ATP1A2

Summary

ATP1A2 (ATPase Na+/K+ transporting subunit alpha 2, HGNC:800) is a protein-coding gene on chromosome 1q23.2, encoding Sodium/potassium-transporting ATPase subunit alpha-2 (P50993). 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 2 subunit. Mutations in this gene result in familial basilar or hemiplegic migraines, and in a rare syndrome known as alternating hemiplegia of childhood.

Source: NCBI Gene 477 — RefSeq curated summary.

At a glance

• Gene–disease (curated): fetal akinesia, respiratory insufficiency, microcephaly, polymicrogyria, and dysmorphic facies (Definitive, ClinGen) — +6 more curated relationships
• GWAS associations: 4
• Clinical variants (ClinVar): 1,554 total — 57 pathogenic, 61 likely-pathogenic
• Phenotypes (HPO): 186
• Druggable target: yes — 5 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_000702

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:800
Approved symbol	ATP1A2
Name	ATPase Na+/K+ transporting subunit alpha 2
Location	1q23.2
Locus type	gene with protein product
Status	Approved
Aliases	FHM2
Ensembl gene	ENSG00000018625
Ensembl biotype	protein_coding
OMIM	182340
Entrez	477

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 9 protein_coding, 4 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000361216, ENST00000392233, ENST00000447527, ENST00000459972, ENST00000463989, ENST00000468587, ENST00000472488, ENST00000478587, ENST00000857223, ENST00000857224, ENST00000857225, ENST00000969831, ENST00000969832, ENST00000969833

RefSeq mRNA: 1 — MANE Select: NM_000702 NM_000702

CCDS: CCDS1196

Canonical transcript exons

ENST00000361216 — 23 exons

Exon	Start	End
ENSE00001166839	160139893	160139984
ENSE00001446285	160141294	160143591
ENSE00001842163	160115759	160115873
ENSE00003474261	160139640	160139741
ENSE00003486504	160120906	160121010
ENSE00003514959	160136247	160136370
ENSE00003520602	160136570	160136715
ENSE00003530405	160121192	160121251
ENSE00003546115	160125136	160125253
ENSE00003547167	160136901	160137031
ENSE00003565393	160127552	160127820
ENSE00003569868	160123213	160123416
ENSE00003570573	160135839	160135993
ENSE00003596189	160135145	160135295
ENSE00003599824	160128980	160129089
ENSE00003609510	160135434	160135602
ENSE00003626788	160130102	160130291
ENSE00003643550	160129266	160129400
ENSE00003646409	160130422	160130597
ENSE00003670855	160128652	160128850
ENSE00003674281	160134484	160134620
ENSE00003680865	160123943	160124056
ENSE00003682292	160124296	160124430

Expression profiles

Bgee: expression breadth ubiquitous, 262 present calls, max score 99.88.

FANTOM5 (CAGE): breadth broad, TPM avg 43.2227 / max 1436.0797, expressed in 461 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
6037	42.3676	445
6038	0.2840	88
6042	0.2299	53
6055	0.1089	33
6039	0.0905	58
6050	0.0834	49
6041	0.0334	22
6040	0.0251	6

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lateral globus pallidus	UBERON:0002476	99.88	gold quality
trigeminal ganglion	UBERON:0001675	99.80	gold quality
superior vestibular nucleus	UBERON:0007227	99.75	gold quality
endothelial cell	CL:0000115	99.74	gold quality
ventral tegmental area	UBERON:0002691	99.74	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	99.68	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	99.66	gold quality
medulla oblongata	UBERON:0001896	99.65	gold quality
paraflocculus	UBERON:0005351	99.65	gold quality
substantia nigra pars reticulata	UBERON:0001966	99.61	gold quality
subthalamic nucleus	UBERON:0001906	99.58	gold quality
globus pallidus	UBERON:0001875	99.57	gold quality
caudate nucleus	UBERON:0001873	99.56	gold quality
substantia nigra pars compacta	UBERON:0001965	99.56	gold quality
vastus lateralis	UBERON:0001379	99.55	gold quality
putamen	UBERON:0001874	99.55	gold quality
gluteal muscle	UBERON:0002000	99.54	gold quality
middle frontal gyrus	UBERON:0002702	99.54	gold quality
body of tongue	UBERON:0011876	99.53	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	99.52	gold quality
dorsal plus ventral thalamus	UBERON:0001897	99.50	gold quality
medial globus pallidus	UBERON:0002477	99.50	gold quality
inferior vagus X ganglion	UBERON:0005363	99.50	gold quality
quadriceps femoris	UBERON:0001377	99.49	gold quality
Brodmann (1909) area 23	UBERON:0013554	99.47	gold quality
pons	UBERON:0000988	99.46	gold quality
skeletal muscle tissue	UBERON:0001134	99.46	gold quality
biceps brachii	UBERON:0001507	99.46	gold quality
nucleus accumbens	UBERON:0001882	99.45	gold quality
gastrocnemius	UBERON:0001388	99.44	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 7.

Experiment	Marker?	Max mean expression
E-GEOD-84465	yes	2702.31
E-GEOD-180759	yes	952.83
E-GEOD-93593	yes	937.03
E-GEOD-98556	yes	669.82
E-HCAD-35	yes	77.03
E-HCAD-25	yes	28.85
E-ANND-3	yes	8.05

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MYC, SP1

miRNA regulators (miRDB)

119 targeting ATP1A2, 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-4795-3P	100.00	74.62	4024
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-4715-3P	99.98	66.03	670
HSA-MIR-4745-5P	99.98	65.95	1028
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-145-5P	99.92	71.13	1836
HSA-MIR-5195-3P	99.92	70.92	1877
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-589-3P	99.91	69.62	2088
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-4648	99.91	67.00	710
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-106B-5P	99.88	74.72	2795
HSA-MIR-20A-5P	99.88	74.76	2769
HSA-MIR-526B-3P	99.88	74.06	2587
HSA-MIR-20B-5P	99.88	74.01	2621

Literature-anchored findings (GeneRIF, showing 40)

