
sigmoid colon	UBERON:0001159	87.39	gold quality
buccal mucosa cell	CL:0002336	86.70	gold quality
lung	UBERON:0002048	86.16	gold quality
cardiac ventricle	UBERON:0002082	85.99	gold quality
mucosa of stomach	UBERON:0001199	85.75	gold quality
heart left ventricle	UBERON:0002084	85.73	gold quality
caput epididymis	UBERON:0004358	85.38	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.15	gold quality
heart	UBERON:0000948	85.12	gold quality
right atrium auricular region	UBERON:0006631	85.10	gold quality
colonic epithelium	UBERON:0000397	85.00	gold quality

Single-cell (SCXA)

Detected in 9 experiment(s), a significant marker in 8.

Experiment	Marker?	Max mean expression
E-CURD-126	yes	2603.00
E-HCAD-36	yes	873.73
E-GEOD-135922	yes	30.13
E-HCAD-11	yes	28.92
E-MTAB-8410	yes	26.47
E-ANND-3	yes	22.98
E-CURD-46	yes	17.77
E-MTAB-10287	yes	15.47
E-MTAB-9543	no	1.22

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

123 targeting SCN7A, 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-3646	100.00	73.56	5283
HSA-MIR-3163	100.00	77.23	8605
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-551B-5P	99.96	71.28	3493

Literature-anchored findings (GeneRIF, showing 4)

• SNP rs7565062 of SCN7A was significantly associated with essential hypertension in a Northern Han Chinese population (PMID:25393565)
• The authors demonstrated that the sodium channel Nax functions as a sodium sensor. With increased extracellular sodium, Nax up-regulates prostasin, which results in activation of the sodium channel ENaC. (PMID:26537257)
• Genomic analyses reveal SCN7A is associated with the prognosis of esophageal squamous cell carcinoma. (PMID:34993672)
• Identification of SCN7A as the key gene associated with tumor mutation burden in gastric cancer. (PMID:35123417)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Scn7a	ENSMUSG00000034810
rattus_norvegicus	Scn7a	ENSRNOG00000029342

Paralogs (26): CACNA1G (ENSG00000006283), SCN4A (ENSG00000007314), CACNA1S (ENSG00000081248), CACNA1I (ENSG00000100346), CACNA1F (ENSG00000102001), NALCN (ENSG00000102452), SCN2A (ENSG00000136531), CACNA1A (ENSG00000141837), SCN1A (ENSG00000144285), CACNA1B (ENSG00000148408), CACNA1C (ENSG00000151067), CATSPER3 (ENSG00000152705), SCN3A (ENSG00000153253), CACNA1D (ENSG00000157388), TPCN2 (ENSG00000162341), CATSPER2 (ENSG00000166762), SCN11A (ENSG00000168356), SCN9A (ENSG00000169432), CATSPER1 (ENSG00000175294), SCN5A (ENSG00000183873), SCN10A (ENSG00000185313), TPCN1 (ENSG00000186815), CATSPER4 (ENSG00000188782), CACNA1H (ENSG00000196557), SCN8A (ENSG00000196876), CACNA1E (ENSG00000198216)

Protein

Protein identifiers

Sodium channel protein type 7 subunit alpha — Q01118 (reviewed: Q01118)

Alternative names: Atypical sodium channel Nav2.1, Nax channel, Sodium channel protein type VII subunit alpha

All UniProt accessions (4): Q01118, A0A494C195, C9JW43, F8WD82

UniProt curated annotations — full annotation on UniProt →

Function. Sodium leak channel functioning as an osmosensor regulating sodium ion levels in various tissues and organs. While most sodium channels are voltage-gated, SCN7A is not and lets sodium flow through membrane along its concentration gradient. In glial cells of the central nervous system, senses body-fluid sodium levels and controls salt intake behavior as well as voluntary water intake through activation of nearby neurons to maintain appropriate sodium levels in the body. By mediating sodium influx into keratinocytes, also plays a role in skin barrier homeostasis.

Subunit / interactions. The sodium channel formed by SCN7A is probably a heterooligomeric complex consisting of the ion conducting pore forming alpha subunit SCN7A and regulatory beta subunits such as SCN3B. Interacts with ATP1A1; activates ATP1A1 and thereby indirectly signals to nearby neurons to regulate sodium homeostasis.

Subcellular location. Cell membrane.

Tissue specificity. Heart and uterus.

Domain organisation. The sequence contains 4 internal repeats, each with 5 hydrophobic segments (S1, S2, S3, S5, S6) and one positively charged segment (S4). Segments S4 are probably the voltage-sensors and are characterized by a series of positively charged amino acids at every third position.

Similarity. Belongs to the sodium channel (TC 1.A.1.10) family. SCN7A subfamily.

RefSeq proteins (1): NP_002967* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001696	Na_channel_asu	Family
IPR005821	Ion_trans_dom	Domain
IPR010526	Na_trans_assoc_dom	Domain
IPR027359	Volt_channel_dom_sf	Homologous_superfamily
IPR043203	VGCC_Ca_Na	Family
IPR044564	Na_chnl_inactivation_gate	Domain
IPR058542	IQ_SCN5A_C	Domain

Pfam: PF00520, PF06512, PF24609

Catalyzed reactions (Rhea), 1 shown:

• Na(+)(in) = Na(+)(out) (RHEA:34963)

UniProt features (171 total): helix 55, topological domain 29, transmembrane region 24, strand 12, turn 9, sequence variant 8, mutagenesis site 6, modified residue 5, glycosylation site 5, disulfide bond 5, intramembrane region 4, repeat 4, compositionally biased region 2, chain 1, region of interest 1, sequence conflict 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
7TJ9	ELECTRON MICROSCOPY	2.9
7TJ8	ELECTRON MICROSCOPY	3.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q01118-F1	74.18	0.15

Functional residue map

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

Post-translational modifications (5): 442, 777, 843, 869, 905

Disulfide bonds (5): 267–307, 658–664, 696–705, 1087–1107, 1451–1466

Glycosylation sites (5): 276, 281, 309, 1103, 1113

Mutagenesis-validated functional residues (6):

Position	Phenotype
724	increased non-selective monoatomic cation leak channel activity; when associated with t-1189 and t-1492.
1189	increased non-selective monoatomic cation leak channel activity; when associated with q-724 and t-1492.
1492	increased non-selective monoatomic cation leak channel activity; when associated with q-724 and t-1189.

