ATP1A1

Summary

ATP1A1 (ATPase Na+/K+ transporting subunit alpha 1, HGNC:799) is a protein-coding gene on chromosome 1p13.1, encoding Sodium/potassium-transporting ATPase subunit alpha-1 (P05023). 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. It is a selective cancer dependency (DepMap: 84.2% of cell lines).

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 1 subunit. Multiple transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 476 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Charcot-Marie-tooth disease, axonal, type 2DD (Strong, GenCC) — +2 more curated relationships
• GWAS associations: 4
• Clinical variants (ClinVar): 922 total — 10 pathogenic, 13 likely-pathogenic
• Phenotypes (HPO): 34
• Druggable target: yes — 5 molecules with ChEMBL bioactivity
• Cancer driver (intOGen): activating (oncogene-like) across 1 cancer types
• Cancer dependency (DepMap): dependent in 84.2% of screened cell lines
• MANE Select transcript: NM_000701

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:799
Approved symbol	ATP1A1
Name	ATPase Na+/K+ transporting subunit alpha 1
Location	1p13.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000163399
Ensembl biotype	protein_coding
OMIM	182310
Entrez	476

Gene structure

Transcript identifiers

Ensembl transcripts: 22 — 17 protein_coding, 4 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000295598, ENST00000369494, ENST00000369496, ENST00000418797, ENST00000440951, ENST00000463382, ENST00000479960, ENST00000488733, ENST00000491156, ENST00000495965, ENST00000537345, ENST00000897938, ENST00000897939, ENST00000897940, ENST00000897941, ENST00000897942, ENST00000897943, ENST00000897944, ENST00000897945, ENST00000945199, ENST00000945200, ENST00000945201

RefSeq mRNA: 3 — MANE Select: NM_000701 NM_000701, NM_001160233, NM_001160234

CCDS: CCDS53351, CCDS53352, CCDS887

Canonical transcript exons

ENST00000295598 — 23 exons

Exon	Start	End
ENSE00001596785	116397888	116398038
ENSE00001601549	116395110	116395285
ENSE00001606107	116388131	116388244
ENSE00001616448	116390213	116390411
ENSE00001621938	116403884	116403975
ENSE00001623942	116398930	116399084
ENSE00001633629	116389439	116389707
ENSE00001634637	116396598	116396734
ENSE00001638847	116401554	116401655
ENSE00001644074	116393531	116393723
ENSE00001655769	116392854	116392988
ENSE00001697909	116387288	116387491
ENSE00001720588	116388638	116388772
ENSE00001752571	116400861	116401006
ENSE00001754252	116390782	116390891
ENSE00001755191	116398621	116398789
ENSE00001789005	116399420	116399543
ENSE00001804292	116384783	116384842
ENSE00001900442	116404416	116404774
ENSE00002716005	116373244	116373523
ENSE00003598098	116401130	116401260
ENSE00003638429	116384014	116384124
ENSE00003667908	116388902	116389019

Expression profiles

Bgee: expression breadth ubiquitous, 305 present calls, max score 99.77.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 96.5852 / max 1905.3538, expressed in 1827 samples.

FANTOM5 promoters (14 alternative TSS)

Promoter ID	TPM avg	Samples expressed
4820	74.6333	1825
4819	8.9663	1766
4821	5.5454	1687
4823	2.6672	1331
4824	2.5944	1177
4827	0.7749	433
4817	0.4720	179
4825	0.3908	178
4833	0.2264	75
4834	0.1188	50

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
renal medulla	UBERON:0000362	99.77	gold quality
right lobe of thyroid gland	UBERON:0001119	99.66	gold quality
left lobe of thyroid gland	UBERON:0001120	99.66	gold quality
ileal mucosa	UBERON:0000331	99.62	gold quality
metanephros cortex	UBERON:0010533	99.61	gold quality
cerebellar hemisphere	UBERON:0002245	99.59	gold quality
mucosa of transverse colon	UBERON:0004991	99.59	gold quality
cerebellar cortex	UBERON:0002129	99.57	gold quality
thyroid gland	UBERON:0002046	99.56	gold quality
right hemisphere of cerebellum	UBERON:0014890	99.56	gold quality
adult mammalian kidney	UBERON:0000082	99.54	gold quality
ileum	UBERON:0002116	99.51	silver quality
islet of Langerhans	UBERON:0000006	99.50	gold quality
gall bladder	UBERON:0002110	99.50	gold quality
rectum	UBERON:0001052	99.48	gold quality
duodenum	UBERON:0002114	99.48	gold quality
body of pancreas	UBERON:0001150	99.44	gold quality
saliva-secreting gland	UBERON:0001044	99.41	gold quality
minor salivary gland	UBERON:0001830	99.41	gold quality
cerebellum	UBERON:0002037	99.40	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	99.33	gold quality
right frontal lobe	UBERON:0002810	99.28	gold quality
small intestine Peyer’s patch	UBERON:0003454	99.28	gold quality
pancreas	UBERON:0001264	99.27	gold quality
right lung	UBERON:0002167	99.27	gold quality
skin of leg	UBERON:0001511	99.25	gold quality
parotid gland	UBERON:0001831	99.25	gold quality
skin of abdomen	UBERON:0001416	99.24	gold quality
upper lobe of left lung	UBERON:0008952	99.21	gold quality
Brodmann (1909) area 9	UBERON:0013540	99.21	gold quality

Single-cell (SCXA)

Detected in 18 experiment(s), a significant marker in 16.

