ATP1A4

Summary

ATP1A4 (ATPase Na+/K+ transporting subunit alpha 4, HGNC:14073) is a protein-coding gene on chromosome 1q23.2, encoding Sodium/potassium-transporting ATPase subunit alpha-4 (Q13733). This is the catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of sodium and potassium ions across the plasma membrane.

The protein encoded by this gene belongs to the family of P-type cation transport ATPases, and to the subfamily of Na+/K+ -ATPases. Na+/K+ -ATPase is an integral membrane protein responsible for establishing and maintaining the electrochemical gradients of Na and K ions across the plasma membrane. These gradients are essential for osmoregulation, for sodium-coupled transport of a variety of organic and inorganic molecules, and for electrical excitability of nerve and muscle. This enzyme is composed of two subunits, a large catalytic subunit (alpha) and a smaller glycoprotein subunit (beta). The catalytic subunit of Na+/K+ -ATPase is encoded by multiple genes. This gene encodes an alpha 4 subunit. Alternatively spliced transcript variants encoding different isoforms have been identified.

Source: NCBI Gene 480 — RefSeq curated summary.

At a glance

• Gene–disease (curated): familial hemiplegic migraine (Limited, GenCC)
• GWAS associations: 2
• Clinical variants (ClinVar): 174 total
• Druggable target: yes — 5 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_144699

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14073
Approved symbol	ATP1A4
Name	ATPase Na+/K+ transporting subunit alpha 4
Location	1q23.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000132681
Ensembl biotype	protein_coding
OMIM	607321
Entrez	480

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 2 protein_coding, 2 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay

ENST00000368081, ENST00000418334, ENST00000466526, ENST00000469023, ENST00000470705, ENST00000477338

RefSeq mRNA: 2 — MANE Select: NM_144699 NM_001001734, NM_144699

CCDS: CCDS1197, CCDS44255

Canonical transcript exons

ENST00000368081 — 22 exons

Exon	Start	End
ENSE00001928211	160151603	160152187
ENSE00002232963	160167278	160167412
ENSE00002280488	160155045	160155248
ENSE00002306305	160153165	160153224
ENSE00002321544	160164156	160164424
ENSE00002357392	160159002	160159136
ENSE00002368955	160159409	160159526
ENSE00002396579	160156045	160156158
ENSE00003468361	160176479	160176602
ENSE00003481452	160166968	160167077
ENSE00003503002	160177519	160177664
ENSE00003525715	160186276	160186367
ENSE00003570411	160181930	160182031
ENSE00003597122	160176092	160176246
ENSE00003606971	160181684	160181814
ENSE00003623277	160171585	160171757
ENSE00003631055	160171251	160171440
ENSE00003638439	160174579	160174747
ENSE00003644517	160173581	160173717
ENSE00003672100	160166528	160166726
ENSE00003690082	160174111	160174261
ENSE00003896564	160186671	160186980

Expression profiles

Bgee: expression breadth ubiquitous, 140 present calls, max score 83.83.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 1.4303 / max 526.5196, expressed in 132 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
6061	1.3764	128
6060	0.0291	3
6059	0.0152	3
6058	0.0096	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	83.83	gold quality
right testis	UBERON:0004534	83.42	gold quality
testis	UBERON:0000473	80.97	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	75.23	gold quality
sperm	CL:0000019	74.98	silver quality
seminal vesicle	UBERON:0000998	72.58	gold quality
gastrocnemius	UBERON:0001388	72.12	gold quality
urinary bladder	UBERON:0001255	71.80	gold quality
muscle of leg	UBERON:0001383	71.61	gold quality
hindlimb stylopod muscle	UBERON:0004252	71.00	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	67.31	gold quality
lymph node	UBERON:0000029	64.64	gold quality
sural nerve	UBERON:0015488	64.05	silver quality
placenta	UBERON:0001987	63.73	gold quality
ventricular zone	UBERON:0003053	61.20	gold quality
gall bladder	UBERON:0002110	59.44	gold quality
tibial nerve	UBERON:0001323	58.49	gold quality
apex of heart	UBERON:0002098	57.71	gold quality
vermiform appendix	UBERON:0001154	55.93	gold quality
monocyte	CL:0000576	55.54	gold quality
prefrontal cortex	UBERON:0000451	55.47	gold quality
leukocyte	CL:0000738	54.40	gold quality
lower esophagus muscularis layer	UBERON:0035833	54.09	gold quality
lower esophagus	UBERON:0013473	53.96	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	53.73	gold quality
skeletal muscle tissue	UBERON:0001134	53.28	gold quality
right frontal lobe	UBERON:0002810	53.13	gold quality
muscle tissue	UBERON:0002385	53.07	gold quality
descending thoracic aorta	UBERON:0002345	52.86	gold quality
anterior cingulate cortex	UBERON:0009835	52.57	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	10.86
E-MTAB-6386	no	26.18
E-CURD-89	no	7.90

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

12 targeting ATP1A4, 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-4267	99.96	66.53	2368
HSA-MIR-4641	99.28	66.64	744
HSA-MIR-4291	99.20	68.88	2969
HSA-MIR-4463	98.56	66.05	1071
HSA-MIR-3928-5P	98.50	67.48	980
HSA-MIR-6806-3P	98.50	67.31	980
HSA-MIR-6870-3P	98.08	65.10	692
HSA-MIR-5196-3P	97.57	65.98	979
HSA-MIR-597-5P	96.82	67.57	732
HSA-MIR-3194-5P	96.80	64.90	1027
HSA-MIR-592	96.59	67.59	817
HSA-MIR-4330	95.44	66.39	993

Literature-anchored findings (GeneRIF, showing 3)

• Human Na,K-ATPase alpha 4 isoform is a sperm-specific protein localized to the flagellum, suggesting a role for human Na,K-ATPase alpha 4 isoform in human sperm physiology. (PMID:16175638)
• These results constitute the first demonstration of the transcriptional control of ATP1A4 gene expression by cAMP and by CREMtau, a transcription factor essential for male germ cell gene expression. (PMID:16894555)
• Human ATP1A4 enhances mouse sperm motility and hyperactivity during capacitation. (PMID:25640246)