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: 206 (showing top): GSE18804_BRAIN_VS_COLON_TUMORAL_MACROPHAGE_UP, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_SODIUM_ION_TRANSMEMBRANE_TRANSPORT, MODULE_64, CHANDRAN_METASTASIS_DN, MORF_RAD51L3, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_MUSCLE_CONTRACTION, chr2q24, WTGAAAT_UNKNOWN, GOBP_CARDIAC_MUSCLE_CELL_CONTRACTION, TGACATY_UNKNOWN, GOBP_SODIUM_ION_HOMEOSTASIS, GOBP_ACTIN_MEDIATED_CELL_CONTRACTION, GOBP_RESPONSE_TO_ABIOTIC_STIMULUS

GO Biological Process (11): osmosensory signaling pathway (GO:0007231), response to bacterium (GO:0009617), cellular homeostasis (GO:0019725), sodium ion transmembrane transport (GO:0035725), sodium ion homeostasis (GO:0055078), cardiac muscle cell action potential involved in contraction (GO:0086002), monoatomic ion transport (GO:0006811), sodium ion transport (GO:0006814), monoatomic ion transmembrane transport (GO:0034220), transmembrane transport (GO:0055085), monoatomic cation transmembrane transport (GO:0098655)

GO Molecular Function (7): voltage-gated sodium channel activity (GO:0005248), sodium channel activity (GO:0005272), transmembrane transporter binding (GO:0044325), osmolarity-sensing monoatomic cation channel activity (GO:1990760), monoatomic ion channel activity (GO:0005216), monoatomic cation channel activity (GO:0005261), protein binding (GO:0005515)

GO Cellular Component (4): voltage-gated sodium channel complex (GO:0001518), plasma membrane (GO:0005886), glial cell projection (GO:0097386), membrane (GO:0016020)

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
transport	2
monoatomic cation channel activity	2
intracellular signal transduction	1
cellular response to osmotic stress	1
response to other organism	1
homeostatic process	1
sodium ion transport	1
monoatomic cation transmembrane transport	1
monoatomic cation homeostasis	1
inorganic ion homeostasis	1
cardiac muscle cell action potential	1
cardiac muscle cell contraction	1
metal ion transport	1
monoatomic ion transport	1
transmembrane transport	1
cellular process	1
monoatomic cation transport	1
monoatomic ion transmembrane transport	1
sodium channel activity	1
sodium ion transmembrane transporter activity	1
protein binding	1
osmosensor activity	1
gated channel activity	1
monoatomic ion transmembrane transporter activity	1
channel activity	1
monoatomic ion channel activity	1
monoatomic cation transmembrane transporter activity	1
binding	1
sodium channel complex	1
plasma membrane protein complex	1
membrane	1
cell periphery	1
plasma membrane bounded cell projection	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1230 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SCN7A	SCNM1	Q9BWG6	749
SCN7A	SCN1B	Q07699	523
SCN7A	SCN3B	Q9NY72	469
SCN7A	FEZF2	Q8TBJ5	418
SCN7A	DYNLRB2	Q8TF09	408
SCN7A	MEIG1	Q5JSS6	405
SCN7A	CARF	Q8N187	396
SCN7A	CACNA2D2	Q9NY47	393
SCN7A	CACNA2D1	P54289	389
SCN7A	NAV2	Q8IVL1	387
SCN7A	TMEM260	Q9NX78	379
SCN7A	TBX6	O95947	376
SCN7A	SNTG2	Q9NY99	375
SCN7A	SCN4B	Q8IWT1	375
SCN7A	SCN9A	Q15858	372

IntAct

6 interactions, top by confidence:

A	B	Type	Score
SCN3B	SCN7A	psi-mi:“MI:0407”(direct interaction)	0.520
SCN7A	SCN3B	psi-mi:“MI:0407”(direct interaction)	0.520
MAPT	SHTN1	psi-mi:“MI:0914”(association)	0.350
ITM2B	ILVBL	psi-mi:“MI:0914”(association)	0.350

BioGRID (4): SCN7A (Affinity Capture-MS), FKBP5 (Cross-Linking-MS (XL-MS)), FKBP4 (Cross-Linking-MS (XL-MS)), DSTN (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A2ARP9, A2ASI5, B1AWN6, B1AYL1, F1LQQ7, O08562, O46669, O70344, O73925, O88420, O88457, O88944, O97531, P02719, P04775, P08104, P0DMA5, P15389, P15390, P35499, P51787, P59111, P97414, Q01118, Q14524, Q28371, Q28644, Q2XVR7, Q62205, Q62968, Q6AXP6, Q6QIY3, Q7RTX7, Q8K3F6, Q96L42, Q96P56, Q99250, Q9ER60, Q9JJV9, Q9JK45

Diamond homologs: A2APX8, A2ASI5, B1AWN6, B1AYL1, D0E0C2, F1LQQ7, O00555, O08562, O46669, O73705, O73706, O73707, O88420, O88457, P02719, P04774, P04775, P08104, P0DMA5, P15389, P15390, P27884, P35498, P35499, P35500, P54282, P56699, P97445, Q01118, Q02789, Q05973, Q14524, Q15858, Q15878, Q20JQ7, Q28371, Q28644, Q2XVR3, Q2XVR4, Q2XVR5

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
SCN7A	“form complex”	“Nax cation channel complex SCN2B-SCN3B variant”	binding
SCN7A	“form complex”	“Nax cation channel complex, SCN3B-SCN4B variant”	binding
SCN7A	“form complex”	“Nax cation channel complex, SCN1B-SCN4B variant”	binding
SCN7A	“form complex”	“Nax cation channel complex, SCN1B-SCN2B variant”	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	1
Uncertain significance	203
Likely benign	42
Benign	28

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
2506526	GRCh37/hg19 2q24.3(chr2:166872248-167334216)	Pathogenic
2664654	NM_002976.4(SCN7A):c.1786C>T (p.Arg596Ter)	Likely pathogenic

SpliceAI

4004 predictions. Top by Δscore:

Variant	Effect	Δscore
2:166410218:A:AC	donor_gain	1.0000
2:166410219:C:CC	donor_gain	1.0000
2:166410321:CCAGG:C	acceptor_gain	1.0000
2:166410322:C:T	acceptor_gain	1.0000
2:166410322:CAGG:C	acceptor_gain	1.0000
2:166413066:A:AC	donor_gain	1.0000
2:166413067:C:CG	donor_gain	1.0000
2:166413067:CAG:C	donor_gain	1.0000
2:166423257:A:AC	donor_gain	1.0000
2:166423258:C:CC	donor_gain	1.0000
2:166423309:TAAA:T	donor_gain	1.0000
2:166423310:AAAA:A	donor_gain	1.0000
2:166427832:TAA:T	donor_gain	1.0000
2:166427833:AAA:A	donor_gain	1.0000
2:166441762:CAA:C	acceptor_gain	1.0000
2:166447614:T:A	donor_gain	1.0000
2:166456865:GATAC:G	donor_loss	1.0000
2:166456866:ATAC:A	donor_loss	1.0000
2:166456867:TAC:T	donor_loss	1.0000
2:166456868:A:AG	donor_loss	1.0000
2:166456869:C:CA	donor_loss	1.0000
2:166456874:T:C	donor_gain	1.0000
2:166462527:CTGA:C	acceptor_gain	1.0000
2:166462531:C:CC	acceptor_gain	1.0000
2:166465460:AC:A	donor_gain	1.0000
2:166465461:CC:C	donor_gain	1.0000
2:166465775:TCTTA:T	donor_loss	1.0000
2:166465776:CTTA:C	donor_loss	1.0000
2:166465777:TTACC:T	donor_loss	1.0000
2:166465778:TACCT:T	donor_loss	1.0000

AlphaMissense

11267 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:166405728:C:G	R1634P	0.990
2:166406065:A:G	W1522R	0.989
2:166406065:A:T	W1522R	0.989
2:166406360:A:C	S1423R	0.986
2:166406360:A:T	S1423R	0.986
2:166406362:T:G	S1423R	0.986
2:166405726:C:G	A1635P	0.985
2:166405744:C:G	A1629P	0.985
2:166406007:A:G	F1541S	0.982
2:166405938:A:G	L1564P	0.981
2:166465852:C:G	C267S	0.979
2:166465853:A:T	C267S	0.979
2:166462525:C:G	C316S	0.977
2:166462526:A:T	C316S	0.977
2:166465483:C:G	C307S	0.977
2:166465484:A:T	C307S	0.977
2:166405734:A:T	I1632N	0.976
2:166405764:C:G	R1622P	0.976
2:166416902:A:C	S1073R	0.976
2:166416902:A:T	S1073R	0.976
2:166416904:T:G	S1073R	0.976
2:166405723:A:C	Y1636D	0.974
2:166406195:A:C	S1478R	0.973
2:166406195:A:T	S1478R	0.973
2:166406197:T:G	S1478R	0.973
2:166427800:G:C	S947R	0.973
2:166427800:G:T	S947R	0.973
2:166427802:T:G	S947R	0.973
2:166465851:A:C	C267W	0.973
2:166406323:A:G	W1436R	0.972

dbSNP variants (sampled 300 via entrez): RS1000005834 (2:166494343 C>T), RS1000010040 (2:166452084 C>G), RS1000044397 (2:166437620 C>A), RS1000057897 (2:166431246 G>A), RS1000059970 (2:166494568 A>AGCAGC), RS1000095335 (2:166446174 T>C), RS1000099440 (2:166464353 T>G), RS1000109718 (2:166430877 C>A,T), RS1000110387 (2:166474777 G>A), RS1000169494 (2:166488554 G>A,T), RS1000199342 (2:166416484 C>T), RS1000280074 (2:166467920 T>C,G), RS1000287415 (2:166425149 T>A,C), RS1000311087 (2:166467643 A>C,G), RS1000454014 (2:166461058 T>C)

Disease associations

OMIM: gene MIM:182392 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
holoprosencephaly	Limited	Autosomal recessive

Mondo (2): Dravet syndrome (MONDO:0100135), holoprosencephaly (MONDO:0016296)

Orphanet (1): Dravet syndrome (Orphanet:33069)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST000406_15	Amyotrophic lateral sclerosis	7.000000e-06
GCST000714_5	Conduct disorder	8.000000e-06
GCST007448_15	Normal facial asymmetry (angle of surface orientation score)	3.000000e-13
GCST008361_7	Response to cognitive-behavioural therapy in major depressive disorder	4.000000e-06
GCST009391_389	Metabolite levels	5.000000e-06
GCST009391_587	Metabolite levels	6.000000e-06

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0009751	facial asymmetry measurement
EFO:0007820	cognitive behavioural therapy
EFO:0010437	triacylglycerol 58:10 measurement
EFO:0010501	indole-3-propionate measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D016142	Holoprosencephaly	C05.660.207.410; C10.500.034.875; C16.131.077.410; C16.131.260.380; C16.131.621.207.410; C16.131.666.034.875; C16.320.180.380

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2331043 (PROTEIN FAMILY), CHEMBL3585 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

20 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 480,768 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL11	IMIPRAMINE	4	48,893
CHEMBL12713	SERTINDOLE	4	8,984
CHEMBL1423	PIMOZIDE	4	17,310
CHEMBL193	NIFEDIPINE	4	74,353
CHEMBL23	DILTIAZEM	4	54,676
CHEMBL45816	MIBEFRADIL	4	7,838
CHEMBL54	HALOPERIDOL	4	60,883
CHEMBL558	MEXILETINE	4	15,463
CHEMBL629	AMITRIPTYLINE	4	52,595
CHEMBL633	AMIODARONE	4	29,704
CHEMBL71	CHLORPROMAZINE	4	45,827
CHEMBL698	TETRACAINE	4	43,379
CHEMBL113461	TEDISAMIL	3	1,251
CHEMBL475534	NITRENDIPINE	3	16,468
CHEMBL5314404	AJMALINE	3
CHEMBL3544913	VIXOTRIGINE	3	374
CHEMBL507974	TETRODOTOXIN	3	1,034
CHEMBL87045	CIFENLINE	2	1,298
CHEMBL2325014	PF-05089771	2	219
CHEMBL3707218	FUNAPIDE	2	219

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

Binding affinities (BindingDB)

3 measured of 3 human assays (3 total across all organisms); most potent 3 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEMBL5082739	IC50	4 nM
Ajmaline	IC50	8200 nM
Tedisamil	IC50	20000 nM