• fat mass, low-density lipoprotein cholesterol, and skeletal muscle glycolytic-to-oxidative enzyme ratio increased more in the alpha2-gene negative subjects with overfeeding, suggesting more unfavorable metabolic changes compared with the (+) subjects (PMID:12496141)
• Structural basis for alpha1 versus alpha2 isoform-distinct behavior of the Na,K-ATPase (PMID:12529322)
• Haploinsufficiency of atp1a2 encoding the Na+/K+ pump alpha2 subunit is associated with familial hemiplegic migraine type 2 (PMID:12539047)
• novel missense mutations in the ATP1A2 Na(+),K(+)-ATPase pump gene on chromosome 1q23 in two families with familial hemiplegic migraine (FHM). affected family members with FHM, benign familial infantile convulsions, or both, carry the mutation (PMID:12953268)
• Patients with type 2 diabetes and controls were leg strength-trained for 30 min 3x per week for 6 weeks. In control subjects Na,K-pump alpha2 was increased by 21% in trained compared to untrained leg, and in diabetics alpha2 content was 41% higher. (PMID:14685860)
• Elevated plasma cholesterol may be responsible for the inhibition of erythrocyte Na+-K+ ATPase activity (PMID:14690302)
• first direct evidence of differential transcriptional control of ATP1A2 gene in the kidney and colon (PMID:14871878)
• the T345A mutation co-segregated with hemiplegic migraine type 2 in our family and was not present in 132 healthy Finnish control individuals (PMID:15133718)
• 3 putative A1A2 mutations (D718N, R763H, P979L) &3 that await validation (P796R, E902K, X1021R)were found in familial hemiplegic migraine. D718N and P979L may predispose to seizures and mental retardation. A1A2 does not play a major role in sporadic HM. (PMID:15159495)
• This study report a novel ATP1A2 mutation in a kindred with features that bridge the phenotypic spectrum between AHC and FHM syndromes, supporting a possible common pathogenesis in a subset of such cases. (PMID:15174025)
• ATP1A2 gene is not associated with the more common migraine syndromes and is not one of the most common hemiplegic migraine genes. (PMID:15210532)
• A novel ATP1A2 heterozygous missense mutation found in a family with multicase Alternating hemiplegia of childhood. (PMID:15286158)
• Missense mutations in this enzyme subunit ause hemiplegic migraine. (PMID:15308625)
• ATP1A2 mutation may have a role in familial hemiplegic migraine type 2 with cerebellar signs (PMID:15459825)
• The entire carboxy-terminus of HKalpha2 is required for stable assembly with beta1-Na+,K+-ATPase and functionality. (PMID:15569317)
• The ATP1A2 gene does not appear to be involved in the ethiopathogenesis of pure benign familial infantile seizures, at least in the explored Italian multiplex families (PMID:16026932)
• missense mutations R689Q and M731T in familial hemiplegic migraine type 2 (PMID:16037212)
• analysis of ATP1A2 mutations in familial hemiplegic migraine (PMID:16088919)
• In conclusion we propose that rare variants in ATP1A2 are involved in the susceptibility to common forms of migraine. (PMID:16110494)
• The authors detected a novel mutation in the ATP1A2 gene (R548H) in members of a family with BM, suggesting that BM and FHM may be allelic disorders. (PMID:16344534)
• This study identified a novel G615R ATP1A2 mutation in the proband and several of her family members. Functional analysis of mutant Na,K-ATPase in cellular survival assays showed a complete loss-of-function effect. (PMID:16437583)
• Study shows that the ATP1A2 gene is probably not involved in migraine with aura. (PMID:16508934)
• Results showed no evidence for a common contribution of ATP1A2 to the pathogenesis of complex inherited migraine with aura. (PMID:16508935)
• analysis of two novel de novo missense mutations in ATP1A2, R593W and V628M, associated with pure familial hemiplegic migraine (PMID:16538223)
• study to identify whether CACNA1A and ATP1A2 are or not related to Brazilian familial hemiplegic migraine (PMID:17119788)
• Elevated Na+ -K+ -ATPase activity postexercise may contribute to reduced fatigue after training. (PMID:17446412)
• Compound heterozygote found in familial hemiplegic migraine. (PMID:17473835)
• confirm the involvement of ATP1A2 gene in the sporadic form of hemiplegic migraine (PMID:17877748)
• the recurrence of ATP1A2 mutations M731T and T376M that affect sodium-potassium pump functioning in two Portuguese FHM families (PMID:17952365)
• Novel ATP1A2 mutations were found in two of the 20 families (10%). The p.Gly900Arg mutation was present in a family with epilepsy and FHM, and the p.Cys702Tyr mutation occurred in a family with occipitotemporal epilepsy and migraine . (PMID:18028407)
• two novel ATP1A2 mutations that were identified in two Portuguese probands with hemiplegic migraine and interesting additional clinical features (PMID:18028456)
• reconstituted FXYD1 protects both alpha1beta1 and alpha2beta1 very strongly against thermal inactivation (PMID:18052210)
• Sequence variants were identified in seven SHM patients: one CACNA1A mutation, five ATP1A2 mutations, and one SCN1A polymorphism. All six mutations caused functional changes in cellular assays. (PMID:18056581)
• D999H is a novel Hemiplegic Migraine, Familial ATP1A2 mutation in an Irish family. (PMID:18184292)
• glyceryl trinitrate infusion failed to induce more migraine in FHM-2 patients than in controls (PMID:18294248)
• Nineteen novel ATP1A2 mutations were identified last year, eleven of them migraine families. A systematic genetic analysis of patients with sporadic hemiplegic migraine revealed five mutations in this gene [review] (PMID:18451712)
• In this study we document the absence of ATP1A2 mutations in two Italian sisters with menstrual BM, suggesting that other genes are involved in the condition. (PMID:18483709)
• We studied four members of a family suffering from typical attacks of familial hemiplegic migraine (FHM) caused by a new mutation, R548C, of ATP1A2 gene in exon 12. (PMID:18498390)
• 4 new variants were found in exons of the ATP1A2 gene in sporadic hemiplegic migraine patients. It does not seem that ATP1A2 is a major gene in SHM. (PMID:18513263)
• A novel de novo nonsense mutation in ATP1A2 associated with sporadic hemiplegic migraine and epileptic seizures. (PMID:18644608)

Cross-species orthologs

12 orthologs

Organism	Symbol	Gene ID
danio_rerio	atp1a2a	ENSDARG00000010472
mus_musculus	Atp1a2	ENSMUSG00000007097
rattus_norvegicus	Atp1a2	ENSRNOG00000007290
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), ATP2B4 (ENSG00000058668), ATP2C2 (ENSG00000064270), ATP2B3 (ENSG00000067842), ATP2B1 (ENSG00000070961), ATP2A3 (ENSG00000074370), ATP12A (ENSG00000075673), ATP1A3 (ENSG00000105409), ATP4A (ENSG00000105675), ATP13A1 (ENSG00000105726), ATP7B (ENSG00000123191), ATP13A4 (ENSG00000127249), ATP1A4 (ENSG00000132681), 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-2 — P50993 (reviewed: P50993)

Alternative names: Sodium pump subunit alpha-2

All UniProt accessions (4): A0A0S2Z3W6, B1AKY9, P50993, H0Y7C1

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, providing the energy for active transport of various nutrients.

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. Interacts with regulatory subunit FXYD1.

Subcellular location. Membrane. Cell membrane.

Disease relevance. Migraine, familial hemiplegic, 2 (FHM2) [MIM:602481] A subtype of migraine with aura associated with hemiparesis in some families. Migraine is a disabling symptom complex of periodic headaches, usually temporal and unilateral. Headaches are often accompanied by irritability, nausea, vomiting and photophobia, preceded by constriction of the cranial arteries. Migraine with aura is characterized by recurrent attacks of reversible neurological symptoms (aura) that precede or accompany the headache. Aura may include a combination of sensory disturbances, such as blurred vision, hallucinations, vertigo, numbness and difficulty in concentrating and speaking. The disease is caused by variants affecting the gene represented in this entry. Alternating hemiplegia of childhood 1 (AHC1) [MIM:104290] A rare syndrome of episodic hemi- or quadriplegia lasting minutes to days. Most cases are accompanied by dystonic posturing, choreoathetoid movements, nystagmus, other ocular motor abnormalities, autonomic disturbances, and progressive cognitive impairment. It is typically distinguished from familial hemiplegic migraine by infantile onset and high prevalence of associated neurological deficits that become increasingly obvious with age. The disease is caused by variants affecting the gene represented in this entry. Fetal akinesia, respiratory insufficiency, microcephaly, polymicrogyria, and dysmorphic facies (FARIMPD) [MIM:619602] An autosomal recessive disease characterized by fetal akinesia, and generalized joint contractures and arthrogryposis at birth. Affected newborns have severe respiratory insufficiency and significant dysmorphic facial features. Malformations of cortical development are seen on brain imaging, most commonly polymicrogyria or other gyral anomalies. Death usually occurs in infancy. The disease is caused by variants affecting the gene represented in this entry. Developmental and epileptic encephalopathy 98 (DEE98) [MIM:619605] A form of epileptic encephalopathy, a heterogeneous group of early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE98 is an autosomal dominant form characterized by onset of seizures in the first decade. The disease is caused by variants affecting the gene represented in this entry.

