SLC26A3

Summary

SLC26A3 (solute carrier family 26 member 3, HGNC:3018) is a protein-coding gene on chromosome 7q22.3-q31.1, encoding Chloride anion exchanger (P40879). Mediates chloride-bicarbonate exchange with a chloride bicarbonate stoichiometry of 2:1 in the intestinal epithelia.

The protein encoded by this gene is a transmembrane glycoprotein that transports chloride ions across the cell membrane in exchange for bicarbonate ions. It is localized to the mucosa of the lower intestinal tract, particularly to the apical membrane of columnar epithelium and some goblet cells. The protein is essential for intestinal chloride absorption, and mutations in this gene have been associated with congenital chloride diarrhea.

Source: NCBI Gene 1811 — RefSeq curated summary.

At a glance

• Gene–disease (curated): congenital secretory chloride diarrhea 1 (Definitive, GenCC)
• GWAS associations: 10
• Clinical variants (ClinVar): 885 total — 62 pathogenic, 60 likely-pathogenic
• Phenotypes (HPO): 21
• Druggable target: yes
• MANE Select transcript: NM_000111

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3018
Approved symbol	SLC26A3
Name	solute carrier family 26 member 3
Location	7q22.3-q31.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000091138
Ensembl biotype	protein_coding
OMIM	126650
Entrez	1811

Gene structure

Transcript identifiers

Ensembl transcripts: 28 — 25 protein_coding, 2 retained_intron, 1 nonsense_mediated_decay

ENST00000340010, ENST00000379083, ENST00000453332, ENST00000468551, ENST00000469651, ENST00000852249, ENST00000852250, ENST00000852251, ENST00000852252, ENST00000852253, ENST00000852254, ENST00000852255, ENST00000852256, ENST00000852257, ENST00000852258, ENST00000852259, ENST00000852260, ENST00000852261, ENST00000852262, ENST00000852263, ENST00000852264, ENST00000852265, ENST00000852266, ENST00000852267, ENST00000852268, ENST00000852269, ENST00000852270, ENST00000852271

RefSeq mRNA: 1 — MANE Select: NM_000111 NM_000111

CCDS: CCDS5748

Canonical transcript exons

ENST00000340010 — 21 exons

Exon	Start	End
ENSE00000715749	107773920	107774153
ENSE00001173592	107793742	107793881
ENSE00001895902	107803111	107803223
ENSE00001932187	107765469	107765878
ENSE00003480483	107776452	107776544
ENSE00003512863	107779668	107779763
ENSE00003523570	107767579	107767644
ENSE00003527364	107786827	107786909
ENSE00003533584	107767766	107767908
ENSE00003552210	107774777	107774872
ENSE00003564336	107772054	107772108
ENSE00003568278	107778175	107778281
ENSE00003580858	107794379	107794597
ENSE00003623676	107791830	107791940
ENSE00003627510	107791048	107791235
ENSE00003633011	107776637	107776706
ENSE00003633076	107782797	107782874
ENSE00003636036	107783205	107783352
ENSE00003639759	107782980	107783093
ENSE00003652935	107789524	107789688
ENSE00003690558	107787357	107787509

Expression profiles

Bgee: expression breadth ubiquitous, 159 present calls, max score 99.94.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 1.7688 / max 771.9284, expressed in 28 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
85626	1.1106	23
85625	0.6582	6