Cross-species orthologs

18 orthologs

Organism	Symbol	Gene ID
danio_rerio	si:dkey-28b4.8	ENSDARG00000002840
danio_rerio	atp1a3a	ENSDARG00000018259
danio_rerio	atp2a1	ENSDARG00000020574
danio_rerio	atp2a2a	ENSDARG00000029439
danio_rerio	atp2a1l	ENSDARG00000035458
danio_rerio	atp2b2	ENSDARG00000063433
danio_rerio	atp1a3b	ENSDARG00000104139
mus_musculus	Atp1a4	ENSMUSG00000007107
rattus_norvegicus	Atp1a4	ENSRNOG00000032378
drosophila_melanogaster	anne	FBGN0052000
drosophila_melanogaster	SPoCk	FBGN0052451
drosophila_melanogaster	CG45062	FBGN0266432
drosophila_melanogaster	CG45063	FBGN0266433
caenorhabditis_elegans		WBGENE00000834
caenorhabditis_elegans	pmr-1	WBGENE00004063
caenorhabditis_elegans		WBGENE00012341
caenorhabditis_elegans		WBGENE00015338
caenorhabditis_elegans		WBGENE00015660

Paralogs (21): ATP2C1 (ENSG00000017260), ATP1A2 (ENSG00000018625), ATP2B4 (ENSG00000058668), ATP2C2 (ENSG00000064270), ATP2B3 (ENSG00000067842), ATP2B1 (ENSG00000070961), ATP2A3 (ENSG00000074370), ATP12A (ENSG00000075673), ATP1A3 (ENSG00000105409), ATP4A (ENSG00000105675), ATP13A1 (ENSG00000105726), ATP7B (ENSG00000123191), ATP13A4 (ENSG00000127249), ATP13A3 (ENSG00000133657), ATP2B2 (ENSG00000157087), ATP13A2 (ENSG00000159363), ATP1A1 (ENSG00000163399), ATP7A (ENSG00000165240), ATP2A2 (ENSG00000174437), ATP13A5 (ENSG00000187527), ATP2A1 (ENSG00000196296)

Protein

Protein identifiers

Sodium/potassium-transporting ATPase subunit alpha-4 — Q13733 (reviewed: Q13733)

Alternative names: Sodium pump subunit alpha-4

All UniProt accessions (3): Q13733, A0A669K9X0, E9PRA5

UniProt curated annotations — full annotation on UniProt →

Function. This is the catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of sodium and potassium ions across the plasma membrane. This action creates the electrochemical gradient of sodium and potassium ions, providing the energy for active transport of various nutrients. Plays a role in sperm motility.

Subunit / interactions. The sodium/potassium-transporting ATPase is composed of a catalytic alpha subunit, an auxiliary non-catalytic beta subunit and an additional regulatory subunit.

Subcellular location. Cell membrane.

Tissue specificity. Specifically expressed in testis. Found in very low levels in skeletal muscle. Expressed in mature sperm (at protein level).

Activity regulation. Specifically inhibited by an endogenous cardiac glycoside, ouabain.

Similarity. Belongs to the cation transport ATPase (P-type) (TC 3.A.3) family. Type IIC subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
Q13733-1	1	yes
Q13733-2	2

RefSeq proteins (2): NP_001001734, NP_653300* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001757	P_typ_ATPase	Family
IPR004014	ATPase_P-typ_cation-transptr_N	Domain
IPR005775	P-type_ATPase_IIC	Family
IPR006068	ATPase_P-typ_cation-transptr_C	Domain
IPR008250	ATPase_P-typ_transduc_dom_A_sf	Homologous_superfamily
IPR018303	ATPase_P-typ_P_site	PTM
IPR023214	HAD_sf	Homologous_superfamily
IPR023298	ATPase_P-typ_TM_dom_sf	Homologous_superfamily
IPR023299	ATPase_P-typ_cyto_dom_N	Homologous_superfamily
IPR036412	HAD-like_sf	Homologous_superfamily
IPR044492	P_typ_ATPase_HD_dom	Domain
IPR050510	Cation_transp_ATPase_P-type	Family
IPR059000	ATPase_P-type_domA	Domain

Pfam: PF00122, PF00689, PF00690, PF13246

Catalyzed reactions (Rhea), 1 shown:

• K(+)(out) + Na(+)(in) + ATP + H2O = K(+)(in) + Na(+)(out) + ADP + phosphate + H(+) (RHEA:18353)

UniProt features (127 total): helix 49, strand 27, turn 13, topological domain 11, transmembrane region 10, sequence variant 4, region of interest 3, compositionally biased region 2, binding site 2, sequence conflict 2, chain 1, active site 1, modified residue 1, splice variant 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
8ZYJ	ELECTRON MICROSCOPY	2.37

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q13733-F1	87.54	0.55

Functional residue map

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

Catalytic / active sites (1): 384 (4-aspartylphosphate intermediate)

Ligand- & substrate-binding residues (2): 723; 727

Post-translational modifications (1): 949

Function

Pathways and Gene Ontology

Reactome pathways

11 pathways

ID	Pathway
R-HSA-5578775	Ion homeostasis
R-HSA-936837	Ion transport by P-type ATPases
R-HSA-9679191	Potential therapeutics for SARS
R-HSA-1643685	Disease
R-HSA-382551	Transport of small molecules
R-HSA-397014	Muscle contraction
R-HSA-5576891	Cardiac conduction
R-HSA-5663205	Infectious disease
R-HSA-9679506	SARS-CoV Infections
R-HSA-9824446	Viral Infection Pathways
R-HSA-983712	Ion channel transport

MSigDB gene sets: 114 (showing top): GOBP_POTASSIUM_ION_TRANSPORT, GOBP_ESTABLISHMENT_OR_MAINTENANCE_OF_TRANSMEMBRANE_ELECTROCHEMICAL_GRADIENT, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_SODIUM_ION_TRANSMEMBRANE_TRANSPORT, GOBP_POTASSIUM_ION_HOMEOSTASIS, GOBP_MALE_GAMETE_GENERATION, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_CILIUM_MOVEMENT, GOBP_INTRACELLULAR_POTASSIUM_ION_HOMEOSTASIS, GOBP_CILIUM_OR_FLAGELLUM_DEPENDENT_CELL_MOTILITY, GOBP_INTRACELLULAR_SODIUM_ION_HOMEOSTASIS, GOBP_SODIUM_ION_HOMEOSTASIS, GOBP_REGULATION_OF_PH, GOBP_MONOATOMIC_ION_HOMEOSTASIS, GOBP_DEVELOPMENTAL_PROCESS_INVOLVED_IN_REPRODUCTION