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

RefSeq proteins (1): NP_000693* (*=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 (55 total): sequence variant 15, topological domain 11, transmembrane region 10, modified residue 10, region of interest 3, binding site 2, propeptide 1, chain 1, compositionally biased region 1, active site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P50993-F1	88.25	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.

Catalytic / active sites (1): 374 (4-aspartylphosphate intermediate)

Ligand- & substrate-binding residues (2): 714; 718

Post-translational modifications (10): 10, 439, 450, 496, 559, 570, 587, 672, 826, 940

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: 708 (showing top): GOBP_POTASSIUM_ION_TRANSPORT, GOBP_ESTABLISHMENT_OR_MAINTENANCE_OF_TRANSMEMBRANE_ELECTROCHEMICAL_GRADIENT, GOBP_MEMBRANE_DEPOLARIZATION, GOBP_NEGATIVE_REGULATION_OF_TRANSMEMBRANE_TRANSPORT, GOBP_RESPIRATORY_GASEOUS_EXCHANGE_BY_RESPIRATORY_SYSTEM, GOBP_COGNITION, GOBP_BEHAVIOR, GOBP_REGULATION_OF_BLOOD_PRESSURE, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_REGULATION_OF_ORGANIC_ACID_TRANSPORT, GOBP_NEUROTRANSMITTER_UPTAKE, GOBP_CELLULAR_RESPONSE_TO_LIPID, YAO_HOXA10_TARGETS_VIA_PROGESTERONE_UP, GOBP_REGULATION_OF_SYNAPTIC_TRANSMISSION_GLUTAMATERGIC, GOBP_CELLULAR_RESPONSE_TO_EXTERNAL_STIMULUS

GO Biological Process (58): neurotransmitter uptake (GO:0001504), behavioral fear response (GO:0001662), regulation of the force of heart contraction (GO:0002026), regulation of respiratory gaseous exchange by nervous system process (GO:0002087), potassium ion transport (GO:0006813), sodium ion transport (GO:0006814), intracellular sodium ion homeostasis (GO:0006883), regulation of muscle contraction (GO:0006937), regulation of smooth muscle contraction (GO:0006940), regulation of striated muscle contraction (GO:0006942), regulation of blood pressure (GO:0008217), adult locomotory behavior (GO:0008344), visual learning (GO:0008542), regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion (GO:0010881), response to auditory stimulus (GO:0010996), neuronal action potential propagation (GO:0019227), regulation of vasoconstriction (GO:0019229), L-ascorbic acid metabolic process (GO:0019852), amygdala development (GO:0021764), olfactory cortex development (GO:0021989), intracellular potassium ion homeostasis (GO:0030007), response to nicotine (GO:0035094), locomotory exploration behavior (GO:0035641), sodium ion transmembrane transport (GO:0035725), response to potassium ion (GO:0035864), sodium ion export across plasma membrane (GO:0036376), locomotion (GO:0040011), negative regulation of heart contraction (GO:0045822), positive regulation of heart contraction (GO:0045823), negative regulation of striated muscle contraction (GO:0045988), ATP metabolic process (GO:0046034), negative regulation of cytosolic calcium ion concentration (GO:0051481), regulation of glutamate uptake involved in transmission of nerve impulse (GO:0051946), regulation of synaptic transmission, glutamatergic (GO:0051966), relaxation of cardiac muscle (GO:0055119), cardiac muscle contraction (GO:0060048), cellular response to mechanical stimulus (GO:0071260), cellular response to steroid hormone stimulus (GO:0071383), potassium ion transmembrane transport (GO:0071805), regulation of cardiac muscle cell contraction (GO:0086004)

GO Molecular Function (16): P-type sodium:potassium-exchanging transporter activity (GO:0005391), steroid binding (GO:0005496), ATP binding (GO:0005524), phosphatase activity (GO:0016791), ATP hydrolysis activity (GO:0016887), ATPase-coupled monoatomic cation transmembrane transporter activity (GO:0019829), potassium ion binding (GO:0030955), sodium ion binding (GO:0031402), protein heterodimerization activity (GO:0046982), protein-folding chaperone binding (GO:0051087), steroid hormone binding (GO:1990239), nucleotide binding (GO:0000166), transporter activity (GO:0005215), protein binding (GO:0005515), P-type potassium transmembrane transporter activity (GO:0008556), metal ion binding (GO:0046872)

GO Cellular Component (17): cytoplasm (GO:0005737), endosome (GO:0005768), endoplasmic reticulum (GO:0005783), plasma membrane (GO:0005886), sodium:potassium-exchanging ATPase complex (GO:0005890), caveola (GO:0005901), cell surface (GO:0009986), intercalated disc (GO:0014704), membrane (GO:0016020), T-tubule (GO:0030315), organelle membrane (GO:0031090), cell projection (GO:0042995), neuronal cell body (GO:0043025), dendritic spine (GO:0043197), extracellular vesicle (GO:1903561), protein-containing complex (GO:0032991), sarcolemma (GO:0042383)

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
cellular anatomical structure	5
regulation of biological quality	2
nervous system process	2
metal ion transport	2
regulation of muscle contraction	2
anatomical structure development	2
alkali metal ion binding	2
endomembrane system	2
membrane	2
neurotransmitter transport	1
import into cell	1
behavioral defense response	1
fear response	1
regulation of heart contraction	1
respiratory gaseous exchange by respiratory system	1
regulation of respiratory system process	1
intracellular monoatomic cation homeostasis	1
sodium ion homeostasis	1
muscle contraction	1
regulation of muscle system process	1
smooth muscle contraction	1
striated muscle contraction	1
blood circulation	1
locomotory behavior	1
adult behavior	1
visual behavior	1
associative learning	1
regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum	1
regulation of cardiac muscle contraction by calcium ion signaling	1
response to mechanical stimulus	1
transmission of nerve impulse	1
action potential propagation	1
vasoconstriction	1
blood vessel diameter maintenance	1
regulation of blood circulation	1
monosaccharide metabolic process	1
carboxylic acid metabolic process	1
lactone metabolic process	1
limbic system development	1
olfactory lobe development	1

Protein interactions and networks

STRING

2566 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ATP1A2	CACNA1A	P78510	931
ATP1A2	SCN1A	P35498	913
ATP1A2	ATP1B2	P14415	888
ATP1A2	ATP1B1	P05026	876
ATP1A2	KCNK18	Q7Z418	806
ATP1A2	ATP1A3	P13637	737
ATP1A2	ATP1B3	P54709	717
ATP1A2	INO80	Q9ULG1	670
ATP1A2	PRRT2	Q7Z6L0	669
ATP1A2	CASQ1	P31415	648
ATP1A2	ASTN2	O75129	631
ATP1A2	KL	Q9UEF7	592
ATP1A2	ST8SIA4	Q92187	588
ATP1A2	CNTN4	Q8IWV2	575
ATP1A2	SLC2A1	P11166	558

