ATP1B3

Summary

ATP1B3 (ATPase Na+/K+ transporting subunit beta 3, HGNC:806) is a protein-coding gene on chromosome 3q23, encoding Sodium/potassium-transporting ATPase subunit beta-3 (P54709). This is the non-catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of Na(+) and K(+) ions across the plasma membrane. It is a selective cancer dependency (DepMap: 25.6% of cell lines).

The protein encoded by this gene belongs to the family of Na+/K+ and H+/K+ ATPases beta chain proteins, 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 beta subunit regulates, through assembly of alpha/beta heterodimers, the number of sodium pumps transported to the plasma membrane. The glycoprotein subunit of Na+/K+ -ATPase is encoded by multiple genes. This gene encodes a beta 3 subunit. This gene encodes a beta 3 subunit. A pseudogene exists for this gene, and it is located on chromosome 2.

Source: NCBI Gene 483 — RefSeq curated summary.

At a glance

• GWAS associations: 16
• Clinical variants (ClinVar): 37 total — 1 pathogenic
• Druggable target: yes — 5 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 25.6% of screened cell lines
• MANE Select transcript: NM_001679

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:806
Approved symbol	ATP1B3
Name	ATPase Na+/K+ transporting subunit beta 3
Location	3q23
Locus type	gene with protein product
Status	Approved
Aliases	FLJ29027, CD298
Ensembl gene	ENSG00000069849
Ensembl biotype	protein_coding
OMIM	601867
Entrez	483

Gene structure

Transcript identifiers

Ensembl transcripts: 18 — 12 protein_coding, 3 nonsense_mediated_decay, 2 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000286371, ENST00000462082, ENST00000465172, ENST00000466678, ENST00000475483, ENST00000482635, ENST00000484727, ENST00000486782, ENST00000487199, ENST00000495216, ENST00000874836, ENST00000874837, ENST00000874838, ENST00000874839, ENST00000874840, ENST00000874841, ENST00000874842, ENST00000936184

RefSeq mRNA: 1 — MANE Select: NM_001679 NM_001679

CCDS: CCDS3121

Canonical transcript exons

ENST00000286371 — 7 exons

Exon	Start	End
ENSE00001818178	141925531	141926549
ENSE00001906827	141876643	141876910
ENSE00003501365	141915970	141916020
ENSE00003545530	141913652	141913836
ENSE00003545847	141907167	141907274
ENSE00003638131	141921977	141922063
ENSE00003662237	141903620	141903748

Expression profiles

Bgee: expression breadth ubiquitous, 301 present calls, max score 99.86.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 78.9625 / max 1025.1913, expressed in 1820 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
38937	71.7089	1819
38933	3.1581	1260
38936	1.8846	384
38935	1.4961	658
38939	0.3755	186
38938	0.2738	113
38934	0.0655	23

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	99.86	gold quality
tongue squamous epithelium	UBERON:0006919	99.75	gold quality
male germ cell	CL:0000015	99.67	gold quality
upper leg skin	UBERON:0004262	99.62	gold quality
skin of hip	UBERON:0001554	99.61	gold quality
gingival epithelium	UBERON:0001949	99.55	gold quality
gingiva	UBERON:0001828	99.47	gold quality
colonic mucosa	UBERON:0000317	99.39	gold quality
stromal cell of endometrium	CL:0002255	99.38	gold quality
pharyngeal mucosa	UBERON:0000355	99.38	gold quality
mammalian vulva	UBERON:0000997	99.30	gold quality
penis	UBERON:0000989	99.28	gold quality
mucosa of transverse colon	UBERON:0004991	99.28	gold quality
mucosa of sigmoid colon	UBERON:0004993	99.28	gold quality
zone of skin	UBERON:0000014	99.27	gold quality
skin of leg	UBERON:0001511	99.26	gold quality
skin of abdomen	UBERON:0001416	99.25	gold quality
cervix squamous epithelium	UBERON:0006922	99.24	gold quality
ileal mucosa	UBERON:0000331	99.21	gold quality
epithelium of nasopharynx	UBERON:0001951	99.20	gold quality
nasopharynx	UBERON:0001728	99.18	gold quality
olfactory bulb	UBERON:0002264	99.18	gold quality
renal medulla	UBERON:0000362	99.11	gold quality
squamous epithelium	UBERON:0006914	99.11	gold quality
lower esophagus mucosa	UBERON:0035834	99.07	gold quality
hair follicle	UBERON:0002073	99.06	gold quality
trigeminal ganglion	UBERON:0001675	99.05	gold quality
nipple	UBERON:0002030	99.04	gold quality
cerebellar hemisphere	UBERON:0002245	99.03	gold quality
upper arm skin	UBERON:0004263	99.03	gold quality

Single-cell (SCXA)

Detected in 11 experiment(s), a significant marker in 11.

Experiment	Marker?	Max mean expression
E-CURD-135	yes	1134.69
E-MTAB-8142	yes	132.25
E-CURD-114	yes	74.57
E-HCAD-4	yes	48.47
E-GEOD-125970	yes	31.63
E-HCAD-1	yes	28.32
E-HCAD-5	yes	23.91
E-CURD-119	yes	22.81
E-CURD-46	yes	16.28
E-MTAB-9467	yes	12.36
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

55 targeting ATP1B3, 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-4692	100.00	67.32	2066
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-4267	99.96	66.53	2368
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-182-5P	99.87	74.03	2589
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-6079	99.84	68.54	1170
HSA-MIR-489-3P	99.80	66.46	839
HSA-MIR-34B-5P	99.78	67.56	1175
HSA-MIR-449C-5P	99.78	67.63	1168
HSA-MIR-1299	99.77	71.24	2389
HSA-MIR-3913-3P	99.74	66.53	938
HSA-MIR-2682-5P	99.73	67.38	1055
HSA-MIR-4699-3P	99.71	70.15	3142
HSA-MIR-548AU-3P	99.70	68.22	1373
HSA-MIR-1197	99.70	67.75	1027
HSA-MIR-5004-5P	99.68	66.63	1294
HSA-MIR-3934-5P	99.67	64.04	846
HSA-MIR-7157-5P	99.66	69.33	1829
HSA-MIR-6757-3P	99.63	66.88	1089
HSA-MIR-875-3P	99.63	69.47	2548

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 25.6% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 11)