Experiment	Marker?	Max mean expression
E-HCAD-10	yes	1847.38
E-MTAB-11121	yes	475.37
E-MTAB-8142	yes	130.79
E-HCAD-1	yes	75.22
E-GEOD-125970	yes	66.85
E-CURD-119	yes	61.38
E-GEOD-134144	yes	31.57
E-GEOD-137537	yes	29.60
E-MTAB-5061	yes	28.23
E-GEOD-81547	yes	25.12
E-MTAB-10553	yes	23.47
E-MTAB-7316	yes	21.60
E-HCAD-9	yes	12.66
E-CURD-114	yes	10.99
E-GEOD-130148	yes	9.25

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ATF1, CREB1, NRF1, SIX4, SP1, SP3, SP4, TCF3, ZEB1

miRNA regulators (miRDB)

21 targeting ATP1A1, 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-4668-3P	100.00	68.74	2635
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-1193	100.00	65.93	529
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-3685	99.62	68.83	1621
HSA-MIR-4499	99.62	67.29	1470
HSA-MIR-5695	99.41	67.48	1047
HSA-MIR-488-5P	99.28	68.12	821
HSA-MIR-3160-5P	99.28	69.07	1938
HSA-MIR-5582-5P	99.27	71.42	1879
HSA-MIR-5585-5P	97.95	68.80	1024
HSA-MIR-630	97.50	66.38	921
HSA-MIR-644A	96.02	66.52	786
HSA-MIR-6753-5P	94.70	64.08	470

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 84.2% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• Atp1a1 activity in VSMC and REC cells of rats, dog, and human show that Atp1a1 does not mediate the involvement of ouabain in the development of hypertension in rats, suggesting that the pathogenesis of human and rat hypertension may differ. (PMID:11926353)
• A search for potential cation binding sites involved calculation of the valence expected from the disposition of oxygen atoms in the models. This identified 3 positions for Na+ & 2 for K+ at which high affinity for the respective cation is expected. (PMID:12461183)
• hypoxia decreases Na,K-ATPase activity in alveolar epithelial cells by triggering its endocytosis through mitochondrial reactive oxygen species and PKC-zeta-mediated phosphorylation of the Na,K-ATPase alpha(1) subunit (PMID:12671055)
• data suggest that activity is reduced in the microvillous membrane of placentas from IUGR pregnancies; changes might impair function of Na(+)-coupled transporters and contribute to reduced growth of fetuses (PMID:12788896)
• sequence 442GDASE446 in the ATP binding pocket of Na/K-ATPase is an important motif and is involved in both the high and low affinity ATP effects rather than in free Mg2+, Na+, and K+ effects (PMID:14522987)
• At high altitude, the amount of mRNA of Na-K-ATPase, CFTR, and beta-actin of brush biopsies did not change in controls but decreased significantly in high altitude pulmonary edema-susceptible subjects (PMID:14555664)
• In the control subjects the Na,K-pump isoform alpha1 was increased by 37% in resistance trained compared to untrained leg, and in the diabetics the alpha1 content was 45% higher in resistance trained compared to untrained leg. (PMID:14685860)
• Na+-K+–ATPase-mediated signal transduction: from protein interaction to cellular function. (PMID:14993422)
• Decreases in erythrocyte membrane Na(+)K(+) ATPase activity is associated with rheumatoid arthritis (PMID:15515123)
• N-glycans linked to the beta2 subunit of the Na,K-ATPase contain apical sorting information, and the high abundance of the beta2 subunit isoform along with the absence of the beta1 subunit, is responsible for the unusual apical location of the Na,K-ATPase (PMID:16230337)
• Mice with the ouabain-sensitive “human-like” alpha1 isoform developed ACTH-induced hypertension to greater extent than WT animals (PMID:16243970)
• Phosphorylation of AP-2 mu2 subunit is essential for Na+,K+-ATPase endocytosis in response to a variety of signals, such as dopamine or reactive oxygen species. (PMID:16498080)
• after an ischaemic insult, alpha1 and beta1 protein subunit abundance and mRNA levels are independently regulated. (PMID:16708288)
• identified a well conserved Na,K-ATPase catalytic alpha-subunit motif that binds to the inositol 1,4,5-trisphosphate receptor and can trigger an anti-apoptotic calcium signal. (PMID:16723354)
• Na, K ATPase alpha subunit is associated with the Na, K ATPase beta3 subunit on the red blood cells. (PMID:17176442)
• Elevated Na+ -K+ -ATPase activity postexercise may contribute to reduced fatigue after training. (PMID:17446412)
• study reports the association of human ATP1A1 (P<0.000005) and Dear (P<0.03) with hypertension in a relatively isolated, case/control hypertension cohort from northern Sardinia (PMID:17446437)
• 31KKE in H1 and 47HRK in H2 of the Na,K-ATPase have distinct roles in modulating the enzyme’s conformational transitions during the catalytic cycle of the enzyme (PMID:17881356)
• after the 4-wk sprint training period, the expression of the muscle Na+-K+ pump alpha1-subunit and Na+/H+-exchanger isoform 1 was higher (PMID:18094063)
• Data show that JNK modulates the effect of caspases and NF-kappaB in the TNF-alpha-induced down-regulation of Na+/K+ATPase in HepG2 cells. (PMID:18348163)
• Ankyrin facilitates intracellular trafficking of alpha1-Na+-K+-ATPase in polarized cells. (PMID:18768923)
• Moderate apoptotic cell shrinkage may be associated with both an increase in K(+) channel permeability and inhibition of the pump whereas more remarkable shrinkage occurs presumably due to inhibition of the pump. (PMID:18769045)
• HEXIM1 may participate in tissue-selective determination of glucocorticoid sensitivity via direct interaction with GR at least in certain gene sets including atp1a1 and scnn1a. (PMID:18801933)
• Significant nominal association with bipolar disooder was observed for single Single Nucleotide Polymorphism(rs11805078 ) in the gene of ATP1A1. (PMID:19058785)
• FXYD3 silencing prevents proper regulation of Na,K-ATPase, which leads to perturbation of cellular Na+ and K+ homeostasis and changes in the expression of Na,K-ATPase isozymes, whose functional properties are incompatible with cell differentiation. (PMID:19109419)
• the sodium pump alpha1 sub-unit has a role in progression of metastatic melanoma (PMID:19243476)
• Data show that PLM associates with and modulates both NKA-alpha1 and NKA-alpha2 in a comparable but not identical manner. (PMID:19638348)
• Cardiac glycosides show distinct isoform specific affinities and different affinity profiles to Na(+),K(+)-ATPase isoforms which have different subcellular localizations in human cardiomyocytes. (PMID:19751721)
• brain-region specific increases in the activities of Na(+)/K(+)-ATPase and Ca(2+)/Mg(2+)-ATPase in autism (PMID:19863947)
• Data conclude that human proximal tubular cells respond to a hyperosmotic challenge with an increase in FXYD2 and Na,K-ATPase protein expression, though to a smaller absolute extent in patient cells. (PMID:19865785)
• These results suggest that Akt plays a major role in Na(+)/K(+)-ATPase intracellular translocation and thus in alveolar fluid reabsorption. (PMID:20332111)
• Results suggest that the association of NHE-1 with Na-K-ATPase is critical for ouabain-mediated regulation of Na-K-ATPase and that these effects may play a role in cardioglycoside-stimulated hypertension. (PMID:20427472)
• Silencing ATP1A1 inhibits the proliferation of HepG2 cells by decreasing the expression of MAPK1 and induces cell cycle arrest. (PMID:20450619)
• The increased maternal AChE and Na(+), K(+)-ATPase activities may be due to the low total antioxidant status determined post vaginal delivery, whereas their decreased activities in prematures to their immaturity. (PMID:20964587)
• Studies indicate that change of Na,K-ATPase activity can influence neurotransmitter release. (PMID:21043236)
• Ouabain could up-regulate Na+, K(+)-ATPase alpha1 subunit expression and reduce beta1-subunit expression which mediated signal transduction and decreased cell-cell adhesions and induced ECV304 cell death. (PMID:21141520)
• FXYD1 raises the affinity of the human alpha1beta1 isoform of Na,K-ATPase for Na ions (PMID:21449573)
• There was overexpression of the alpha1 or alpha3 NaK subunits in more than half of the medulloblastomas. (PMID:21498719)
• A significant increase in the expression of ATP1A1, which encodes the alpha1-subunit of the Na(+)/K(+)-ATPase, was identified in HNF1B patients consistent with its role in Mg(2+) homeostasis. (PMID:22269832)
• Data show that Na(+),K(+)-ATPase activity was >50% lower and membrane-associated tubulin content was >200% higher in erythrocyte membranes from diabetic patients. (PMID:22565168)