IntAct

42 interactions, top by confidence:

A	B	Type	Score
ATP6V0A4	ATP6AP2	psi-mi:“MI:0914”(association)	0.530
ATP1A3	AGPAT2	psi-mi:“MI:0914”(association)	0.530
IFIT3	ATP1A2	psi-mi:“MI:0915”(physical association)	0.400
DST	ATP1A2	psi-mi:“MI:0915”(physical association)	0.400
PCNA	ATP1A2	psi-mi:“MI:0915”(physical association)	0.370
PRNP	WDR91	psi-mi:“MI:0914”(association)	0.350
APBB1	SSPOP	psi-mi:“MI:0914”(association)	0.350
CAND1	GTPBP10	psi-mi:“MI:0914”(association)	0.350
CUL3	PXDNL	psi-mi:“MI:0914”(association)	0.350
H4C16		psi-mi:“MI:0914”(association)	0.350
DOCK5	DPYSL4	psi-mi:“MI:0914”(association)	0.350
ROGDI		psi-mi:“MI:0914”(association)	0.350
P2RY8		psi-mi:“MI:0914”(association)	0.350
ARHGEF16	HSPA8	psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350
PA	DDX39A	psi-mi:“MI:0914”(association)	0.350
CFTR	POTEF	psi-mi:“MI:0914”(association)	0.350
SLC16A11	ESYT2	psi-mi:“MI:0914”(association)	0.350
BMI1	MEIS3P1	psi-mi:“MI:0914”(association)	0.350
GABARAP		psi-mi:“MI:0914”(association)	0.350
MAPT	SHTN1	psi-mi:“MI:0914”(association)	0.350
RIMS1	KIF2A	psi-mi:“MI:0914”(association)	0.350
ATP1A3	TMEM223	psi-mi:“MI:0914”(association)	0.350
TPX2	MAP1LC3B2	psi-mi:“MI:0914”(association)	0.350
ROGDI	ATP2A1	psi-mi:“MI:0914”(association)	0.350
CNGA4	CCDC22	psi-mi:“MI:0914”(association)	0.350
IL2RA	LTN1	psi-mi:“MI:0914”(association)	0.350

BioGRID (71): ATP1A2 (Affinity Capture-MS), ATP1A2 (Affinity Capture-MS), ATP1A2 (Co-fractionation), ATP1A2 (Co-fractionation), ATP6V0D1 (Co-fractionation), ATP6V1A (Co-fractionation), CCT7 (Co-fractionation), VDAC1 (Co-fractionation), VDAC2 (Co-fractionation), ATP1A2 (Proximity Label-MS), ATP1A2 (Affinity Capture-MS), ATP1A2 (Affinity Capture-MS), ATP1A2 (Affinity Capture-MS), ATP1A2 (Affinity Capture-MS), ATP1A2 (Affinity Capture-MS)

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

1554 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	57
Likely pathogenic	61
Uncertain significance	669
Likely benign	522
Benign	104

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1013256	NM_000702.4(ATP1A2):c.1810C>T (p.Arg604Ter)	Pathogenic
1027522	NM_000702.4(ATP1A2):c.2285-2A>C	Pathogenic
1071760	NM_000702.4(ATP1A2):c.1097G>T (p.Gly366Val)	Pathogenic
1072573	NM_000702.4(ATP1A2):c.2501G>A (p.Arg834Gln)	Pathogenic
12917	NM_000702.4(ATP1A2):c.2291T>C (p.Leu764Pro)	Pathogenic
12918	NM_000702.4(ATP1A2):c.2659T>C (p.Trp887Arg)	Pathogenic
12922	NM_000702.4(ATP1A2):c.901G>A (p.Gly301Arg)	Pathogenic
12923	NM_000702.4(ATP1A2):c.1033A>G (p.Thr345Ala)	Pathogenic
12925	NM_000702.4(ATP1A2):c.2936C>T (p.Pro979Leu)	Pathogenic
12926	NM_000702.4(ATP1A2):c.1643G>A (p.Arg548His)	Pathogenic
1356232	NM_000702.4(ATP1A2):c.1453A>T (p.Lys485Ter)	Pathogenic
1388779	NM_000702.4(ATP1A2):c.855dup (p.Ile286fs)	Pathogenic
1439209	NM_000702.4(ATP1A2):c.2357C>T (p.Pro786Leu)	Pathogenic
1459217	NM_000702.4(ATP1A2):c.720_721del (p.Ile240fs)	Pathogenic
1719913	NM_000702.4(ATP1A2):c.1130G>T (p.Gly377Val)	Pathogenic
1943929	NM_000702.4(ATP1A2):c.869_872del (p.Ile290fs)	Pathogenic
2009052	NM_000702.4(ATP1A2):c.991C>G (p.Pro331Ala)	Pathogenic
2011853	NM_000702.4(ATP1A2):c.524del (p.Lys175fs)	Pathogenic
2042154	NM_000702.4(ATP1A2):c.2708G>A (p.Trp903Ter)	Pathogenic
2202868	NM_000702.4(ATP1A2):c.2977CTC[1] (p.Leu994del)	Pathogenic
222078	NM_000702.4(ATP1A2):c.571G>A (p.Val191Met)	Pathogenic
2571598	NM_000702.4(ATP1A2):c.2278del (p.Glu760fs)	Pathogenic
2699167	NM_000702.4(ATP1A2):c.2126_2127del (p.Val709fs)	Pathogenic
2713294	NM_000702.4(ATP1A2):c.1405A>T (p.Arg469Ter)	Pathogenic
2734006	NM_000702.4(ATP1A2):c.605G>A (p.Arg202Gln)	Pathogenic
2752869	NM_000702.4(ATP1A2):c.2432C>G (p.Thr811Arg)	Pathogenic
2814730	NM_000702.4(ATP1A2):c.1570G>T (p.Glu524Ter)	Pathogenic
2859530	NM_000702.4(ATP1A2):c.2983dup (p.Ile995fs)	Pathogenic
3393233	NM_000702.4(ATP1A2):c.1459C>T (p.Gln487Ter)	Pathogenic
3598996	NM_000702.4(ATP1A2):c.36dup (p.Ala13fs)	Pathogenic

SpliceAI

3065 predictions. Top by Δscore:

Variant	Effect	Δscore
1:160120900:CCTCA:C	acceptor_loss	1.0000
1:160120901:CTCA:C	acceptor_loss	1.0000
1:160120903:CAGGC:C	acceptor_loss	1.0000
1:160120904:A:AG	acceptor_gain	1.0000
1:160120904:A:T	acceptor_loss	1.0000
1:160120904:AG:A	acceptor_gain	1.0000
1:160120904:AGGCT:A	acceptor_gain	1.0000
1:160120905:G:A	acceptor_gain	1.0000
1:160120905:G:GC	acceptor_gain	1.0000
1:160120905:GGC:G	acceptor_gain	1.0000
1:160120905:GGCT:G	acceptor_gain	1.0000
1:160120905:GGCTG:G	acceptor_gain	1.0000
1:160120999:G:GT	donor_gain	1.0000
1:160121189:CA:C	acceptor_loss	1.0000
1:160121190:A:AG	acceptor_gain	1.0000
1:160121191:G:GG	acceptor_gain	1.0000
1:160123396:G:GT	donor_gain	1.0000
1:160123416:TG:T	donor_loss	1.0000
1:160123417:G:GG	donor_gain	1.0000
1:160123939:CCAGC:C	acceptor_loss	1.0000
1:160123940:CAGCT:C	acceptor_loss	1.0000
1:160123941:A:AC	acceptor_loss	1.0000
1:160123941:A:AG	acceptor_gain	1.0000
1:160123942:G:GA	acceptor_gain	1.0000
1:160123942:GCT:G	acceptor_gain	1.0000
1:160123942:GCTAT:G	acceptor_gain	1.0000
1:160124057:G:GG	donor_gain	1.0000
1:160124058:T:A	donor_loss	1.0000
1:160124294:A:AG	acceptor_gain	1.0000
1:160124295:G:GG	acceptor_gain	1.0000