• role in T and B lymphocyte activation (PMID:12456588)
• These results evidenced that the beta3 subunit of Na, K ATPase is expressed on RBC membrane but the epitope recognized by mAb P-3E10 is hidden in normal RBCs. we showed the association of beta3 subunit and alpha subunit of Na, K ATPase. (PMID:17176442)
• Elevated Na+ -K+ -ATPase activity postexercise may contribute to reduced fatigue after training. (PMID:17446412)
• B7H3 and ATP1B3 are overexpressed in tumor endothelial cells, favoring an angiogenic phenotype. (PMID:24236063)
• Data suggest that ATP1B3 is binding partner of BST-2 and regulates stability of BST-2; ATP1B3 is co-factor that accelerates BST-2 degradation and reduces BST-2-mediated restriction of HIV-1 replication/tropism and NFkappaB activation. (PMID:26694617)
• Our study demonstrated that ATP1B3 inhibit EV71 replication by enhancing the production of type-I interferons, which could act as a potential therapeutic target in EV71 infection. (PMID:27240146)
• ligation of the Na, K ATPase beta3 subunit on monocytes by mAb P-3E10 arbitrated T cell hypofunction. This mAb might be a promising novel immunotherapeutic antibody for the treatment of hyperresponsive T cell associated diseases. (PMID:29940031)
• These results demonstrate that CASPR1 binds with ATP1B3 and thereby contributes to the regulation of Na(+)/K(+)-ATPase maturation and trafficking to the plasma membrane in brain microvascular endothelial cells. (PMID:30792309)
• ATP1B3 Restricts Hepatitis B Virus Replication Via Reducing the Expression of the Envelope Proteins. (PMID:33534085)
• Integrative Transcriptomic, Proteomic and Functional Analysis Reveals ATP1B3 as a Diagnostic and Potential Therapeutic Target in Hepatocellular Carcinoma. (PMID:33868261)
• [Screening and identification of key genes ATP1B3 and ENAH in the progression of hepatocellular carcinoma: based on data mining and clinical validation]. (PMID:35790431)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	atp1b3a	ENSDARG00000015790
danio_rerio	atp1b3b	ENSDARG00000042837
mus_musculus	Atp1b3	ENSMUSG00000032412
rattus_norvegicus	Atp1b3	ENSRNOG00000011501
rattus_norvegicus	AABR07070238.1	ENSRNOG00000022382

Paralogs (4): ATP1B4 (ENSG00000101892), ATP1B2 (ENSG00000129244), ATP1B1 (ENSG00000143153), ATP4B (ENSG00000186009)

Protein

Protein identifiers

Sodium/potassium-transporting ATPase subunit beta-3 — P54709 (reviewed: P54709)

Alternative names: Sodium/potassium-dependent ATPase subunit beta-3

All UniProt accessions (7): P54709, C9J6S2, C9JA36, C9JXZ1, F8WBY4, H7C4L9, H7C547

UniProt curated annotations — full annotation on UniProt →

Function. This is the non-catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of Na(+) and K(+) ions across the plasma membrane. The exact function of the beta-3 subunit is not known.

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 catalytic alpha subunit ATP12A.

Subcellular location. Apical cell membrane. Basolateral cell membrane. Melanosome.

Domain organisation. The C-terminal lobe folds into an immunoglobulin-like domain and may mediate cell adhesion properties.

Similarity. Belongs to the X(+)/potassium ATPases subunit beta family.

Isoforms (2)

UniProt ID	Names	Canonical?
P54709-1	1	yes
P54709-2	2

RefSeq proteins (1): NP_001670* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000402	Na/K_ATPase_sub_beta	Family
IPR038702	Na/K_ATPase_sub_beta_sf	Homologous_superfamily

Pfam: PF00287

UniProt features (12 total): disulfide bond 3, topological domain 2, splice variant 2, glycosylation site 2, chain 1, transmembrane region 1, region of interest 1

Structure

Experimental structures (PDB)

8 structures.

PDB	Method	Resolution (Å)
24RC	ELECTRON MICROSCOPY	2.61
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
9KCR	ELECTRON MICROSCOPY	3.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P54709-F1	89.87	0.68

Functional residue map

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

Disulfide bonds (3): 128–144, 154–170, 191–250

Glycosylation sites (2): 124, 240

Function

Pathways and Gene Ontology

Reactome pathways

14 pathways

ID	Pathway
R-HSA-210991	Basigin interactions
R-HSA-5578775	Ion homeostasis
R-HSA-936837	Ion transport by P-type ATPases
R-HSA-9679191	Potential therapeutics for SARS
R-HSA-109582	Hemostasis
R-HSA-1643685	Disease
R-HSA-202733	Cell surface interactions at the vascular wall
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: 330 (showing top): GOBP_POTASSIUM_ION_TRANSPORT, TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_MONOCYTE_UP, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, GOBP_SODIUM_ION_TRANSMEMBRANE_TRANSPORT, GOBP_POTASSIUM_ION_HOMEOSTASIS, GOBP_POSITIVE_REGULATION_OF_SODIUM_ION_TRANSPORT, GOBP_POSITIVE_REGULATION_OF_POTASSIUM_ION_TRANSPORT, GOBP_PROTEIN_LOCALIZATION_TO_CELL_PERIPHERY, GOBP_POSITIVE_REGULATION_OF_TRANSMEMBRANE_TRANSPORT, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_REGULATION_OF_SODIUM_ION_TRANSPORT, NFKB_Q6, OUELLET_OVARIAN_CANCER_INVASIVE_VS_LMP_UP, SCHUHMACHER_MYC_TARGETS_UP, RUTELLA_RESPONSE_TO_CSF2RB_AND_IL4_UP

GO Biological Process (14): intracellular sodium ion homeostasis (GO:0006883), intracellular potassium ion homeostasis (GO:0030007), sodium ion transmembrane transport (GO:0035725), sodium ion export across plasma membrane (GO:0036376), protein stabilization (GO:0050821), potassium ion transmembrane transport (GO:0071805), protein localization to plasma membrane (GO:0072659), membrane repolarization (GO:0086009), positive regulation of sodium ion export across plasma membrane (GO:1903278), positive regulation of potassium ion import across plasma membrane (GO:1903288), potassium ion import across plasma membrane (GO:1990573), monoatomic ion transport (GO:0006811), potassium ion transport (GO:0006813), sodium ion transport (GO:0006814)

GO Molecular Function (5): ATPase activator activity (GO:0001671), protein-macromolecule adaptor activity (GO:0030674), ATPase binding (GO:0051117), transporter activator activity (GO:0141109), protein binding (GO:0005515)

