SLC9A3

Summary

SLC9A3 (solute carrier family 9 member A3, HGNC:11073) is a protein-coding gene on chromosome 5p15.33, encoding Sodium/hydrogen exchanger 3 (P48764). Plasma membrane Na(+)/H(+) antiporter.

The protein encoded by this gene is an epithelial brush border Na/H exchanger that uses an inward sodium ion gradient to expel acids from the cell. Defects in this gene are a cause of congenital secretory sodium diarrhea. Pseudogenes of this gene exist on chromosomes 10 and 22.

Source: NCBI Gene 6550 — RefSeq curated summary.

At a glance

• Gene–disease (curated): congenital secretory sodium diarrhea 8 (Strong, GenCC) — +2 more curated relationships
• GWAS associations: 10
• Clinical variants (ClinVar): 825 total — 16 pathogenic, 5 likely-pathogenic
• Phenotypes (HPO): 50
• Druggable target: yes — 3 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_004174

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11073
Approved symbol	SLC9A3
Name	solute carrier family 9 member A3
Location	5p15.33
Locus type	gene with protein product
Status	Approved
Aliases	NHE-3
Ensembl gene	ENSG00000066230
Ensembl biotype	protein_coding
OMIM	182307
Entrez	6550

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 3 protein_coding, 1 retained_intron

ENST00000264938, ENST00000507407, ENST00000514375, ENST00000644203

RefSeq mRNA: 2 — MANE Select: NM_004174 NM_001284351, NM_004174

CCDS: CCDS3855, CCDS64116

Canonical transcript exons

ENST00000264938 — 17 exons

Exon	Start	End
ENSE00000515952	475561	475671
ENSE00000719045	474883	475132
ENSE00000719053	476020	476092
ENSE00000719060	476202	476378
ENSE00000719068	476543	476672
ENSE00000719076	477332	477444
ENSE00000719082	479836	479965
ENSE00000719099	482548	482750
ENSE00000719104	483262	483482
ENSE00000719108	484520	484697
ENSE00000719113	485153	485231
ENSE00000892901	488316	488476
ENSE00001169533	491769	492071
ENSE00001198340	524112	524449
ENSE00001272455	470456	473382
ENSE00003516705	481565	481635
ENSE00003667052	482068	482157

Expression profiles

Bgee: expression breadth ubiquitous, 164 present calls, max score 95.97.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 1.1927 / max 318.0121, expressed in 108 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
60716	1.1927	108

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of transverse colon	UBERON:0004991	95.97	gold quality
sural nerve	UBERON:0015488	94.28	gold quality
metanephros cortex	UBERON:0010533	92.84	gold quality
gall bladder	UBERON:0002110	92.83	gold quality
body of stomach	UBERON:0001161	86.79	gold quality
transverse colon	UBERON:0001157	85.52	gold quality
small intestine Peyer’s patch	UBERON:0003454	84.40	gold quality
nerve	UBERON:0001021	84.34	gold quality
tibial nerve	UBERON:0001323	84.34	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	83.54	gold quality
stomach	UBERON:0000945	82.31	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.60	gold quality
small intestine	UBERON:0002108	81.37	gold quality
right uterine tube	UBERON:0001302	80.30	gold quality
adult mammalian kidney	UBERON:0000082	79.55	gold quality
vermiform appendix	UBERON:0001154	79.12	gold quality
esophagus mucosa	UBERON:0002469	76.45	gold quality
lower esophagus mucosa	UBERON:0035834	76.07	gold quality
rectum	UBERON:0001052	75.86	gold quality
fundus of stomach	UBERON:0001160	75.80	gold quality
right hemisphere of cerebellum	UBERON:0014890	75.07	gold quality
intestine	UBERON:0000160	73.98	gold quality
skin of abdomen	UBERON:0001416	73.07	gold quality
cortex of kidney	UBERON:0001225	72.58	gold quality
colon	UBERON:0001155	72.46	gold quality
stromal cell of endometrium	CL:0002255	72.15	gold quality
cerebellar hemisphere	UBERON:0002245	71.68	gold quality
large intestine	UBERON:0000059	71.58	gold quality
cerebellar cortex	UBERON:0002129	71.57	gold quality
esophagus	UBERON:0001043	71.48	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.60

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): BMAL1, CDX2, CLOCK, EGR1, GATA5, PPARG, SP1, SP3, STAT3

miRNA regulators (miRDB)

32 targeting SLC9A3, 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-4283	100.00	66.42	2097
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-1200	99.71	70.42	1838
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-762	99.58	66.61	1994
HSA-MIR-4498	99.47	67.42	2360
HSA-MIR-3960	99.41	66.11	96
HSA-MIR-125A-5P	99.36	70.59	1640
HSA-MIR-125B-5P	99.36	70.36	1662
HSA-MIR-328-5P	99.08	64.65	1000
HSA-MIR-5001-5P	99.05	66.76	1972
HSA-MIR-4324	99.04	70.14	1569
HSA-MIR-7113-3P	98.75	65.71	1120
HSA-MIR-330-5P	98.73	67.63	1788
HSA-MIR-8072	98.27	66.24	83
HSA-MIR-326	98.25	66.44	1565
HSA-MIR-5087	98.01	69.09	965
HSA-MIR-4468	98.01	66.85	1187
HSA-MIR-892B	98.00	67.11	821
HSA-MIR-10400-5P	96.91	66.00	56
HSA-MIR-4467	96.51	64.44	69
HSA-MIR-6769A-3P	94.91	61.36	412
HSA-MIR-744-5P	93.78	65.29	230
HSA-MIR-10396A-5P	93.49	65.54	172
HSA-MIR-4649-5P	93.02	63.85	141
HSA-MIR-6729-5P	93.02	62.76	138
HSA-MIR-4508	90.37	59.62	240
HSA-MIR-3178	89.40	60.05	100

Literature-anchored findings (GeneRIF, showing 40)

• studies suggest that the NHE3 expression is regulated by a combination of cis elements and their cognate transcription factors that include the AP-2 and Sp1 family members (PMID:11841999)
• NHE3 is important for cAMP sensitivity of receptor-mediated, clathrin-dependent endocytosis (PMID:12167607)
• Functional NHE3 activity is required to allow optimal absorption of dipeptides across the human intestinal epithelium. (PMID:12397398)
• Albumin-induced increases in expression and activity of NHE3 in proximal tubule cells suggest a possible mechanism for Na+ retention in response to proteinuria. (PMID:12799307)
• binding of the KOR to NHERF-1/EBP50 facilitates oligomerization of NHERF-1/EBP50, leading to stimulation of NHE3. (PMID:15070904)
• Ezrin is necessary for NHE3 recruitment to the apical membrane and NHE3-dependent pH(i) increases triggered by Na(+)-glucose cotransport. (PMID:15197272)
• high degree of structural conservation of the NHE3 gene (PMID:15201541)
• Akt2-dependent ezrin phosphorylation leads to NHE3 translocation and activation (PMID:15531580)
• Amino acid uptake via hPAT1 is inhibited by activators of the cAMP pathway indirectly through inhibition of NHE3 activity. (PMID:15754324)
• PLG has the potential to simultaneously regulate calcium signaling pathways and regulate pHi via an association with NHE3 linked to DPP IV, necessary for tumor cell proliferation and invasiveness (PMID:15911629)
• Co-expression of NHE3 with SLC26A3 supports its function and may have an impact on pathophysiology of male subfertility both in congenital chloride diarrhoea and in cystic fibrosis, as well as spermatoceles. (PMID:16421216)
• Transcriptional stimulation of the human NHE3 promoter activity by PMA: PKC independence and involvement of the transcription factor EGR-1. (PMID:16464174)
• These data indicate that IFN-gamma and TNF-alpha may repress the NHE3 promoter activity in C2BBe1 cells by PKA-mediated phosphorylation of Sp1 and Sp3 transcription factors. (PMID:16760259)
• Acute effect of glucocorticoids on NHE3 is mediated by a glucocorticoid receptor dependent mechanism that activates SGK1 in a nongenomic manner. (PMID:16971495)
• NHE3 expression is required for dome formation in confluent polarized epithelial cells. (PMID:17276988)
• Syt I plays a pivotal role in mediating cAMP- and Ca(2+)-induced endocytosis of NHE3 (but not in inhibition of activity) through cargo recognition of NHE3 and subsequent recruitment of AP2-clathrin assembly required for membrane endocytosis (PMID:17307723)
• Our data suggest that the differential regulation of NHE3 gene expression by NaB and IFN-gamma/TNF-alpha is mediated through alternative pathways that converge on Sp1/Sp3. (PMID:17540780)
• No mutation was found in the coding regions and intron-exon boundaries of the genes for CA II, CA IV, CA XIV, kNCB1, NHE3, NHE8, NHRF1, NHRF2 and SLC26A6 amplified from genomic DNA of family members with pRTA. (PMID:17881426)
• Level of NHE3 expression in brainstem tissue may contribute to the vulnerability of infants for sudden infant death syndrome. (PMID:18085326)
• Enteropathogenic Escherichia coli EspF was found to be responsible for decreased NHE3 activity; however, neither EspF-induced apoptosis nor the interaction of EspF with sorting nexin-9, an endocytic protein, were involved. (PMID:18433466)
• CK2 binds to the NHE3 C terminus and stimulates basal NHE3 activity by phosphorylating a separate single site on the NHE3 C terminus (PMID:18614797)
• The role of aldosterone in sodium absorption by intestinal cells via multiple changes in cellular processes, including SGK1 NHE3 and sodium pump activity is reported. (PMID:18801914)
• Functional coupling of the downregulated in adenoma Cl-/base exchanger DRA and the apical Na+/H+ exchangers NHE2 and NHE3 in intestinal epithelial cells. (PMID:19056765)
• These data indicate that 5-HT suppresses the transcriptional activity of the NHE3 promoter and this effect may be mediated by PKCalpha and modulation of DNA-binding affinities of Sp1 and Sp3. (PMID:19303862)
• AII increases, in an aldosterone independent fashion, activity and expression of the apical sodium/hydrogen exchanger NHE3 in cultured Caco2BBE cells. (PMID:19338654)
• Report morphological adaptation with preserved proliferation/NHE3 content in the colon of patients with short bowel syndrome. (PMID:19389806)
• The PLC-gamma-binding site in NHE3 was identified (amino acids 586-605) and shown to be a critical regulatory domain for protein complex formation. (PMID:19473983)
• The functional and molecular expression of NHEs in cultured human endolymphatic sac (ES) epithelial cells was determined and the effect of IFN-gamma on NHE function, was examined. (PMID:19479940)
• NHERF3 colocalizes and directly binds NHE3 at the plasma membrane under basal conditions. (PMID:19535329)
• Our findings suggest the involvement of polymorphisms in the NHE3 gene and promoter in cases of SIDS, which may result in an overexpression of NHE3 in the medulla oblongata. (PMID:19772970)
• intestinal epithelial Syt 1 plays an important role in cAMP-stimulated endocytosis of apical NHE3 through cAMP-dependent phosphorylation of S605 that is required for NHE3 and Syt 1 association (PMID:19926819)
• betaPix up-regulates NHE3 membrane expression and activity by Shank2-mediated protein-protein interaction and by activating Rho GTPases in the apical regions of epithelial cells (PMID:20080968)
• single-nucleotide polymorphisms and haplotypes in SLC9A3 in whites are significantly associated with preeclampsia. (PMID:20691413)
• the potential role of SLC9A3 as a modifier of CF lung disease severity was examined. (PMID:20967843)
• It was shown that lysophosphatidic acid 5 receptor transactivated the epidermal growth factor receptor and that inhibition of epidermal growth factor receptor blocked lysophosphatidic acid 5 receptor-dependent activation of NHE3. (PMID:21832242)
• SLC9A3 is downregulated in patients with ulcerative colitis. (PMID:22447429)
• Single nucleotide polymorphism in SLC9A3 gene is associated with cystic fibrosis. (PMID:22466613)
• In conclusion, LA-induced increase in NHE3 expression may contribute to the upregulation of intestinal electrolyte absorption and might underlie the potential antidiarrheal effects of probiotics. (PMID:23086913)
• High urine NHE3 is associated with ischemic acute tubular necrosis than other causes of acute kidney injury. (PMID:23324582)
• Data suggest that EGFR (epidermal growth factor receptor) activation mediates PPARG- (peroxisome proliferator-activated receptor gamma-) induced sodium and water reabsorption via upregulation of NHE3 and AQP1 (aquaporin 1) in proximal tubules. (PMID:23370527)