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
colonic mucosa	UBERON:0000317	99.94	gold quality
mucosa of sigmoid colon	UBERON:0004993	99.93	gold quality
rectum	UBERON:0001052	99.70	gold quality
mucosa of transverse colon	UBERON:0004991	99.68	gold quality
seminal vesicle	UBERON:0000998	99.43	gold quality
ileal mucosa	UBERON:0000331	99.29	gold quality
jejunal mucosa	UBERON:0000399	99.15	gold quality
duodenum	UBERON:0002114	96.00	gold quality
transverse colon	UBERON:0001157	92.87	gold quality
small intestine Peyer’s patch	UBERON:0003454	85.87	gold quality
small intestine	UBERON:0002108	85.80	gold quality
intestine	UBERON:0000160	85.49	gold quality
vermiform appendix	UBERON:0001154	85.41	gold quality
large intestine	UBERON:0000059	85.37	gold quality
colon	UBERON:0001155	84.72	gold quality
corpus epididymis	UBERON:0004359	82.98	gold quality
sperm	CL:0000019	82.08	gold quality
caecum	UBERON:0001153	81.77	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	81.04	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.92	gold quality
male germ cell	CL:0000015	79.40	gold quality
gall bladder	UBERON:0002110	78.49	gold quality
colonic epithelium	UBERON:0000397	78.20	gold quality
jejunum	UBERON:0002115	77.02	gold quality
sigmoid colon	UBERON:0001159	73.47	gold quality
caput epididymis	UBERON:0004358	73.42	gold quality
muscle layer of sigmoid colon	UBERON:0035805	67.44	gold quality
smooth muscle tissue	UBERON:0001135	61.08	gold quality
nipple	UBERON:0002030	61.01	silver quality
cauda epididymis	UBERON:0004360	60.24	silver quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-8410	yes	3218.87
E-GEOD-125970	yes	3133.74
E-ANND-2	no	12551.58
E-CURD-119	no	9537.75
E-GEOD-131882	no	2996.43
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): BMAL1, CDX1, CIITA, ETS1, FOS, GATA1, GLI3, HMGA1, HNF1A, HNF4A, HR, JUN, POU2F1, POU2F2, STAT1, TBP, YBX1, YY1

miRNA regulators (miRDB)

45 targeting SLC26A3, 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-3163	100.00	77.23	8605
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-221-3P	99.86	71.56	1329
HSA-MIR-222-3P	99.86	71.35	1337
HSA-MIR-320A-3P	99.77	69.73	2107
HSA-MIR-320B	99.77	69.73	2107
HSA-MIR-320C	99.77	69.73	2107
HSA-MIR-320D	99.77	69.73	2107
HSA-MIR-4429	99.77	69.62	2111
HSA-MIR-4517	99.76	69.19	1867
HSA-MIR-187-5P	99.74	70.26	1404
HSA-MIR-494-3P	99.70	71.45	2795
HSA-MIR-1283	99.69	72.42	3009
HSA-MIR-5093	99.67	69.26	2291
HSA-MIR-561-3P	99.64	70.90	3647
HSA-MIR-4743-3P	99.62	68.12	2095
HSA-MIR-510-3P	99.54	70.06	2965
HSA-MIR-142-5P	99.48	70.92	2416
HSA-MIR-5590-3P	99.48	70.91	2429
HSA-MIR-2392	99.43	67.50	708
HSA-MIR-548V	99.29	69.47	1157
HSA-MIR-29A-5P	99.08	68.59	1813
HSA-MIR-10524-5P	99.05	66.08	963
HSA-MIR-320A-5P	98.88	66.75	1248

Literature-anchored findings (GeneRIF, showing 40)