GO Cellular Component (9): plasma membrane (GO:0005886), sodium:potassium-exchanging ATPase complex (GO:0005890), basolateral plasma membrane (GO:0016323), apical plasma membrane (GO:0016324), sperm flagellum (GO:0036126), melanosome (GO:0042470), extracellular exosome (GO:0070062), cytoplasm (GO:0005737), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-10 pathways:

Category	Pathways
Cell surface interactions at the vascular wall	1
Cardiac conduction	1
Ion channel transport	1
SARS-CoV Infections	1
Hemostasis	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
intracellular monoatomic cation homeostasis	2
monoatomic cation transmembrane transport	2
metal ion transport	2
molecular function activator activity	2
plasma membrane region	2
cellular anatomical structure	2
sodium ion homeostasis	1
potassium ion homeostasis	1
sodium ion transport	1
sodium ion transmembrane transport	1
export across plasma membrane	1
regulation of protein stability	1
potassium ion transport	1
protein localization to membrane	1
protein localization to cell periphery	1
regulation of membrane potential	1
sodium ion export across plasma membrane	1
positive regulation of sodium ion transmembrane transport	1
regulation of sodium ion export across plasma membrane	1
positive regulation of potassium ion transmembrane transport	1
regulation of potassium ion import	1
potassium ion import across plasma membrane	1
potassium ion transmembrane transport	1
inorganic cation import across plasma membrane	1
transport	1
ATP-dependent activity	1
protein binding	1
molecular adaptor activity	1
enzyme binding	1
transporter activity	1
transporter regulator activity	1
binding	1
membrane	1
cell periphery	1
cation-transporting ATPase complex	1
plasma membrane protein complex	1
basal plasma membrane	1
apical part of cell	1
9+2 motile cilium	1
pigment granule	1

Protein interactions and networks

STRING

1270 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ATP1B3	ATP1A3	P13637	883
ATP1B3	ATP1A4	Q13733	881
ATP1B3	ATP1A1	P05023	869
ATP1B3	PAIP2B	Q9ULR5	810
ATP1B3	SLC1A1	P43005	787
ATP1B3	ADCY6	O43306	763
ATP1B3	ATP1A2	P50993	717
ATP1B3	PIGQ	Q9BRB3	548
ATP1B3	SLC1A5	Q15758	504
ATP1B3	PXK	Q7Z7A4	497
ATP1B3	ATP1B1	P05026	477
ATP1B3	GCGR	P47871	465
ATP1B3	OTX1	P32242	442
ATP1B3	MITF	O75030	437
ATP1B3	RHNO1	Q9BSD3	432

IntAct

124 interactions, top by confidence:

A	B	Type	Score
ATP1A1	ATP1B1	psi-mi:“MI:0914”(association)	0.910
TSPAN15	ADAM10	psi-mi:“MI:0914”(association)	0.840
TSPAN5	ADAM10	psi-mi:“MI:0914”(association)	0.800
CD9	ADAM10	psi-mi:“MI:0914”(association)	0.750
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
EMC1	EMC8	psi-mi:“MI:0914”(association)	0.640
SLC12A2	CLGN	psi-mi:“MI:0914”(association)	0.640
SLC17A5	LGALS8	psi-mi:“MI:0914”(association)	0.640
CANX	PGRMC1	psi-mi:“MI:0914”(association)	0.570
ATP1B3	TMEM98	psi-mi:“MI:0915”(physical association)	0.560
STOM	ATP1B3	psi-mi:“MI:0915”(physical association)	0.560
ATP1B3	SMAGP	psi-mi:“MI:0915”(physical association)	0.560
ATP1B3	CTXN3	psi-mi:“MI:0915”(physical association)	0.560
SNX5	SNX2	psi-mi:“MI:0914”(association)	0.550
REEP5	SCAMP1	psi-mi:“MI:0914”(association)	0.530
SUPT5H	POLR2D	psi-mi:“MI:0914”(association)	0.530
ATP1A3	AGPAT2	psi-mi:“MI:0914”(association)	0.530
ATP1B3	HMGCR	psi-mi:“MI:0914”(association)	0.530
	TK2	psi-mi:“MI:0915”(physical association)	0.400
HSCB	ATP1B3	psi-mi:“MI:0915”(physical association)	0.370
PCNA	ATP1B3	psi-mi:“MI:0915”(physical association)	0.370
MAPK6		psi-mi:“MI:0914”(association)	0.350
PLEKHA7	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
LAMP1	HAX1	psi-mi:“MI:0914”(association)	0.350
IFITM3	STX12	psi-mi:“MI:0914”(association)	0.350
P2RY6	ESYT2	psi-mi:“MI:0914”(association)	0.350

BioGRID (354): KIAA0922 (Affinity Capture-MS), EMC1 (Affinity Capture-MS), ATP12A (Affinity Capture-MS), TCTN2 (Affinity Capture-MS), HLA-C (Affinity Capture-MS), PIGO (Affinity Capture-MS), ALG9 (Affinity Capture-MS), KIAA2013 (Affinity Capture-MS), POMGNT2 (Affinity Capture-MS), MANEAL (Affinity Capture-MS), REEP5 (Affinity Capture-MS), SCARB1 (Affinity Capture-MS), KIAA1715 (Affinity Capture-MS), TM9SF4 (Affinity Capture-MS), PCDH20 (Affinity Capture-MS)

ESM2 similar proteins: A5A6J8, P05026, P05027, P05028, P05029, P06583, P07340, P08251, P13638, P14094, P14231, P14415, P18434, P18597, P18598, P21188, P30715, P30716, P33704, P33879, P43002, P50992, P51164, P51165, P51575, P51577, P54709, Q17QL5, Q202B1, Q24048, Q28030, Q2HZ96, Q4R4V5, Q5E9U1, Q5F362, Q5J583, Q5R6C0, Q5R8S8, Q6AY41, Q8L8W0

Diamond homologs: A5A6J8, A7MB71, P05026, P05027, P05028, P05029, P06583, P07340, P08251, P13638, P14094, P14231, P14415, P18434, P18597, P18598, P21188, P25169, P30715, P30716, P33704, P33879, P43002, P51165, P54709, P97370, Q202B1, Q24046, Q28030, Q2HZ96, Q3T0C6, Q4R4V5, Q5J583, Q5R8S8, Q60489, Q63377, Q8WMG3, Q99ME6, Q9BDK6, Q9GLC3