ChEMBL bioactivities

112 potent at pChembl≥5 of 125 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
11.00	IC50	0.01	nM	CHEMBL4217988
9.40	IC50	0.4	nM	CHEMBL3657855
9.22	IC50	0.6	nM	CHEMBL3662190
9.22	IC50	0.6	nM	CHEMBL5094715
9.10	IC50	0.8	nM	CHEMBL3318132
9.10	IC50	0.8	nM	CHEMBL5082131
9.05	IC50	0.9	nM	CHEMBL4588728
8.96	IC50	1.1	nM	CHEMBL3657932
8.96	IC50	1.1	nM	CHEMBL3657855
8.80	IC50	1.6	nM	CHEMBL3657851
8.74	IC50	1.8	nM	CHEMBL5079176
8.74	IC50	1.8	nM	CHEMBL5094715
8.68	IC50	2.1	nM	CHEMBL3416886
8.66	IC50	2.2	nM	CHEMBL3657938
8.64	IC50	2.3	nM	CHEMBL3657939
8.62	IC50	2.4	nM	CHEMBL5082321
8.49	IC50	3.2	nM	CHEMBL3945969
8.46	Kd	3.5	nM	CHEMBL4444707
8.44	IC50	3.6	nM	CHEMBL5091342
8.40	IC50	4	nM	CHEMBL5082739
8.26	IC50	5.5	nM	CHEMBL3662226
8.11	IC50	7.7	nM	CHEMBL5071877
8.01	IC50	9.8	nM	CHEMBL5080495
8.00	IC50	10	nM	CHEMBL4454760
7.96	IC50	11	nM	PF-05089771
7.85	IC50	14	nM	CHEMBL3657932
7.80	IC50	16	nM	CHEMBL5094715
7.72	IC50	19	nM	CHEMBL4547737
7.66	Kd	22	nM	CHEMBL4471012
7.66	IC50	22	nM	CHEMBL5080891
7.64	IC50	23	nM	CHEMBL3662226
7.60	IC50	25	nM	CHEMBL3657851
7.58	IC50	26	nM	CHEMBL5082131
7.51	IC50	31	nM	CHEMBL5071877
7.47	IC50	34	nM	CHEMBL5080495
7.47	IC50	34	nM	CHEMBL5079176
7.44	IC50	36	nM	TETRODOTOXIN
7.42	IC50	38	nM	CHEMBL5082739
7.38	IC50	42	nM	CHEMBL5080891
7.36	IC50	44	nM	CHEMBL4458532
7.31	IC50	49	nM	CHEMBL3657855
7.27	IC50	54	nM	PIMOZIDE
7.27	IC50	54	nM	FUNAPIDE
7.25	IC50	56	nM	TETRACAINE
7.18	IC50	66	nM	CHEMBL5091342
7.16	IC50	70	nM	CHEMBL5196338
7.14	IC50	72	nM	CHEMBL5176104
7.10	IC50	80	nM	CHEMBL5208962
7.10	IC50	80	nM	CHEMBL5178152
7.05	IC50	90	nM	CHEMBL5202508