Cross-species orthologs

12 orthologs

Organism	Symbol	Gene ID
danio_rerio	atp1a1a.4	ENSDARG00000001870
danio_rerio	atp1a1a.1	ENSDARG00000002791
danio_rerio	atp1a1a.2	ENSDARG00000007739
danio_rerio	atp1a1b	ENSDARG00000019856
danio_rerio	atp1a1a.3	ENSDARG00000039131
danio_rerio	atp1a1a.5	ENSDARG00000040252
mus_musculus	Atp1a1	ENSMUSG00000033161
rattus_norvegicus	Atp1a1	ENSRNOG00000030019
drosophila_melanogaster	JYalpha	FBGN0267363
caenorhabditis_elegans		WBGENE00000834
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), ATP1A4 (ENSG00000132681), ATP13A3 (ENSG00000133657), ATP2B2 (ENSG00000157087), ATP13A2 (ENSG00000159363), ATP7A (ENSG00000165240), ATP2A2 (ENSG00000174437), ATP13A5 (ENSG00000187527), ATP2A1 (ENSG00000196296)

Protein

Protein identifiers

Sodium/potassium-transporting ATPase subunit alpha-1 — P05023 (reviewed: P05023)

Alternative names: Sodium pump subunit alpha-1

All UniProt accessions (4): P05023, Q5TC01, Q5TC02, Q5TC05

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. Could also be part of an osmosensory signaling pathway that senses body-fluid sodium levels and controls salt intake behavior as well as voluntary water intake to regulate sodium homeostasis.

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. Interacts with regulatory subunit FXYD3. Interacts with SIK1. Binds the HLA class II histocompatibility antigen DR1. Interacts with SLC35G1 and STIM1. Interacts with CLN3; this interaction regulates the sodium/potassium-transporting ATPase complex localization at the plasma membrane. Interacts with SCN7A; activates ATP1A1 P-type sodium:potassium-exchanging transporter activity which indirectly signals to nearby neurons to regulate sodium homeostasis.

Subcellular location. Cell membrane. Basolateral cell membrane. Sarcolemma. Cell projection. Axon. Melanosome.

Post-translational modifications. Phosphorylation on Tyr-10 modulates pumping activity. Phosphorylation of Ser-943 by PKA modulates the response of ATP1A1 to PKC. Dephosphorylation by protein phosphatase 2A (PP2A) following increases in intracellular sodium, leading to increase catalytic activity.

Disease relevance. Charcot-Marie-Tooth disease, axonal, type 2DD (CMT2DD) [MIM:618036] A dominant axonal form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies (designated CMT1 when they are dominantly inherited) and primary peripheral axonal neuropathies (CMT2). Neuropathies of the CMT2 group are characterized by signs of axonal degeneration in the absence of obvious myelin alterations, normal or slightly reduced nerve conduction velocities, and progressive distal muscle weakness and atrophy. The disease is caused by variants affecting the gene represented in this entry. Hypomagnesemia, seizures, and impaired intellectual development 2 (HOMGSMR2) [MIM:618314] An autosomal dominant disease characterized by generalized seizures in infancy, severe hypomagnesemia, and renal magnesium wasting. Seizures persist despite magnesium supplementation and are associated with significant intellectual disability. The disease is caused by variants affecting the gene represented in this entry.

Miscellaneous. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

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

Isoforms (4)

UniProt ID	Names	Canonical?
P05023-1	1, Long	yes
P05023-2	2, Short
P05023-3	3
P05023-4	4

RefSeq proteins (3): NP_000692, NP_001153705, NP_001153706 (=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

Enzyme classification (BRENDA):

• EC 7.2.2.3 — P-type Na+ transporter (BRENDA: 47 organisms, 27 substrates, 95 inhibitors, 20 Km, 0 kcat entries)

Substrate kinetics (BRENDA)

5 substrates with measured Km, best-characterized 5. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ATP	0.029–1.66	7
NA+	0.1–56.7	4
NA+/IN	0.02–2	2
LI+/IN	0.06	1
NA+[SIDE 1]	16.1	1

Catalyzed reactions (Rhea), 1 shown:

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

UniProt features (163 total): helix 49, strand 36, modified residue 15, topological domain 11, sequence variant 11, transmembrane region 10, turn 8, sequence conflict 7, region of interest 4, splice variant 4, binding site 3, compositionally biased region 2, propeptide 1, chain 1, active site 1

Structure

Experimental structures (PDB)

13 structures.