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 134 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
R-HSA-425393	7	9.5×	5e-03
RHOQ GTPase cycle	5	9.4×	9e-03
ER-Phagosome pathway	6	8.1×	9e-03
SLC-mediated transmembrane transport	9	5.5×	7e-03
Transport of small molecules	13	3.4×	9e-03

GO biological processes:

GO term	Partners	Fold	FDR
amino acid transport	6	15.3×	1e-03
transport across blood-brain barrier	7	10.3×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	20
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
57835	GRCh38/hg38 3q23-24(chr3:141751960-148246189)x1	Pathogenic

SpliceAI

1452 predictions. Top by Δscore:

Variant	Effect	Δscore
3:141903615:TACA:T	acceptor_loss	1.0000
3:141907161:TTATA:T	acceptor_loss	1.0000
3:141907164:TA:T	acceptor_loss	1.0000
3:141907165:A:AG	acceptor_gain	1.0000
3:141907166:G:GG	acceptor_gain	1.0000
3:141907273:AC:A	donor_gain	1.0000
3:141907275:G:GG	donor_gain	1.0000
3:141921969:A:AG	acceptor_gain	1.0000
3:141921970:A:G	acceptor_gain	1.0000
3:141903618:A:AG	acceptor_gain	0.9900
3:141903619:G:GG	acceptor_gain	0.9900
3:141903619:GGTTT:G	acceptor_gain	0.9900
3:141903745:CCAGG:C	donor_loss	0.9900
3:141903747:AGG:A	donor_loss	0.9900
3:141903749:G:C	donor_loss	0.9900
3:141903750:T:A	donor_loss	0.9900
3:141907163:ATAG:A	acceptor_gain	0.9900
3:141907166:GGA:G	acceptor_gain	0.9900
3:141907166:GGACT:G	acceptor_gain	0.9900
3:141907271:AAAC:A	donor_gain	0.9900
3:141907272:AAC:A	donor_gain	0.9900
3:141907274:CG:C	donor_loss	0.9900
3:141907278:AGT:A	donor_loss	0.9900
3:141907279:G:GG	donor_gain	0.9900
3:141907279:G:T	donor_loss	0.9900
3:141913835:GA:G	donor_gain	0.9900
3:141919462:GAT:G	donor_gain	0.9900
3:141922060:GCAT:G	donor_gain	0.9900
3:141922064:G:GG	donor_gain	0.9900
3:141925526:GCCA:G	acceptor_loss	0.9900

AlphaMissense

1836 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:141925609:T:A	C250S	0.997
3:141925610:G:C	C250S	0.997
3:141903634:T:C	F42L	0.996
3:141903636:C:A	F42L	0.996
3:141903636:C:G	F42L	0.996
3:141913833:C:A	N176K	0.996
3:141913833:C:G	N176K	0.996
3:141925609:T:C	C250R	0.996
3:141925660:T:C	F267L	0.996
3:141925662:T:A	F267L	0.996
3:141925662:T:G	F267L	0.996
3:141903670:T:C	F54L	0.995
3:141903672:C:A	F54L	0.995
3:141903672:C:G	F54L	0.995
3:141913735:T:A	C144S	0.995
3:141913736:G:C	C144S	0.995
3:141913835:G:C	R177T	0.995
3:141913836:A:C	R177S	0.995
3:141913836:A:T	R177S	0.995
3:141922037:T:C	F215L	0.995
3:141922039:C:A	F215L	0.995
3:141922039:C:G	F215L	0.995
3:141876907:T:A	W36R	0.994
3:141876907:T:C	W36R	0.994
3:141907170:T:C	L81P	0.994
3:141876892:C:A	R31S	0.993
3:141913735:T:C	C144R	0.993
3:141913827:A:C	K174N	0.993
3:141913827:A:T	K174N	0.993
3:141916009:T:A	C191S	0.993

dbSNP variants (sampled 300 via entrez): RS1000099204 (3:141884262 G>A,C), RS1000129013 (3:141910566 A>G), RS1000130822 (3:141902369 A>C,G,T), RS1000193111 (3:141905501 A>G), RS1000224389 (3:141905894 A>G), RS1000224588 (3:141902142 A>C,G), RS1000336152 (3:141908193 T>A,C), RS1000430197 (3:141920547 AAG>A), RS1000549270 (3:141886864 G>A), RS1000557045 (3:141903288 A>G), RS1000572573 (3:141896969 T>C), RS1000653487 (3:141882557 A>G), RS1000799294 (3:141895002 A>C), RS1000805989 (3:141926509 A>C), RS1000808891 (3:141899900 A>C)

Disease associations

OMIM: gene MIM:601867 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

16 associations (top):

Study	Trait	p-value
GCST003246_1	Testicular germ cell tumor	2.000000e-09
GCST004621_135	Red cell distribution width	1.000000e-11
GCST006804_72	Red cell distribution width	1.000000e-11
GCST006871_1	Total hippocampal volume	3.000000e-09
GCST006988_141	Blond vs. brown/black hair color	4.000000e-19
GCST007096_130	Pulse pressure	2.000000e-08
GCST007097_61	Pulse pressure	2.000000e-06
GCST007097_62	Pulse pressure	2.000000e-06
GCST008155_8	Waist-hip ratio	6.000000e-06
GCST010699_19	Brain morphology (min-P)	6.000000e-10
GCST010701_77	Cortical surface area (MOSTest)	4.000000e-09
GCST010702_94	Subcortical volume (MOSTest)	1.000000e-08
GCST010703_324	Brain morphology (MOSTest)	1.000000e-10
GCST010796_1636	Electrocardiogram morphology (amplitude at temporal datapoints)	4.000000e-08
GCST90002404_57	Red cell distribution width	8.000000e-22
GCST90002407_413	White blood cell count	8.000000e-10

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0009188	Red cell distribution width
EFO:0005035	hippocampal volume
EFO:0003924	hair color
EFO:0005763	pulse pressure measurement
EFO:0004343	waist-hip ratio
EFO:0004346	neuroimaging measurement
EFO:0004327	electrocardiography

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL2095186 (PROTEIN COMPLEX GROUP), CHEMBL3256 (SINGLE PROTEIN), 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)