PubChem BioAssay actives

112 with measured affinity, of 168 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
3-cyano-4-[2-[2-[(2-piperidin-4-ylethylamino)methyl]-4-pyridinyl]-4-[3-(trifluoromethyl)phenyl]phenoxy]-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide	1525384: Inhibition of human Nav1.7 expressed in HEK293 cells by electrophysiology assay	ic50	<0.0001	uM
4-(1-adamantylmethoxy)-N-(azetidin-1-ylsulfonyl)-5-cyclopropyl-2-fluorobenzamide	1525384: Inhibition of human Nav1.7 expressed in HEK293 cells by electrophysiology assay	ic50	0.0004	uM
5-cyclopropyl-4-[[1-[(1S)-1-(3,5-dichlorophenyl)ethyl]piperidin-4-yl]methoxy]-2-fluoro-N-methylsulfonylbenzamide	1831646: Inhibition of full length human Nav1.7 expressed in HEK cells by whole cell voltage clamp analysis	ic50	0.0006	uM
5-cyclopropyl-N-cyclopropylsulfonyl-2-fluoro-4-[(6-methylspiro[2.5]octan-6-yl)methoxy]benzamide	1525384: Inhibition of human Nav1.7 expressed in HEK293 cells by electrophysiology assay	ic50	0.0006	uM
5-cyclopropyl-4-[[1-[2-(3,5-dichlorophenyl)propan-2-yl]piperidin-4-yl]methoxy]-2-fluoro-N-methylsulfonylbenzamide	1831640: Displacement of [3H]GX-545 Nav1.7 (unknown origin) expressed in HEK cells by liquid scintillation counting based radioligand competition assay	ic50	0.0008	uM
(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-6-amino-2-[[(2S)-6-amino-2-[[(1R,4S,7S,13S,16R,21R,24S,27S,30S,33S,36S,39S,42R,45S,48S,51S,54S,57S,60R,65R,68S,71S,74S)-27,57-bis(4-aminobutyl)-21-[[(2S)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]-24-(3-amino-3-oxopropyl)-54,74-bis(3-carbamimidamidopropyl)-13,51-bis(2-carboxyethyl)-45-(carboxymethyl)-39-[(1R)-1-hydroxyethyl]-48-(hydroxymethyl)-30,36,68-tris(1H-indol-3-ylmethyl)-71-(2-methylpropyl)-7,33-bis(2-methylsulfanylethyl)-3,6,9,12,15,22,25,28,31,34,37,40,43,46,49,52,55,58,67,70,73,76,81-tricosaoxo-4-propan-2-yl-18,19,62,63,78,79-hexathia-2,5,8,11,14,23,26,29,32,35,38,41,44,47,50,53,56,59,66,69,72,75,82-tricosazatricyclo[40.34.4.216,60]dooctacontane-65-carbonyl]amino]hexanoyl]amino]hexanoyl]amino]hexanoyl]amino]-4-methylpentanoyl]amino]-3-(1H-indol-3-yl)propanoic acid	1525384: Inhibition of human Nav1.7 expressed in HEK293 cells by electrophysiology assay	ic50	0.0008	uM
(3S)-3-amino-4-oxo-4-[[(1R,4S,7S,10S,13S,16S,19R,24R,27S,30S,33S,36S,39S,42S,45R,51S,54S,57S,60R,65R,68S,71S,74S,77S,83S)-7,30,36,42,57-pentakis(4-aminobutyl)-77-benzyl-39,68-bis(3-carbamimidamidopropyl)-24-[[(2S)-1-[[(2S)-1-[[(2S)-3-carboxy-1-[[(2S)-1-[[(2S,3R)-1-[[(2S)-1-[[(1S,2R)-1-carboxy-2-hydroxypropyl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-1-oxopropan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]carbamoyl]-4,13-bis(2-carboxyethyl)-10,16,83-tris(carboxymethyl)-27,71-bis[(4-hydroxyphenyl)methyl]-54-(1H-imidazol-5-ylmethyl)-51-(2-methylpropyl)-33,74-bis(2-methylsulfanylethyl)-2,5,8,11,14,17,26,29,32,35,38,41,44,47,50,53,56,59,66,69,72,75,78,81,84,91-hexacosaoxo-21,22,62,63,87,88-hexathia-3,6,9,12,15,18,25,28,31,34,37,40,43,46,49,52,55,58,67,70,73,76,79,82,85,90-hexacosazatricyclo[43.40.4.219,60]hennonacontan-65-yl]amino]butanoic acid	1525384: Inhibition of human Nav1.7 expressed in HEK293 cells by electrophysiology assay	ic50	0.0009	uM
4-(1-adamantylmethoxy)-5-cyclopropyl-N-cyclopropylsulfonyl-2-fluorobenzamide	1831640: Displacement of [3H]GX-545 Nav1.7 (unknown origin) expressed in HEK cells by liquid scintillation counting based radioligand competition assay	ic50	0.0011	uM
4-(1-adamantylmethoxy)-5-cyclopropyl-2-fluoro-N-methylsulfonylbenzamide	1831640: Displacement of [3H]GX-545 Nav1.7 (unknown origin) expressed in HEK cells by liquid scintillation counting based radioligand competition assay	ic50	0.0016	uM
5-cyclopropyl-4-[[1-[(1R)-1-(3,5-dichlorophenyl)ethyl]piperidin-4-yl]methoxy]-2-fluoro-N-methylsulfonylbenzamide	1831640: Displacement of [3H]GX-545 Nav1.7 (unknown origin) expressed in HEK cells by liquid scintillation counting based radioligand competition assay	ic50	0.0018	uM
(3S)-3-amino-4-[[(1R,4S,10S,13S,16S,19S,22S,25R,30R,33S,36S,39S,42S,45S,48S,51R,54S,57S,60S,63S,69S,72R,77R,80S,86S,89S,92S,95S)-30-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-1-oxohexan-2-yl]carbamoyl]-22,36,95-tris(4-aminobutyl)-16,60-bis(2-amino-2-oxoethyl)-86-benzyl-4-[(2S)-butan-2-yl]-45,69,92-tris(3-carbamimidamidopropyl)-13,19-bis(carboxymethyl)-42-[(1R)-1-hydroxyethyl]-48-(hydroxymethyl)-39-(1H-imidazol-4-ylmethyl)-33-(1H-indol-3-ylmethyl)-57,80-bis(2-methylpropyl)-89-(2-methylsulfanylethyl)-2,3a,5,11,14,17,20,23,32,35,38,41,44,47,50,53,56,59,62,68,71,78,81,84,87,90,93,96-octacosaoxo-54-propan-2-yl-a,27,28,74,75,99-hexathia-2a,3,6,12,15,18,21,24,31,34,37,40,43,46,49,52,55,58,61,67,70,79,82,85,88,91,94,97-octacosazapentacyclo[49.46.4.225,72.06,10.063,67]trihectan-77-yl]amino]-4-oxobutanoic acid	1525384: Inhibition of human Nav1.7 expressed in HEK293 cells by electrophysiology assay	ic50	0.0021	uM
4-(1-adamantylmethoxy)-5-cyclopropyl-2-fluoro-N-pyrrolidin-1-ylsulfonylbenzamide	1831640: Displacement of [3H]GX-545 Nav1.7 (unknown origin) expressed in HEK cells by liquid scintillation counting based radioligand competition assay	ic50	0.0022	uM
4-(1-adamantylmethoxy)-5-cyclopropyl-2-fluoro-N-morpholin-4-ylsulfonylbenzamide	1831640: Displacement of [3H]GX-545 Nav1.7 (unknown origin) expressed in HEK cells by liquid scintillation counting based radioligand competition assay	ic50	0.0023	uM
5-cyclopropyl-4-[[1-[(3,5-dichlorophenyl)methyl]piperidin-4-yl]methoxy]-2-fluoro-N-methylsulfonylbenzamide	1831640: Displacement of [3H]GX-545 Nav1.7 (unknown origin) expressed in HEK cells by liquid scintillation counting based radioligand competition assay	ic50	0.0024	uM
1-[4-(3-chloro-5-fluorophenyl)-5-fluoro-2-methoxyphenyl]-N-(1,2-oxazol-3-yl)-2-oxoquinoline-6-sulfonamide	1525384: Inhibition of human Nav1.7 expressed in HEK293 cells by electrophysiology assay	ic50	0.0032	uM
4-[[1-[[2-chloro-5-(trifluoromethyl)phenyl]methyl]piperidin-4-yl]methoxy]-5-cyclopropyl-2-fluoro-N-methylsulfonylbenzamide	1525416: Binding affinity to human recombinant Nav1.7 by radioligand binding assay	kd	0.0035	uM
4-[(1-benzhydrylpiperidin-4-yl)methoxy]-5-cyclopropyl-2-fluoro-N-methylsulfonylbenzamide	1831640: Displacement of [3H]GX-545 Nav1.7 (unknown origin) expressed in HEK cells by liquid scintillation counting based radioligand competition assay	ic50	0.0036	uM
4-(1-adamantylmethoxy)-5-cyclopropyl-2-fluoro-N-(oxetan-3-ylsulfonyl)benzamide	1831640: Displacement of [3H]GX-545 Nav1.7 (unknown origin) expressed in HEK cells by liquid scintillation counting based radioligand competition assay	ic50	0.0040	uM
4-[(1-benzhydrylazetidin-3-yl)methoxy]-5-cyclopropyl-2-fluoro-N-methylsulfonylbenzamide	1831640: Displacement of [3H]GX-545 Nav1.7 (unknown origin) expressed in HEK cells by liquid scintillation counting based radioligand competition assay	ic50	0.0055	uM
5-cyclopropyl-2-fluoro-N-methylsulfonyl-4-[[1-[[4-(trifluoromethoxy)phenyl]methyl]piperidin-4-yl]methoxy]benzamide	1831640: Displacement of [3H]GX-545 Nav1.7 (unknown origin) expressed in HEK cells by liquid scintillation counting based radioligand competition assay	ic50	0.0077	uM
5-cyclopropyl-4-[[1-(3,5-dichlorobenzoyl)piperidin-4-yl]methoxy]-2-fluoro-N-methylsulfonylbenzamide	1831640: Displacement of [3H]GX-545 Nav1.7 (unknown origin) expressed in HEK cells by liquid scintillation counting based radioligand competition assay	ic50	0.0098	uM