AlphaMissense

6676 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:160124033:T:C	S158P	1.000
1:160124036:T:C	F159L	1.000
1:160124038:C:A	F159L	1.000
1:160124038:C:G	F159L	1.000
1:160124312:G:C	R171P	1.000
1:160125152:T:C	L216S	1.000
1:160125157:G:A	G218R	1.000
1:160125157:G:C	G218R	1.000
1:160125158:G:A	G218E	1.000
1:160125158:G:C	G218A	1.000
1:160125158:G:T	G218V	1.000
1:160125222:T:A	N239K	1.000
1:160125222:T:G	N239K	1.000
1:160125253:G:C	G250R	1.000
1:160127599:G:C	G266R	1.000
1:160127600:G:A	G266D	1.000
1:160127600:G:T	G266V	1.000
1:160127606:T:A	I268K	1.000
1:160127608:G:C	A269P	1.000
1:160127609:C:A	A269D	1.000
1:160127615:T:C	L271P	1.000
1:160127618:C:A	A272D	1.000
1:160127704:G:A	G301R	1.000
1:160127704:G:C	G301R	1.000
1:160128659:T:C	L342P	1.000
1:160128671:C:A	A346D	1.000
1:160128730:G:C	G366R	1.000
1:160128731:G:A	G366D	1.000
1:160128746:T:A	I371N	1.000
1:160128746:T:G	I371S	1.000

dbSNP variants (sampled 300 via entrez): RS1000030717 (1:160127754 G>A), RS1000053536 (1:160131756 G>A), RS1000129485 (1:160122615 T>C), RS1000141418 (1:160134891 G>A,T), RS1000185818 (1:160130332 A>C), RS1000206796 (1:160122401 A>T), RS1000276298 (1:160118582 G>A,T), RS1000413216 (1:160116215 G>T), RS1000464163 (1:160123920 C>G,T), RS1000639881 (1:160129357 C>T), RS1000721199 (1:160117748 G>A,T), RS1000784114 (1:160116474 G>A), RS1001039220 (1:160114423 ACAGGGGTACTC>A), RS1001151861 (1:160117523 G>A), RS1001176901 (1:160121070 C>G,T)

Disease associations

OMIM: gene MIM:182340 | disease phenotypes: MIM:141500, MIM:108600, MIM:104290, MIM:619605, MIM:602481, MIM:619602, MIM:614886, MIM:208150, MIM:308350, MIM:607745

GenCC curated gene-disease

Disease	Classification	Inheritance
migraine, familial hemiplegic, 2	Definitive	Autosomal dominant
alternating hemiplegia of childhood 1	Strong	Autosomal dominant
fetal akinesia, respiratory insufficiency, microcephaly, polymicrogyria, and dysmorphic facies	Strong	Autosomal recessive
developmental and epileptic encephalopathy 98	Strong	Autosomal dominant
alternating hemiplegia of childhood	Supportive	Autosomal dominant
familial or sporadic hemiplegic migraine	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (2)

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

Disease	Classification	Inheritance
fetal akinesia, respiratory insufficiency, microcephaly, polymicrogyria, and dysmorphic facies	Definitive	AR
hemiplegic migraine-developmental and epileptic encephalopathy spectrum	Definitive	AD

Mondo (18): familial hemiplegic migraine (MONDO:0000700), spastic ataxia (MONDO:0017845), alternating hemiplegia of childhood 1 (MONDO:0007087), developmental and epileptic encephalopathy 98 (MONDO:0030472), migraine, familial hemiplegic, 2 (MONDO:0011232), fetal akinesia, respiratory insufficiency, microcephaly, polymicrogyria, and dysmorphic facies (MONDO:0859204), peroxisome biogenesis disorder 12A (Zellweger) (MONDO:0013951), fetal akinesia deformation sequence (MONDO:0008824), periodic paralysis (MONDO:0016122), developmental and epileptic encephalopathy, 1 (MONDO:0010632), breast ductal adenocarcinoma (MONDO:0005590), hemiplegic migraine-developmental and epileptic encephalopathy spectrum (MONDO:0100539), hemiplegia (MONDO:0001170), polymicrogyria (MONDO:0000087), epilepsy (MONDO:0005027)

Orphanet (8): Spastic ataxia (Orphanet:316226), Alternating hemiplegia of childhood (Orphanet:2131), Familial or sporadic hemiplegic migraine (Orphanet:569), Zellweger syndrome (Orphanet:912), Periodic paralysis (Orphanet:206976), Polymicrogyria (Orphanet:35981), Self-limited neonatal-infantile epilepsy (Orphanet:140927), Self-limited infantile epilepsy (Orphanet:306)

HPO phenotypes

186 total (30 of 186 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000023	Inguinal hernia
HP:0000252	Microcephaly
HP:0000297	Facial hypotonia
HP:0000348	High forehead
HP:0000360	Tinnitus
HP:0000365	Hearing impairment
HP:0000494	Downslanted palpebral fissures
HP:0000504	Abnormality of vision
HP:0000508	Ptosis
HP:0000546	Retinal degeneration
HP:0000565	Esotropia
HP:0000575	Scotoma
HP:0000577	Exotropia
HP:0000622	Blurred vision
HP:0000639	Nystagmus
HP:0000648	Optic atrophy
HP:0000651	Diplopia
HP:0000657	Oculomotor apraxia
HP:0000668	Hypodontia
HP:0000708	Atypical behavior
HP:0000712	Emotional lability
HP:0000717	Autism
HP:0000718	Aggressive behavior
HP:0000750	Delayed speech and language development
HP:0000817	Reduced eye contact
HP:0000975	Hyperhidrosis
HP:0000980	Pallor
HP:0001125	Transient unilateral blurring of vision

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST001773_1	Response to antipsychotic treatment	2.000000e-07
GCST010796_5351	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-08
GCST010796_5352	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-08
GCST010796_5353	Electrocardiogram morphology (amplitude at temporal datapoints)	9.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004327	electrocardiography

MeSH disease descriptors (8)

Descriptor	Name	Tree numbers
D018270	Carcinoma, Ductal, Breast	C04.557.470.200.025.232.500; C04.557.470.615.132.500; C04.588.180.390; C17.800.090.500.390
D004827	Epilepsy	C10.228.140.490
D006429	Hemiplegia	C10.597.622.295; C23.888.592.636.312
D065706	Polymicrogyria	C10.500.507.500.500; C16.131.666.507.500.500
C536589	Alternating hemiplegia of childhood (supp.)
C537246	Hemiplegic migraine, familial type 2 (supp.)
C536647	Pena Shokeir syndrome, type 1 (supp.)
C564815	Spastic Ataxia (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (4): CHEMBL2095186 (PROTEIN COMPLEX GROUP), CHEMBL6066560 (PROTEIN COMPLEX), CHEMBL6066561 (PROTEIN COMPLEX), CHEMBL6066562 (PROTEIN COMPLEX)

