FXYD2

Summary

FXYD2 (FXYD domain containing ion transport regulator 2, HGNC:4026) is a protein-coding gene on chromosome 11q23.3, encoding Sodium/potassium-transporting ATPase subunit gamma (P54710). May be involved in forming the receptor site for cardiac glycoside binding or may modulate the transport function of the sodium ATPase.

This gene encodes a member of the FXYD family of transmembrane proteins. This particular protein encodes the sodium/potassium-transporting ATPase subunit gamma. Mutations in this gene have been associated with Renal Hypomagnesemia-2. Alternatively spliced transcript variants have been described. Read-through transcripts have been observed between this locus and the upstream FXYD domain-containing ion transport regulator 6 (FXYD6, GeneID 53826) locus.

Source: NCBI Gene 486 — RefSeq curated summary.

At a glance

• Gene–disease (curated): renal hypomagnesemia 2 (Strong, GenCC)
• GWAS associations: 3
• Clinical variants (ClinVar): 67 total — 1 pathogenic
• Phenotypes (HPO): 9
• Druggable target: yes — 5 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001680

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4026
Approved symbol	FXYD2
Name	FXYD domain containing ion transport regulator 2
Location	11q23.3
Locus type	gene with protein product
Status	Approved
Aliases	MGC12372
Ensembl gene	ENSG00000137731
Ensembl biotype	protein_coding
OMIM	601814
Entrez	486

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 13 protein_coding, 3 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000260287, ENST00000292079, ENST00000317594, ENST00000514385, ENST00000528014, ENST00000532119, ENST00000533281, ENST00000534383, ENST00000910769, ENST00000910770, ENST00000910771, ENST00000910772, ENST00000910773, ENST00000910774, ENST00000910775, ENST00000910776, ENST00000960084

RefSeq mRNA: 2 — MANE Select: NM_001680 NM_001680, NM_021603

CCDS: CCDS8385, CCDS8386

Canonical transcript exons

ENST00000292079 — 6 exons

Exon	Start	End
ENSE00001130350	117820057	117820372
ENSE00003484020	117820666	117820696
ENSE00003553678	117820859	117820895
ENSE00003595432	117822679	117822717
ENSE00003649316	117824654	117824744
ENSE00003676408	117822406	117822480

Expression profiles

Bgee: expression breadth ubiquitous, 162 present calls, max score 99.94.

FANTOM5 (CAGE): breadth broad, TPM avg 6.6448 / max 1732.7047, expressed in 352 samples.

FANTOM5 promoters (14 alternative TSS)

Promoter ID	TPM avg	Samples expressed
122508	2.6556	60
122513	2.5837	124
122510	0.3320	139
122507	0.2270	25
122516	0.1870	50
122512	0.1737	42
122509	0.1623	80
122511	0.1039	17
122505	0.0704	22
122517	0.0632	26

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
metanephros cortex	UBERON:0010533	99.94	gold quality
body of pancreas	UBERON:0001150	99.33	gold quality
gall bladder	UBERON:0002110	99.29	gold quality
islet of Langerhans	UBERON:0000006	98.10	gold quality
pancreas	UBERON:0001264	97.53	gold quality
adult mammalian kidney	UBERON:0000082	94.14	gold quality
cortex of kidney	UBERON:0001225	90.24	gold quality
minor salivary gland	UBERON:0001830	89.14	gold quality
kidney	UBERON:0002113	86.46	gold quality
right lobe of liver	UBERON:0001114	85.60	gold quality
saliva-secreting gland	UBERON:0001044	85.35	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	83.76	gold quality
mouth mucosa	UBERON:0003729	82.89	gold quality
metanephros	UBERON:0000081	82.46	gold quality
right ovary	UBERON:0002118	78.06	gold quality
colonic epithelium	UBERON:0000397	78.02	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	77.88	silver quality
left ovary	UBERON:0002119	76.83	gold quality
apex of heart	UBERON:0002098	76.53	gold quality
left uterine tube	UBERON:0001303	75.13	gold quality
lymph node	UBERON:0000029	74.96	gold quality
body of uterus	UBERON:0009853	74.36	gold quality
spleen	UBERON:0002106	73.85	gold quality
granulocyte	CL:0000094	72.91	gold quality
ovary	UBERON:0000992	72.56	gold quality
liver	UBERON:0002107	71.90	gold quality
muscle layer of sigmoid colon	UBERON:0035805	71.10	gold quality
smooth muscle tissue	UBERON:0001135	70.45	gold quality
renal medulla	UBERON:0000362	70.13	gold quality
omental fat pad	UBERON:0010414	69.51	gold quality