(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-6-amino-2-[[(2S)-6-amino-2-[[(1R,4S,7S,13S,16R,21R,24S,27S,30S,33S,36S,39S,42R,45S,48S,51S,54S,57S,60R,65R,68S,71S,74S)-21-[[(2S)-2-[[(2S)-2-[[(2S)-1-(2-aminoacetyl)pyrrolidine-2-carbonyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-27,57-bis(4-aminobutyl)-24,36-bis(3-amino-3-oxopropyl)-54,74-bis(3-carbamimidamidopropyl)-13,51-bis(2-carboxyethyl)-45-(carboxymethyl)-39-[(1R)-1-hydroxyethyl]-48-(hydroxymethyl)-30,68-bis(1H-indol-3-ylmethyl)-71-(2-methylpropyl)-7,33-bis(2-methylsulfanylethyl)-3,6,9,12,15,22,25,28,31,34,37,40,43,46,49,52,55,58,67,70,73,76,81-tricosaoxo-4-propan-2-yl-18,19,62,63,78,79-hexathia-2,5,8,11,14,23,26,29,32,35,38,41,44,47,50,53,56,59,66,69,72,75,82-tricosazatricyclo[40.34.4.216,60]dooctacontane-65-carbonyl]amino]hexanoyl]amino]hexanoyl]amino]hexanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoic acid	1525384: Inhibition of human Nav1.7 expressed in HEK293 cells by electrophysiology assay	ic50	0.0100	uM
4-[2-(5-amino-1H-pyrazol-4-yl)-4-chlorophenoxy]-5-chloro-2-fluoro-N-(1,3-thiazol-4-yl)benzenesulfonamide	1525384: Inhibition of human Nav1.7 expressed in HEK293 cells by electrophysiology assay	ic50	0.0110	uM
[(3aS,4R,10aS)-2,6-diamino-10,10-dihydroxy-3a,4,8,9-tetrahydro-1H-pyrrolo[1,2-c]purin-4-yl]methyl acetate	1525384: Inhibition of human Nav1.7 expressed in HEK293 cells by electrophysiology assay	ic50	0.0190	uM
4-[[1-[(4-chlorophenyl)methyl]piperidin-4-yl]methoxy]-5-cyclopropyl-2-fluoro-N-methylsulfonylbenzamide	1831640: Displacement of [3H]GX-545 Nav1.7 (unknown origin) expressed in HEK cells by liquid scintillation counting based radioligand competition assay	ic50	0.0220	uM
N-cyclopropylsulfonyl-1-[(3R)-1-[(1R)-1-(3,5-dichlorophenyl)ethyl]pyrrolidin-3-yl]-6-fluoro-3-methylindazole-5-carboxamide	1525416: Binding affinity to human recombinant Nav1.7 by radioligand binding assay	kd	0.0220	uM
(1R,5R,6R,7R,9S,11S,12S,13S,14S)-3-amino-14-(hydroxymethyl)-8,10-dioxa-2,4-diazatetracyclo[7.3.1.17,11.01,6]tetradec-3-ene-5,9,12,13,14-pentol	1525384: Inhibition of human Nav1.7 expressed in HEK293 cells by electrophysiology assay	ic50	0.0360	uM
N-[(3aS,4S,9S,10aS)-2,6-diamino-4-[(2,5-dioxopyrrolidin-1-yl)methyl]-10,10-dihydroxy-3a,4,8,9-tetrahydro-1H-pyrrolo[1,2-c]purin-9-yl]-1,1-dimethyl-2,3-dihydroindene-4-carboxamide	1525384: Inhibition of human Nav1.7 expressed in HEK293 cells by electrophysiology assay	ic50	0.0440	uM
Pimozide	1207165: Inhibition of Na channel (species unknown)	ic50	0.0540	uM
(7S)-1’-[[5-(trifluoromethyl)furan-2-yl]methyl]spiro[6H-furo[2,3-f][1,3]benzodioxole-7,3’-indole]-2’-one	1525384: Inhibition of human Nav1.7 expressed in HEK293 cells by electrophysiology assay	ic50	0.0540	uM
Tetracaine	1891560: Inhibition of recombinant human Nav 1.7 expressed in HEK293F cells incubated for 3 mins by FRET based membrane potential assay	ic50	0.0560	uM
4-[2-oxo-1-(2-piperidin-1-ylethyl)quinolin-6-yl]oxybenzonitrile	1891560: Inhibition of recombinant human Nav 1.7 expressed in HEK293F cells incubated for 3 mins by FRET based membrane potential assay	ic50	0.0700	uM
N-[(3aS,4S,9S,10aS)-2,6-diamino-4-[(2,5-dioxopyrrolidin-1-yl)methyl]-10,10-dihydroxy-3a,4,8,9-tetrahydro-1H-pyrrolo[1,2-c]purin-9-yl]-5,6,7,8-tetrahydronaphthalene-1-carboxamide	1875833: Inhibition of human Nav1.7 expressed in HEK293 cells at -120 mV holding potential by automated patch clamp electrophysiology recording	ic50	0.0720	uM
4-[2-[2-(4-methylpiperazin-1-yl)-2-oxoethoxy]quinolin-6-yl]oxybenzonitrile	1891560: Inhibition of recombinant human Nav 1.7 expressed in HEK293F cells incubated for 3 mins by FRET based membrane potential assay	ic50	0.0800	uM
4-[2-(2-oxo-2-piperazin-1-ylethoxy)quinolin-6-yl]oxybenzonitrile	1891560: Inhibition of recombinant human Nav 1.7 expressed in HEK293F cells incubated for 3 mins by FRET based membrane potential assay	ic50	0.0800	uM
4-[2-(2-piperidin-1-ylethoxy)quinolin-6-yl]oxybenzonitrile	1891560: Inhibition of recombinant human Nav 1.7 expressed in HEK293F cells incubated for 3 mins by FRET based membrane potential assay	ic50	0.0900	uM
4-[(1-benzylpiperidin-4-yl)methoxy]-5-cyclopropyl-2-fluoro-N-methylsulfonylbenzamide	1831640: Displacement of [3H]GX-545 Nav1.7 (unknown origin) expressed in HEK cells by liquid scintillation counting based radioligand competition assay	ic50	0.1400	uM
4-[2-(2-oxo-2-piperidin-1-ylethoxy)quinolin-6-yl]oxybenzonitrile	1891560: Inhibition of recombinant human Nav 1.7 expressed in HEK293F cells incubated for 3 mins by FRET based membrane potential assay	ic50	0.2400	uM
1-(4-methylpiperazin-1-yl)-2-[6-[[5-(trifluoromethyl)-2-pyridinyl]oxy]quinolin-2-yl]oxyethanone	1891560: Inhibition of recombinant human Nav 1.7 expressed in HEK293F cells incubated for 3 mins by FRET based membrane potential assay	ic50	0.2600	uM
4-[2-(2-morpholin-4-yl-2-oxoethoxy)quinolin-6-yl]oxybenzonitrile	1891560: Inhibition of recombinant human Nav 1.7 expressed in HEK293F cells incubated for 3 mins by FRET based membrane potential assay	ic50	0.3200	uM
[(3aS,4R,10aS)-2,6-diamino-10,10-dihydroxy-3a,4,8,9-tetrahydro-1H-pyrrolo[1,2-c]purin-4-yl]methyl carbamate	1525384: Inhibition of human Nav1.7 expressed in HEK293 cells by electrophysiology assay	ic50	0.4100	uM
4-[2-[6-[[5-(trifluoromethyl)-2-pyridinyl]oxy]quinolin-2-yl]oxyacetyl]piperazin-2-one	1891560: Inhibition of recombinant human Nav 1.7 expressed in HEK293F cells incubated for 3 mins by FRET based membrane potential assay	ic50	0.4800	uM
1-piperazin-1-yl-2-[6-[[5-(trifluoromethyl)-2-pyridinyl]oxy]quinolin-2-yl]oxyethanone	1891560: Inhibition of recombinant human Nav 1.7 expressed in HEK293F cells incubated for 3 mins by FRET based membrane potential assay	ic50	0.5500	uM
4-[2-[2-oxo-2-(3-oxopiperazin-1-yl)ethoxy]quinolin-6-yl]oxybenzonitrile	1891560: Inhibition of recombinant human Nav 1.7 expressed in HEK293F cells incubated for 3 mins by FRET based membrane potential assay	ic50	0.5600	uM
(3-methylsulfonylazetidin-1-yl)-[6-[[5-(trifluoromethyl)-2-pyridinyl]oxy]quinolin-2-yl]methanone	1891560: Inhibition of recombinant human Nav 1.7 expressed in HEK293F cells incubated for 3 mins by FRET based membrane potential assay	ic50	0.7800	uM
piperazin-1-yl-[6-[4-(trifluoromethylsulfonyl)phenoxy]quinolin-2-yl]methanone	1891560: Inhibition of recombinant human Nav 1.7 expressed in HEK293F cells incubated for 3 mins by FRET based membrane potential assay	ic50	0.8100	uM
piperazin-1-yl-[6-[4-(trifluoromethyl)phenoxy]quinolin-2-yl]methanone	1891560: Inhibition of recombinant human Nav 1.7 expressed in HEK293F cells incubated for 3 mins by FRET based membrane potential assay	ic50	0.9000	uM
N-[(3R)-2-oxooxolan-3-yl]-6-[[5-(trifluoromethyl)-2-pyridinyl]oxy]quinoline-2-carboxamide	1891560: Inhibition of recombinant human Nav 1.7 expressed in HEK293F cells incubated for 3 mins by FRET based membrane potential assay	ic50	0.9100	uM
piperazin-1-yl-[6-[[5-(trifluoromethyl)-2-pyridinyl]oxy]quinolin-2-yl]methanone	1891560: Inhibition of recombinant human Nav 1.7 expressed in HEK293F cells incubated for 3 mins by FRET based membrane potential assay	ic50	0.9200	uM
4-[2-oxo-1-(2-piperidin-1-ylethyl)quinolin-6-yl]benzonitrile	1891560: Inhibition of recombinant human Nav 1.7 expressed in HEK293F cells incubated for 3 mins by FRET based membrane potential assay	ic50	0.9400	uM