Cross-species orthologs

10 orthologs

Organism	Symbol	Gene ID
danio_rerio	slc9a3.2	ENSDARG00000036722
danio_rerio	slc9a3.1	ENSDARG00000058498
mus_musculus	Slc9a3	ENSMUSG00000036123
rattus_norvegicus	Slc9a3	ENSRNOG00000015159
drosophila_melanogaster	Nhe3	FBGN0028703
drosophila_melanogaster	Nhe2	FBGN0040297
caenorhabditis_elegans		WBGENE00003730
caenorhabditis_elegans		WBGENE00003732
caenorhabditis_elegans		WBGENE00003733
caenorhabditis_elegans		WBGENE00003734

Paralogs (10): SLC9A7 (ENSG00000065923), SLC9A1 (ENSG00000090020), SLC9A2 (ENSG00000115616), SLC9A5 (ENSG00000135740), SLC9C2 (ENSG00000162753), SLC9C1 (ENSG00000172139), SLC9A4 (ENSG00000180251), SLC9A9 (ENSG00000181804), SLC9A8 (ENSG00000197818), SLC9A6 (ENSG00000198689)

Protein

Protein identifiers

Sodium/hydrogen exchanger 3 — P48764 (reviewed: P48764)

Alternative names: Na(+)/H(+) exchanger 3, Solute carrier family 9 member 3

All UniProt accessions (2): P48764, A0A2R8Y780

UniProt curated annotations — full annotation on UniProt →

Function. Plasma membrane Na(+)/H(+) antiporter. Exchanges intracellular H(+) ions for extracellular Na(+) in 1:1 stoichiometry, playing a key role in salt and fluid absorption and pH homeostasis. Major apical Na(+)/H(+) exchanger in kidney and intestine playing an important role in renal and intestine Na(+) absorption and blood pressure regulation.

Subunit / interactions. Homodimer. Found in the forms of complex and dynamic macromolecular complexes. Binds NHERF1 and NHERF2. Interacts with CHP1; increases SLC9A3 trafficking and activity at the plasma membrane. Interacts with CHP2 and SHANK2. Interacts with PDZK1 (via C-terminal PDZ domain). Interacts with NHERF4 and interaction decrease in response to elevated calcium ion levels. Interacts with AHCYL1; the interaction is required for SLC9A3 activity. Interacts with SNX27 (via PDZ domains); directs SLC9A3 membrane insertion from early endosomes to the plasma membrane. Interacts with EZR; interaction targets SLC9A3 to the apical membrane.

Subcellular location. Apical cell membrane. Cell membrane. Recycling endosome membrane. Early endosome membrane.

Post-translational modifications. Phosphorylated by PKA, which inhibits activity. Phosphorylation at Ser-663 by SGK1 is associated with increased abundance at the cell membrane. Phosphorylation at Ser-718 by CSNK2A1 regulates SLC9A3 activity through the formation of multiple signaling complexes.

Disease relevance. Diarrhea 8, secretory sodium, congenital (DIAR8) [MIM:616868] A disease characterized by watery secretory diarrhea with prenatal onset, prominent abdominal distension after birth due to dilated fluid-filled loops of intestine, elevated fecal sodium concentrations and low urinary sodium concentrations. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Seems to switch between active and inactive modes in response to various stimuli. Activated directly or indirectly by membrane phosphatidylinositol (PIs). Regulated by a variety of auxiliary proteins, which facilitate the maturation, cell surface expression and function of the transporter. Inhibited specifically by the drug tenapanor.

Domain organisation. The C-terminal intracellular domain is subject to extensive post-translational modifications and binding partner interactions which regulate transporter activity, scaffolding functions, downstream events and localization.

Similarity. Belongs to the monovalent cation:proton antiporter 1 (CPA1) transporter (TC 2.A.36) family.

Isoforms (2)

UniProt ID	Names	Canonical?
P48764-1	1	yes
P48764-2	2

RefSeq proteins (2): NP_001271280, NP_004165* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004709	NaH_exchanger	Family
IPR006153	Cation/H_exchanger_TM	Domain
IPR018410	Na/H_exchanger_3/5	Family
IPR018422	Cation/H_exchanger_CPA1	Family

Pfam: PF00999

Catalyzed reactions (Rhea), 1 shown:

• Na(+)(in) + H(+)(out) = Na(+)(out) + H(+)(in) (RHEA:29419)

UniProt features (102 total): helix 29, topological domain 14, transmembrane region 13, turn 8, modified residue 8, binding site 7, sequence variant 6, region of interest 5, mutagenesis site 5, compositionally biased region 2, signal peptide 1, chain 1, glycosylation site 1, splice variant 1, strand 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
7X2U	ELECTRON MICROSCOPY	3.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P48764-F1	66.04	0.16

Functional residue map

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

Ligand- & substrate-binding residues (7): 138; 141; 142; 398; 497; 498; 500

Post-translational modifications (8): 555, 563, 592, 607, 663, 718, 810, 813

Glycosylation sites (1): 241

Mutagenesis-validated functional residues (5):

Position	Phenotype
397	abolishes sodium:proton antiporter activity. does not affect cell membrane expression or localization to recycling endos
500	increases sodium:proton antiporter activity.
635	decreases cell membrane expression. increases sodium:proton antiporter activity.
637	increases sodium:proton antiporter activity; when associated with a-638.
638	increases sodium:proton antiporter activity; when associated with a-638.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-425986	Sodium/Proton exchangers
R-HSA-382551	Transport of small molecules
R-HSA-425393
R-HSA-425407	SLC-mediated transmembrane transport

MSigDB gene sets: 223 (showing top): GOBP_POTASSIUM_ION_TRANSPORT, BENPORATH_ES_WITH_H3K27ME3, PEREZ_TP63_TARGETS, GOBP_SODIUM_ION_TRANSMEMBRANE_TRANSPORT, GOCC_CELL_SURFACE, TGACCTY_ERR1_Q2, GOBP_MONOATOMIC_CATION_TRANSPORT, COUP_01, PID_RHOA_PATHWAY, TAKEDA_TARGETS_OF_NUP98_HOXA9_FUSION_10D_UP, GOBP_INTRACELLULAR_SODIUM_ION_HOMEOSTASIS, NIKOLSKY_BREAST_CANCER_5P15_AMPLICON, GOBP_SODIUM_ION_HOMEOSTASIS, GOMF_PROTON_TRANSMEMBRANE_TRANSPORTER_ACTIVITY, GOBP_REGULATION_OF_PH