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)

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs6688363	Efficacy	3	olanzapine	Schizophrenia

GtoPdb / IUPHAR curated pharmacology

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

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

Binding affinities (BindingDB)

16 measured of 18 human assays (18 total across all organisms); most potent 16 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
DEt (12)	KI	53 nM
DEtDA (10)	KI	69 nM
DbisGly (14)	KI	80 nM
DMe (11)	KI	101 nM
DSCar (8)	KI	102 nM
DGly (2)	KI	124 nM
CS337	KI	139 nM
DGlyN (4)	KI	152 nM
Dbis	KI	196 nM
DMeCF3 (13)	KI	199 nM
DAlaN (5)	KI	232 nM
DSerN (7)	KI	242 nM
DPrN (9)	KI	249 nM
DOH (1)	KI	311 nM
DSer (6)	KI	316 nM
DGlMe (3)	KI	540 nM

ChEMBL bioactivities

284 potent at pChembl≥5 of 336 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.52	IC50	3	nM	CHEMBL2092909
8.43	Ki	3.7	nM	CHEMBL5765464
8.41	Ki	3.9	nM	CHEMBL5876237
8.40	Ki	4	nM	CHEMBL5879229
8.38	Ki	4.2	nM	CHEMBL5765464
8.37	Ki	4.3	nM	CHEMBL5765464
8.37	Ki	4.3	nM	CHEMBL5879229
8.32	IC50	4.79	nM	CHEMBL1651648
8.29	Ki	5.1	nM	CHEMBL5876237
8.28	Ki	5.3	nM	CHEMBL5879229
8.27	Ki	5.4	nM	CHEMBL5879229
8.27	Ki	5.4	nM	CHEMBL5765464
8.25	Ki	5.6	nM	CHEMBL5832044
8.24	Ki	5.8	nM	CHEMBL5748673
8.22	Ki	6	nM	CHEMBL5879229
8.17	Ki	6.8	nM	CHEMBL5832044
8.17	IC50	6.79	nM	CHEMBL1651648
8.15	IC50	7	nM	CHEMBL2092738
8.15	IC50	7.04	nM	CHEMBL1651624
8.14	Ki	7.2	nM	CHEMBL6026321
8.10	IC50	8	nM	CHEMBL3085467
8.10	IC50	8	nM	CHEMBL3085497
8.10	Ki	8	nM	CHEMBL5879229
8.10	Ki	8	nM	CHEMBL5765464
8.10	IC50	8	nM	DIGITOXIGENIN
8.10	IC50	8	nM	DIGITOXIN
8.09	Ki	8.1	nM	CHEMBL6056661
8.07	Ki	8.6	nM	CHEMBL5876237
8.05	IC50	9	nM	CHEMBL3085468
8.01	Ki	9.8	nM	CHEMBL5957388
8.00	Ki	10	nM	CHEMBL5748673
8.00	Ki	10.1	nM	CHEMBL5832044
7.99	Ki	10.3	nM	CHEMBL5791351
7.98	Ki	10.5	nM	CHEMBL5957388
7.98	IC50	10.5	nM	CHEMBL3349024
7.97	Ki	10.8	nM	CHEMBL5768226
7.97	IC50	10.7	nM	CHEMBL3350144
7.96	Ki	11.1	nM	CHEMBL5851200
7.93	Ki	11.7	nM	CHEMBL5910596
7.92	Ki	12.1	nM	CHEMBL6026321
7.92	IC50	12	nM	CHEMBL2069010
7.91	Ki	12.4	nM	CHEMBL6030183
7.89	Ki	13	nM	CHEMBL6056661
7.84	Ki	14.6	nM	CHEMBL6056661
7.84	Ki	14.3	nM	CHEMBL6026321
7.84	Ki	14.4	nM	CHEMBL6031986
7.84	Ki	14.3	nM	CHEMBL5851200
7.82	Ki	15.2	nM	CHEMBL5910596
7.82	Ki	15.3	nM	CHEMBL5910596
7.82	Ki	15.3	nM	CHEMBL5768226