GO Biological Process (20): monoatomic ion transport (GO:0006811), potassium ion transport (GO:0006813), sodium ion transport (GO:0006814), intracellular sodium ion homeostasis (GO:0006883), cell surface receptor signaling pathway (GO:0007166), spermatogenesis (GO:0007283), fertilization (GO:0009566), intracellular potassium ion homeostasis (GO:0030007), flagellated sperm motility (GO:0030317), obsolete regulation of cellular pH (GO:0030641), sodium ion transmembrane transport (GO:0035725), sodium ion export across plasma membrane (GO:0036376), regulation of membrane potential (GO:0042391), establishment of localization in cell (GO:0051649), potassium ion transmembrane transport (GO:0071805), transport across blood-brain barrier (GO:0150104), proton transmembrane transport (GO:1902600), potassium ion import across plasma membrane (GO:1990573), establishment or maintenance of transmembrane electrochemical gradient (GO:0010248), intracellular monoatomic cation homeostasis (GO:0030003)

GO Molecular Function (10): P-type sodium:potassium-exchanging transporter activity (GO:0005391), ATP binding (GO:0005524), ATP hydrolysis activity (GO:0016887), ATPase-coupled monoatomic cation transmembrane transporter activity (GO:0019829), kinase binding (GO:0019900), metal ion binding (GO:0046872), nucleotide binding (GO:0000166), transporter activity (GO:0005215), protein binding (GO:0005515), P-type potassium transmembrane transporter activity (GO:0008556)

GO Cellular Component (8): plasma membrane (GO:0005886), sodium:potassium-exchanging ATPase complex (GO:0005890), cell projection (GO:0042995), membrane raft (GO:0045121), sperm midpiece (GO:0097225), photoreceptor cell cilium (GO:0097733), rod photoreceptor outer segment (GO:0120200), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-8 pathways:

Category	Pathways
Cardiac conduction	1
Ion channel transport	1
SARS-CoV Infections	1
Muscle contraction	1
Disease	1
Viral Infection Pathways	1
Infectious disease	1
Transport of small molecules	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
monoatomic cation transmembrane transport	3
cellular anatomical structure	3
metal ion transport	2
intracellular monoatomic cation homeostasis	2
monoatomic ion transmembrane transport	2
transport	1
sodium ion homeostasis	1
signal transduction	1
developmental process involved in reproduction	1
male gamete generation	1
sexual reproduction	1
reproductive process	1
potassium ion homeostasis	1
cilium-dependent cell motility	1
cilium movement involved in cell motility	1
sperm motility	1
sodium ion transport	1
sodium ion transmembrane transport	1
export across plasma membrane	1
regulation of biological quality	1
establishment of localization	1
cellular localization	1
potassium ion transport	1
vascular transport	1
potassium ion transmembrane transport	1
inorganic cation import across plasma membrane	1
intracellular monoatomic ion homeostasis	1
monoatomic cation homeostasis	1
P-type sodium transporter activity	1
P-type potassium transmembrane transporter activity	1
establishment or maintenance of transmembrane electrochemical gradient	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
ribonucleoside triphosphate phosphatase activity	1
ATP-dependent activity	1
monoatomic cation transmembrane transporter activity	1
active monoatomic ion transmembrane transporter activity	1
ATPase-coupled transmembrane transporter activity	1
enzyme binding	1
cation binding	1

Protein interactions and networks

STRING

2094 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ATP1A4	ATP1B3	P54709	881
ATP1A4	FXYD2	P54710	874
ATP1A4	ATP1B1	P05026	850
ATP1A4	KCNJ5	P48544	799
ATP1A4	ATP1B2	P14415	769
ATP1A4	CACNA1D	Q01668	733
ATP1A4	CYP11B2	P19099	696
ATP1A4	INO80	Q9ULG1	670
ATP1A4	AMY2B	P19961	648
ATP1A4	CACNA1H	O95180	598
ATP1A4	CLCN2	P51788	596
ATP1A4	LHB	P01229	588
ATP1A4	ARMC5	Q96C12	579
ATP1A4	CYP11B1	P15538	571
ATP1A4	SLC9A3	P48764	562

IntAct

24 interactions, top by confidence:

A	B	Type	Score
RPGR	NPHP1	psi-mi:“MI:0914”(association)	0.560
CHRM3	PLD2	psi-mi:“MI:0914”(association)	0.530
CD244	MTX2	psi-mi:“MI:0914”(association)	0.530
ATP1A3	AGPAT2	psi-mi:“MI:0914”(association)	0.530
LRRCC1		psi-mi:“MI:0914”(association)	0.350
CHRM3		psi-mi:“MI:0914”(association)	0.350
H4C16		psi-mi:“MI:0914”(association)	0.350
RPGR	NPHP1	psi-mi:“MI:0914”(association)	0.350
ATP1B4	RTN2	psi-mi:“MI:0914”(association)	0.350
P2RY8		psi-mi:“MI:0914”(association)	0.350
PA	ESYT2	psi-mi:“MI:0914”(association)	0.350
CACNA1C	IGLL5	psi-mi:“MI:0914”(association)	0.350
LRRCC1	MYH7B	psi-mi:“MI:0914”(association)	0.350
WWC1	CIT	psi-mi:“MI:0914”(association)	0.350
ATP1B4	SYNGR3	psi-mi:“MI:0914”(association)	0.350
P2RY8	GFAP	psi-mi:“MI:0914”(association)	0.350
KLHL9	MYH7	psi-mi:“MI:0914”(association)	0.350
CHTOP	MYH7B	psi-mi:“MI:0914”(association)	0.350
C5orf24	MYH7B	psi-mi:“MI:0914”(association)	0.350
PRKAR1B	ZNF749	psi-mi:“MI:0914”(association)	0.350
IZUMO1	PTPRF	psi-mi:“MI:0914”(association)	0.350
	ESYT2	psi-mi:“MI:0914”(association)	0.350
PTP4A3	ATP1A4	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (37): ATP1A4 (Affinity Capture-MS), ATP1A4 (Affinity Capture-MS), ATP1A4 (Affinity Capture-MS), ATP1A4 (Affinity Capture-MS), ATP1A4 (Affinity Capture-MS), ATP1A4 (Affinity Capture-MS), ATP1A4 (Affinity Capture-MS), ATP1A4 (Affinity Capture-MS), ATP1A4 (Affinity Capture-MS), ATP1A4 (Affinity Capture-MS), ATP1A4 (Affinity Capture-MS), ATP1A4 (Synthetic Lethality), RIC8A (Two-hybrid), CTAG1B (Two-hybrid), CTAG1A (Two-hybrid)

ESM2 similar proteins: A2VDL6, D2WKD8, P04074, P05023, P05024, P05025, P06685, P06686, P06687, P07038, P09572, P09626, P13607, P13637, P17326, P18907, P19156, P20648, P24797, P24798, P25489, P27112, P28774, P30714, P35317, P50993, P50996, P50997, P54707, P54708, P58312, Q08DA1, Q13733, Q5RCD8, Q5RDR3, Q64392, Q64436, Q64541, Q6PIC6, Q6PIE5