Single-cell (SCXA)

Detected in 20 experiment(s), a significant marker in 19.

Experiment	Marker?	Max mean expression
E-HCAD-10	yes	10332.10
E-MTAB-8495	yes	8770.64
E-GEOD-124472	yes	7934.30
E-HCAD-9	yes	7181.52
E-MTAB-6701	yes	5978.61
E-MTAB-5061	yes	4843.61
E-GEOD-114530	yes	4652.45
E-HCAD-24	yes	3873.89
E-GEOD-81547	yes	3297.65
E-MTAB-10553	yes	2927.05
E-HCAD-31	yes	2324.43
E-HCAD-38	yes	1706.42
E-GEOD-83139	yes	1369.77
E-ENAD-27	yes	1304.09
E-CURD-79	yes	1303.27

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): HNF1B, PCBD1, RUNX1

miRNA regulators (miRDB)

10 targeting FXYD2, 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-4514	99.99	67.10	1870
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-940	99.37	66.14	2064
HSA-MIR-6808-5P	99.31	66.23	2150
HSA-MIR-6893-5P	99.31	66.25	2119
HSA-MIR-874-5P	96.93	63.92	1014
HSA-MIR-4538	95.61	65.34	449

Literature-anchored findings (GeneRIF, showing 17)

• Expression in transfectants reduces Na+ and K+ affinity of Na,K-ATPase. Endogenous expression in certain nephron segments correlates with low Na+ affinity in Na,K-ATPase. (PMID:10559186)
• the TM domain of FYXD2 effects the shift in apparent Na+ affinity (PMID:12907667)
• Activity of GLAST directs FXYD2 protein/gamma subunit to the cell surface, that leads to the activation of the astroglial sodium pump. (PMID:17316900)
• structures of the FXYD proteins (with emphasis on 1-4), as well as their dynamics and their associations with the lipid (PMID:18000745)
• results suggest that FXYD2 can mediate basolateral extrusion of magnesium from cultured renal epithelial cells and provide new insights into the understanding of the possible physiological roles of FXYD2 wild-type and mutant proteins. (PMID:18448590)
• 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)
• Study reveals, in various human tissues, the specific expression of FXYD2, which may associate with Na, K-ATPase in selected cell types and modulate its catalytic properties. (PMID:19879113)
• Datab propose human FXYD2gammaa as a novel beta cell-specific biomarker. (PMID:20379810)
• wild type HNF1B specifically induces FXYD2A transcription whereas all HNF1B mutants partially prevented it. (PMID:21130072)
• findings confirm the presence of an FXYD2 peptide in the crab gill Na,K-ATPase and demonstrate that this peptide plays an important role in regulating enzyme activity (PMID:22588134)
• This is the first report demonstrating the potential utility of FXYD2 immunohistochemistry in the diagnosis of chromophobe renal cell carcinoma (PMID:23196795)
• PCBD1 (dimerization cofactor of HNF-1alpha) is coactivator of the HNF1B-mediated transcription necessary for fine tuning ATPase Na+/K+ transporting gamma 1 polypeptide (FXYD2) transcription in the distal convoluted tubule. (PMID:24204001)
• our findings suggested that FXYD2c played a role in regulation of NKA activity by enhancing the expression of NKA in HK-2 cells upon hypertonic challenge. (PMID:24258619)
• FXYD2b could regulate the Na,K-ATPase by modulating the effective membrane surface electrostatics near the ion binding sites of the pump. (PMID:24794573)
• Recurrent FXYD2 p.Gly41Arg mutation is associated with isolated dominant hypomagnesaemia. (PMID:25765846)
• FXYD2 is functionally upregulated in ovarian clear cell carcinoma and may serve as a promising prognostic biomarker and therapeutic target of cardiac glycosides in OCCC (PMID:26910837)
• Downregulation of FXYD2 Is Associated with Poor Prognosis and Increased Regulatory T Cell Infiltration in Clear Cell Renal Cell Carcinoma. (PMID:36313180)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Fxyd2	ENSMUSG00000059412
rattus_norvegicus	Fxyd2	ENSRNOG00000016469