CTD chemical–gene interactions

24 total (human), top 24 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Panobinostat	affects cotreatment, decreases expression	2
Nickel	decreases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, decreases expression	2
methylmercuric chloride	decreases expression	1
bisphenol A	affects cotreatment, decreases methylation	1
trichostatin A	decreases expression	1
sodium arsenite	increases expression	1
2-bromopalmitate	decreases reaction, increases abundance, increases palmitoylation	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
clothianidin	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
incobotulinumtoxinA	decreases expression	1
Arsenic Trioxide	decreases expression	1
Fulvestrant	decreases methylation, affects cotreatment	1
Benzo(a)pyrene	decreases methylation	1
Cadmium	decreases reaction, increases abundance, increases palmitoylation	1
Doxorubicin	decreases expression	1
Niclosamide	decreases expression	1
Valproic Acid	increases expression	1
Aflatoxin B1	decreases methylation	1
Cadmium Chloride	decreases reaction, increases abundance, increases palmitoylation	1
Okadaic Acid	decreases expression	1

ChEMBL screening assays

48 unique, capped per target: 32 binding, 16 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3430568	Functional	Inhibition of Na channel (species unknown)	Simulation of multiple ion channel block provides improved early prediction of compounds’ clinical torsadogenic risk. — Cardiovasc Res
CHEMBL4880115	Binding	Na+ channel CEREP ligand profiling	Data for DCP probe A-079