Diamond homologs: A0A143ZZK9, A2VDL6, A7L9Z8, B9QMJ0, D2WKD8, O13397, O13398, O14983, O23087, O34431, O46674, O55143, O75185, O77696, P04074, P04191, P05023, P06685, P07038, P09572, P09626, P09627, P11507, P11607, P11718, P12522, P13585, P13586, P16615, P17326, P18596, P18907, P19156, P20431, P20647, P20648, P22189, P22700, P25489, P27112

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	148
Likely benign	6
Benign	6

Top pathogenic / likely-pathogenic (0)

SpliceAI

3120 predictions. Top by Δscore:

Variant	Effect	Δscore
1:160156038:C:G	acceptor_gain	1.0000
1:160156039:CCTCA:C	acceptor_loss	1.0000
1:160156040:CTCA:C	acceptor_loss	1.0000
1:160156041:TCA:T	acceptor_loss	1.0000
1:160156042:CA:C	acceptor_loss	1.0000
1:160156043:A:AG	acceptor_gain	1.0000
1:160156044:G:GA	acceptor_gain	1.0000
1:160156044:G:GC	acceptor_loss	1.0000
1:160156044:GCT:G	acceptor_gain	1.0000
1:160156044:GCTCT:G	acceptor_gain	1.0000
1:160156154:CTCAG:C	donor_loss	1.0000
1:160156156:CAG:C	donor_loss	1.0000
1:160156157:AGGTA:A	donor_loss	1.0000
1:160156158:GGTA:G	donor_loss	1.0000
1:160156159:GTAG:G	donor_loss	1.0000
1:160156160:T:A	donor_loss	1.0000
1:160159403:TCCCA:T	acceptor_loss	1.0000
1:160159404:CCCA:C	acceptor_loss	1.0000
1:160159405:CCAG:C	acceptor_loss	1.0000
1:160159406:CAGGT:C	acceptor_loss	1.0000
1:160159407:A:G	acceptor_loss	1.0000
1:160159407:AGGT:A	acceptor_gain	1.0000
1:160159408:GGTG:G	acceptor_gain	1.0000
1:160159523:GAAGG:G	donor_loss	1.0000
1:160159524:AAG:A	donor_loss	1.0000
1:160159525:AG:A	donor_loss	1.0000
1:160159526:GGTG:G	donor_loss	1.0000
1:160159528:T:G	donor_loss	1.0000
1:160159541:A:G	donor_gain	1.0000
1:160166519:T:TA	acceptor_gain	1.0000

AlphaMissense

6773 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:160166630:G:C	D384H	1.000
1:160166631:A:C	D384A	1.000
1:160167389:T:C	F490L	1.000
1:160167391:T:A	F490L	1.000
1:160167391:T:G	F490L	1.000
1:160173599:G:C	D625H	1.000
1:160173600:A:C	D625A	1.000
1:160173600:A:G	D625G	1.000
1:160173600:A:T	D625V	1.000
1:160173615:C:A	A630D	1.000
1:160166631:A:G	D384G	0.999
1:160166631:A:T	D384V	0.999
1:160166632:C:A	D384E	0.999
1:160166632:C:G	D384E	0.999
1:160166633:A:C	K385Q	0.999
1:160166633:A:G	K385E	0.999
1:160166635:G:C	K385N	0.999
1:160166635:G:T	K385N	0.999
1:160166640:G:A	G387D	0.999
1:160166646:T:A	L389H	0.999
1:160166646:T:C	L389P	0.999
1:160166661:T:C	M394T	0.999
1:160171305:G:C	G516R	0.999
1:160171698:G:C	D599H	0.999
1:160171699:A:G	D599G	0.999
1:160173597:G:A	G624E	0.999
1:160173601:T:A	D625E	0.999
1:160173601:T:G	D625E	0.999
1:160173614:G:C	A630P	0.999
1:160173626:G:C	A634P	0.999

dbSNP variants (sampled 300 via entrez): RS1000031088 (1:160163853 G>A), RS1000066659 (1:160172297 G>A), RS1000114606 (1:160169367 G>A), RS1000153213 (1:160171019 A>T), RS1000174511 (1:160160827 G>T), RS1000253220 (1:160170809 T>C), RS1000275295 (1:160165929 G>T), RS1000366947 (1:160181261 G>C), RS1000396542 (1:160155666 T>C), RS1000450161 (1:160168143 C>A,T), RS1000728165 (1:160156844 G>A,T), RS1000798101 (1:160162343 T>G), RS1000862231 (1:160161079 G>T), RS1000911095 (1:160151662 C>A,T), RS1001284377 (1:160185861 G>A)

Disease associations

OMIM: gene MIM:607321 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
familial hemiplegic migraine	Limited	Autosomal dominant

Mondo (1): familial hemiplegic migraine (MONDO:0000700)

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST001356_19	Gout	1.000000e-07
GCST008572_5	Composite immunoglobulin trait (IgA/IgG)	4.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2095186 (PROTEIN COMPLEX GROUP)

Molecules with ChEMBL bioactivity

5 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 160,774 (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
CHEMBL1503	OMEPRAZOLE	4	52,284
CHEMBL1751	DIGOXIN	4	67,342
CHEMBL254219	DIGITOXIN	4	16,757
CHEMBL480	LANSOPRAZOLE	4	24,317
CHEMBL2068971	ROSTAFUROXIN	2	74

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

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: transporter — Na⁺/K⁺-ATPases