PDB	Method	Resolution (Å)
9WAJ	ELECTRON MICROSCOPY	2.39
24RC	ELECTRON MICROSCOPY	2.61
7E20	ELECTRON MICROSCOPY	2.7
9WAK	ELECTRON MICROSCOPY	2.86
7E21	ELECTRON MICROSCOPY	2.9
9KCI	ELECTRON MICROSCOPY	2.9
9KCK	ELECTRON MICROSCOPY	2.9
9KCL	ELECTRON MICROSCOPY	2.9
9KCM	ELECTRON MICROSCOPY	2.9
9KCG	ELECTRON MICROSCOPY	3.1
9KCJ	ELECTRON MICROSCOPY	3.1
7E1Z	ELECTRON MICROSCOPY	3.2
9KCR	ELECTRON MICROSCOPY	3.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P05023-F1	88.86	0.66

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): 376 (4-aspartylphosphate intermediate)

Ligand- & substrate-binding residues (3): 487; 717; 721

Post-translational modifications (15): 9, 10, 16, 21, 40, 47, 228, 260, 452, 484, 542, 661, 668, 675, 943

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: 466 (showing top): GOBP_POTASSIUM_ION_TRANSPORT, GOBP_ESTABLISHMENT_OR_MAINTENANCE_OF_TRANSMEMBRANE_ELECTROCHEMICAL_GRADIENT, SHEPARD_BMYB_MORPHOLINO_UP, GOBP_REGULATION_OF_BLOOD_PRESSURE, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOBP_NEGATIVE_REGULATION_OF_LIPID_METABOLIC_PROCESS, GOBP_SODIUM_ION_TRANSMEMBRANE_TRANSPORT, GOBP_GLUCOCORTICOID_METABOLIC_PROCESS, CHIANG_LIVER_CANCER_SUBCLASS_UNANNOTATED_DN, MAZ_Q6, GOBP_NEGATIVE_REGULATION_OF_STEROID_METABOLIC_PROCESS, DITTMER_PTHLH_TARGETS_UP, GOBP_REGULATION_OF_HORMONE_LEVELS, GOBP_NEGATIVE_REGULATION_OF_LIPID_BIOSYNTHETIC_PROCESS

GO Biological Process (30): regulation of the force of heart contraction (GO:0002026), regulation of sodium ion transport (GO:0002028), intracellular sodium ion homeostasis (GO:0006883), osmosensory signaling pathway (GO:0007231), regulation of blood pressure (GO:0008217), response to xenobiotic stimulus (GO:0009410), establishment or maintenance of transmembrane electrochemical gradient (GO:0010248), intracellular potassium ion homeostasis (GO:0030007), negative regulation of glucocorticoid biosynthetic process (GO:0031947), sodium ion transmembrane transport (GO:0035725), sodium ion export across plasma membrane (GO:0036376), negative regulation of heart contraction (GO:0045822), positive regulation of heart contraction (GO:0045823), positive regulation of striated muscle contraction (GO:0045989), relaxation of cardiac muscle (GO:0055119), cellular response to steroid hormone stimulus (GO:0071383), potassium ion transmembrane transport (GO:0071805), cardiac muscle cell action potential involved in contraction (GO:0086002), membrane repolarization (GO:0086009), membrane repolarization during cardiac muscle cell action potential (GO:0086013), cell communication by electrical coupling involved in cardiac conduction (GO:0086064), proton transmembrane transport (GO:1902600), response to glycoside (GO:1903416), potassium ion import across plasma membrane (GO:1990573), monoatomic ion transport (GO:0006811), potassium ion transport (GO:0006813), sodium ion transport (GO:0006814), intracellular monoatomic cation homeostasis (GO:0030003), sodium ion homeostasis (GO:0055078), heart contraction (GO:0060047)

GO Molecular Function (15): P-type sodium:potassium-exchanging transporter activity (GO:0005391), ATP binding (GO:0005524), phosphatase activity (GO:0016791), ATP hydrolysis activity (GO:0016887), potassium ion binding (GO:0030955), sodium ion binding (GO:0031402), transmembrane transporter binding (GO:0044325), 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 (21): endoplasmic reticulum (GO:0005783), Golgi apparatus (GO:0005794), plasma membrane (GO:0005886), sodium:potassium-exchanging ATPase complex (GO:0005890), postsynaptic density (GO:0014069), membrane (GO:0016020), basolateral plasma membrane (GO:0016323), apical plasma membrane (GO:0016324), lateral plasma membrane (GO:0016328), T-tubule (GO:0030315), axon (GO:0030424), organelle membrane (GO:0031090), protein-containing complex (GO:0032991), sperm flagellum (GO:0036126), sarcolemma (GO:0042383), melanosome (GO:0042470), membrane raft (GO:0045121), photoreceptor inner segment membrane (GO:0060342), extracellular exosome (GO:0070062), extracellular vesicle (GO:1903561), cell projection (GO:0042995)

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
regulation of heart contraction	3
cellular anatomical structure	3
plasma membrane region	3
regulation of biological quality	2
sodium ion transport	2
intracellular monoatomic cation homeostasis	2
monoatomic cation transmembrane transport	2
heart contraction	2
cardiac muscle cell action potential	2
alkali metal ion binding	2
protein binding	2
cytoplasm	2
endomembrane system	2
intracellular membrane-bounded organelle	2
membrane	2
plasma membrane	2
regulation of metal ion transport	1
sodium ion homeostasis	1
intracellular signal transduction	1
cellular response to osmotic stress	1
blood circulation	1
response to chemical	1
monoatomic ion transmembrane transport	1
potassium ion homeostasis	1
glucocorticoid biosynthetic process	1
regulation of glucocorticoid biosynthetic process	1
negative regulation of steroid hormone biosynthetic process	1
sodium ion transmembrane transport	1
export across plasma membrane	1
negative regulation of blood circulation	1
positive regulation of blood circulation	1
striated muscle contraction	1
regulation of striated muscle contraction	1
positive regulation of muscle contraction	1
relaxation of muscle	1
cellular response to hormone stimulus	1
response to steroid hormone	1
cellular response to lipid	1
potassium ion transport	1
cardiac muscle cell contraction	1