Paralogs (6): FXYD5 (ENSG00000089327), FXYD3 (ENSG00000089356), FXYD6 (ENSG00000137726), FXYD4 (ENSG00000150201), FXYD7 (ENSG00000221946), FXYD1 (ENSG00000266964)

Protein

Protein identifiers

Sodium/potassium-transporting ATPase subunit gamma — P54710 (reviewed: P54710)

Alternative names: FXYD domain-containing ion transport regulator 2, Sodium pump gamma chain

All UniProt accessions (1): P54710

UniProt curated annotations — full annotation on UniProt →

Function. May be involved in forming the receptor site for cardiac glycoside binding or may modulate the transport function of the sodium ATPase.

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

Subcellular location. Membrane.

Tissue specificity. Expressed in the distal convoluted tubule in the kidney. Found on basolateral membranes of nephron epithelial cells.

Disease relevance. Hypomagnesemia 2 (HOMG2) [MIM:154020] A disorder due to primary renal wasting of magnesium. Plasma levels of other electrolytes are normal. The only abnormality found, in addition to low magnesium levels, is lowered renal excretion of calcium resulting in hypocalciuria. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the FXYD family.

Isoforms (2)

UniProt ID	Names	Canonical?
P54710-1	1, A	yes
P54710-2	2, B

RefSeq proteins (2): NP_001671, NP_067614 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000272	Ion-transport_regulator_FXYD	Family
IPR047282	ATNG	Family
IPR047297	FXYD_motif	Conserved_site

Pfam: PF02038

UniProt features (6 total): chain 1, transmembrane region 1, splice variant 1, sequence variant 1, helix 1, strand 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
7E20	ELECTRON MICROSCOPY	2.7
7E21	ELECTRON MICROSCOPY	2.9
7E1Z	ELECTRON MICROSCOPY	3.2
2MKV	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P54710-F1	76.04	0.36

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: 236 (showing top): GOBP_POTASSIUM_ION_TRANSPORT, GOBP_ESTABLISHMENT_OR_MAINTENANCE_OF_TRANSMEMBRANE_ELECTROCHEMICAL_GRADIENT, GRUETZMANN_PANCREATIC_CANCER_DN, GOBP_SODIUM_ION_TRANSMEMBRANE_TRANSPORT, ENK_UV_RESPONSE_KERATINOCYTE_UP, MODULE_64, GOBP_POTASSIUM_ION_HOMEOSTASIS, GOBP_HYPEROSMOTIC_RESPONSE, HNF1_Q6, GOBP_POSITIVE_REGULATION_OF_SODIUM_ION_TRANSPORT, XU_HGF_SIGNALING_NOT_VIA_AKT1_48HR_DN, GOBP_POSITIVE_REGULATION_OF_TRANSMEMBRANE_TRANSPORT, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_REGULATION_OF_SODIUM_ION_TRANSPORT, NFKB_Q6