• Two missense mutations (S206P, D468V), two splicing defects (IVS12-1G>C, IVS13-2delA), one nonsense mutation (Q436X), one insertion/deletion mutation (2104-2105delGGins29-bp), and an intragenic deletion of SLC26A3 gene. (PMID:11524734)
• Functional characterization of three novel tissue-specific anion exchangers SLC26A7, -A8, and -A9. (SLC26A7).(SLC26A8).(SLC26A9) three entries (PMID:11834742)
• DRA binds to the second PDZ domain of E3KARP in a model that links transporters in the proximal colon through dimerization of E3KARP. (PMID:12369822)
• DRA differs from other bicarbonate transport proteins because its transport activity is not stimulated by direct interaction with Carbonic anhydrase II (PMID:12372813)
• Truncation of up to 44 C-terminal amino acids from the putatively cytoplasmic C-terminal hydrophilic domain left transport function unimpaired, but deletion of the adjacent STAS (sulfate transporter anti-sigma factor antagonist) domain abolished function. (PMID:12651923)
• DRA mediated electroneutral Cl-/HCO3- exchange but OH- was not transported and SO4(2-)/HCO3- exchange was minimal (PMID:15480750)
• male subfertility is a clinical manifestation of CLD (PMID:16412765)
• Tissue-specific co-expression of SLC26A3 with CFTR and NHE3 supports diverse functions of SLC26A3 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)
• findings were used to develop a turnover cycle for Cl- and HCO3- transport by slc26a3 (PMID:16606687)
• indirect evidence against a role of DRA in pancreatic HCO3 secretion (PMID:16715296)
• Involvement of transcription factors in DRA expression in intestinal differentiated epithelial cells. (PMID:17761837)
• In a heterologous mammalian expression system biochemical, immunohistochemical, and ion transport experiments suggest that the four Congenital chloride-losing diarrhea mutations cause SLC26A3 transporter misfolding and/or mistrafficking (PMID:18216024)
• 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)
• Regulation of intestinal Cl-/HCO3- exchanger SLC26A3 by intracellular pH. (PMID:19321737)
• In HEK cells, which express little PDZK1, additional transfection of PDZK1 was required for UTP to inhibit DRA. (PMID:19447883)
• glycoprotein gene SLC26A3 new susceptibility loci for ulcerative colitis in the Japanese population. (PMID:19915573)
• studies provide evidence for the involvement of STAT1 in the inhibition of SLC26A3 gene expression by IFN-gamma in the human intestine (PMID:19940027)
• Increase in DRA promoter activity and expression may contribute to the upregulation of intestinal electrolyte absorption and might underlie the potential antidiarrheal effects of Lactobacillus acidophilus. (PMID:20044511)
• These results suggest that the activity of DRA depends on its LR association, on its interaction with NHERF family proteins, and on phosphatidylinositol 3-kinase activity. (PMID:20634435)
• Endogenous and recombinant human/mouse Slc26a3 do not exhibit electrogenic 2Cl-/1HCO- exchange. Acute induction of Slc26a3 Cl-/HCO3- exchange is associated with secondary membrane potential changes representing homeostatic responses. (PMID:21068358)
• study describes 2 novel mutations in 2 siblings with congenital chloride diarrhea (CLD)from Andalusia; show the presence of compound heterozygous mutations as the cause of CLD in this family (PMID:21150650)
• This review summarizes the current knowledge of SLC26A3 mutations and polymorphisms in congenital chloride diarrhea. [Review] (PMID:21394828)
• Data from pediatric patients with congenital chloride diarrhea identifies 7 novel mutations in SLC26A3, including 3 missense changes of highly conserved residues. (PMID:21694535)
• these data indicate that N-glycosylation of SLC26A3 is important for cell surface expression and for protection from proteolytic degradation that may contribute to the understanding of pathogenesis of congenital disorders of glycosylation. (PMID:22159084)
• The SLC26A3-NHERF4 interaction was modulated by phosphorylation; serine 329 of NHERF4-PDZ3 played a critical role in modulating binding selectivity. (PMID:22627094)
• This is the first report to demonstrate the genetic background of congenital chloride diarrhea in a single ethnic group of East Asian descent (Korean). The c.2063-1G>T mutation wa found in at least one allele of all patients. (PMID:23274434)
• Slc26a3 contributes to sulfate secretion via DIDS-senstive bicarbonate-sulfate exchange in addition to being the principal DIDS-resistant chloride-bicarbonate exchanger. (PMID:23660504)
• few patients develop illnesses because of SLC26A3 mutations. (PMID:23756661)
• Efficacy of lactobacillus acidophilus or its secreted soluble factors in alleviating inflammation and inflammation-associated dysregulation of DRA activity could justify their therapeutic potential in inflammatory diarrheal diseases. (PMID:25059823)
• Data demonstrate an upregulation of SLC26A3 via activation of the ERK1/2 pathway that may underlie potential antidiarrheal effects of Bifidobacterium sp. (PMID:25143346)
• A variety of mutations in SLC26A3 are responsible for CCD. A total of 55 mutations in SLC26A3 have been reported (PMID:25711268)
• Expression of NHE3 and DRA was reduced with high tacrolimus levels and impaired renal function after intestinal transplantation. (PMID:27109987)
• Results indicate the involvement of SLC26A3 along with SLC26A6 in transporting HCO3(-) essential for embryo cleavage, possibly working in concert with CFTR through a Cl(-) recycling pathway. (PMID:27346053)
• We report the first Tunisian case of SLC26A3 gene mutation in congenital chloride diarrhea. Our patient was homozygous for G187X mutation. Both parents were heterozygous for the same mutation. (PMID:27525615)
• Genetic variations of the SLC26A3 rs2108225 is associated with enhance the risk of ulcerative colitis. (PMID:28397232)
• This study confirms the molecular heterogeneity of sporadic congenital chloride diarrhea, adding 12 novel SLC26A3 mutations to the list of known pathogenic mutations. (PMID:28644346)
• In intestinal cells, TNF activates NF-kappaB, which reduces expression of the Cl(-) / HCO3(-) exchanger SLC26A3, via direct binding to the promoter region. (PMID:28823863)
• Molecular analysis of human solute carrier SLC26A2, SLC26A3, and SLC26A4 anion transporter disease-causing mutations using 3-dimensional homology modeling has been presented. (PMID:28941661)
• missense mutation in SLC26A3 is associated with human male subfertility and impaired activation of CFTR (PMID:29079751)
• TNFalpha may act reciprocally with DRA, leading to the development of intestinal inflammation. (PMID:29286110)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	slc26a3.2	ENSDARG00000003615
danio_rerio	slc26a3.1	ENSDARG00000007371
mus_musculus	Slc26a3	ENSMUSG00000001225
rattus_norvegicus	Slc26a3	ENSRNOG00000006878