Protein interactions and networks

STRING

2464 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ATP1A1	FXYD2	P54710	885
ATP1A1	ATP1B3	P54709	869
ATP1A1	ATP1B1	P05026	850
ATP1A1	KCNJ5	P48544	802
ATP1A1	ATP1B2	P14415	763
ATP1A1	INO80	Q9ULG1	763
ATP1A1	CACNA1D	Q01668	740
ATP1A1	SLC12A1	Q13621	714
ATP1A1	CYP11B2	P19099	702
ATP1A1	AMY2B	P19961	653
ATP1A1	CACNA1H	O95180	604
ATP1A1	CLCN2	P51788	598
ATP1A1	LHB	P01229	588
ATP1A1	ARMC5	Q96C12	583
ATP1A1	CYP11B1	P15538	578

IntAct

301 interactions, top by confidence:

A	B	Type	Score
ATP1A1	ATP1B1	psi-mi:“MI:0915”(physical association)	0.910
ATP1A1	ATP1B1	psi-mi:“MI:0407”(direct interaction)	0.910
TSPAN15	ADAM10	psi-mi:“MI:0914”(association)	0.840
TSPAN5	ADAM10	psi-mi:“MI:0914”(association)	0.800
EGFR	GAPDH	psi-mi:“MI:0914”(association)	0.790
CD9	ADAM10	psi-mi:“MI:0914”(association)	0.750
PKMYT1	CCNB2	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
ATP1B1	SLC4A1	psi-mi:“MI:0914”(association)	0.670
MAPK7	PFDN6	psi-mi:“MI:0914”(association)	0.640
VP24	KPNA6	psi-mi:“MI:0914”(association)	0.620
NDRG1	ATP1A1	psi-mi:“MI:0915”(physical association)	0.560
ILK	HAX1	psi-mi:“MI:0914”(association)	0.530
IRAK1	SEC16A	psi-mi:“MI:0914”(association)	0.530
CD81	C2orf72	psi-mi:“MI:0914”(association)	0.530
	XPO1	psi-mi:“MI:0914”(association)	0.530
ILK	ILVBL	psi-mi:“MI:0914”(association)	0.530

BioGRID (755): ATP1A1 (Affinity Capture-MS), ATP1A1 (Affinity Capture-Western), ATP1A1 (Affinity Capture-MS), ATP1A1 (Affinity Capture-MS), ATP1A1 (Biochemical Activity), ATP1A1 (Biochemical Activity), ATP1A1 (Affinity Capture-MS), ATP1A1 (Affinity Capture-MS), ATP1A1 (Affinity Capture-MS), ATP1A1 (Affinity Capture-MS), ATP1A1 (Affinity Capture-MS), ATP1A1 (Affinity Capture-MS), ATP1A1 (Co-fractionation), ATP1A1 (Co-fractionation), ATP1A1 (Co-fractionation)

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

3 interactions.

A	Effect	B	Mechanism
PRKCZ	“up-regulates activity”	ATP1A1	phosphorylation
MAPK1	“down-regulates activity”	ATP1A1	phosphorylation
PRKCA	“down-regulates activity”	ATP1A1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 198 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Signaling by ERBB2 ECD mutants	5	26.2×	2e-04
GRB2 events in ERBB2 signaling	5	24.8×	2e-04
VEGFR2 mediated cell proliferation	5	22.3×	3e-04
SHC1 events in ERBB2 signaling	5	18.6×	4e-04
Signaling by ERBB2 TMD/JMD mutants	5	18.6×	4e-04
Signaling by ERBB2 KD Mutants	5	16.5×	5e-04
FCERI mediated MAPK activation	6	16.2×	2e-04
Signaling by high-kinase activity BRAF mutants	6	14.9×	3e-04

GO biological processes:

GO term	Partners	Fold	FDR
learning or memory	7	10.4×	7e-03

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: activating (oncogene-like) across 1 cancer types — BRCA.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	10
Likely pathogenic	13
Uncertain significance	353
Likely benign	451
Benign	43

Top pathogenic / likely-pathogenic (23)

Variant ID	HGVS	Classification
162465	NM_000701.8(ATP1A1):c.299_313del (p.Phe100_Leu104del)	Pathogenic
162466	NM_000701.8(ATP1A1):c.311T>G (p.Leu104Arg)	Pathogenic
162468	NM_000701.8(ATP1A1):c.995T>G (p.Val332Gly)	Pathogenic
1687398	NM_000701.8(ATP1A1):c.905T>G (p.Leu302Arg)	Pathogenic
3256184	NM_000701.8(ATP1A1):c.2629G>A (p.Gly877Ser)	Pathogenic
545677	NM_000701.8(ATP1A1):c.143T>G (p.Leu48Arg)	Pathogenic
545678	NM_000701.8(ATP1A1):c.1798C>G (p.Pro600Ala)	Pathogenic
617641	NM_000701.8(ATP1A1):c.905T>C (p.Leu302Pro)	Pathogenic
617642	NM_000701.8(ATP1A1):c.907G>C (p.Gly303Arg)	Pathogenic
619298	NM_000701.8(ATP1A1):c.2791T>C (p.Trp931Arg)	Pathogenic
1029934	NM_000701.8(ATP1A1):c.2531T>C (p.Leu844Pro)	Likely pathogenic
1174506	NM_000701.8(ATP1A1):c.1001A>G (p.Glu334Gly)	Likely pathogenic
1685248	NM_000701.8(ATP1A1):c.1799C>G (p.Pro600Arg)	Likely pathogenic
1695549	NM_000701.8(ATP1A1):c.1999G>A (p.Gly667Ser)	Likely pathogenic
3237519	NM_000701.8(ATP1A1):c.821C>G (p.Ala274Gly)	Likely pathogenic
3337828	NM_000701.8(ATP1A1):c.1028G>A (p.Cys343Tyr)	Likely pathogenic
3572864	NM_000701.8(ATP1A1):c.620C>T (p.Ser207Phe)	Likely pathogenic
3775372	NM_000701.8(ATP1A1):c.2590G>A (p.Gly864Arg)	Likely pathogenic
4795487	NM_000701.8(ATP1A1):c.1001A>C (p.Glu334Ala)	Likely pathogenic
545679	NM_000701.8(ATP1A1):c.1798C>A (p.Pro600Thr)	Likely pathogenic
617643	NM_000701.8(ATP1A1):c.2576T>G (p.Met859Arg)	Likely pathogenic
689711	NM_000701.8(ATP1A1):c.998C>G (p.Pro333Arg)	Likely pathogenic
995868	NM_000701.8(ATP1A1):c.2809_2819del (p.Cys937fs)	Likely pathogenic