GO Biological Process (15): intracellular sodium ion homeostasis (GO:0006883), negative regulation of cell population proliferation (GO:0008285), establishment or maintenance of transmembrane electrochemical gradient (GO:0010248), intracellular potassium ion homeostasis (GO:0030007), sodium ion export across plasma membrane (GO:0036376), transmembrane transport (GO:0055085), cellular hyperosmotic salinity response (GO:0071475), proton transmembrane transport (GO:1902600), positive regulation of sodium ion export across plasma membrane (GO:1903278), potassium ion import across plasma membrane (GO:1990573), monoatomic ion transport (GO:0006811), potassium ion transport (GO:0006813), sodium ion transport (GO:0006814), regulation of monoatomic ion transport (GO:0043269), obsolete inorganic cation transmembrane transport (GO:0098662)

GO Molecular Function (5): ATPase activator activity (GO:0001671), sodium channel regulator activity (GO:0017080), protein-macromolecule adaptor activity (GO:0030674), protein binding (GO:0005515), ion channel regulator activity (GO:0099106)

GO Cellular Component (5): plasma membrane (GO:0005886), sodium:potassium-exchanging ATPase complex (GO:0005890), basolateral plasma membrane (GO:0016323), extracellular exosome (GO:0070062), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-8 pathways:

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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular monoatomic cation homeostasis	2
transport	2
metal ion transport	2
sodium ion homeostasis	1
cell population proliferation	1
regulation of cell population proliferation	1
negative regulation of cellular process	1
monoatomic ion transmembrane transport	1
potassium ion homeostasis	1
sodium ion transmembrane transport	1
export across plasma membrane	1
cellular process	1
hyperosmotic salinity response	1
cellular response to salt stress	1
cellular hyperosmotic response	1
monoatomic cation transmembrane transport	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
potassium ion transmembrane transport	1
inorganic cation import across plasma membrane	1
monoatomic ion transport	1
regulation of transport	1
ATP-dependent activity	1
molecular function activator activity	1
sodium channel activity	1
ion channel regulator activity	1
protein binding	1
molecular adaptor activity	1
binding	1
monoatomic ion channel activity	1
channel regulator activity	1
membrane	1
cell periphery	1
cation-transporting ATPase complex	1
plasma membrane protein complex	1
basal plasma membrane	1
plasma membrane region	1
extracellular vesicle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

772 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FXYD2	CLDN16	Q9Y5I7	923
FXYD2	ATP1A1	P05023	885
FXYD2	ATP1A3	P13637	885
FXYD2	ATP1A4	Q13733	874
FXYD2	CLDN19	Q8N6F1	853
FXYD2	ATP1B1	P05026	833
FXYD2	SLC12A3	P55017	828
FXYD2	FXYD4	P59646	777
FXYD2	TRPM6	Q9BX84	719
FXYD2	ATP2A1	O14983	680
FXYD2	FXYD3	Q14802	680
FXYD2	FXYD5	Q96DB9	674
FXYD2	SLC37A4	O43826	654
FXYD2	CNNM2	Q9H8M5	570
FXYD2	IL10RA	Q13651	549
FXYD2	KMT2A	Q03164	549

IntAct

8 interactions, top by confidence:

A	B	Type	Score
ATP1A1	ATP1B1	psi-mi:“MI:0915”(physical association)	0.910
	SHTN1	psi-mi:“MI:0914”(association)	0.350
	TMEM223	psi-mi:“MI:0914”(association)	0.350

BioGRID (10): FXYD2 (Synthetic Lethality), FXYD2 (Two-hybrid), FXYD2 (Two-hybrid), FXYD2 (Affinity Capture-MS), FXYD2 (Affinity Capture-MS), FXYD2 (Affinity Capture-MS), FXYD2 (PCA), FXYD2 (PCA), RRS1 (Two-hybrid), FXYD2 (Affinity Capture-MS)

ESM2 similar proteins: D4A6L0, I3LMB3, O00168, O73698, O76095, O77049, O88823, O88824, O97797, P0C851, P54710, P56513, P59645, P59646, Q04645, Q04646, Q04679, Q04680, Q08CB3, Q14802, Q1RMB5, Q1XF11, Q3MHZ5, Q3SZX0, Q3UPR0, Q4R566, Q5RB29, Q5T848, Q61835, Q63113, Q66IQ1, Q6X9T8, Q70RD5, Q810F0, Q86XR5, Q8C419, Q8K467, Q8NEW7, Q8QZT4, Q8R143