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05044819	PHASE4	ACTIVE_NOT_RECRUITING	Assessment of Potential for Chronic Liver Injury in Participants Treated With Epidiolex (Cannabidiol) Oral Solution
NCT06598449	PHASE4	RECRUITING	Assessment of Safety of the Use of Fenfluramine in Children With Dravet Syndrome Under 24 Months of Age
NCT06924827	PHASE4	NOT_YET_RECRUITING	A Study to Investigate the Transition of Children From ‘Artisanal Cannabidiol (CBD) to Epidiolex
NCT07112365	PHASE4	NOT_YET_RECRUITING	The FINTEPLA as an Anti-SUDEP Therapy in Dravet Syndrome Project
NCT00098475	PHASE3	ACTIVE_NOT_RECRUITING	Lenalidomide and Dexamethasone With or Without Thalidomide in Treating Patients With Multiple Myeloma
NCT00114101	PHASE3	ACTIVE_NOT_RECRUITING	Lenalidomide in Treating Patients With Multiple Myeloma Undergoing Autologous Stem Cell Transplant
NCT00644228	PHASE3	ACTIVE_NOT_RECRUITING	Lenalidomide and Dexamethasone With or Without Bortezomib in Treating Patients With Previously Untreated Multiple Myeloma
NCT00869206	PHASE3	COMPLETED	Zoledronic Acid in Treating Patients With Metastatic Breast Cancer, Metastatic Prostate Cancer, or Multiple Myeloma With Bone Involvement
NCT02091375	PHASE3	COMPLETED	Antiepileptic Efficacy Study of GWP42003-P in Children and Young Adults With Dravet Syndrome (GWPCARE1)
NCT02174094	PHASE3	WITHDRAWN	Clobazam as Adjunctive Therapy in Paediatric Patients Aged ≥1 to ≤16 Years With Dravet Syndrome
NCT02187809	PHASE3	TERMINATED	Safety and Tolerability of Clobazam as Adjunctive Therapy in Paediatric Patients Aged ≥1 to ≤16 Years With Dravet Syndrome
NCT02224573	PHASE3	COMPLETED	An Open Label Extension Study of Cannabidiol (GWP42003-P) in Children and Adults With Dravet or Lennox-Gastaut Syndromes
NCT02224703	PHASE3	COMPLETED	GWPCARE2 A Study to Investigate the Efficacy and Safety of Cannabidiol (GWP42003-P) in Children and Young Adults With Dravet Syndrome
NCT02318563	PHASE3	WITHDRAWN	Cannabidiol Oral Solution as an Adjunctive Therapy for Treatment of Participants With Inadequately Controlled Dravet Syndrome
NCT02682927	PHASE3	COMPLETED	A Trial of Two Fixed Doses of ZX008 (Fenfluramine HCl) in Children and Young Adults With Dravet Syndrome
NCT02823145	PHASE3	COMPLETED	An Open-Label Extension Trial to Assess the Long-Term Safety of ZX008 (Fenfluramine Hydrochloride HCl) Oral Solution in Children and Young Adults With Dravet Syndrome
NCT02926898	PHASE3	COMPLETED	A 2-Part Study to Investigate the Dose-Ranging Safety and Pharmacokinetics, Followed by the Efficacy and Safety of ZX008 (Fenfluramine Hydrochloride) Oral Solution as an Adjunctive Therapy in Children ≥ 2 Years Old and Young Adults With Dravet Syndrome
NCT03299842	PHASE3	TERMINATED	A Study to Assess the Usability of the Embrace Seizure Detection Watch in Children and Young Adults With Dravet Syndrome
NCT03936777	PHASE3	COMPLETED	A Study to Investigate the Long-Term Safety of ZX008 (Fenfluramine Hydrochloride) Oral Solution in Children and Adults With Epileptic Encephalopathy Including Dravet Syndrome and Lennox-Gastaut Syndrome
NCT04462770	PHASE3	RECRUITING	A Study of EPX-100 (Clemizole Hydrochloride) in Participants With Dravet Syndrome
NCT04611438	PHASE3	UNKNOWN	Research on Cognitive Effect of Cannabidiol on Dravet Syndrome and Lennox-Gastaut SyndromeGastaut Syndrome
NCT04940624	PHASE3	COMPLETED	A Study of Soticlestat as an Add-on Therapy in Children and Young Adults With Dravet Syndrome
NCT05163314	PHASE3	TERMINATED	A Study of Soticlestat as an Add-on Therapy in Children and Adults With Dravet Syndrome or Lennox-Gastaut Syndrome
NCT05560282	PHASE3	TERMINATED	Fenfluramine for Adult Dravet Patients
NCT06118255	PHASE3	ACTIVE_NOT_RECRUITING	A Study to Evaluate Safety, Tolerability, and Pharmacokinetics of Fenfluramine (Hydrochloride) in Infants 1 Year to Less Than 2 Years of Age With Dravet Syndrome
NCT06422377	PHASE3	TERMINATED	A Study Evaluating Soticlestat in Participants With Dravet Syndrome or Lennox-Gastaut Syndrome Who Have Been Exposed to Fenfluramine
NCT06660394	PHASE3	RECRUITING	A Phase 3, Placebo-Controlled Study to Investigate LP352 in Children and Adults With Dravet Syndrome (DS)
NCT06872125	PHASE3	RECRUITING	A Double-blind Study Evaluating the Efficacy, Safety, and Tolerability of Zorevunersen in Patients With Dravet Syndrome
NCT00066638	PHASE2	COMPLETED	FR901228 in Treating Patients With Relapsed or Refractory Multiple Myeloma
NCT00088855	PHASE2	COMPLETED	Bortezomib and Pegylated Liposomal Doxorubicin Hydrochloride in Treating Patients With Previously Untreated Symptomatic Multiple Myeloma
NCT00445692	PHASE2	COMPLETED	Lenalidomide, Dexamethasone, and Clarithromycin in Treating Patients Who Have Undergone Stem Cell Transplant for Multiple Myeloma
NCT00839956	PHASE2	COMPLETED	Bortezomib and Vorinostat in Treating Patients With Multiple Myeloma Who Have Undergone Autologous Stem Cell Transplant
NCT01028716	PHASE2	TERMINATED	Donor Peripheral Blood Stem Cell Transplant in Treating Patients With Hematologic Malignancies
NCT01251172	PHASE2	WITHDRAWN	RO4929097 After Autologous Stem Cell Transplant in Treating Patients With Multiple Myeloma
NCT01605032	PHASE2	COMPLETED	Busulfan, Melphalan, and Bortezomib Before First-Line Stem Cell Transplant in Treating Patients With Multiple Myeloma
NCT01607073	PHASE2	COMPLETED	Verapamil as Therapy for Children and Young Adults With Dravet Syndrome
NCT02091206	PHASE2	COMPLETED	A Dose-ranging Pharmacokinetics and Safety Study of GWP42003-P in Children With Dravet Syndrome (GWPCARE1)
NCT03635073	PHASE2	TERMINATED	A Study of Soticlestat in Adults and Children With Rare Epilepsies
NCT03650452	PHASE2	COMPLETED	A Phase 2, Multicenter, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy, Safety, and Tolerability of TAK-935 (OV935) as an Adjunctive Therapy in Pediatric Participants With Developmental and/or Epileptic Encephalopathies
NCT04740476	PHASE2	ACTIVE_NOT_RECRUITING	An Open-Label Extension Study of STK-001 for Patients With Dravet Syndrome