SpliceAI

3343 predictions. Top by Δscore:

Variant	Effect	Δscore
1:116373520:GGGG:G	donor_gain	1.0000
1:116373521:GGGG:G	donor_gain	1.0000
1:116384002:A:AG	acceptor_gain	1.0000
1:116384003:T:G	acceptor_gain	1.0000
1:116384008:CTACA:C	acceptor_loss	1.0000
1:116384010:ACAG:A	acceptor_gain	1.0000
1:116384011:C:G	acceptor_gain	1.0000
1:116384011:CAGG:C	acceptor_loss	1.0000
1:116384012:A:AG	acceptor_gain	1.0000
1:116384012:AG:A	acceptor_gain	1.0000
1:116384012:AGGTT:A	acceptor_gain	1.0000
1:116384013:G:A	acceptor_loss	1.0000
1:116384013:G:GT	acceptor_gain	1.0000
1:116384013:GG:G	acceptor_gain	1.0000
1:116384013:GGT:G	acceptor_gain	1.0000
1:116384013:GGTT:G	acceptor_gain	1.0000
1:116384013:GGTTG:G	acceptor_gain	1.0000
1:116384120:CTATG:C	donor_gain	1.0000
1:116384121:TATG:T	donor_gain	1.0000
1:116384121:TATGG:T	donor_loss	1.0000
1:116384122:ATG:A	donor_gain	1.0000
1:116384122:ATGG:A	donor_loss	1.0000
1:116384123:TG:T	donor_gain	1.0000
1:116384124:GG:G	donor_gain	1.0000
1:116384125:G:GG	donor_gain	1.0000
1:116384770:T:A	acceptor_gain	1.0000
1:116384779:TTA:T	acceptor_loss	1.0000
1:116384780:TA:T	acceptor_loss	1.0000
1:116384781:A:AG	acceptor_gain	1.0000
1:116384781:AG:A	acceptor_gain	1.0000

AlphaMissense

6740 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:116388918:T:A	L218H	1.000
1:116388918:T:C	L218P	1.000
1:116388923:G:C	G220R	1.000
1:116388923:G:T	G220C	1.000
1:116388924:G:A	G220D	1.000
1:116388924:G:T	G220V	1.000
1:116388988:C:A	N241K	1.000
1:116388988:C:G	N241K	1.000
1:116389019:G:C	G252R	1.000
1:116389486:G:A	G268R	1.000
1:116389486:G:C	G268R	1.000
1:116389487:G:A	G268E	1.000
1:116389487:G:T	G268V	1.000
1:116389493:T:A	I270N	1.000
1:116389495:G:C	A271P	1.000
1:116389496:C:A	A271D	1.000
1:116389502:T:C	L273P	1.000
1:116389580:C:A	A299D	1.000
1:116389591:G:C	G303R	1.000
1:116389673:C:A	A330D	1.000
1:116389682:C:A	P333Q	1.000
1:116389687:G:C	G335R	1.000
1:116390220:T:C	L344P	1.000
1:116390226:T:C	L346P	1.000
1:116390232:C:A	A348D	1.000
1:116390257:C:G	C356W	1.000
1:116390291:G:A	G368R	1.000
1:116390291:G:C	G368R	1.000
1:116390291:G:T	G368W	1.000
1:116390292:G:A	G368E	1.000

dbSNP variants (sampled 300 via entrez): RS1000050482 (1:116377256 T>C,G), RS1000067960 (1:116393809 G>A), RS1000274622 (1:116401271 A>G), RS1000368331 (1:116400453 G>C), RS1000639979 (1:116387971 G>A), RS1000690709 (1:116374129 A>G), RS1000713653 (1:116381352 A>C), RS1000725645 (1:116374370 G>A), RS1000743378 (1:116380992 C>A,T), RS1000897291 (1:116373349 G>A,C), RS1001073074 (1:116395546 C>T), RS1001079889 (1:116379309 G>A), RS1001244950 (1:116403146 A>G), RS1001408392 (1:116400633 G>C), RS1001439444 (1:116400376 G>A)

Disease associations

OMIM: gene MIM:182310 | disease phenotypes: MIM:618036, MIM:618314, MIM:600996, MIM:604772, MIM:609260

GenCC curated gene-disease

Disease	Classification	Inheritance
hypomagnesemia, seizures, and intellectual disability 2	Strong	Autosomal dominant
Charcot-Marie-tooth disease, axonal, type 2DD	Strong	Autosomal dominant
neurodevelopmental disorder	Strong	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
Charcot-Marie-tooth disease, axonal, type 2DD	Moderate	AD

Mondo (9): intellectual disability (MONDO:0001071), Charcot-Marie-tooth disease, axonal, type 2DD (MONDO:0054833), hypomagnesemia, seizures, and intellectual disability 2 (MONDO:0020788), prostate cancer (MONDO:0008315), aldosterone-producing adrenal cortex adenoma (MONDO:0016505), catecholaminergic polymorphic ventricular tachycardia 1 (MONDO:0011484), Charcot-Marie-Tooth disease type 2A2 (MONDO:0012231), neuromuscular disease (MONDO:0019056), neurodevelopmental disorder (MONDO:0700092)