Diamond homologs: G1TZA0, I3LMB3, O00168, O08589, O13001, O97797, P54710, P56513, P58549, P58550, P59645, P59646, P59647, P59648, P59649, Q04645, Q04646, Q04679, Q04680, Q14802, Q3MHZ5, Q3SZX0, Q3ZBJ3, Q4R566, Q5RB29, Q61835, Q63113, Q91XV6, Q96DB9, Q9D164, Q9D2W0, Q9H0Q3, Q9Z239, W5P3P0, P97808, C0HJJ0

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
HNF1B	“up-regulates quantity by expression”	FXYD2	“transcriptional regulation”
PCBD1	“up-regulates quantity by expression”	FXYD2	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	18
Likely benign	26
Benign	18

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
7684	NM_001680.5(FXYD2):c.121G>A (p.Gly41Arg)	Pathogenic

SpliceAI

1240 predictions. Top by Δscore:

Variant	Effect	Δscore
11:117820697:C:CC	acceptor_gain	1.0000
11:117820855:TCA:T	donor_loss	1.0000
11:117820855:TCACC:T	donor_loss	1.0000
11:117820857:A:T	donor_loss	1.0000
11:117820897:T:C	acceptor_gain	1.0000
11:117820897:T:TC	acceptor_gain	1.0000
11:117822402:TTA:T	donor_loss	1.0000
11:117822403:TA:T	donor_loss	1.0000
11:117822404:A:AC	donor_gain	1.0000
11:117822405:C:CT	donor_gain	1.0000
11:117822484:C:CT	acceptor_gain	1.0000
11:117822485:G:T	acceptor_gain	1.0000
11:117822572:C:CT	acceptor_gain	1.0000
11:117820664:A:T	donor_loss	0.9900
11:117820665:C:CT	donor_loss	0.9900
11:117820665:CCTG:C	donor_gain	0.9900
11:117820692:TTTGC:T	acceptor_gain	0.9900
11:117820693:TTGC:T	acceptor_gain	0.9900
11:117820694:TGCCT:T	acceptor_loss	0.9900
11:117820695:GCCTG:G	acceptor_loss	0.9900
11:117820697:CTG:C	acceptor_loss	0.9900
11:117820698:T:C	acceptor_loss	0.9900
11:117820891:TCTGC:T	acceptor_loss	0.9900
11:117820893:TGCC:T	acceptor_loss	0.9900
11:117820895:CC:C	acceptor_loss	0.9900
11:117820895:CCT:C	acceptor_gain	0.9900
11:117820896:C:CA	acceptor_loss	0.9900
11:117820896:C:CC	acceptor_gain	0.9900
11:117820896:CTT:C	acceptor_loss	0.9900
11:117822399:CACTT:C	donor_loss	0.9900

AlphaMissense

430 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:117822435:G:T	A37D	0.997
11:117822465:C:G	R27P	0.996
11:117822423:C:T	G41E	0.994
11:117822424:C:G	G41R	0.994
11:117822424:C:T	G41R	0.994
11:117822444:G:T	A34D	0.994
11:117822468:A:T	V26D	0.993
11:117822686:G:C	F19L	0.991
11:117822686:G:T	F19L	0.991
11:117822688:A:G	F19L	0.991
11:117822466:G:T	R27S	0.990
11:117822453:A:G	L31P	0.988
11:117822687:A:C	F19C	0.988
11:117822441:C:T	G35E	0.986
11:117822456:C:T	G30D	0.984
11:117822442:C:G	G35R	0.983
11:117822442:C:T	G35R	0.983
11:117822459:C:T	G29E	0.983
11:117822420:A:G	L42P	0.982
11:117822431:G:C	F38L	0.981
11:117822431:G:T	F38L	0.981
11:117822433:A:G	F38L	0.981
11:117822420:A:T	L42H	0.975
11:117822420:A:C	L42R	0.974
11:117822426:A:T	V40E	0.972
11:117822457:C:G	G30R	0.971
11:117822477:T:C	Y23C	0.970
11:117822438:A:C	L36R	0.969
11:117822480:T:A	D22V	0.968
11:117822411:A:T	L45H	0.963