GO Biological Process (10): monoatomic ion transport (GO:0006811), regulation of intracellular pH (GO:0051453), potassium ion transmembrane transport (GO:0071805), sodium ion import across plasma membrane (GO:0098719), monoatomic cation transport (GO:0006812), sodium ion transport (GO:0006814), regulation of pH (GO:0006885), sodium ion transmembrane transport (GO:0035725), transmembrane transport (GO:0055085), proton transmembrane transport (GO:1902600)

GO Molecular Function (7): sodium:proton antiporter activity (GO:0015385), potassium:proton antiporter activity (GO:0015386), PDZ domain binding (GO:0030165), phosphatidylinositol binding (GO:0035091), identical protein binding (GO:0042802), protein binding (GO:0005515), antiporter activity (GO:0015297)

GO Cellular Component (11): early endosome (GO:0005769), plasma membrane (GO:0005886), brush border (GO:0005903), cell surface (GO:0009986), apical plasma membrane (GO:0016324), brush border membrane (GO:0031526), early endosome membrane (GO:0031901), recycling endosome membrane (GO:0055038), extracellular exosome (GO:0070062), endosome (GO:0005768), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Metal ion SLC transporters	1
Transport of small molecules	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
monoatomic cation transmembrane transport	3
transport	2
metal cation:proton antiporter activity	2
apical part of cell	2
cellular anatomical structure	2
endosome membrane	2
regulation of pH	1
intracellular monoatomic cation homeostasis	1
regulation of biological quality	1
potassium ion transport	1
sodium ion transmembrane transport	1
inorganic cation import across plasma membrane	1
monoatomic ion transport	1
metal ion transport	1
monoatomic cation homeostasis	1
biological regulation	1
sodium ion transport	1
cellular process	1
sodium ion transmembrane transporter activity	1
solute:potassium antiporter activity	1
protein domain specific binding	1
anion binding	1
protein binding	1
binding	1
secondary active transmembrane transporter activity	1
endosome	1
membrane	1
cell periphery	1
microvillus	1
cluster of actin-based cell projections	1
plasma membrane region	1
brush border	1
apical plasma membrane	1
cell projection membrane	1
early endosome	1
recycling endosome	1
extracellular vesicle	1
endomembrane system	1
cytoplasmic vesicle	1

Protein interactions and networks

STRING

1532 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLC9A3	NHERF2	Q15599	993
SLC9A3	NHERF1	O14745	992
SLC9A3	PDZK1	Q5T2W1	941
SLC9A3	SLC26A3	P40879	902
SLC9A3	SLC26A6	Q9BXS9	898
SLC9A3	EZR	P15311	885
SLC9A3	SLC12A1	Q13621	836
SLC9A3	CUBN	O60494	835
SLC9A3	CFTR	P13569	826
SLC9A3	CLCN5	P51795	814
SLC9A3	LRP2	P98164	801
SLC9A3	SLC5A2	P31639	794
SLC9A3	SLC4A4	Q9Y6R1	789
SLC9A3	CA2	P00918	756
SLC9A3	SLC5A1	P13866	732

IntAct

134 interactions, top by confidence:

A	B	Type	Score
SLC9A3	MAST2	psi-mi:“MI:0407”(direct interaction)	0.660
MAST2	SLC9A3	psi-mi:“MI:0915”(physical association)	0.660
SLC9A3	MAST2	psi-mi:“MI:0915”(physical association)	0.660
SLC9A3	CHP1	psi-mi:“MI:0407”(direct interaction)	0.650
SLC9A3	SCRIB	psi-mi:“MI:0407”(direct interaction)	0.590
SLC9A3	PDZK1	psi-mi:“MI:0407”(direct interaction)	0.440
SLC9A3	NHERF2	psi-mi:“MI:0407”(direct interaction)	0.440
SHANK1	SLC9A3	psi-mi:“MI:0407”(direct interaction)	0.440
SLC9A3	MAST1	psi-mi:“MI:0407”(direct interaction)	0.440
SLC9A3	GRID2IP	psi-mi:“MI:0407”(direct interaction)	0.440
SLC9A3	PICK1	psi-mi:“MI:0407”(direct interaction)	0.440
SLC9A3	ARHGAP21	psi-mi:“MI:0407”(direct interaction)	0.440
APBA3	SLC9A3	psi-mi:“MI:0407”(direct interaction)	0.440
MPP2	SLC9A3	psi-mi:“MI:0407”(direct interaction)	0.440
SLC9A3	DLG4	psi-mi:“MI:0407”(direct interaction)	0.440
SLC9A3	CASK	psi-mi:“MI:0407”(direct interaction)	0.440
SLC9A3	SNTB1	psi-mi:“MI:0407”(direct interaction)	0.440
SLC9A3	MAGI3	psi-mi:“MI:0407”(direct interaction)	0.440
SLC9A3	MAGI2	psi-mi:“MI:0407”(direct interaction)	0.440
SLC9A3	PDZRN4	psi-mi:“MI:0407”(direct interaction)	0.440
SLC9A3	LNX2	psi-mi:“MI:0407”(direct interaction)	0.440
SLC9A3	MAGI1	psi-mi:“MI:0407”(direct interaction)	0.440
SLC9A3	GRIP1	psi-mi:“MI:0407”(direct interaction)	0.440
SLC9A3	TJP3	psi-mi:“MI:0407”(direct interaction)	0.440
SLC9A3	LNX1	psi-mi:“MI:0407”(direct interaction)	0.440
SLC9A3	GORASP1	psi-mi:“MI:0407”(direct interaction)	0.440
SLC9A3	TIAM2	psi-mi:“MI:0407”(direct interaction)	0.440
SLC9A3	PATJ	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (134): SLC9A3 (Affinity Capture-Western), SLC9A3 (Two-hybrid), SLC9A3 (Two-hybrid), SLC9A3 (Affinity Capture-Western), SLC9A3 (Reconstituted Complex), CHP2 (Affinity Capture-Western), SLC9A3 (Reconstituted Complex), CHP1 (Affinity Capture-Western), SLC9A3R2 (Reconstituted Complex), SLC9A3 (Affinity Capture-RNA), USP7 (Affinity Capture-Western), USP10 (Affinity Capture-Western), RAB5A (Affinity Capture-Western), SLC9A3 (Affinity Capture-RNA), SLC9A3 (Affinity Capture-MS)

ESM2 similar proteins: A0A0G2KQY6, A0A6I8PMZ8, A0JPN2, A4IGY6, A5D7L5, A7T1N0, B3DHU2, O43868, O75899, O88871, O94402, P04919, P0DX17, P23562, P26432, P26433, P48764, P55205, Q08E40, Q0DHJ5, Q0DWA9, Q0VCH8, Q15043, Q28C60, Q4VAE3, Q504Y0, Q5FVQ0, Q5FWH7, Q5RAB7, Q5Z413, Q6DCK1, Q6L8F3, Q6PI78, Q75N73, Q78IQ7, Q80T41, Q8K596, Q8VIH3, Q8W469, Q91W10

Diamond homologs: A1L3P4, B2RXE2, D3ZJ86, D4A7H1, F7B113, G3X939, M5A7P9, O13726, P19634, P23791, P26431, P26432, P26433, P26434, P48761, P48762, P48763, P48764, Q01345, Q04121, Q14940, Q28362, Q3ZAS0, Q4L208, Q4R8V4, Q552S0, Q56XP4, Q58916, Q5ZJ75, Q61165, Q68KI4, Q6AI14, Q84WG1, Q8BLV3, Q8BUE1, Q8BZ00, Q8IVB4, Q8R4D1, Q8RWU6, Q8S396

SIGNOR signaling

11 interactions.

A	Effect	B	Mechanism
SLC9A3	“down-regulates quantity”	hydron	relocalization
SLC9A3	“up-regulates quantity”	sodium(1+)	relocalization
PKA	“down-regulates activity”	SLC9A3	phosphorylation
AMPK	“down-regulates activity”	SLC9A3	phosphorylation
SGK1	“up-regulates activity”	SLC9A3	phosphorylation
MAST2	“down-regulates activity”	SLC9A3	phosphorylation
PRKG2	“down-regulates activity”	SLC9A3	phosphorylation
EGR1	“up-regulates quantity by expression”	SLC9A3	“transcriptional regulation”
SP1	“up-regulates quantity by expression”	SLC9A3	“transcriptional regulation”
SP3	“up-regulates quantity by expression”	SLC9A3	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 85 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
Ras activation upon Ca2+ influx through NMDA receptor	5	50.1×	2e-06
Unblocking of NMDA receptors, glutamate binding and activation	5	47.7×	2e-06
Negative regulation of NMDA receptor-mediated neuronal transmission	5	47.7×	2e-06
Assembly and cell surface presentation of NMDA receptors	10	44.5×	1e-12
Dopamine Neurotransmitter Release Cycle	5	43.5×	2e-06
Long-term potentiation	5	41.7×	3e-06
Neurexins and neuroligins	11	38.0×	7e-13
Protein-protein interactions at synapses	7	32.6×	1e-07