GtoPdb / IUPHAR curated pharmacology

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

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

ChEMBL bioactivities

237 potent at pChembl≥5 of 289 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
8.37	Ki	4.3	nM	CHEMBL5765464
8.37	Ki	4.3	nM	CHEMBL5879229
8.32	IC50	4.79	nM	CHEMBL1651648
8.25	Ki	5.6	nM	CHEMBL5832044
8.24	Ki	5.8	nM	CHEMBL5748673
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	IC50	8	nM	DIGITOXIGENIN
8.10	IC50	8	nM	DIGITOXIN
8.09	Ki	8.1	nM	CHEMBL6056661
8.05	IC50	9	nM	CHEMBL3085468
8.01	Ki	9.8	nM	CHEMBL5957388
7.99	Ki	10.3	nM	CHEMBL5791351
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	IC50	12	nM	CHEMBL2069010
7.91	Ki	12.4	nM	CHEMBL6030183
7.84	Ki	14.4	nM	CHEMBL6031986
7.80	IC50	16	nM	CHEMBL2068887
7.80	IC50	16	nM	CHEMBL3349024
7.79	Ki	16.3	nM	CHEMBL5780414
7.75	IC50	17.8	nM	CHEMBL1159613
7.70	IC50	20	nM	DIGITOXIGENIN
7.70	Ki	20.1	nM	CHEMBL5814784
7.70	IC50	20	nM	CHEMBL2068894
7.70	IC50	20	nM	CHEMBL2068887
7.66	IC50	22	nM	BUFALIN
7.61	Ki	24.7	nM	CHEMBL6005633
7.60	IC50	25	nM	CHEMBL2068888
7.56	Ki	27.6	nM	CHEMBL5961305
7.55	IC50	28.2	nM	CHEMBL3350144
7.54	Ki	28.8	nM	DIGITOXIN
7.52	IC50	30	nM	CHEMBL2068896
7.52	IC50	30	nM	CHEMBL2068909
7.41	IC50	38.9	nM	CHEMBL3349024
7.40	IC50	40	nM	CHEMBL126930
7.40	IC50	40	nM	CHEMBL2069036
7.37	Ki	42.8	nM	DIGOXIN
7.35	IC50	45	nM	CHEMBL2069112