ChEMBL bioactivities

212 potent at pChembl≥5 of 264 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.52	IC50	3	nM	CHEMBL2092909
8.32	IC50	4.79	nM	CHEMBL1651648
8.17	IC50	6.79	nM	CHEMBL1651648
8.15	IC50	7	nM	CHEMBL2092738
8.15	IC50	7.04	nM	CHEMBL1651624
8.10	IC50	8	nM	CHEMBL3085467
8.10	IC50	8	nM	CHEMBL3085497
8.10	IC50	8	nM	DIGITOXIGENIN
8.10	IC50	8	nM	DIGITOXIN
8.05	IC50	9	nM	CHEMBL3085468
7.98	IC50	10.5	nM	CHEMBL3349024
7.97	IC50	10.7	nM	CHEMBL3350144
7.92	IC50	12	nM	CHEMBL2069010
7.80	IC50	16	nM	CHEMBL2068887
7.80	IC50	16	nM	CHEMBL3349024
7.75	IC50	17.8	nM	CHEMBL1159613
7.70	IC50	20	nM	DIGITOXIGENIN
7.70	IC50	20	nM	CHEMBL2068894
7.70	IC50	20	nM	CHEMBL2068887
7.66	IC50	22	nM	BUFALIN
7.60	IC50	25	nM	CHEMBL2068888
7.55	IC50	28.2	nM	CHEMBL3350144
7.52	IC50	30	nM	CHEMBL2068896
7.52	IC50	30	nM	CHEMBL2068909
7.41	IC50	38.9	nM	CHEMBL3349024
7.40	IC50	40	nM	CHEMBL126930
7.40	IC50	40	nM	CHEMBL2069036
7.35	IC50	45	nM	CHEMBL2069112
7.30	IC50	50	nM	CHEMBL2069053
7.22	IC50	60	nM	CHEMBL2069110
7.22	IC50	60.3	nM	CHEMBL3349024
7.22	IC50	60	nM	CHEMBL2115485
7.20	IC50	63	nM	DIGITOXIGENIN
7.19	IC50	64.5	nM	CHEMBL1159613
7.16	IC50	70	nM	CHEMBL3085496
7.12	IC50	75	nM	CHEMBL2092910
7.10	IC50	80	nM	CHEMBL2068983
7.10	IC50	80	nM	CHEMBL2069040
7.06	IC50	88	nM	CHEMBL2068949
7.06	IC50	87	nM	CHEMBL3265172
7.03	IC50	93.3	nM	CHEMBL3349024
7.00	IC50	100	nM	CHEMBL2068885
7.00	IC50	100	nM	CHEMBL333694
7.00	IC50	100	nM	CHEMBL126063
7.00	IC50	99	nM	CHEMBL2069062
7.00	IC50	100	nM	CHEMBL2069059
6.92	IC50	120	nM	DIGITOXIGENIN
6.89	IC50	130	nM	CHEMBL125966
6.89	IC50	130	nM	CHEMBL124276
6.89	IC50	129	nM	CHEMBL3349024