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	10	71.7×	4e-14
protein localization to synapse	6	56.7×	1e-07
receptor clustering	7	53.9×	1e-08
regulation of postsynaptic membrane neurotransmitter receptor levels	7	42.8×	4e-08
protein-containing complex assembly	9	12.7×	3e-06
cell-cell adhesion	10	12.5×	6e-07
regulation of small GTPase mediated signal transduction	5	8.9×	5e-03
chemical synaptic transmission	7	6.7×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	16
Likely pathogenic	5
Uncertain significance	266
Likely benign	457
Benign	43

Top pathogenic / likely-pathogenic (21)

Variant ID	HGVS	Classification
1358263	NM_004174.4(SLC9A3):c.796del (p.Val266fs)	Pathogenic
1455912	NC_000005.9:g.(?473494)(524437_?)del	Pathogenic
2111813	NM_004174.4(SLC9A3):c.1007_1011dup (p.Thr338fs)	Pathogenic
2203602	NM_004174.4(SLC9A3):c.1446+1G>A	Pathogenic
224595	NM_004174.4(SLC9A3):c.932C>T (p.Ala311Val)	Pathogenic
224596	NM_004174.4(SLC9A3):c.341TCT[3] (p.Phe117del)	Pathogenic
224597	NM_004174.4(SLC9A3):c.1145G>A (p.Arg382Gln)	Pathogenic
224600	NM_004174.4(SLC9A3):c.782dup (p.Thr262fs)	Pathogenic
2849118	NM_004174.4(SLC9A3):c.2376del (p.Tyr793fs)	Pathogenic
3255340	NM_004174.4(SLC9A3):c.1446+1delinsCA	Pathogenic
3255341	NM_004174.4(SLC9A3):c.1052dup (p.Met352fs)	Pathogenic
3651914	NM_004174.4(SLC9A3):c.1638C>A (p.Tyr546Ter)	Pathogenic
4715241	NM_004174.4(SLC9A3):c.1270del (p.Val424fs)	Pathogenic
4715548	NM_004174.4(SLC9A3):c.712G>T (p.Gly238Ter)	Pathogenic
4735948	NM_004174.4(SLC9A3):c.164_165insT (p.Tyr56fs)	Pathogenic
986310	NM_004174.4(SLC9A3):c.1214A>G (p.Asp405Gly)	Pathogenic
1348279	NM_004174.4(SLC9A3):c.1443_1446+150del	Likely pathogenic
2119078	NM_004174.4(SLC9A3):c.933-2A>G	Likely pathogenic
2757909	NM_004174.4(SLC9A3):c.676-2A>G	Likely pathogenic
3255342	NM_004174.4(SLC9A3):c.650C>T (p.Ser217Leu)	Likely pathogenic
3644985	NM_004174.4(SLC9A3):c.1357-1G>A	Likely pathogenic

SpliceAI

4036 predictions. Top by Δscore:

Variant	Effect	Δscore
5:475555:CCCCA:C	donor_loss	1.0000
5:475556:CCCA:C	donor_loss	1.0000
5:475557:CCAC:C	donor_loss	1.0000
5:475558:CA:C	donor_loss	1.0000
5:475559:ACCTG:A	donor_loss	1.0000
5:475560:CC:C	donor_loss	1.0000
5:475623:ATCT:A	donor_gain	1.0000
5:475667:CAAGT:C	acceptor_gain	1.0000
5:475669:AGT:A	acceptor_gain	1.0000
5:475672:C:CC	acceptor_gain	1.0000
5:475672:CT:C	acceptor_loss	1.0000
5:476015:CGCA:C	donor_loss	1.0000
5:476016:GCACC:G	donor_loss	1.0000
5:476017:CA:C	donor_loss	1.0000
5:476018:ACC:A	donor_loss	1.0000
5:476089:TTCT:T	acceptor_gain	1.0000
5:476090:TCTC:T	acceptor_loss	1.0000
5:476091:CT:C	acceptor_gain	1.0000
5:476093:C:A	acceptor_loss	1.0000
5:476093:C:CC	acceptor_gain	1.0000
5:476200:A:AC	donor_gain	1.0000
5:476200:AC:A	donor_gain	1.0000
5:476200:ACC:A	donor_gain	1.0000
5:476200:ACCCG:A	donor_gain	1.0000
5:476201:C:CC	donor_gain	1.0000
5:476201:C:CG	donor_loss	1.0000
5:476201:CC:C	donor_gain	1.0000
5:476201:CCC:C	donor_gain	1.0000
5:476201:CCCG:C	donor_gain	1.0000
5:476201:CCCGC:C	donor_gain	1.0000

AlphaMissense

5412 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:479856:C:G	A543P	1.000
5:479870:A:G	L538P	1.000
5:479855:G:T	A543D	0.999
5:479864:A:G	L540P	0.999
5:483437:G:C	N326K	0.999
5:483437:G:T	N326K	0.999
5:484678:G:C	S258R	0.999
5:484678:G:T	S258R	0.999
5:484680:T:G	S258R	0.999
5:476574:A:G	L620P	0.998
5:479878:G:C	F535L	0.998
5:479878:G:T	F535L	0.998
5:479880:A:G	F535L	0.998
5:483352:C:G	G355R	0.998
5:483362:G:C	F351L	0.998
5:483362:G:T	F351L	0.998
5:483364:A:G	F351L	0.998
5:483468:C:T	G316D	0.998
5:484592:G:T	P287H	0.998
5:488331:G:C	N220K	0.998
5:488331:G:T	N220K	0.998
5:488433:G:C	S186R	0.998
5:488433:G:T	S186R	0.998
5:488435:T:G	S186R	0.998
5:492009:C:G	G92R	0.998
5:476290:C:G	R660P	0.997
5:477418:G:C	F558L	0.997
5:477418:G:T	F558L	0.997
5:477420:A:G	F558L	0.997
5:479859:C:G	D542H	0.997

dbSNP variants (sampled 300 via entrez): RS1000003778 (5:475373 G>A), RS1000011746 (5:487952 G>A,C), RS1000092921 (5:514908 C>T), RS1000211402 (5:500021 C>T), RS1000243399 (5:523926 G>A), RS1000283668 (5:490384 C>CCT), RS1000301955 (5:472069 G>A), RS1000425349 (5:490574 A>G), RS1000476907 (5:495058 A>G), RS1000518512 (5:513506 G>A), RS1000531992 (5:486121 G>A,T), RS1000569193 (5:471853 G>A,C), RS1000635960 (5:470636 G>A,C), RS1000651486 (5:519774 G>A,C), RS1000721743 (5:510142 G>A)

Disease associations

OMIM: gene MIM:182307 | disease phenotypes: MIM:616868, MIM:181500

GenCC curated gene-disease

Disease	Classification	Inheritance
congenital secretory sodium diarrhea 8	Strong	Autosomal recessive
congenital sodium diarrhea	Supportive	Autosomal dominant
cystic fibrosis	Supportive	Autosomal recessive

Mondo (5): congenital secretory sodium diarrhea 8 (MONDO:0014808), schizophrenia (MONDO:0005090), autism spectrum disorder (MONDO:0005258), congenital sodium diarrhea (MONDO:0015170), cystic fibrosis (MONDO:0009061)

Orphanet (3): Congenital sodium diarrhea (Orphanet:103908), NON RARE IN EUROPE: Schizophrenia (Orphanet:3140), NON RARE IN EUROPE: Autism (Orphanet:106)

HPO phenotypes

50 total (30 of 50 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000246	Sinusitis
HP:0000365	Hearing impairment
HP:0000716	Depression
HP:0000739	Anxiety
HP:0000787	Nephrolithiasis
HP:0000938	Osteopenia
HP:0000939	Osteoporosis
HP:0001392	Abnormality of the liver
HP:0001394	Cirrhosis
HP:0001508	Failure to thrive
HP:0001561	Polyhydramnios
HP:0001738	Exocrine pancreatic insufficiency
HP:0002020	Gastroesophageal reflux
HP:0002024	Malabsorption
HP:0002035	Rectal prolapse
HP:0002037	Inflammation of the large intestine
HP:0002099	Asthma
HP:0002105	Hemoptysis
HP:0002107	Pneumothorax
HP:0002110	Bronchiectasis
HP:0002205	Recurrent respiratory infections
HP:0002570	Steatorrhea
HP:0002724	Recurrent Aspergillus infections
HP:0002726	Recurrent Staphylococcus aureus infections
HP:0002783	Recurrent lower respiratory tract infections
HP:0002842	Recurrent Burkholderia cepacia infections
HP:0002910	Elevated circulating hepatic transaminase concentration
HP:0003251	Male infertility
HP:0003270	Abdominal distention

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST001728_1	Ulcerative colitis	2.000000e-08
GCST003143_24	Lung disease severity in cystic fibrosis	8.000000e-10
GCST003143_25	Lung disease severity in cystic fibrosis	1.000000e-11
GCST003143_26	Lung disease severity in cystic fibrosis	9.000000e-07
GCST003143_27	Lung disease severity in cystic fibrosis	2.000000e-06
GCST003143_28	Lung disease severity in cystic fibrosis	4.000000e-09
GCST003143_29	Lung disease severity in cystic fibrosis	7.000000e-12
GCST004133_71	Ulcerative colitis	2.000000e-07
GCST007831_7	Anti-thyroglobulin (TgAb) levels in Hashimoto’s thyroiditis	6.000000e-06
GCST008059_200	Estimated glomerular filtration rate	2.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007744	lung disease severity measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D003550	Cystic Fibrosis	C06.689.202; C08.381.187; C16.320.190; C16.614.213