PubChem BioAssay actives

228 with measured affinity, of 391 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
3-[(3S,10S,12S,13S,14S,17R)-3-[(2R,4S,5S,6S)-5-[(2S,4S,5S,6S)-5-[(2,4-dimethyl-1,4-oxazepan-7-yl)oxy]-4-hydroxy-6-methyloxan-2-yl]oxy-4-hydroxy-6-methyloxan-2-yl]oxy-12,14-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	1802889: Na,K-ATPase Inhibition Assay from Article 10.1074/jbc.M114.557629: “Digoxin derivatives with enhanced selectivity for the a2 isoform of Na,K-ATPase: effects on intraocular pressure in rabbits.”	ki	0.0156	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-[(3S,10S,12S,13S,14S,17R)-3-[(2R,4S,5S,6S)-5-[(2S,4S,5S,6S)-5-[[4-(2-aminoethyl)-2-methyl-1,4-oxazepan-7-yl]oxy]-4-hydroxy-6-methyloxan-2-yl]oxy-4-hydroxy-6-methyloxan-2-yl]oxy-12,14-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	1802889: Na,K-ATPase Inhibition Assay from Article 10.1074/jbc.M114.557629: “Digoxin derivatives with enhanced selectivity for the a2 isoform of Na,K-ATPase: effects on intraocular pressure in rabbits.”	ki	0.0167	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
3-[(3S,10S,12S,13S,14S,17R)-3-[(2R,4S,5S,6S)-5-[(2S,4S,5S,6S)-5-[(4-ethyl-2-methyl-1,4-oxazepan-7-yl)oxy]-4-hydroxy-6-methyloxan-2-yl]oxy-4-hydroxy-6-methyloxan-2-yl]oxy-12,14-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	1802889: Na,K-ATPase Inhibition Assay from Article 10.1074/jbc.M114.557629: “Digoxin derivatives with enhanced selectivity for the a2 isoform of Na,K-ATPase: effects on intraocular pressure in rabbits.”	ki	0.0185	uM
[7-[(2S,3S,4S,6S)-6-[(2S,3S,4S,6R)-6-[[(3S,10S,12S,13S,14S,17R)-12,14-dihydroxy-10,13-dimethyl-17-(5-oxo-2H-furan-3-yl)-1,2,3,4,5,6,7,8,9,11,12,15,16,17-tetradecahydrocyclopenta[a]phenanthren-3-yl]oxy]-4-hydroxy-2-methyloxan-3-yl]oxy-4-hydroxy-2-methyloxan-3-yl]oxy-2-methyl-1,4-oxazepan-4-yl]urea	1802889: Na,K-ATPase Inhibition Assay from Article 10.1074/jbc.M114.557629: “Digoxin derivatives with enhanced selectivity for the a2 isoform of Na,K-ATPase: effects on intraocular pressure in rabbits.”	ki	0.0200	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
2-[7-[(2S,3S,4S,6S)-6-[(2S,3S,4S,6R)-6-[[(3S,10S,12S,13S,14S,17R)-12,14-dihydroxy-10,13-dimethyl-17-(5-oxo-2H-furan-3-yl)-1,2,3,4,5,6,7,8,9,11,12,15,16,17-tetradecahydrocyclopenta[a]phenanthren-3-yl]oxy]-4-hydroxy-2-methyloxan-3-yl]oxy-4-hydroxy-2-methyloxan-3-yl]oxy-2-methyl-1,4-oxazepan-4-yl]acetamide	1802889: Na,K-ATPase Inhibition Assay from Article 10.1074/jbc.M114.557629: “Digoxin derivatives with enhanced selectivity for the a2 isoform of Na,K-ATPase: effects on intraocular pressure in rabbits.”	ki	0.0204	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
2-[7-[(2S,3S,4S,6S)-6-[(2S,3S,4S,6R)-6-[[(3S,10S,12S,13S,14S,17R)-12,14-dihydroxy-10,13-dimethyl-17-(5-oxo-2H-furan-3-yl)-1,2,3,4,5,6,7,8,9,11,12,15,16,17-tetradecahydrocyclopenta[a]phenanthren-3-yl]oxy]-4-hydroxy-2-methyloxan-3-yl]oxy-4-hydroxy-2-methyloxan-3-yl]oxy-2-methyl-1,4-oxazepan-4-yl]acetic acid	1802889: Na,K-ATPase Inhibition Assay from Article 10.1074/jbc.M114.557629: “Digoxin derivatives with enhanced selectivity for the a2 isoform of Na,K-ATPase: effects on intraocular pressure in rabbits.”	ki	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
3-[7-[(2S,3S,4S,6S)-6-[(2S,3S,4S,6R)-6-[[(3S,10S,12S,13S,14S,17R)-12,14-dihydroxy-10,13-dimethyl-17-(5-oxo-2H-furan-3-yl)-1,2,3,4,5,6,7,8,9,11,12,15,16,17-tetradecahydrocyclopenta[a]phenanthren-3-yl]oxy]-4-hydroxy-2-methyloxan-3-yl]oxy-4-hydroxy-2-methyloxan-3-yl]oxy-2-methyl-1,4-oxazepan-4-yl]pentanedioic acid	1802889: Na,K-ATPase Inhibition Assay from Article 10.1074/jbc.M114.557629: “Digoxin derivatives with enhanced selectivity for the a2 isoform of Na,K-ATPase: effects on intraocular pressure in rabbits.”	ki	0.0349	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
3-[(3S,10S,12S,13S,14S,17R)-12,14-dihydroxy-3-[(2R,4S,5S,6S)-4-hydroxy-5-[(2S,4S,5S,6S)-4-hydroxy-6-methyl-5-[[2-methyl-4-(2,2,2-trifluoroethyl)-1,4-oxazepan-7-yl]oxy]oxan-2-yl]oxy-6-methyloxan-2-yl]oxy-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	1802889: Na,K-ATPase Inhibition Assay from Article 10.1074/jbc.M114.557629: “Digoxin derivatives with enhanced selectivity for the a2 isoform of Na,K-ATPase: effects on intraocular pressure in rabbits.”	ki	0.0440	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
3-[7-[(2S,3S,4S,6S)-6-[(2S,3S,4S,6R)-6-[[(3S,10S,12S,13S,14S,17R)-12,14-dihydroxy-10,13-dimethyl-17-(5-oxo-2H-furan-3-yl)-1,2,3,4,5,6,7,8,9,11,12,15,16,17-tetradecahydrocyclopenta[a]phenanthren-3-yl]oxy]-4-hydroxy-2-methyloxan-3-yl]oxy-4-hydroxy-2-methyloxan-3-yl]oxy-2-methyl-1,4-oxazepan-4-yl]propanamide	1802889: Na,K-ATPase Inhibition Assay from Article 10.1074/jbc.M114.557629: “Digoxin derivatives with enhanced selectivity for the a2 isoform of Na,K-ATPase: effects on intraocular pressure in rabbits.”	ki	0.0470	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
Digoxin	1802889: Na,K-ATPase Inhibition Assay from Article 10.1074/jbc.M114.557629: “Digoxin derivatives with enhanced selectivity for the a2 isoform of Na,K-ATPase: effects on intraocular pressure in rabbits.”	ki	0.0550	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
2-[7-[(2S,3S,4S,6S)-6-[(2S,3S,4S,6R)-6-[[(3S,10S,12S,13S,14S,17R)-12,14-dihydroxy-10,13-dimethyl-17-(5-oxo-2H-furan-3-yl)-1,2,3,4,5,6,7,8,9,11,12,15,16,17-tetradecahydrocyclopenta[a]phenanthren-3-yl]oxy]-4-hydroxy-2-methyloxan-3-yl]oxy-4-hydroxy-2-methyloxan-3-yl]oxy-2-methyl-1,4-oxazepan-4-yl]propanamide	1802889: Na,K-ATPase Inhibition Assay from Article 10.1074/jbc.M114.557629: “Digoxin derivatives with enhanced selectivity for the a2 isoform of Na,K-ATPase: effects on intraocular pressure in rabbits.”	ki	0.0670	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
3-[(3S,5R,8R,9S,10S,12R,13S,14S,17R)-3-[(2R,4S,5S,6R)-5-[(2S,4S,5S,6R)-4,5-dihydroxy-6-methyloxan-2-yl]oxy-4-hydroxy-6-methyloxan-2-yl]oxy-12,14-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	1802889: Na,K-ATPase Inhibition Assay from Article 10.1074/jbc.M114.557629: “Digoxin derivatives with enhanced selectivity for the a2 isoform of Na,K-ATPase: effects on intraocular pressure in rabbits.”	ki	0.0740	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
3-[(1R,3S,5S,8R,9S,10R,11R,13R,14S,17R)-1,5,11,14-tetrahydroxy-10-(hydroxymethyl)-13-methyl-3-[(2R,3R,4R,5R,6S)-3,4,5-trihydroxy-6-methyloxan-2-yl]oxy-2,3,4,6,7,8,9,11,12,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-17-yl]-2H-furan-5-one	1802889: Na,K-ATPase Inhibition Assay from Article 10.1074/jbc.M114.557629: “Digoxin derivatives with enhanced selectivity for the a2 isoform of Na,K-ATPase: effects on intraocular pressure in rabbits.”	ki	0.0900	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
methyl 2-[7-[(2S,3S,4S,6S)-6-[(2S,3S,4S,6R)-6-[[(3S,10S,12S,13S,14S,17R)-12,14-dihydroxy-10,13-dimethyl-17-(5-oxo-2H-furan-3-yl)-1,2,3,4,5,6,7,8,9,11,12,15,16,17-tetradecahydrocyclopenta[a]phenanthren-3-yl]oxy]-4-hydroxy-2-methyloxan-3-yl]oxy-4-hydroxy-2-methyloxan-3-yl]oxy-2-methyl-1,4-oxazepan-4-yl]acetate	1802889: Na,K-ATPase Inhibition Assay from Article 10.1074/jbc.M114.557629: “Digoxin derivatives with enhanced selectivity for the a2 isoform of Na,K-ATPase: effects on intraocular pressure in rabbits.”	ki	0.1280	uM