PubChem BioAssay actives

210 with measured affinity, of 373 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-[(3S,8R,9S,10S,13R,14R,17S)-14-hydroxy-10,13-dimethyl-3-[[(2R,3S,4S,5R,6S)-3,4,5,6-tetrahydroxyoxan-2-yl]methoxy]-1,2,3,4,5,6,7,8,9,11,12,15,16,17-tetradecahydrocyclopenta[a]phenanthren-17-yl]-2H-furan-5-one	49025: Inhibition of [3H]ouabain binding to Na/K ATP-ase in dog heart muscle	ic50	0.0030	uM
3-[(3S,5R,8R,9S,10S,13R,14S,17R)-14-hydroxy-10,13-dimethyl-3-[(2R,3R,4R,5R,6S)-3,4,5-trihydroxy-6-methyloxan-2-yl]oxy-1,2,3,4,5,6,7,8,9,11,12,15,16,17-tetradecahydrocyclopenta[a]phenanthren-17-yl]-2H-furan-5-one	146845: Inhibition of hog kidney Na+, K+-dependent ATPase	ic50	0.0048	uM
3-[(3S,5R,8R,9S,10S,13R,14S,17R)-3-[(2R,4S,5S,6R)-4,5-dihydroxy-6-methyloxan-2-yl]oxy-14-hydroxy-10,13-dimethyl-1,2,3,4,5,6,7,8,9,11,12,15,16,17-tetradecahydrocyclopenta[a]phenanthren-17-yl]-2H-furan-5-one	146845: Inhibition of hog kidney Na+, K+-dependent ATPase	ic50	0.0070	uM
3-[(3S,8R,9S,10S,13R,14R,17R)-14-hydroxy-10,13-dimethyl-3-[[(2R,3S,4S,5R,6S)-3,4,5,6-tetrahydroxyoxan-2-yl]methoxy]-1,2,3,4,5,6,7,8,9,11,12,15,16,17-tetradecahydrocyclopenta[a]phenanthren-17-yl]-2H-furan-5-one	49025: Inhibition of [3H]ouabain binding to Na/K ATP-ase in dog heart muscle	ic50	0.0070	uM
3-[(3S,5R,8R,9S,10S,13R,14S,17R)-3,14-dihydroxy-10,13-dimethyl-1,2,3,4,5,6,7,8,9,11,12,15,16,17-tetradecahydrocyclopenta[a]phenanthren-17-yl]-2H-furan-5-one	56911: Inhibition of [3H]- ouabain binding to digitalis receptor	ic50	0.0080	uM
3-[(3S,5R,8R,9S,10S,13R,14S,17R)-3-[(2R,4S,5S,6R)-5-[(2S,4S,5S,6R)-5-[(2S,4S,5S,6R)-4,5-dihydroxy-6-methyloxan-2-yl]oxy-4-hydroxy-6-methyloxan-2-yl]oxy-4-hydroxy-6-methyloxan-2-yl]oxy-14-hydroxy-10,13-dimethyl-1,2,3,4,5,6,7,8,9,11,12,15,16,17-tetradecahydrocyclopenta[a]phenanthren-17-yl]-2H-furan-5-one	56911: Inhibition of [3H]- ouabain binding to digitalis receptor	ic50	0.0080	uM
3-[(3S,5S,8R,9S,10S,13R,14R,17R)-3-[[(2S,3R,4R,6S)-3,4-dihydroxy-6-[[(2S,3R,4R,6S)-3,4,6-trihydroxyoxan-2-yl]methoxy]oxan-2-yl]methoxy]-14-hydroxy-10,13-dimethyl-1,2,3,4,5,6,7,8,9,11,12,15,16,17-tetradecahydrocyclopenta[a]phenanthren-17-yl]-2H-furan-5-one	49025: Inhibition of [3H]ouabain binding to Na/K ATP-ase in dog heart muscle	ic50	0.0080	uM
3-[(3S,5S,8R,9S,10S,13R,14R,17R)-3-[[(2S,3R,4R,6S)-6-[[(2S,3R,4R,6S)-3,4-dihydroxy-6-[[(2S,3R,4R,6S)-3,4,6-trihydroxyoxan-2-yl]methoxy]oxan-2-yl]methoxy]-3,4-dihydroxyoxan-2-yl]methoxy]-14-hydroxy-10,13-dimethyl-1,2,3,4,5,6,7,8,9,11,12,15,16,17-tetradecahydrocyclopenta[a]phenanthren-17-yl]-2H-furan-5-one	49025: Inhibition of [3H]ouabain binding to Na/K ATP-ase in dog heart muscle	ic50	0.0080	uM
3-[(3S,5S,8R,9S,10S,13R,14R,17R)-14-hydroxy-10,13-dimethyl-3-[[(2S,3R,4R,6S)-3,4,6-trihydroxyoxan-2-yl]methoxy]-1,2,3,4,5,6,7,8,9,11,12,15,16,17-tetradecahydrocyclopenta[a]phenanthren-17-yl]-2H-furan-5-one	49025: Inhibition of [3H]ouabain binding to Na/K ATP-ase in dog heart muscle	ic50	0.0090	uM
3-[(3S,5R,8R,9S,10S,13R,14S,17R)-14-hydroxy-10,13-dimethyl-3-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-1,2,3,4,5,6,7,8,9,11,12,15,16,17-tetradecahydrocyclopenta[a]phenanthren-17-yl]-2H-furan-5-one	146845: Inhibition of hog kidney Na+, K+-dependent ATPase	ic50	0.0105	uM
3-[(3S,5R,8R,9S,10S,13R,14S,17R)-14-hydroxy-10,13-dimethyl-3-[(2R,3S,4S,5S,6S)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-1,2,3,4,5,6,7,8,9,11,12,15,16,17-tetradecahydrocyclopenta[a]phenanthren-17-yl]-2H-furan-5-one	146845: Inhibition of hog kidney Na+, K+-dependent ATPase	ic50	0.0107	uM
(2R,4S,5R)-2-[[(3S,5R,8R,9S,10S,13R,14S,17S)-14-hydroxy-10,13-dimethyl-17-(nitromethyl)-1,2,3,4,5,6,7,8,9,11,12,15,16,17-tetradecahydrocyclopenta[a]phenanthren-3-yl]oxy]-6-methyloxane-3,4,5-triol	56911: Inhibition of [3H]- ouabain binding to digitalis receptor	ic50	0.0120	uM
(3S,5R,8R,9S,10S,13R,14S,17R)-17-[(E,3E)-3-(2-aminoethoxyimino)prop-1-enyl]-10,13-dimethyl-1,2,3,4,5,6,7,8,9,11,12,15,16,17-tetradecahydrocyclopenta[a]phenanthrene-3,14-diol	146853: 50% displacement of the specific [3H]ouabain binding from the dog kidney Na+/K+ ATPase	ic50	0.0160	uM
3-[(13R)-14-hydroxy-10,13-dimethyl-3-[(2S,3R,4S,5R,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-1,2,3,4,5,6,7,8,9,11,12,15,16,17-tetradecahydrocyclopenta[a]phenanthren-17-yl]-2H-furan-5-one	146845: Inhibition of hog kidney Na+, K+-dependent ATPase	ic50	0.0178	uM
(3S,5R,8R,9S,10S,13R,14S,17S)-17-[(E)-3-aminopropoxyiminomethyl]-10,13-dimethyl-1,2,3,4,5,6,7,8,9,11,12,15,16,17-tetradecahydrocyclopenta[a]phenanthrene-3,14-diol;oxalic acid	146858: In vitro inhibitory concentration against dog kidney Na+/K+ ATPase	ic50	0.0200	uM
5-[(3S,5R,8R,9S,10S,13R,14S,17R)-3,14-dihydroxy-10,13-dimethyl-1,2,3,4,5,6,7,8,9,11,12,15,16,17-tetradecahydrocyclopenta[a]phenanthren-17-yl]pyran-2-one	1941870: Inhibition of NA+/K+ ATPase (unknown origin) activity	ic50	0.0220	uM
(3S,5R,8R,9S,10S,13R,14S,17R)-17-[(E,3E)-3-[2-(dimethylamino)ethoxyimino]prop-1-enyl]-10,13-dimethyl-1,2,3,4,5,6,7,8,9,11,12,15,16,17-tetradecahydrocyclopenta[a]phenanthrene-3,14-diol	146853: 50% displacement of the specific [3H]ouabain binding from the dog kidney Na+/K+ ATPase	ic50	0.0250	uM
(3S,5R,8R,9S,10S,13R,14S,17R)-17-[(E,3E)-3-[2-(dimethylamino)ethoxyimino]prop-1-enyl]-10,13-dimethyl-1,2,3,4,5,6,7,8,9,11,12,15,16,17-tetradecahydrocyclopenta[a]phenanthrene-3,14-diol;oxalic acid	146858: In vitro inhibitory concentration against dog kidney Na+/K+ ATPase	ic50	0.0300	uM
(3S,5R,8R,9S,10S,13R,14S,17R)-17-[(E,3E)-3-(2-aminoethoxyimino)-2-methylprop-1-enyl]-10,13-dimethyl-1,2,3,4,5,6,7,8,9,11,12,15,16,17-tetradecahydrocyclopenta[a]phenanthrene-3,14-diol;(E)-but-2-enedioic acid	146858: In vitro inhibitory concentration against dog kidney Na+/K+ ATPase	ic50	0.0300	uM
(2R,4bS,7S,8aR)-2-[(1E,3S)-1-(2-aminoethoxyimino)pentan-3-yl]-7-hydroxy-2,4b-dimethyl-4,4a,5,6,7,8,8a,9,10,10a-decahydro-3H-phenanthren-1-one	146843: Binding affinity towards Na+,K+ -ATPase isolated from dog kidney.	ic50	0.0400	uM
(3S,5R,8R,9S,10S,13R,14S,17S)-17-[(E)-2-(dimethylamino)ethoxyiminomethyl]-10,13-dimethyl-1,2,3,4,5,6,7,8,9,11,12,15,16,17-tetradecahydrocyclopenta[a]phenanthrene-3,14-diol	146853: 50% displacement of the specific [3H]ouabain binding from the dog kidney Na+/K+ ATPase	ic50	0.0400	uM
(2R,4S,5R)-2-[[(3S,5R,8R,9S,10S,13R,14S,17R)-14-hydroxy-10,13-dimethyl-17-(2-nitroethyl)-1,2,3,4,5,6,7,8,9,11,12,15,16,17-tetradecahydrocyclopenta[a]phenanthren-3-yl]oxy]-6-methyloxane-3,4,5-triol	56911: Inhibition of [3H]- ouabain binding to digitalis receptor	ic50	0.0450	uM
(3S,5R,8R,9S,10S,13R,14S,17S)-17-[(2E)-2-(2-aminoethoxyimino)ethyl]-10,13-dimethyl-1,2,3,4,5,6,7,8,9,11,12,15,16,17-tetradecahydrocyclopenta[a]phenanthrene-3,14-diol	146843: Binding affinity towards Na+,K+ -ATPase isolated from dog kidney.	ic50	0.0500	uM