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3273 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

3 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 358 (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
CHEMBL3301627	TENAPANOR HYDROCHLORIDE	4	28
CHEMBL3304485	TENAPANOR	4	201
CHEMBL64360	ENIPORIDE	2	129

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: transporter — SLC9 family of sodium/hydrogen exchangers

Most potent curated ligand interactions (3 total), top 3:

Ligand	Action	Affinity	Parameter
repunapanor	Inhibition	8.62	pIC50
tenapanor	Inhibition	7.0	pIC50
amiloride	Inhibition	4.0	pKi

ChEMBL bioactivities

623 potent at pChembl≥5 of 629 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.70	IC50	0.2	nM	CHEMBL3904640
9.30	IC50	0.5012	nM	TENAPANOR
9.30	IC50	0.5	nM	CHEMBL3973684
8.90	IC50	1.259	nM	CHEMBL5176968
8.80	IC50	1.585	nM	CHEMBL3990220
8.80	IC50	1.585	nM	CHEMBL5170002
8.70	IC50	2	nM	CHEMBL3967635
8.70	IC50	1.995	nM	CHEMBL3987020
8.70	IC50	1.995	nM	CHEMBL3942614
8.70	IC50	1.995	nM	CHEMBL5202545
8.70	IC50	2	nM	CHEMBL3987020
8.70	IC50	2	nM	CHEMBL3942614
8.58	IC50	2.63	nM	CHEMBL3948263
8.58	IC50	2.63	nM	CHEMBL4283742
8.58	IC50	2.63	nM	CHEMBL5845250
8.55	IC50	2.818	nM	CHEMBL3950900
8.55	IC50	2.818	nM	CHEMBL3954388
8.55	IC50	2.82	nM	CHEMBL5861528
8.55	IC50	2.82	nM	CHEMBL3954388
8.53	IC50	2.951	nM	CHEMBL3937928
8.53	IC50	2.95	nM	CHEMBL3937928
8.50	IC50	3.162	nM	CHEMBL3921641
8.50	IC50	3.16	nM	CHEMBL3921641
8.45	IC50	3.548	nM	CHEMBL3972753
8.45	IC50	3.55	nM	CHEMBL3972753
8.40	IC50	4	nM	CHEMBL3978001
8.40	IC50	4	nM	CHEMBL3946835
8.40	IC50	3.981	nM	CHEMBL3967281
8.40	IC50	3.981	nM	CHEMBL3968950
8.40	IC50	3.981	nM	CHEMBL3923266
8.40	IC50	3.981	nM	CHEMBL3956501
8.40	IC50	3.981	nM	CHEMBL5183104
8.40	IC50	3.98	nM	CHEMBL3967281
8.40	IC50	3.98	nM	CHEMBL3968950
8.40	IC50	3.98	nM	CHEMBL5815625
8.40	IC50	3.98	nM	CHEMBL3956501
8.37	IC50	4.266	nM	CHEMBL3947060
8.37	IC50	4.266	nM	CHEMBL4279223
8.37	IC50	4.27	nM	CHEMBL4279223
8.35	IC50	4.467	nM	CHEMBL3979252
8.35	IC50	4.467	nM	CHEMBL3976345
8.35	IC50	4.47	nM	CHEMBL3976345
8.35	IC50	4.47	nM	CHEMBL3979252
8.30	IC50	5.012	nM	CHEMBL3972891
8.30	IC50	5.012	nM	CHEMBL3906068
8.30	IC50	5.012	nM	CHEMBL3903230
8.30	IC50	5.012	nM	CHEMBL3909990
8.30	IC50	5.012	nM	CHEMBL3911722
8.30	IC50	5.012	nM	CHEMBL3891308
8.30	IC50	5.012	nM	TENAPANOR