dbSNP variants (sampled 300 via entrez): RS1000349117 (11:117827469 G>A), RS1000486413 (11:117827331 C>T), RS1000549075 (11:117825747 G>C,T), RS1000820143 (11:117826244 G>A,T), RS1001652061 (11:117822198 A>C,T), RS1001717937 (11:117828152 A>G), RS1001871070 (11:117826630 G>A,C), RS1002122596 (11:117822387 T>TGGGGGG), RS1002382730 (11:117821242 G>A,T), RS1002427268 (11:117826163 A>G), RS1002715449 (11:117823562 C>G,T), RS1002799052 (11:117823771 G>A), RS1002940978 (11:117828994 G>A,C,T), RS1003091264 (11:117828791 G>A), RS1003432258 (11:117827522 T>C)

Disease associations

OMIM: gene MIM:601814 | disease phenotypes: MIM:154020

GenCC curated gene-disease

Disease	Classification	Inheritance
renal hypomagnesemia 2	Strong	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
renal hypomagnesemia 2	Moderate	AD

Mondo (1): renal hypomagnesemia 2 (MONDO:0007937)

Orphanet (1): Autosomal dominant primary hypomagnesemia with hypocalciuria (Orphanet:34528)

HPO phenotypes

9 total (9 of 9 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000083	Renal insufficiency
HP:0000934	Chondrocalcinosis
HP:0001250	Seizure
HP:0002900	Hypokalemia
HP:0002917	Hypomagnesemia
HP:0003127	Hypocalciuria
HP:0003324	Generalized muscle weakness
HP:0005567	Renal magnesium wasting

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST003997_18	Myopia	1.000000e-11
GCST006993_11	Hippocampal volume in Alzheimer’s disease dementia	1.000000e-07
GCST010002_199	Refractive error	3.000000e-34

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0005035	hippocampal volume

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C537152	Hypomagnesemia 2, renal (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

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

Molecules with ChEMBL bioactivity

5 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 160,774 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1503	OMEPRAZOLE	4	52,284
CHEMBL1751	DIGOXIN	4	67,342
CHEMBL254219	DIGITOXIN	4	16,757
CHEMBL480	LANSOPRAZOLE	4	24,317
CHEMBL2068971	ROSTAFUROXIN	2	74

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

GtoPdb / IUPHAR curated pharmacology

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

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

ChEMBL bioactivities

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

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

PubChem BioAssay actives

210 with measured affinity, of 373 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases expression, affects methylation	5
Aflatoxin B1	increases expression, affects expression	3
sodium arsenite	affects methylation, decreases expression	2
Tetrachlorodibenzodioxin	increases expression	2
aristolochic acid I	decreases expression	1
dicrotophos	decreases expression	1
propionaldehyde	decreases expression	1
bisphenol A	affects expression	1
ethyl-p-hydroxybenzoate	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
manganese chloride	increases expression	1
aflatoxin B2	increases methylation	1
cupric chloride	affects expression	1
jinfukang	affects cotreatment, increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Zoledronic Acid	decreases expression	1
Leflunomide	decreases expression	1
Acetaminophen	increases expression	1
Arsenic	affects expression	1
Barium	decreases activity	1
Benzene	decreases expression	1
Calcium	decreases reaction, increases transport, decreases activity	1
Cisplatin	affects cotreatment, increases expression	1
Deoxyglucose	decreases reaction, increases transport	1
Inulin	decreases reaction, increases transport	1
Manganese	increases expression	1
Methyl Methanesulfonate	increases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Quercetin	increases expression	1
Silicon Dioxide	decreases expression	1

ChEMBL screening assays

45 unique, capped per target: 45 binding

Representative assays (with source publication via chembl_document):

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

Clinical trials (associated diseases)

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