(E)-but-2-enedioic acid;(3S,5R,8R,9S,10S,13R,14S,17R)-17-[(E,3E)-3-[2-(dimethylamino)ethoxyimino]-2-methylprop-1-enyl]-10,13-dimethyl-1,2,3,4,5,6,7,8,9,11,12,15,16,17-tetradecahydrocyclopenta[a]phenanthrene-3,14-diol	146858: In vitro inhibitory concentration against dog kidney Na+/K+ ATPase	ic50	0.0600	uM
6-[[(3S,8R,9S,10S,13R,14R,17S)-14-hydroxy-17-[(1S)-1-hydroxyethyl]-10,13-dimethyl-1,2,3,4,5,6,7,8,9,11,12,15,16,17-tetradecahydrocyclopenta[a]phenanthren-3-yl]oxy]-2-(hydroxymethyl)oxane-3,4-diol	146854: Compound is evaluated for inhibition of specific binding of [3H]ouabain to membranes from dog heart	ic50	0.0600	uM
3-[(5R,8R,9S,10S,13R,14R,17R)-14-hydroxy-10,13-dimethyl-1,2,3,4,5,6,7,8,9,11,12,15,16,17-tetradecahydrocyclopenta[a]phenanthren-17-yl]-2H-furan-5-one	49025: Inhibition of [3H]ouabain binding to Na/K ATP-ase in dog heart muscle	ic50	0.0700	uM
(2R,3R,4R,5R,6R)-6-[[(3R)-14-hydroxy-17-(1-hydroxyethyl)-10,13-dimethyl-1,2,3,4,5,6,7,8,9,11,12,15,16,17-tetradecahydrocyclopenta[a]phenanthren-3-yl]oxymethyl]oxane-2,3,4,5-tetrol	49025: Inhibition of [3H]ouabain binding to Na/K ATP-ase in dog heart muscle	ic50	0.0750	uM
(3S,5R,8R,9S,10S,13R,14S,17R)-17-[(1E,3E)-6-aminohexa-1,3-dienyl]-10,13-dimethyl-1,2,3,4,5,6,7,8,9,11,12,15,16,17-tetradecahydrocyclopenta[a]phenanthrene-3,14-diol	146858: In vitro inhibitory concentration against dog kidney Na+/K+ ATPase	ic50	0.0800	uM
(3S,5R,8R,9S,10S,13R,14S,17S)-17-[(3Z)-3-(2-aminoethoxyimino)propyl]-10,13-dimethyl-1,2,3,4,5,6,7,8,9,11,12,15,16,17-tetradecahydrocyclopenta[a]phenanthrene-3,14-diol	146858: In vitro inhibitory concentration against dog kidney Na+/K+ ATPase	ic50	0.0800	uM
3-[(3S,5R,8R,9S,10S,13R,14S,17R)-14-hydroxy-10,13-dimethyl-3-[(2R,3R,4R,5R,6S)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-1,2,3,4,5,6,7,8,9,11,12,15,16,17-tetradecahydrocyclopenta[a]phenanthren-17-yl]-2H-furan-5-one	146845: Inhibition of hog kidney Na+, K+-dependent ATPase	ic50	0.0870	uM
(3S,4R,6R)-6-[[(3S,5R,8R,9S,10S,13R,14S,17S)-14-hydroxy-10,13-dimethyl-17-(nitromethyl)-1,2,3,4,5,6,7,8,9,11,12,15,16,17-tetradecahydrocyclopenta[a]phenanthren-3-yl]oxy]-2-methyloxane-3,4-diol	56911: Inhibition of [3H]- ouabain binding to digitalis receptor	ic50	0.0880	uM
(2R,4S,5R)-2-[[(3S,5R,8R,9S,10S,13R,14S,17S)-17-(aminomethyl)-14-hydroxy-10,13-dimethyl-1,2,3,4,5,6,7,8,9,11,12,15,16,17-tetradecahydrocyclopenta[a]phenanthren-3-yl]oxy]-6-methyloxane-3,4,5-triol;hydrochloride	56911: Inhibition of [3H]- ouabain binding to digitalis receptor	ic50	0.0990	uM
(2R,4bS,7S,8aR)-2-[(1E,3S)-1-[2-(dimethylamino)ethoxyimino]pentan-3-yl]-7-hydroxy-2,4b-dimethyl-4,4a,5,6,7,8,8a,9,10,10a-decahydro-3H-phenanthren-1-one	146843: Binding affinity towards Na+,K+ -ATPase isolated from dog kidney.	ic50	0.1000	uM
(2R,4bS,7S,8aR)-2-[(2S,4E)-4-(2-aminoethoxyimino)butan-2-yl]-7-hydroxy-2,4b-dimethyl-4,4a,5,6,7,8,8a,9,10,10a-decahydro-3H-phenanthren-1-one	146843: Binding affinity towards Na+,K+ -ATPase isolated from dog kidney.	ic50	0.1000	uM
2-[(E)-[(3S,5R,8R,9S,10S,13R,14S,17S)-3,14-dihydroxy-10,13-dimethyl-1,2,3,4,5,6,7,8,9,11,12,15,16,17-tetradecahydrocyclopenta[a]phenanthren-17-yl]methylideneamino]guanidine;hydrochloride	146856: Displacement of [3H]ouabain from dog kidney Na+/K+ ATPase	ic50	0.1000	uM
(3S,5R,8R,9S,10S,13R,14S,17S)-17-[(3Z)-3-[2-(dimethylamino)ethoxyimino]propyl]-10,13-dimethyl-1,2,3,4,5,6,7,8,9,11,12,15,16,17-tetradecahydrocyclopenta[a]phenanthrene-3,14-diol;oxalic acid	146858: In vitro inhibitory concentration against dog kidney Na+/K+ ATPase	ic50	0.1000	uM
(2R,4bS,7S,8aR)-2-[(2S,4E)-4-[2-(dimethylamino)ethoxyimino]butan-2-yl]-7-hydroxy-2,4b-dimethyl-4,4a,5,6,7,8,8a,9,10,10a-decahydro-3H-phenanthren-1-one	146843: Binding affinity towards Na+,K+ -ATPase isolated from dog kidney.	ic50	0.1300	uM
2-(dimethylamino)ethyl (E)-4-[(2R,4bS,7S,8aR)-7-hydroxy-2,4b-dimethyl-1-oxo-4,4a,5,6,7,8,8a,9,10,10a-decahydro-3H-phenanthren-2-yl]hex-2-enoate	146843: Binding affinity towards Na+,K+ -ATPase isolated from dog kidney.	ic50	0.1300	uM
1-[(3R)-14-hydroxy-10,13-dimethyl-3-[[(2R,3R,4R,5R,6R)-3,4,5,6-tetrahydroxyoxan-2-yl]methoxy]-1,2,3,4,5,6,7,8,9,11,12,15,16,17-tetradecahydrocyclopenta[a]phenanthren-17-yl]ethanone	49025: Inhibition of [3H]ouabain binding to Na/K ATP-ase in dog heart muscle	ic50	0.1500	uM
Digoxin	1970782: Inhibition of NA+/K+ ATPase (unknown origin) activity incubated for 15 mins in presence of ATP by ADP-Glo assay	ic50	0.1600	uM
(2R,4bS,7S,8aS)-2-[(1E,3S)-1-(2-aminoethoxyimino)pentan-3-yl]-7-hydroxy-2,4b-dimethyl-4,4a,5,6,7,8,8a,9,10,10a-decahydro-3H-phenanthren-1-one	146843: Binding affinity towards Na+,K+ -ATPase isolated from dog kidney.	ic50	0.1600	uM
(3S,5R,8R,9S,10S,13R,14S,17S)-17-[(E)-2-aminoethoxyiminomethyl]-10,13-dimethyl-1,2,3,4,5,6,7,8,9,11,12,15,16,17-tetradecahydrocyclopenta[a]phenanthrene-3,14-diol;(E)-but-2-enedioic acid	146858: In vitro inhibitory concentration against dog kidney Na+/K+ ATPase	ic50	0.1600	uM
2-[(E)-1-[(3S,5R,8R,9S,10S,13R,14S,17S)-3,14-dihydroxy-10,13-dimethyl-1,2,3,4,5,6,7,8,9,11,12,15,16,17-tetradecahydrocyclopenta[a]phenanthren-17-yl]ethylideneamino]guanidine	146856: Displacement of [3H]ouabain from dog kidney Na+/K+ ATPase	ic50	0.1995	uM
(3S,5R,8R,9S,10S,13R,14S,17S)-17-[(E)-(4,5-dihydro-1H-imidazol-2-ylhydrazinylidene)methyl]-10,13-dimethyl-1,2,3,4,5,6,7,8,9,11,12,15,16,17-tetradecahydrocyclopenta[a]phenanthrene-3,14-diol	146856: Displacement of [3H]ouabain from dog kidney Na+/K+ ATPase	ic50	0.1995	uM
(3S,5R,8R,9S,10S,13R,14S,17S)-17-[(2E)-2-(3-aminopropoxyimino)ethyl]-10,13-dimethyl-1,2,3,4,5,6,7,8,9,11,12,15,16,17-tetradecahydrocyclopenta[a]phenanthrene-3,14-diol	146843: Binding affinity towards Na+,K+ -ATPase isolated from dog kidney.	ic50	0.2000	uM
3-[(1R)-1-[(2R,4bS,7S,8aR)-7-hydroxy-2,4b-dimethyl-1-oxo-4,4a,5,6,7,8,8a,9,10,10a-decahydro-3H-phenanthren-2-yl]propyl]-2H-furan-5-one	146843: Binding affinity towards Na+,K+ -ATPase isolated from dog kidney.	ic50	0.2000	uM
(2R,4bS,7S,8aR)-2-[(1E,3S)-1-(2-aminoethoxyimino)hexan-3-yl]-7-hydroxy-2,4b-dimethyl-4,4a,5,6,7,8,8a,9,10,10a-decahydro-3H-phenanthren-1-one	146843: Binding affinity towards Na+,K+ -ATPase isolated from dog kidney.	ic50	0.2000	uM
(3S,5R,8R,9S,10S,13R,14S,17R)-17-[(E,3E)-3-(3-aminopropoxyimino)-2-methylprop-1-enyl]-10,13-dimethyl-1,2,3,4,5,6,7,8,9,11,12,15,16,17-tetradecahydrocyclopenta[a]phenanthrene-3,14-diol;oxalic acid	146858: In vitro inhibitory concentration against dog kidney Na+/K+ ATPase	ic50	0.2000	uM
(3S,5R,8R,9S,10S,13R,14S,17S)-17-[(2E)-2-[2-(dimethylamino)ethoxyimino]ethyl]-10,13-dimethyl-1,2,3,4,5,6,7,8,9,11,12,15,16,17-tetradecahydrocyclopenta[a]phenanthrene-3,14-diol	146843: Binding affinity towards Na+,K+ -ATPase isolated from dog kidney.	ic50	0.2500	uM
2-(dimethylamino)ethyl (E,4R)-4-[(2R,4bS,7S,8aR)-7-hydroxy-2,4b-dimethyl-1-oxo-4,4a,5,6,7,8,8a,9,10,10a-decahydro-3H-phenanthren-2-yl]hex-2-enoate	146843: Binding affinity towards Na+,K+ -ATPase isolated from dog kidney.	ic50	0.2500	uM