PubChem BioAssay actives

100 with measured affinity, of 119 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
4-[[(1S,2S)-2-[(3R)-3-aminopiperidin-1-yl]-4,6-dichloro-2,3-dihydro-1H-inden-1-yl]oxy]-2,3-dichlorobenzenesulfonamide	1321755: Inhibition of human NHE3 expressed in LAP1 cell assessed as intracellular pH recovery measured for 2 mins by CECF-AM dye based FLIPR assay	ic50	0.0002	uM
1-[2-[2-[2-[[3-[(4S)-6,8-dichloro-2-methyl-3,4-dihydro-1H-isoquinolin-4-yl]phenyl]sulfonylamino]ethoxy]ethoxy]ethyl]-3-[4-[2-[2-[2-[[3-[(4R)-6,8-dichloro-2-methyl-3,4-dihydro-1H-isoquinolin-4-yl]phenyl]sulfonylamino]ethoxy]ethoxy]ethylcarbamoylamino]butyl]urea	1954584: Inhibition of human NHE3	ic50	0.0005	uM
Tenapanor	1893592: Inhibition of human NHE3 expressed in opossum kidney cells assessed as reduction in Na-HEPES buffer-mediated pH recovery in presence of NEH1 inhibitor ethyl isopropyl amiloride by BCECF-AM dye based fluorescence assay	ic50	0.0005	uM
N-[2-[2-[2-[2-[[3-[(4S)-6,8-dichloro-2-methyl-3,4-dihydro-1H-isoquinolin-4-yl]phenyl]sulfonylamino]ethoxy]ethoxy]ethoxy]ethyl]-3-[2-[2-[2-[2-[[3-[(4S)-6,8-dichloro-2-methyl-3,4-dihydro-1H-isoquinolin-4-yl]phenyl]sulfonylamino]ethoxy]ethoxy]ethoxy]ethylamino]-2,3-dihydroxypropanamide	1893592: Inhibition of human NHE3 expressed in opossum kidney cells assessed as reduction in Na-HEPES buffer-mediated pH recovery in presence of NEH1 inhibitor ethyl isopropyl amiloride by BCECF-AM dye based fluorescence assay	ic50	0.0013	uM
N,N’-bis[2-[2-[2-[[3-[(4S)-6,8-dichloro-2-methyl-3,4-dihydro-1H-isoquinolin-4-yl]phenyl]sulfonylamino]ethoxy]ethoxy]ethyl]butanediamide	1893592: Inhibition of human NHE3 expressed in opossum kidney cells assessed as reduction in Na-HEPES buffer-mediated pH recovery in presence of NEH1 inhibitor ethyl isopropyl amiloride by BCECF-AM dye based fluorescence assay	ic50	0.0016	uM
1-[2-[2-[2-[[3-[(4S)-6,8-dichloro-2-methyl-3,4-dihydro-1H-isoquinolin-4-yl]phenyl]sulfonylamino]ethoxy]ethoxy]ethyl]-3-[4-[2-[2-[2-[[3-[(4S)-6,8-dichloro-2-methyl-3,4-dihydro-1H-isoquinolin-4-yl]phenyl]sulfonylamino]ethoxy]ethoxy]ethylcarbamoylamino]phenyl]urea	1893592: Inhibition of human NHE3 expressed in opossum kidney cells assessed as reduction in Na-HEPES buffer-mediated pH recovery in presence of NEH1 inhibitor ethyl isopropyl amiloride by BCECF-AM dye based fluorescence assay	ic50	0.0016	uM
1-[2-[2-[2-[2-[[3-[(4S)-6,8-dichloro-2-methyl-3,4-dihydro-1H-isoquinolin-4-yl]phenyl]sulfonylamino]ethoxy]ethoxy]ethoxy]ethyl]-3-[3-[2-[2-[2-[2-[[3-[(4S)-6,8-dichloro-2-methyl-3,4-dihydro-1H-isoquinolin-4-yl]phenyl]sulfonylamino]ethoxy]ethoxy]ethoxy]ethylcarbamoylamino]propyl]urea	1893592: Inhibition of human NHE3 expressed in opossum kidney cells assessed as reduction in Na-HEPES buffer-mediated pH recovery in presence of NEH1 inhibitor ethyl isopropyl amiloride by BCECF-AM dye based fluorescence assay	ic50	0.0020	uM
1-[(1S,2S)-4,6-dichloro-1-(2-chloro-4-methylsulfonylphenoxy)-2,3-dihydro-1H-inden-2-yl]-1,4-diazepane	1321755: Inhibition of human NHE3 expressed in LAP1 cell assessed as intracellular pH recovery measured for 2 mins by CECF-AM dye based FLIPR assay	ic50	0.0020	uM
N-[2-[2-[2-[[4-(6,8-dichloro-2-methyl-3,4-dihydro-1H-isoquinolin-4-yl)phenyl]sulfonylamino]ethoxy]ethoxy]ethyl]-3-[2-[2-[2-[[4-(6,8-dichloro-2-methyl-3,4-dihydro-1H-isoquinolin-4-yl)phenyl]sulfonylamino]ethoxy]ethoxy]ethylamino]-2,3-dihydroxypropanamide	1893592: Inhibition of human NHE3 expressed in opossum kidney cells assessed as reduction in Na-HEPES buffer-mediated pH recovery in presence of NEH1 inhibitor ethyl isopropyl amiloride by BCECF-AM dye based fluorescence assay	ic50	0.0040	uM
(3R)-1-[(1S,2S)-4,6-dichloro-1-(4-methylsulfonylphenoxy)-2,3-dihydro-1H-inden-2-yl]piperidin-3-amine	1321755: Inhibition of human NHE3 expressed in LAP1 cell assessed as intracellular pH recovery measured for 2 mins by CECF-AM dye based FLIPR assay	ic50	0.0040	uM
2-[[(3R)-1-[(1S,2S)-4,6-dichloro-1-(4-methylsulfonylphenoxy)-2,3-dihydro-1H-inden-2-yl]piperidin-3-yl]amino]ethanol	1321755: Inhibition of human NHE3 expressed in LAP1 cell assessed as intracellular pH recovery measured for 2 mins by CECF-AM dye based FLIPR assay	ic50	0.0040	uM
1-[(1S,2S)-4,6-dichloro-1-(4-methylsulfonylphenoxy)-2,3-dihydro-1H-inden-2-yl]-1,4-diazepane	1321755: Inhibition of human NHE3 expressed in LAP1 cell assessed as intracellular pH recovery measured for 2 mins by CECF-AM dye based FLIPR assay	ic50	0.0060	uM
1,3-bis[2-[2-[2-[2-[[3-[(4S)-6,8-dichloro-2-methyl-3,4-dihydro-1H-isoquinolin-4-yl]phenyl]sulfonylamino]ethoxy]ethoxy]ethoxy]ethyl]urea	1893592: Inhibition of human NHE3 expressed in opossum kidney cells assessed as reduction in Na-HEPES buffer-mediated pH recovery in presence of NEH1 inhibitor ethyl isopropyl amiloride by BCECF-AM dye based fluorescence assay	ic50	0.0079	uM
N-[2-[2-[2-[[3-[(4S)-6,8-dichloro-2-methyl-3,4-dihydro-1H-isoquinolin-4-yl]phenyl]sulfonylamino]ethoxy]ethoxy]ethyl]-2-[2-[2-[2-[2-[[3-[(4S)-6,8-dichloro-2-methyl-3,4-dihydro-1H-isoquinolin-4-yl]phenyl]sulfonylamino]ethoxy]ethoxy]ethylamino]-2-oxoethoxy]acetamide	1893592: Inhibition of human NHE3 expressed in opossum kidney cells assessed as reduction in Na-HEPES buffer-mediated pH recovery in presence of NEH1 inhibitor ethyl isopropyl amiloride by BCECF-AM dye based fluorescence assay	ic50	0.0079	uM
2-[(1S,2S)-4,6-dichloro-1-(4-methylsulfonylphenoxy)-2,3-dihydro-1H-inden-2-yl]-2,7-diazaspiro[4.4]nonane	1321755: Inhibition of human NHE3 expressed in LAP1 cell assessed as intracellular pH recovery measured for 2 mins by CECF-AM dye based FLIPR assay	ic50	0.0110	uM
1-[(1S,2S)-4,6-dichloro-1-[4-(3,5-dimethyl-1,2,4-triazol-4-yl)phenoxy]-2,3-dihydro-1H-inden-2-yl]-4-methyl-1,4-diazepane	1321755: Inhibition of human NHE3 expressed in LAP1 cell assessed as intracellular pH recovery measured for 2 mins by CECF-AM dye based FLIPR assay	ic50	0.0170	uM
N’-[(1S,2S)-4,6-dichloro-1-(4-methylsulfonylphenoxy)-2,3-dihydro-1H-inden-2-yl]-N,N,N’-trimethylethane-1,2-diamine	1321755: Inhibition of human NHE3 expressed in LAP1 cell assessed as intracellular pH recovery measured for 2 mins by CECF-AM dye based FLIPR assay	ic50	0.0200	uM
(3R)-1-[(1S,2S)-4,6-dichloro-1-(4-methylsulfonylphenoxy)-2,3-dihydro-1H-inden-2-yl]-3-methylpiperazine	1321755: Inhibition of human NHE3 expressed in LAP1 cell assessed as intracellular pH recovery measured for 2 mins by CECF-AM dye based FLIPR assay	ic50	0.0200	uM
1-[(1S,2S)-4,6-dichloro-1-(4-methylsulfonylphenoxy)-2,3-dihydro-1H-inden-2-yl]piperazine	1321755: Inhibition of human NHE3 expressed in LAP1 cell assessed as intracellular pH recovery measured for 2 mins by CECF-AM dye based FLIPR assay	ic50	0.0220	uM
1-[(1S,2S)-4,6-dichloro-1-[4-(3,5-dimethyl-1,2,4-triazol-4-yl)phenoxy]-2,3-dihydro-1H-inden-2-yl]-1,4-diazepane	1321755: Inhibition of human NHE3 expressed in LAP1 cell assessed as intracellular pH recovery measured for 2 mins by CECF-AM dye based FLIPR assay	ic50	0.0230	uM
(3R)-1-[(1S,2S)-4,6-dichloro-1-(4-imidazol-1-ylphenoxy)-2,3-dihydro-1H-inden-2-yl]piperidin-3-amine	1321755: Inhibition of human NHE3 expressed in LAP1 cell assessed as intracellular pH recovery measured for 2 mins by CECF-AM dye based FLIPR assay	ic50	0.0230	uM
(2R,3S,4R,5R)-N-[3-[(4S)-6,8-dichloro-2-methyl-3,4-dihydro-1H-isoquinolin-4-yl]phenyl]-2,3,4,5,6-pentahydroxyhexanamide	1893592: Inhibition of human NHE3 expressed in opossum kidney cells assessed as reduction in Na-HEPES buffer-mediated pH recovery in presence of NEH1 inhibitor ethyl isopropyl amiloride by BCECF-AM dye based fluorescence assay	ic50	0.0251	uM
(3aR,6aS)-5-[(1S,2S)-4,6-dichloro-1-(4-methylsulfonylphenoxy)-2,3-dihydro-1H-inden-2-yl]-2,3,3a,4,6,6a-hexahydro-1H-pyrrolo[3,4-c]pyrrole	1321755: Inhibition of human NHE3 expressed in LAP1 cell assessed as intracellular pH recovery measured for 2 mins by CECF-AM dye based FLIPR assay	ic50	0.0280	uM
(3R)-1-[(1S,2S)-4,6-dichloro-1-[4-(1,2,4-triazol-1-yl)phenoxy]-2,3-dihydro-1H-inden-2-yl]piperidin-3-amine	1321755: Inhibition of human NHE3 expressed in LAP1 cell assessed as intracellular pH recovery measured for 2 mins by CECF-AM dye based FLIPR assay	ic50	0.0300	uM
2-[4-[(1S,2S)-4,6-dichloro-1-(4-methylsulfonylphenoxy)-2,3-dihydro-1H-inden-2-yl]-1,4-diazepan-1-yl]ethanol	1321755: Inhibition of human NHE3 expressed in LAP1 cell assessed as intracellular pH recovery measured for 2 mins by CECF-AM dye based FLIPR assay	ic50	0.0300	uM
N-[2-[2-[2-[[4-(6,8-dichloro-2-methyl-3,4-dihydro-1H-isoquinolin-4-yl)phenyl]sulfonylamino]ethoxy]ethoxy]ethyl]-2-[2-[2-[2-[2-[[4-(6,8-dichloro-2-methyl-3,4-dihydro-1H-isoquinolin-4-yl)phenyl]sulfonylamino]ethoxy]ethoxy]ethylamino]-2-oxoethoxy]acetamide	1893592: Inhibition of human NHE3 expressed in opossum kidney cells assessed as reduction in Na-HEPES buffer-mediated pH recovery in presence of NEH1 inhibitor ethyl isopropyl amiloride by BCECF-AM dye based fluorescence assay	ic50	0.0316	uM
(3R)-1-[(1S,2S)-4,6-dichloro-1-[4-(3,5-dimethyl-1,2,4-triazol-4-yl)-2-fluorophenoxy]-2,3-dihydro-1H-inden-2-yl]pyrrolidin-3-ol	1321755: Inhibition of human NHE3 expressed in LAP1 cell assessed as intracellular pH recovery measured for 2 mins by CECF-AM dye based FLIPR assay	ic50	0.0340	uM