Orphanet (7): Autosomal dominant Charcot-Marie-Tooth disease type 2DD (Orphanet:521414), Familial prostate cancer (Orphanet:1331), Adrenocortical carcinoma with pure aldosterone hypersecretion (Orphanet:231625), Catecholaminergic polymorphic ventricular tachycardia (Orphanet:3286), Autosomal dominant Charcot-Marie-Tooth disease type 2A2 (Orphanet:99947), Neuromuscular disease (Orphanet:68381), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

34 total (30 of 34 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000103	Polyuria
HP:0000121	Nephrocalcinosis
HP:0000128	Renal potassium wasting
HP:0000729	Autistic behavior
HP:0000752	Hyperactivity
HP:0001250	Seizure
HP:0001263	Global developmental delay
HP:0001265	Hyporeflexia
HP:0001284	Areflexia
HP:0001761	Pes cavus
HP:0002119	Ventriculomegaly
HP:0002133	Status epilepticus
HP:0002194	Delayed gross motor development
HP:0002197	Generalized-onset seizure
HP:0002460	Distal muscle weakness
HP:0002465	Poor speech
HP:0002900	Hypokalemia
HP:0002917	Hypomagnesemia
HP:0003376	Steppage gait
HP:0003394	Muscle spasm
HP:0003581	Adult onset
HP:0003593	Infantile onset
HP:0003621	Juvenile onset
HP:0003623	Neonatal onset
HP:0003677	Slowly progressive
HP:0003693	Distal amyotrophy
HP:0005567	Renal magnesium wasting
HP:0006872	Cerebral hypoplasia
HP:0006886	Impaired distal vibration sensation

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST005330_3	Coffee consumption	8.000000e-07
GCST006976_129	Macular thickness	2.000000e-08
GCST011743_30	HDL cholesterol levels in HIV infection	6.000000e-06
GCST90020026_618	Hip index	1.000000e-08

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0006782	cups of coffee per day measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0008039	BMI-adjusted hip circumference

MeSH disease descriptors (6)

Descriptor	Name	Tree numbers
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D065886	Neurodevelopmental Disorders	F03.625
D009468	Neuromuscular Diseases	C10.668
D011471	Prostatic Neoplasms	C04.588.945.440.770; C12.100.500.260.750; C12.100.500.565.625; C12.200.294.260.750; C12.200.294.565.625; C12.200.758.409.750; C12.900.619.750
C563409	Arrhythmogenic Right Ventricular Dysplasia, Familial, 2 (supp.)
C563757	Charcot-Marie-Tooth Disease, Axonal, Type 2A2 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL1807 (SINGLE PROTEIN), CHEMBL2095186 (PROTEIN COMPLEX GROUP), CHEMBL6066559 (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
CHEMBL1751	DIGOXIN	4	67,342
CHEMBL1503	OMEPRAZOLE	4	52,284
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

Most potent curated ligand interactions (2 total), top 2:

Ligand	Action	Affinity	Parameter
digitoxin	Inhibition	8.1	pIC50
digoxin	Inhibition	6.4	pIC50

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

245 potent at pChembl≥5 of 299 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	Kd	6.82	nM	CHEMBL3752910
8.17	ED50	6.82	nM	CHEMBL3752910
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
7.60	Ki	25	nM	CHEMBL5765464
7.55	IC50	28.2	nM	CHEMBL3350144
7.52	IC50	30	nM	CHEMBL2068896
7.52	IC50	30	nM	CHEMBL2068909
7.51	Ki	30.7	nM	CHEMBL5879229
7.50	Ki	31.6	nM	CHEMBL5876237
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
7.24	Ki	57.9	nM	CHEMBL5832044
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
7.15	Ki	70.4	nM	CHEMBL5910596
7.14	Ki	72.6	nM	CHEMBL5851200
7.12	IC50	75	nM	CHEMBL2092910
7.10	IC50	80	nM	CHEMBL2068983
7.10	IC50	80	nM	CHEMBL2069040
7.07	Ki	86.1	nM	CHEMBL6026321
7.06	Ki	87.7	nM	CHEMBL5957388
7.06	IC50	88	nM	CHEMBL2068949
7.06	IC50	87	nM	CHEMBL3265172

PubChem BioAssay actives

234 with measured affinity, of 402 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
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2147906: Binding affinity to human ATP1A1 incubated for 45 mins by Kinobead based pull down assay	kd	0.0068	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
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	0.0530	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-[(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	0.0690	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
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	0.0800	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	0.0970	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
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	0.1010	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	0.1020	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	0.1240	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
3-[(3S,5R,8R,9S,10S,12R,13S,14S,17R)-3,12,14-trihydroxy-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	0.1390	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
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	0.1520	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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	increases expression, affects expression, affects cotreatment, increases methylation, decreases expression	5
sodium arsenite	decreases expression, increases abundance, increases expression	3
Valproic Acid	affects expression, decreases methylation, increases expression	3
Cyclosporine	decreases expression	3
Ouabain	decreases reaction, increases expression, affects binding	2
Phenylmercuric Acetate	increases expression, affects cotreatment	2
Tobacco Smoke Pollution	affects expression, decreases expression	2
bisphenol F	increases expression	1
moringin	affects cotreatment, increases expression	1
beauvericin	affects cotreatment, increases expression	1
2,4,6-tribromophenol	decreases expression	1
triphenyl phosphate	affects expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
deoxynivalenol	decreases expression	1
lead acetate	decreases expression	1
sodium arsenate	decreases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, decreases expression, affects localization, increases expression	1
sodium bichromate	decreases expression	1
tetrabromobisphenol A	decreases expression	1
perfluorooctanoic acid	decreases expression	1
coumarin	increases phosphorylation	1
trimethyltin chloride	decreases expression	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
bisindolylmaleimide I	decreases reaction, increases expression	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one	decreases reaction, increases expression	1
FTI 277	decreases reaction, increases activity, increases expression	1
chloropicrin	increases expression	1