PubChem BioAssay actives

211 with measured affinity, of 375 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
3-[(3S,8R,9S,10S,13R,14R,17S)-14-hydroxy-10,13-dimethyl-3-[[(2R,3S,4S,5R,6S)-3,4,5,6-tetrahydroxyoxan-2-yl]methoxy]-1,2,3,4,5,6,7,8,9,11,12,15,16,17-tetradecahydrocyclopenta[a]phenanthren-17-yl]-2H-furan-5-one	49025: Inhibition of [3H]ouabain binding to Na/K ATP-ase in dog heart muscle	ic50	0.0030	uM
3-[(3S,5R,8R,9S,10S,13R,14S,17R)-14-hydroxy-10,13-dimethyl-3-[(2R,3R,4R,5R,6S)-3,4,5-trihydroxy-6-methyloxan-2-yl]oxy-1,2,3,4,5,6,7,8,9,11,12,15,16,17-tetradecahydrocyclopenta[a]phenanthren-17-yl]-2H-furan-5-one	146845: Inhibition of hog kidney Na+, K+-dependent ATPase	ic50	0.0048	uM
3-[(3S,5R,8R,9S,10S,13R,14S,17R)-3-[(2R,4S,5S,6R)-4,5-dihydroxy-6-methyloxan-2-yl]oxy-14-hydroxy-10,13-dimethyl-1,2,3,4,5,6,7,8,9,11,12,15,16,17-tetradecahydrocyclopenta[a]phenanthren-17-yl]-2H-furan-5-one	146845: Inhibition of hog kidney Na+, K+-dependent ATPase	ic50	0.0070	uM
3-[(3S,8R,9S,10S,13R,14R,17R)-14-hydroxy-10,13-dimethyl-3-[[(2R,3S,4S,5R,6S)-3,4,5,6-tetrahydroxyoxan-2-yl]methoxy]-1,2,3,4,5,6,7,8,9,11,12,15,16,17-tetradecahydrocyclopenta[a]phenanthren-17-yl]-2H-furan-5-one	49025: Inhibition of [3H]ouabain binding to Na/K ATP-ase in dog heart muscle	ic50	0.0070	uM
3-[(3S,5R,8R,9S,10S,13R,14S,17R)-3,14-dihydroxy-10,13-dimethyl-1,2,3,4,5,6,7,8,9,11,12,15,16,17-tetradecahydrocyclopenta[a]phenanthren-17-yl]-2H-furan-5-one	56911: Inhibition of [3H]- ouabain binding to digitalis receptor	ic50	0.0080	uM
3-[(3S,5R,8R,9S,10S,13R,14S,17R)-3-[(2R,4S,5S,6R)-5-[(2S,4S,5S,6R)-5-[(2S,4S,5S,6R)-4,5-dihydroxy-6-methyloxan-2-yl]oxy-4-hydroxy-6-methyloxan-2-yl]oxy-4-hydroxy-6-methyloxan-2-yl]oxy-14-hydroxy-10,13-dimethyl-1,2,3,4,5,6,7,8,9,11,12,15,16,17-tetradecahydrocyclopenta[a]phenanthren-17-yl]-2H-furan-5-one	56911: Inhibition of [3H]- ouabain binding to digitalis receptor	ic50	0.0080	uM
3-[(3S,5S,8R,9S,10S,13R,14R,17R)-3-[[(2S,3R,4R,6S)-3,4-dihydroxy-6-[[(2S,3R,4R,6S)-3,4,6-trihydroxyoxan-2-yl]methoxy]oxan-2-yl]methoxy]-14-hydroxy-10,13-dimethyl-1,2,3,4,5,6,7,8,9,11,12,15,16,17-tetradecahydrocyclopenta[a]phenanthren-17-yl]-2H-furan-5-one	49025: Inhibition of [3H]ouabain binding to Na/K ATP-ase in dog heart muscle	ic50	0.0080	uM
3-[(3S,5S,8R,9S,10S,13R,14R,17R)-3-[[(2S,3R,4R,6S)-6-[[(2S,3R,4R,6S)-3,4-dihydroxy-6-[[(2S,3R,4R,6S)-3,4,6-trihydroxyoxan-2-yl]methoxy]oxan-2-yl]methoxy]-3,4-dihydroxyoxan-2-yl]methoxy]-14-hydroxy-10,13-dimethyl-1,2,3,4,5,6,7,8,9,11,12,15,16,17-tetradecahydrocyclopenta[a]phenanthren-17-yl]-2H-furan-5-one	49025: Inhibition of [3H]ouabain binding to Na/K ATP-ase in dog heart muscle	ic50	0.0080	uM
3-[(3S,5S,8R,9S,10S,13R,14R,17R)-14-hydroxy-10,13-dimethyl-3-[[(2S,3R,4R,6S)-3,4,6-trihydroxyoxan-2-yl]methoxy]-1,2,3,4,5,6,7,8,9,11,12,15,16,17-tetradecahydrocyclopenta[a]phenanthren-17-yl]-2H-furan-5-one	49025: Inhibition of [3H]ouabain binding to Na/K ATP-ase in dog heart muscle	ic50	0.0090	uM
3-[(3S,5R,8R,9S,10S,13R,14S,17R)-14-hydroxy-10,13-dimethyl-3-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-1,2,3,4,5,6,7,8,9,11,12,15,16,17-tetradecahydrocyclopenta[a]phenanthren-17-yl]-2H-furan-5-one	146845: Inhibition of hog kidney Na+, K+-dependent ATPase	ic50	0.0105	uM
3-[(3S,5R,8R,9S,10S,13R,14S,17R)-14-hydroxy-10,13-dimethyl-3-[(2R,3S,4S,5S,6S)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-1,2,3,4,5,6,7,8,9,11,12,15,16,17-tetradecahydrocyclopenta[a]phenanthren-17-yl]-2H-furan-5-one	146845: Inhibition of hog kidney Na+, K+-dependent ATPase	ic50	0.0107	uM
(2R,4S,5R)-2-[[(3S,5R,8R,9S,10S,13R,14S,17S)-14-hydroxy-10,13-dimethyl-17-(nitromethyl)-1,2,3,4,5,6,7,8,9,11,12,15,16,17-tetradecahydrocyclopenta[a]phenanthren-3-yl]oxy]-6-methyloxane-3,4,5-triol	56911: Inhibition of [3H]- ouabain binding to digitalis receptor	ic50	0.0120	uM
(3S,5R,8R,9S,10S,13R,14S,17R)-17-[(E,3E)-3-(2-aminoethoxyimino)prop-1-enyl]-10,13-dimethyl-1,2,3,4,5,6,7,8,9,11,12,15,16,17-tetradecahydrocyclopenta[a]phenanthrene-3,14-diol	146853: 50% displacement of the specific [3H]ouabain binding from the dog kidney Na+/K+ ATPase	ic50	0.0160	uM
3-[(13R)-14-hydroxy-10,13-dimethyl-3-[(2S,3R,4S,5R,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-1,2,3,4,5,6,7,8,9,11,12,15,16,17-tetradecahydrocyclopenta[a]phenanthren-17-yl]-2H-furan-5-one	146845: Inhibition of hog kidney Na+, K+-dependent ATPase	ic50	0.0178	uM
(3S,5R,8R,9S,10S,13R,14S,17S)-17-[(E)-3-aminopropoxyiminomethyl]-10,13-dimethyl-1,2,3,4,5,6,7,8,9,11,12,15,16,17-tetradecahydrocyclopenta[a]phenanthrene-3,14-diol;oxalic acid	146858: In vitro inhibitory concentration against dog kidney Na+/K+ ATPase	ic50	0.0200	uM
5-[(3S,5R,8R,9S,10S,13R,14S,17R)-3,14-dihydroxy-10,13-dimethyl-1,2,3,4,5,6,7,8,9,11,12,15,16,17-tetradecahydrocyclopenta[a]phenanthren-17-yl]pyran-2-one	1941870: Inhibition of NA+/K+ ATPase (unknown origin) activity	ic50	0.0220	uM
(3S,5R,8R,9S,10S,13R,14S,17R)-17-[(E,3E)-3-[2-(dimethylamino)ethoxyimino]prop-1-enyl]-10,13-dimethyl-1,2,3,4,5,6,7,8,9,11,12,15,16,17-tetradecahydrocyclopenta[a]phenanthrene-3,14-diol	146853: 50% displacement of the specific [3H]ouabain binding from the dog kidney Na+/K+ ATPase	ic50	0.0250	uM