1-[2-[2-[2-[2-[[3-(6,8-dichloro-2-methyl-3,4-dihydro-1H-isoquinolin-4-yl)phenyl]sulfonylamino]ethoxy]ethoxy]ethoxy]ethyl]-3-[4-[2-[2-[2-[2-[[3-(6,8-dichloro-2-methyl-3,4-dihydro-1H-isoquinolin-4-yl)phenyl]sulfonylamino]ethoxy]ethoxy]ethoxy]ethylcarbamoylamino]butyl]urea	1893592: Inhibition of human NHE3 expressed in opossum kidney cells assessed as reduction in Na-HEPES buffer-mediated pH recovery in presence of NEH1 inhibitor ethyl isopropyl amiloride by BCECF-AM dye based fluorescence assay	ic50	0.0398	uM
1-N,4-N-bis[2-[2-[2-[2-[[4-(6,8-dichloro-2-methyl-3,4-dihydro-1H-isoquinolin-4-yl)phenyl]sulfonylamino]ethoxy]ethoxy]ethoxy]ethyl]benzene-1,4-dicarboxamide	1893592: Inhibition of human NHE3 expressed in opossum kidney cells assessed as reduction in Na-HEPES buffer-mediated pH recovery in presence of NEH1 inhibitor ethyl isopropyl amiloride by BCECF-AM dye based fluorescence assay	ic50	0.0398	uM
1-[(1S,2S)-6,7-dichloro-1-(4-methylsulfonylphenoxy)-2,3-dihydro-1H-inden-2-yl]-1,4-diazepane	1321755: Inhibition of human NHE3 expressed in LAP1 cell assessed as intracellular pH recovery measured for 2 mins by CECF-AM dye based FLIPR assay	ic50	0.0430	uM
N’-[(1S,2S)-4,6-dichloro-1-(4-methylsulfonylphenoxy)-2,3-dihydro-1H-inden-2-yl]-N,N,N’-trimethylpropane-1,3-diamine	1321755: Inhibition of human NHE3 expressed in LAP1 cell assessed as intracellular pH recovery measured for 2 mins by CECF-AM dye based FLIPR assay	ic50	0.0480	uM
(2R,3S,4R,5R)-N-[3-(6,8-dichloro-2-methyl-3,4-dihydro-1H-isoquinolin-4-yl)phenyl]-2,3,4,5,6-pentahydroxyhexanamide	1893592: Inhibition of human NHE3 expressed in opossum kidney cells assessed as reduction in Na-HEPES buffer-mediated pH recovery in presence of NEH1 inhibitor ethyl isopropyl amiloride by BCECF-AM dye based fluorescence assay	ic50	0.0501	uM
1-N,4-N-bis[2-[2-[2-[2-[[3-(6,8-dichloro-2-methyl-3,4-dihydro-1H-isoquinolin-4-yl)phenyl]sulfonylamino]ethoxy]ethoxy]ethoxy]ethyl]benzene-1,4-dicarboxamide	1893592: Inhibition of human NHE3 expressed in opossum kidney cells assessed as reduction in Na-HEPES buffer-mediated pH recovery in presence of NEH1 inhibitor ethyl isopropyl amiloride by BCECF-AM dye based fluorescence assay	ic50	0.0501	uM
(3R)-1-[(1S,2S)-4,6-dichloro-1-(4-methylsulfonylphenoxy)-2,3-dihydro-1H-inden-2-yl]-N-(2-fluoroethyl)piperidin-3-amine	1321755: Inhibition of human NHE3 expressed in LAP1 cell assessed as intracellular pH recovery measured for 2 mins by CECF-AM dye based FLIPR assay	ic50	0.0560	uM
N-[2-[2-[2-[[3-(6,8-dichloro-2-methyl-3,4-dihydro-1H-isoquinolin-4-yl)phenyl]sulfonylamino]ethoxy]ethoxy]ethyl]-3-[2-[2-[2-[[3-(6,8-dichloro-2-methyl-3,4-dihydro-1H-isoquinolin-4-yl)phenyl]sulfonylamino]ethoxy]ethoxy]ethylamino]-2,3-dihydroxypropanamide	1893592: Inhibition of human NHE3 expressed in opossum kidney cells assessed as reduction in Na-HEPES buffer-mediated pH recovery in presence of NEH1 inhibitor ethyl isopropyl amiloride by BCECF-AM dye based fluorescence assay	ic50	0.0631	uM
1,3-bis[2-[2-[2-[2-[[4-(6,8-dichloro-2-methyl-3,4-dihydro-1H-isoquinolin-4-yl)phenyl]sulfonylamino]ethoxy]ethoxy]ethoxy]ethyl]urea	1893592: Inhibition of human NHE3 expressed in opossum kidney cells assessed as reduction in Na-HEPES buffer-mediated pH recovery in presence of NEH1 inhibitor ethyl isopropyl amiloride by BCECF-AM dye based fluorescence assay	ic50	0.0631	uM
N,N’-bis[2-[2-[2-[[4-(6,8-dichloro-2-methyl-3,4-dihydro-1H-isoquinolin-4-yl)phenyl]sulfonylamino]ethoxy]ethoxy]ethyl]butanediamide	1893592: Inhibition of human NHE3 expressed in opossum kidney cells assessed as reduction in Na-HEPES buffer-mediated pH recovery in presence of NEH1 inhibitor ethyl isopropyl amiloride by BCECF-AM dye based fluorescence assay	ic50	0.0631	uM
1-[(1S,2S)-4,6-dichloro-1-(4-methylsulfonylphenoxy)-2,3-dihydro-1H-inden-2-yl]-4-(2-methoxyethyl)-1,4-diazepane	1321755: Inhibition of human NHE3 expressed in LAP1 cell assessed as intracellular pH recovery measured for 2 mins by CECF-AM dye based FLIPR assay	ic50	0.0640	uM
4-[3-chloro-4-[[(1S,2S)-2-pyrrolidin-1-yl-2,3-dihydro-1H-inden-1-yl]oxy]phenyl]-3,5-dimethyl-1,2,4-triazole	1321755: Inhibition of human NHE3 expressed in LAP1 cell assessed as intracellular pH recovery measured for 2 mins by CECF-AM dye based FLIPR assay	ic50	0.0780	uM
N-[2-[2-[2-[2-[[3-(6,8-dichloro-2-methyl-3,4-dihydro-1H-isoquinolin-4-yl)phenyl]sulfonylamino]ethoxy]ethoxy]ethoxy]ethyl]-3-[2-[2-[2-[2-[[3-(6,8-dichloro-2-methyl-3,4-dihydro-1H-isoquinolin-4-yl)phenyl]sulfonylamino]ethoxy]ethoxy]ethoxy]ethylamino]-2,3-dihydroxypropanamide	1893592: Inhibition of human NHE3 expressed in opossum kidney cells assessed as reduction in Na-HEPES buffer-mediated pH recovery in presence of NEH1 inhibitor ethyl isopropyl amiloride by BCECF-AM dye based fluorescence assay	ic50	0.0794	uM
(3R)-1-[(1S,2S)-6-chloro-1-[2-chloro-4-(3,5-dimethyl-1,2,4-triazol-4-yl)phenoxy]-2,3-dihydro-1H-inden-2-yl]pyrrolidin-3-ol	1321755: Inhibition of human NHE3 expressed in LAP1 cell assessed as intracellular pH recovery measured for 2 mins by CECF-AM dye based FLIPR assay	ic50	0.0900	uM
1-[(1S,2S)-4,6-dichloro-1-(4-methylsulfonylphenoxy)-2,3-dihydro-1H-inden-2-yl]-4-methyl-1,4-diazepane	1321755: Inhibition of human NHE3 expressed in LAP1 cell assessed as intracellular pH recovery measured for 2 mins by CECF-AM dye based FLIPR assay	ic50	0.0930	uM
4-[3-chloro-4-[[(1S,2S)-6-chloro-2-pyrrolidin-1-yl-2,3-dihydro-1H-inden-1-yl]oxy]phenyl]-3,5-dimethyl-1,2,4-triazole	1321755: Inhibition of human NHE3 expressed in LAP1 cell assessed as intracellular pH recovery measured for 2 mins by CECF-AM dye based FLIPR assay	ic50	0.0940	uM
2-[[3-(6,8-dichloro-2-methyl-3,4-dihydro-1H-isoquinolin-4-yl)phenyl]sulfonylamino]acetic acid	1893592: Inhibition of human NHE3 expressed in opossum kidney cells assessed as reduction in Na-HEPES buffer-mediated pH recovery in presence of NEH1 inhibitor ethyl isopropyl amiloride by BCECF-AM dye based fluorescence assay	ic50	0.1000	uM
3,5-dimethyl-4-[4-[[(1S,2S)-2-pyrrolidin-1-yl-2,3-dihydro-1H-inden-1-yl]oxy]-3-(trifluoromethyl)phenyl]-1,2,4-triazole	1321755: Inhibition of human NHE3 expressed in LAP1 cell assessed as intracellular pH recovery measured for 2 mins by CECF-AM dye based FLIPR assay	ic50	0.1180	uM
2,3-dichloro-4-[[(1S,2S)-2-pyrrolidin-1-yl-2,3-dihydro-1H-inden-1-yl]oxy]benzenesulfonamide	1321755: Inhibition of human NHE3 expressed in LAP1 cell assessed as intracellular pH recovery measured for 2 mins by CECF-AM dye based FLIPR assay	ic50	0.1230	uM
1-[(1S,2S)-4-chloro-6-fluoro-1-(4-methylsulfonylphenoxy)-2,3-dihydro-1H-inden-2-yl]piperazine	1321755: Inhibition of human NHE3 expressed in LAP1 cell assessed as intracellular pH recovery measured for 2 mins by CECF-AM dye based FLIPR assay	ic50	0.1230	uM
1-[(1S,2S)-5,7-dichloro-1-(4-methylsulfonylphenoxy)-2,3-dihydro-1H-inden-2-yl]piperazine	1321755: Inhibition of human NHE3 expressed in LAP1 cell assessed as intracellular pH recovery measured for 2 mins by CECF-AM dye based FLIPR assay	ic50	0.1350	uM
N-[2-[2-[2-[2-[[4-(6,8-dichloro-2-methyl-3,4-dihydro-1H-isoquinolin-4-yl)phenyl]sulfonylamino]ethoxy]ethoxy]ethoxy]ethyl]-3-[2-[2-[2-[2-[[4-(6,8-dichloro-2-methyl-3,4-dihydro-1H-isoquinolin-4-yl)phenyl]sulfonylamino]ethoxy]ethoxy]ethoxy]ethylamino]-2,3-dihydroxypropanamide	1893592: Inhibition of human NHE3 expressed in opossum kidney cells assessed as reduction in Na-HEPES buffer-mediated pH recovery in presence of NEH1 inhibitor ethyl isopropyl amiloride by BCECF-AM dye based fluorescence assay	ic50	0.1585	uM
(3R)-1-[(1S,2S)-4,6-dichloro-1-(4-methylsulfonylphenoxy)-2,3-dihydro-1H-inden-2-yl]-3-fluoropyrrolidine	1321755: Inhibition of human NHE3 expressed in LAP1 cell assessed as intracellular pH recovery measured for 2 mins by CECF-AM dye based FLIPR assay	ic50	0.1660	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
3-(2-(3-guanidino-2-methyl-3-oxo-propenyl)-5-methylphenyl)-N-isopropylidene-2-methyl-acrylamide dihydrochloride	decreases activity	2
Resveratrol	affects cotreatment, decreases expression, increases expression, increases uptake	2
Benzo(a)pyrene	affects methylation, increases methylation	2
Valproic Acid	increases expression, increases methylation	2
sotorasib	affects cotreatment, decreases expression	1
bisphenol A	increases methylation, affects cotreatment	1
benzo(e)pyrene	increases methylation	1
bisphenol S	affects cotreatment, decreases methylation	1
jinfukang	affects cotreatment, increases expression	1
trametinib	decreases expression, affects cotreatment	1
NVP-BKM120	affects cotreatment, decreases expression	1
Agent Orange	decreases methylation, increases abundance	1
Decitabine	increases expression	1
Fulvestrant	affects cotreatment, increases methylation, decreases methylation	1
Air Pollutants	increases abundance, increases expression	1
Allergens	increases expression	1
Arsenic	affects methylation	1
Cisplatin	affects cotreatment, increases expression	1
Defoliants, Chemical	decreases methylation, increases abundance	1
Dexamethasone	increases expression	1
Fluorouracil	decreases expression	1
Folic Acid	decreases expression	1
Methapyrilene	increases methylation	1
Plant Extracts	affects cotreatment, decreases expression	1
Smoke	decreases expression	1
Sodium Chloride	increases expression, increases uptake	1
Tetrachlorodibenzodioxin	decreases methylation, increases abundance	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	increases expression	1
Acrylamide	decreases expression	1
Particulate Matter	increases abundance, increases expression	1