CTD chemical–gene interactions

49 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Aflatoxin B1	decreases expression, decreases methylation, increases methylation, affects expression	5
trichostatin A	affects cotreatment, increases expression	3
Benzo(a)pyrene	decreases expression, increases expression, increases methylation	3
Doxorubicin	decreases expression	3
Valproic Acid	decreases expression, increases expression	3
bisphenol A	affects expression, decreases expression	2
sodium arsenite	decreases expression, increases expression	2
Daunorubicin	decreases expression	2
Mitoxantrone	decreases expression	2
Nickel	decreases expression	2
Ouabain	increases expression, affects binding, decreases reaction	2
methylmercuric chloride	decreases expression	1
propionaldehyde	increases expression	1
mancozeb	decreases expression	1
perfluorooctanoic acid	increases expression	1
benzo(e)pyrene	decreases methylation	1
perfluorooctane sulfonic acid	increases expression	1
perfluoro-n-nonanoic acid	decreases expression	1
2,7-dihydroxynaphthalene	decreases expression	1
4-chloro-N-((4-(1,1-dimethylethyl)phenyl)methyl)-3-ethyl-1-methyl-1H-pyrazole-5-carboxamide	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
perfluorohexanesulfonic acid	decreases expression	1
clothianidin	decreases expression	1
dorsomorphin	increases expression, affects cotreatment	1
Decitabine	affects expression	1
Sunitinib	decreases expression	1
Acetaminophen	decreases expression	1
Calcitriol	affects cotreatment, increases expression	1
Carbamazepine	affects expression	1
Cisplatin	affects expression	1

ChEMBL screening assays

49 unique, capped per target: 49 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

Cellosaurus cell lines

1 cell lines: 1 induced pluripotent stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_E9CW	SDCHi007-A	Induced pluripotent stem cell	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05260125	PHASE4	RECRUITING	Comparison of the Efficacy of Ultrasound Guided vs Non-guided Suprascapular Nerve Block Treatment in Stroke Patients
NCT00004637	PHASE4	COMPLETED	Double-Blind, Placebo-Controlled Trial of Vitamin E as Add-on Therapy for Children With Epilepsy
NCT00043914	PHASE4	COMPLETED	Measurement Of Serum Levels Of Two Antiepileptic Drugs During Conversion In Patients With Epilepsy
NCT00132223	PHASE4	UNKNOWN	Effects on the Diagnostic Accuracy of Magnetic Imaging Angiographies of the Supra-Aortic Vessels by Three Different Magnetic Resonance Contrast Agents in Patients
NCT00133081	PHASE4	UNKNOWN	Study to Improve the Treatment of Epilepsy (SITE)
NCT00137709	PHASE4	UNKNOWN	Hormone Profiles in Adults With Newly Diagnosed Epilepsy
NCT00154076	PHASE4	COMPLETED	A Multicenter Comparative Trial of Zonisamide and Topiramate as Initial Monotherapy in Untreated Epilepsies
NCT00165828	PHASE4	TERMINATED	Efficacy and Safety of an add-on Treatment With Zonisamide in Adults With Focal Epileptic Seizures With or Without Secondary Generalization
NCT00181116	PHASE4	COMPLETED	Levetiracetam for Benign Rolandic Epilepsy
NCT00207935	PHASE4	COMPLETED	Use of Sustained Release Antiepileptic Medication (Depakote® ER) for Pediatric Epilepsy in a Mental Retardation/Developmental Disorder Population
NCT00215592	PHASE4	COMPLETED	Open Label, Zonegran (Zonisamide) In Partial Onset Seizures
NCT00266604	PHASE4	COMPLETED	A Study to Evaluate the Dosing, Effectiveness and Safety of Topiramate for the Treatment of Epilepsy
NCT00288639	PHASE4	COMPLETED	Lyrica (Pregabalin) Administered as an Add-on Therapy for Partial Seizures (LEADER).
NCT00312676	PHASE4	UNKNOWN	Compare Tolerability of an Overnight Switch to Gradual Switch Between Two Different Forms of Depakote
NCT00323947	PHASE4	COMPLETED	Methylphenidate for Treating Attention Deficit Hyperactivity Disorder in Children With Both ADHD and Epilepsy
NCT00385411	PHASE4	COMPLETED	Study of Valproate in Young Patients Suffering From Epilepsy
NCT00522418	PHASE4	TERMINATED	Study Comparing Best Medical Practice With or Without VNS Therapy in Pharmacoresistant Partial Epilepsy Patients
NCT00537940	PHASE4	COMPLETED	Comparative Study Of Pregabalin And Gabapentin As Adjunctive Therapy In Subjects With Partial Seizures
NCT00552526	PHASE4	UNKNOWN	Ketogenic Diet vs.Antiepileptic Drug Treatment in Drug Resistant Epilepsy
NCT00564915	PHASE4	COMPLETED	RCT of the Efficacy of the Ketogenic Diet in the Treatment of Epilepsy
NCT00571155	PHASE4	COMPLETED	Trial of Levetiracetam in Patients With Primary Brain Tumors and Symptomatic Seizures Who Undergo Surgery
NCT00572195	PHASE4	COMPLETED	RNS® System LTT Study
NCT00610532	PHASE4	TERMINATED	Evaluating the Transporter Protein Inhibitor Probenecid In Patients With Epilepsy
NCT00630357	PHASE4	COMPLETED	Trial to Evaluate the Safety and Efficacy of Keppra After Conversion to Mono-therapy in Subjects With Partial Epilepsy
NCT00630630	PHASE4	COMPLETED	Study on Safety and Efficacy of Levetiracetam in the Adjunctive Treatment of Female Subjects With C1 Catamenial Epilepsy
NCT00630968	PHASE4	COMPLETED	S.K.A.T.E.: Safety of Keppra as Adjunctive Therapy in Epilepsy
NCT00631150	PHASE4	COMPLETED	A Phase IV-Pharmacovigilance Study of Keppra Greece - S.K.A.T.E.: Safety of Keppra as Adjunctive Therapy in Epilepsy
NCT00659958	PHASE4	COMPLETED	ZAGAL Study: Evaluating Effectiveness and Tolerability of Zonisamide as Adjunctive Therapy in Patients With Partial Onset Seizures Treated With Two Antiepileptic Drugs
NCT00713622	PHASE4	COMPLETED	Comparing The Effect On Cognition Of Adjunctive Therapy With Zonisamide Versus Sodium Valproate
NCT00807989	PHASE4	COMPLETED	The Efficacy and Safety of Low Dose Combination of LTG and VPA Compared to CBZ Monotherapy
NCT00832884	PHASE4	COMPLETED	The Safety of Intravenous Lacosamide
NCT00869622	PHASE4	COMPLETED	Antiepileptic Drugs and Osteoporotic Prevention Trial
NCT00896987	PHASE4	COMPLETED	Lamotrigine Cognitive Function Study in Adult Untreated Epilepsies
NCT00952081	PHASE4	COMPLETED	A Pilot Study to Evaluate Efficacy and Safety of Clevidipine in Neurosurgical Patients
NCT01118455	PHASE4	TERMINATED	Trial to Assess Vagus Nerve Stimulation Therapy vs. Anti-Epileptic Drug (AED) Treatment in Children With Refractory Seizures
NCT01127165	PHASE4	COMPLETED	Low and High Dose Zonisamide in Children as Monotherapy
NCT01127256	PHASE4	COMPLETED	Comparative Study of Zonisamide and Carbamazepine as an Initial Monotherapy: Efficacy and Safety Evaluation
NCT01140867	PHASE4	COMPLETED	Open-label, Multi-center Trial of Zonisamide as Adjunctive Therapy in Patients With Uncontrolled Partial Epilepsy
NCT01175954	PHASE4	COMPLETED	Cognitive and Behavioral Effects of Lacosamide
NCT01229735	PHASE4	COMPLETED	Levetiracetam Versus Topiramate as Adjunctive Therapy to Evaluate Efficacy and Safety in Subjects With Refractory Partial Onset Seizures