(3S,5R,8R,9S,10S,13R,14S,17R)-17-[(E,3E)-3-[2-(dimethylamino)ethoxyimino]prop-1-enyl]-10,13-dimethyl-1,2,3,4,5,6,7,8,9,11,12,15,16,17-tetradecahydrocyclopenta[a]phenanthrene-3,14-diol;oxalic acid	146858: In vitro inhibitory concentration against dog kidney Na+/K+ ATPase	ic50	0.0300	uM
(3S,5R,8R,9S,10S,13R,14S,17R)-17-[(E,3E)-3-(2-aminoethoxyimino)-2-methylprop-1-enyl]-10,13-dimethyl-1,2,3,4,5,6,7,8,9,11,12,15,16,17-tetradecahydrocyclopenta[a]phenanthrene-3,14-diol;(E)-but-2-enedioic acid	146858: In vitro inhibitory concentration against dog kidney Na+/K+ ATPase	ic50	0.0300	uM
(2R,4bS,7S,8aR)-2-[(1E,3S)-1-(2-aminoethoxyimino)pentan-3-yl]-7-hydroxy-2,4b-dimethyl-4,4a,5,6,7,8,8a,9,10,10a-decahydro-3H-phenanthren-1-one	146843: Binding affinity towards Na+,K+ -ATPase isolated from dog kidney.	ic50	0.0400	uM
(3S,5R,8R,9S,10S,13R,14S,17S)-17-[(E)-2-(dimethylamino)ethoxyiminomethyl]-10,13-dimethyl-1,2,3,4,5,6,7,8,9,11,12,15,16,17-tetradecahydrocyclopenta[a]phenanthrene-3,14-diol	146853: 50% displacement of the specific [3H]ouabain binding from the dog kidney Na+/K+ ATPase	ic50	0.0400	uM
(2R,4S,5R)-2-[[(3S,5R,8R,9S,10S,13R,14S,17R)-14-hydroxy-10,13-dimethyl-17-(2-nitroethyl)-1,2,3,4,5,6,7,8,9,11,12,15,16,17-tetradecahydrocyclopenta[a]phenanthren-3-yl]oxy]-6-methyloxane-3,4,5-triol	56911: Inhibition of [3H]- ouabain binding to digitalis receptor	ic50	0.0450	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2147908: Binding affinity to human ATP1B3 incubated for 45 mins by Kinobead based pull down assay	kd	0.0492	uM
(3S,5R,8R,9S,10S,13R,14S,17S)-17-[(2E)-2-(2-aminoethoxyimino)ethyl]-10,13-dimethyl-1,2,3,4,5,6,7,8,9,11,12,15,16,17-tetradecahydrocyclopenta[a]phenanthrene-3,14-diol	146843: Binding affinity towards Na+,K+ -ATPase isolated from dog kidney.	ic50	0.0500	uM
(E)-but-2-enedioic acid;(3S,5R,8R,9S,10S,13R,14S,17R)-17-[(E,3E)-3-[2-(dimethylamino)ethoxyimino]-2-methylprop-1-enyl]-10,13-dimethyl-1,2,3,4,5,6,7,8,9,11,12,15,16,17-tetradecahydrocyclopenta[a]phenanthrene-3,14-diol	146858: In vitro inhibitory concentration against dog kidney Na+/K+ ATPase	ic50	0.0600	uM
6-[[(3S,8R,9S,10S,13R,14R,17S)-14-hydroxy-17-[(1S)-1-hydroxyethyl]-10,13-dimethyl-1,2,3,4,5,6,7,8,9,11,12,15,16,17-tetradecahydrocyclopenta[a]phenanthren-3-yl]oxy]-2-(hydroxymethyl)oxane-3,4-diol	146854: Compound is evaluated for inhibition of specific binding of [3H]ouabain to membranes from dog heart	ic50	0.0600	uM
3-[(5R,8R,9S,10S,13R,14R,17R)-14-hydroxy-10,13-dimethyl-1,2,3,4,5,6,7,8,9,11,12,15,16,17-tetradecahydrocyclopenta[a]phenanthren-17-yl]-2H-furan-5-one	49025: Inhibition of [3H]ouabain binding to Na/K ATP-ase in dog heart muscle	ic50	0.0700	uM
(2R,3R,4R,5R,6R)-6-[[(3R)-14-hydroxy-17-(1-hydroxyethyl)-10,13-dimethyl-1,2,3,4,5,6,7,8,9,11,12,15,16,17-tetradecahydrocyclopenta[a]phenanthren-3-yl]oxymethyl]oxane-2,3,4,5-tetrol	49025: Inhibition of [3H]ouabain binding to Na/K ATP-ase in dog heart muscle	ic50	0.0750	uM
(3S,5R,8R,9S,10S,13R,14S,17R)-17-[(1E,3E)-6-aminohexa-1,3-dienyl]-10,13-dimethyl-1,2,3,4,5,6,7,8,9,11,12,15,16,17-tetradecahydrocyclopenta[a]phenanthrene-3,14-diol	146858: In vitro inhibitory concentration against dog kidney Na+/K+ ATPase	ic50	0.0800	uM
(3S,5R,8R,9S,10S,13R,14S,17S)-17-[(3Z)-3-(2-aminoethoxyimino)propyl]-10,13-dimethyl-1,2,3,4,5,6,7,8,9,11,12,15,16,17-tetradecahydrocyclopenta[a]phenanthrene-3,14-diol	146858: In vitro inhibitory concentration against dog kidney Na+/K+ ATPase	ic50	0.0800	uM
3-[(3S,5R,8R,9S,10S,13R,14S,17R)-14-hydroxy-10,13-dimethyl-3-[(2R,3R,4R,5R,6S)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-1,2,3,4,5,6,7,8,9,11,12,15,16,17-tetradecahydrocyclopenta[a]phenanthren-17-yl]-2H-furan-5-one	146845: Inhibition of hog kidney Na+, K+-dependent ATPase	ic50	0.0870	uM
(3S,4R,6R)-6-[[(3S,5R,8R,9S,10S,13R,14S,17S)-14-hydroxy-10,13-dimethyl-17-(nitromethyl)-1,2,3,4,5,6,7,8,9,11,12,15,16,17-tetradecahydrocyclopenta[a]phenanthren-3-yl]oxy]-2-methyloxane-3,4-diol	56911: Inhibition of [3H]- ouabain binding to digitalis receptor	ic50	0.0880	uM
(2R,4S,5R)-2-[[(3S,5R,8R,9S,10S,13R,14S,17S)-17-(aminomethyl)-14-hydroxy-10,13-dimethyl-1,2,3,4,5,6,7,8,9,11,12,15,16,17-tetradecahydrocyclopenta[a]phenanthren-3-yl]oxy]-6-methyloxane-3,4,5-triol;hydrochloride	56911: Inhibition of [3H]- ouabain binding to digitalis receptor	ic50	0.0990	uM
(2R,4bS,7S,8aR)-2-[(1E,3S)-1-[2-(dimethylamino)ethoxyimino]pentan-3-yl]-7-hydroxy-2,4b-dimethyl-4,4a,5,6,7,8,8a,9,10,10a-decahydro-3H-phenanthren-1-one	146843: Binding affinity towards Na+,K+ -ATPase isolated from dog kidney.	ic50	0.1000	uM
(2R,4bS,7S,8aR)-2-[(2S,4E)-4-(2-aminoethoxyimino)butan-2-yl]-7-hydroxy-2,4b-dimethyl-4,4a,5,6,7,8,8a,9,10,10a-decahydro-3H-phenanthren-1-one	146843: Binding affinity towards Na+,K+ -ATPase isolated from dog kidney.	ic50	0.1000	uM
2-[(E)-[(3S,5R,8R,9S,10S,13R,14S,17S)-3,14-dihydroxy-10,13-dimethyl-1,2,3,4,5,6,7,8,9,11,12,15,16,17-tetradecahydrocyclopenta[a]phenanthren-17-yl]methylideneamino]guanidine;hydrochloride	146856: Displacement of [3H]ouabain from dog kidney Na+/K+ ATPase	ic50	0.1000	uM
(3S,5R,8R,9S,10S,13R,14S,17S)-17-[(3Z)-3-[2-(dimethylamino)ethoxyimino]propyl]-10,13-dimethyl-1,2,3,4,5,6,7,8,9,11,12,15,16,17-tetradecahydrocyclopenta[a]phenanthrene-3,14-diol;oxalic acid	146858: In vitro inhibitory concentration against dog kidney Na+/K+ ATPase	ic50	0.1000	uM