CTD chemical–gene interactions

14 total (human), top 14 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases expression	3
Benzo(a)pyrene	affects methylation, increases methylation	2
aristolochic acid I	increases expression	1
terbufos	increases methylation	1
aflatoxin B2	increases methylation	1
CGP 52608	affects binding, increases reaction	1
theaflavin-3,3’-digallate	affects expression	1
Resveratrol	affects cotreatment, decreases expression	1
Copper	affects cotreatment, decreases expression	1
Diethylhexyl Phthalate	increases expression	1
Fonofos	increases methylation	1
Methotrexate	increases expression	1
Parathion	increases methylation	1
Sodium Selenite	increases expression	1

ChEMBL screening assays

45 unique, capped per target: 45 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1691887	Binding	Inhibition of human Na+/ K+ ATPase at up to 10 uM	Lersivirine, a nonnucleoside reverse transcriptase inhibitor with activity against drug-resistant human immunodeficiency virus type 1. — Antimicrob Agents Chemother

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00358839	Not specified	COMPLETED	Calcitonin Gene Related Peptide-Induced Headache in Patients With Familial Hemiplegic Migraine Type 1 and 2.
NCT00541736	Not specified	COMPLETED	Glyceryl-Trinitrate-Induced Headache in Patients With Familial Hemiplegic Migraine
NCT00687947	Not specified	COMPLETED	Calcitonin Gene-related Peptide in Familial Hemiplegic Migraine (FHM) and Migraine With Aura (MA)