ChEMBL screening assays

20 unique, capped per target: 18 binding, 2 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2173336	Binding	Inhibition of NHE3 transfected in Chinese hamster PS120 assessed as intracellular pH change up to 16 uM	Identification of a potent sodium hydrogen exchanger isoform 1 (NHE1) inhibitor with a suitable profile for chronic dosing and demonstrated cardioprotective effects in a preclinical model of myocardial infarction in the rat. — J Med Chem
CHEMBL5723545	Functional	Affinity On-target Cellular interaction: (Inhibition of Na+/H+ exchange, detection of fluorescence changes in acridine orange pH indicator, mouse fibroblast L cell line) EUB0002709aCl SLC9A3	Affinity On-target Cellular Literature for EUbOPEN Chemogenomic Library

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_E0ZQ	Ubigene NCI-H1299 SLC9A3 KO	Cancer cell line	Male
CVCL_TP19	HAP1 SLC9A3 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00157690	PHASE4	COMPLETED	Study of Alendronate to Prevent and Treat Osteoporosis in Cystic Fibrosis Patients
NCT00208078	PHASE4	TERMINATED	Effect of Non-Invasive Ventilation in Cystic Fibrosis Patient With Chronic Respiratory Failure.
NCT00244270	PHASE4	COMPLETED	Cystic Fibrosis and Totally Implantable Vascular Access Devices
NCT00333385	PHASE4	TERMINATED	Continuous Versus Short Infusions of Ceftazidime in Cystic Fibrosis
NCT00411736	PHASE4	COMPLETED	Scandinavian Cystic Fibrosis Azithromycin Study
NCT00418470	PHASE4	TERMINATED	Prolonging the Duration of Peripheral Venous Catheters in Cystic Fibrosis People
NCT00431964	PHASE4	COMPLETED	Effect of Azithromycin on Lung Function in 6-18 Year-olds With Cystic Fibrosis (CF) Not Infected With P. Aeruginosa
NCT00434278	PHASE4	TERMINATED	A Trial of Pulmozyme Withdrawal on Exercise Tolerance in Cystic Fibrosis Subjects With Severe Lung Disease (TOPIC)
NCT00483769	PHASE4	COMPLETED	One Year Glargine Treatment in CFRD Children and Adolescents
NCT00528190	PHASE4	COMPLETED	Treatment of Aspergillus Fumigatus (a Fungal Infection) in Patients With Cystic Fibrosis
NCT00557089	PHASE4	COMPLETED	The Effect of rhDNase on Ventilation Inhomogeneity in Patients With Cystic Fibrosis
NCT00572975	PHASE4	COMPLETED	Malabsorption Blood Test:Toward a Novel Approach to Quantify Steatorrhea
NCT00680316	PHASE4	TERMINATED	A Study of Pulmozyme® (Dornase Alpha) in 3- to 5-Year-Old Patients With Cystic Fibrosis
NCT00685035	PHASE4	COMPLETED	Comparison of Airway Clearance Therapy in Cystic Fibrosis Using the Same VEST Therapy Device But With Different Settings
NCT00744250	PHASE4	TERMINATED	Intraduodenal Aspiration Study to Assess the Bioavailability of Oral Pancrecarb® Compared to Placebo Control
NCT00787917	PHASE4	TERMINATED	An Exploratory Study to Assess Multiple Doses of Omalizumab in Patients With Cystic Fibrosis Complicated by Acute Bronchopulmonary Aspergillosis (ABPA)
NCT00843817	PHASE4	COMPLETED	RhDNase and Biodistribution of PMN Serine Proteases in Cystic Fibrosis Sputum
NCT00890370	PHASE4	COMPLETED	Should Any One Airway Clearance Technique be Recommended for People With Cystic Fibrosis?
NCT00996424	PHASE4	TERMINATED	The Effect of Inhaled N-Acetylcysteine Compared to Normal Saline on Sputum Rheology and Lung Function
NCT01044719	PHASE4	UNKNOWN	Duration of Antibiotics in Infective Exacerbations of Cystic Fibrosis
NCT01100606	PHASE4	COMPLETED	A Study to Evaluate the Mode of Administration and Safety of EUR-1008 (APT-1008) in Infants 1 to 12 Months of Age
NCT01131507	PHASE4	COMPLETED	PR-018: An Open-Label, Safety Extension of Study PR-011
NCT01207245	PHASE4	COMPLETED	Circadian Rhythm In Tobramycin Elimination In Cystic Fibrosis
NCT01323101	PHASE4	COMPLETED	Doxycycline Effects on Inflammation in Cystic Fibrosis
NCT01327703	PHASE4	COMPLETED	Control of Steatorrhea in Participants With Cystic Fibrosis and Exocrine Pancreatic Insufficiency
NCT01377792	PHASE4	COMPLETED	Study of Long-term Treatment With Hypertonic Saline in Patients With Cystic Fibrosis
NCT01400750	PHASE4	COMPLETED	Comparison of 2 Treatment Regimens for Eradication of P Aeruginosa Infection in Children With Cystic Fibrosis
NCT01429259	PHASE4	COMPLETED	Population Pharmacokinetics of Prolonged Infusion Meropenem in Cystic Fibrosis (CF) Children
NCT01608555	PHASE4	COMPLETED	Tobramycin 300 mg Once-a-day (o.d.) Aerosol in Adults With Cystic Fibrosis
NCT01667094	PHASE4	UNKNOWN	A Study Comparing Continuous Infusion Antibiotics to Standard Treatment for Lung Infections in Cystic Fibrosis
NCT01694069	PHASE4	TERMINATED	Continuous Infusion Piperacillin-tazobactam for the Treatment of Cystic Fibrosis
NCT01702415	PHASE4	WITHDRAWN	Zoledronic Acid in Cystic Fibrosis
NCT01712334	PHASE4	COMPLETED	A Study of the Comparable Efficacy and Safety of Pulmozyme (Dornase Alfa) Delivered by the eRapid Nebulizer System in Patients With Cystic Fibrosis
NCT01737983	PHASE4	COMPLETED	Effect of Lactobacillus Reuteri in Cystic Fibrosis
NCT01844778	PHASE4	COMPLETED	Ease of Use and Microbial Contamination of Tobramycin Inhalation Powder (TIP) Versus Nebulised Tobramycin Inhalation Solution (TIS) and Nebulised Colistimethate (COLI)
NCT01880346	PHASE4	COMPLETED	Comparison of Absorption of Vitamin D in Cystic Fibrosis
NCT01882400	PHASE4	COMPLETED	Assessment of Response to Treatment of Osteoporosis With Oral Bisphosphonates in Patients With Muscular Dystrophy
NCT01937325	PHASE4	UNKNOWN	CPET in CF Patients With One G551D Mutation Taking VX770
NCT02015663	PHASE4	TERMINATED	Tobramycin Inhalation Powder (TIP) Administered Once Daily Continuously Versus TIP Administered BID in 28 Day on / 28 Day Off Cycles
NCT02048592	PHASE4	UNKNOWN	Impact of Immunonutrition on the Patients With Cystic Fibrosis