(2R,4bS,7S,8aR)-2-[(2S,4E)-4-[2-(dimethylamino)ethoxyimino]butan-2-yl]-7-hydroxy-2,4b-dimethyl-4,4a,5,6,7,8,8a,9,10,10a-decahydro-3H-phenanthren-1-one	146843: Binding affinity towards Na+,K+ -ATPase isolated from dog kidney.	ic50	0.1300	uM
2-(dimethylamino)ethyl (E)-4-[(2R,4bS,7S,8aR)-7-hydroxy-2,4b-dimethyl-1-oxo-4,4a,5,6,7,8,8a,9,10,10a-decahydro-3H-phenanthren-2-yl]hex-2-enoate	146843: Binding affinity towards Na+,K+ -ATPase isolated from dog kidney.	ic50	0.1300	uM
1-[(3R)-14-hydroxy-10,13-dimethyl-3-[[(2R,3R,4R,5R,6R)-3,4,5,6-tetrahydroxyoxan-2-yl]methoxy]-1,2,3,4,5,6,7,8,9,11,12,15,16,17-tetradecahydrocyclopenta[a]phenanthren-17-yl]ethanone	49025: Inhibition of [3H]ouabain binding to Na/K ATP-ase in dog heart muscle	ic50	0.1500	uM
Digoxin	1970782: Inhibition of NA+/K+ ATPase (unknown origin) activity incubated for 15 mins in presence of ATP by ADP-Glo assay	ic50	0.1600	uM
(2R,4bS,7S,8aS)-2-[(1E,3S)-1-(2-aminoethoxyimino)pentan-3-yl]-7-hydroxy-2,4b-dimethyl-4,4a,5,6,7,8,8a,9,10,10a-decahydro-3H-phenanthren-1-one	146843: Binding affinity towards Na+,K+ -ATPase isolated from dog kidney.	ic50	0.1600	uM
(3S,5R,8R,9S,10S,13R,14S,17S)-17-[(E)-2-aminoethoxyiminomethyl]-10,13-dimethyl-1,2,3,4,5,6,7,8,9,11,12,15,16,17-tetradecahydrocyclopenta[a]phenanthrene-3,14-diol;(E)-but-2-enedioic acid	146858: In vitro inhibitory concentration against dog kidney Na+/K+ ATPase	ic50	0.1600	uM
2-[(E)-1-[(3S,5R,8R,9S,10S,13R,14S,17S)-3,14-dihydroxy-10,13-dimethyl-1,2,3,4,5,6,7,8,9,11,12,15,16,17-tetradecahydrocyclopenta[a]phenanthren-17-yl]ethylideneamino]guanidine	146856: Displacement of [3H]ouabain from dog kidney Na+/K+ ATPase	ic50	0.1995	uM
(3S,5R,8R,9S,10S,13R,14S,17S)-17-[(E)-(4,5-dihydro-1H-imidazol-2-ylhydrazinylidene)methyl]-10,13-dimethyl-1,2,3,4,5,6,7,8,9,11,12,15,16,17-tetradecahydrocyclopenta[a]phenanthrene-3,14-diol	146856: Displacement of [3H]ouabain from dog kidney Na+/K+ ATPase	ic50	0.1995	uM
(3S,5R,8R,9S,10S,13R,14S,17S)-17-[(2E)-2-(3-aminopropoxyimino)ethyl]-10,13-dimethyl-1,2,3,4,5,6,7,8,9,11,12,15,16,17-tetradecahydrocyclopenta[a]phenanthrene-3,14-diol	146843: Binding affinity towards Na+,K+ -ATPase isolated from dog kidney.	ic50	0.2000	uM
3-[(1R)-1-[(2R,4bS,7S,8aR)-7-hydroxy-2,4b-dimethyl-1-oxo-4,4a,5,6,7,8,8a,9,10,10a-decahydro-3H-phenanthren-2-yl]propyl]-2H-furan-5-one	146843: Binding affinity towards Na+,K+ -ATPase isolated from dog kidney.	ic50	0.2000	uM
(2R,4bS,7S,8aR)-2-[(1E,3S)-1-(2-aminoethoxyimino)hexan-3-yl]-7-hydroxy-2,4b-dimethyl-4,4a,5,6,7,8,8a,9,10,10a-decahydro-3H-phenanthren-1-one	146843: Binding affinity towards Na+,K+ -ATPase isolated from dog kidney.	ic50	0.2000	uM
(3S,5R,8R,9S,10S,13R,14S,17R)-17-[(E,3E)-3-(3-aminopropoxyimino)-2-methylprop-1-enyl]-10,13-dimethyl-1,2,3,4,5,6,7,8,9,11,12,15,16,17-tetradecahydrocyclopenta[a]phenanthrene-3,14-diol;oxalic acid	146858: In vitro inhibitory concentration against dog kidney Na+/K+ ATPase	ic50	0.2000	uM
(3S,5R,8R,9S,10S,13R,14S,17S)-17-[(2E)-2-[2-(dimethylamino)ethoxyimino]ethyl]-10,13-dimethyl-1,2,3,4,5,6,7,8,9,11,12,15,16,17-tetradecahydrocyclopenta[a]phenanthrene-3,14-diol	146843: Binding affinity towards Na+,K+ -ATPase isolated from dog kidney.	ic50	0.2500	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, increases methylation	6
sodium arsenite	increases expression, decreases expression, increases abundance, affects cotreatment	4
nickel sulfate	decreases expression, increases expression	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression, increases expression	2
Arsenic	affects methylation, decreases expression, increases abundance	2
Smoke	decreases expression, increases abundance	2
Tretinoin	affects cotreatment, increases expression, decreases expression	2
Aflatoxin B1	increases expression, increases methylation	2
bisphenol A	decreases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, decreases expression, affects localization, increases expression	1
salinomycin	decreases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
4-hydroxy-2-nonenal	decreases expression	1
beta-methylcholine	affects expression	1
bisphenol B	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
LDN 193189	affects cotreatment, decreases expression	1
bisphenol AF	increases expression	1
Acetaminophen	increases expression	1
Air Pollutants	increases abundance, decreases expression	1
Benzene	increases expression	1
Benzo(a)pyrene	increases expression	1
Caffeine	decreases phosphorylation	1
Coal	decreases expression, increases abundance	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Dexamethasone	increases expression	1
Dietary Carbohydrates	increases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Furaldehyde	affects localization, decreases expression, affects cotreatment	1
Hydrogen Peroxide	affects expression	1

ChEMBL screening assays

47 unique, capped per target: 47 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

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D1VF	Abcam A-549 ATP1B3 KO	Cancer cell line	Male
CVCL_D2A1	Abcam HCT 116 ATP1B3 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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