ChEMBL screening assays

50 unique, capped per target: 50 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3595969	Binding	Inhibition of human kidney Na(+)/K(+) ATPase alpha-1 assessed as amount of Pi release after 1 hr by colorimetric method	γ-Benzylidene digoxin derivatives synthesis and molecular modeling: Evaluation of anticancer and the Na,K-ATPase activity effect. — Bioorg Med Chem

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_RW40	OR6 [Chlorocebus aethiops]	Transformed cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT00029224	PHASE4	COMPLETED	Treatment With Zoledronic Acid in Patients With Breast Cancer, Multiple Myeloma, and Prostate Cancer With Cancer Related Bone Lesions
NCT00035997	PHASE4	COMPLETED	Open-label Trial on the Effect of I.V. Zoledronic Acid 4 mg on Bone Density in Hormone Sensitive Prostate Cancer Patients With Bone Metastasis
NCT00063609	PHASE4	COMPLETED	The Effect of Zoledronic Acid on Bone Loss in Prostate Cancer Patients Undergoing Androgen Deprivation Therapy
NCT00103623	PHASE4	SUSPENDED	The Plenaxis® Experience Study
NCT00106392	PHASE4	COMPLETED	A Safety and Efficacy Study of Prograf in the Prevention of Erectile Dysfunction After Radical Prostatectomy
NCT00185029	PHASE4	UNKNOWN	MR-Lymphography and Lymph Node Staging in Prostate Cancer
NCT00199485	PHASE4	COMPLETED	Angelica Sinensis for the Treatment of Hot Flashes in Men Undergoing LHRH Therapy for Prostate Cancer
NCT00219219	PHASE4	COMPLETED	Zoledronic Acid in the Prevention of Skeletal-related Events in Hormone Refractory and Hormone-sensitive Prostate Cancer Patients With Bone Metastases
NCT00219271	PHASE4	COMPLETED	Effect Of Zoledronic Acid On Circulating And Bone Marrow-Residing Prostate Cancer Cells In Patients With Clinically Localized Prostate Cancer
NCT00237146	PHASE4	COMPLETED	Study to Evaluate Zoledronic Acid on Quality of Life and Skeletal-related Events as Adjuvant Treatment in Patients With Hormone-naïve Prostate Cancer and Bone Metastasis Who Have Undergone Orchiectomy
NCT00242554	PHASE4	COMPLETED	Open-label Phase IV Clinical Trial to Evaluate the Safety and Tolerability of Zoledronic Acid in Patients With Prostate Cancer and Bone Metastases
NCT00280098	PHASE4	COMPLETED	Docetaxel in the Treatment of Hormone Refractory Prostate Cancer
NCT00293696	PHASE4	COMPLETED	Casodex/Zoladex Biomarkers in Localised Prostate Cancer
NCT00334139	PHASE4	COMPLETED	Effect of Zoledronic Acid on Bone Metabolism in Patients With Bone Metastasis and Prostate or Breast Cancer
NCT00375765	PHASE4	COMPLETED	Effects On Dihydrotestosterone Regulated Gene Expression In Benign Prostatic Hyperplasia Or Prostate Cancer
NCT00391690	PHASE4	COMPLETED	Evaluation of Bone Markers as Diagnostic Tools for Early Detection of Bone Metastases in Patients With High Risk Prostate Cancer
NCT00422708	PHASE4	COMPLETED	Local Anesthesia for Prostate Biopsy
NCT00526331	PHASE4	COMPLETED	Evaluation of Arterial Pressure Based Cardiac Output for Goal-Directed Perioperative Therapy
NCT00590213	PHASE4	COMPLETED	Compare the Value of Prophylactic Versus Therapeutic Breast Radiotherapy in CASODEX
NCT00629330	PHASE4	TERMINATED	Dissemination of Prostate Cancer Screening to PCP’s in African American Communities
NCT00771966	PHASE4	COMPLETED	Radical Prostatectomy and Perioperative Fluid Therapy
NCT00805701	PHASE4	COMPLETED	Study Assessing The Efficacy And Safety Of Avodart (Dutasteride) At Improving Urinary Symptoms In Men With Prostate Cancer Who Are Undergoing Seed Implantation
NCT00859027	PHASE4	COMPLETED	Effect Of Risedronate On Bone Mass In Older Men Receiving Neoadjuvant Therapy For Prostate Cancer
NCT00906269	PHASE4	UNKNOWN	Can Hyperbaric Oxygen Improve Erectile Function Following Surgery for Prostate Cancer
NCT00953277	PHASE4	COMPLETED	Study of Nerve Reconstruction Using AVANCE in Subjects Who Undergo Robotic Assisted Prostatectomy for Treatment of Prostate Cancer
NCT00982800	PHASE4	COMPLETED	Does Postoperative Gabapentin Reduce Pain, Opioid Consumption and Anxiety and Have a Positive Effect on Health Related Quality of Life After Radical Prostatectomy?
NCT01083199	PHASE4	COMPLETED	Global Performance Evaluation of the AMS CONTINUUM™ Device
NCT01136226	PHASE4	COMPLETED	Evaluate Recovery of Testosterone for Patients Using Eligard
NCT01161563	PHASE4	COMPLETED	Randomized Crossover Trial to Assess the Tolerability of Gonadotropin Releasing Hormone (GnRH) Analogue Administration
NCT01230905	PHASE4	COMPLETED	Study to Monitor the Effects of Androgen Suppression Treatment on the Heart
NCT01296672	PHASE4	COMPLETED	3 Month Finasteride Challenge Test Can Significantly Improve the Performance of Screening for Prostate Cancer
NCT01365143	PHASE4	TERMINATED	Prospective Randomized Trial Comparing Robotic Versus Open Radical Prostatectomy
NCT01379742	PHASE4	UNKNOWN	Comparison of Between ThinSeed™ and OncoSeed™ for Permanent Prostate Brachytherapy
NCT01486563	PHASE4	COMPLETED	Hydroxyethyl Starch and Renal Function After Radical Prostatectomy