Paralogs (9): SLC26A4 (ENSG00000091137), SLC26A8 (ENSG00000112053), SLC26A1 (ENSG00000145217), SLC26A7 (ENSG00000147606), SLC26A2 (ENSG00000155850), SLC26A5 (ENSG00000170615), SLC26A9 (ENSG00000174502), SLC26A11 (ENSG00000181045), SLC26A6 (ENSG00000225697)

Protein

Protein identifiers

Chloride anion exchanger — P40879 (reviewed: P40879)

Alternative names: Down-regulated in adenoma, Solute carrier family 26 member 3

All UniProt accessions (3): P40879, C9JFJ2, F8WBL6

UniProt curated annotations — full annotation on UniProt →

Function. Mediates chloride-bicarbonate exchange with a chloride bicarbonate stoichiometry of 2:1 in the intestinal epithelia. Plays a role in the chloride and bicarbonate homeostasis during sperm epididymal maturation and capacitation.

Subunit / interactions. Interacts with CFTR, SLC26A6 and NHERF1. Interacts with PDZK1. Interacts (via PDZ-binding motif) with NHERF4 (via the third PDZ domain); interaction leads to decreased expression of SLC26A3 on the cell membrane resulting in its reduced exchanger activity.

Subcellular location. Apical cell membrane. Membrane. Cell membrane.

Tissue specificity. Expressed in the colon. Expression is significantly decreased in adenomas (polyps) and adenocarcinomas of the colon.

Post-translational modifications. N-glycosylation is required for efficient cell surface expression, and protection from proteolytic degradation.

Disease relevance. Diarrhea 1, secretory chloride, congenital (DIAR1) [MIM:214700] A disease characterized by voluminous watery stools containing an excess of chloride. The children with this disease are often premature. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Inhibited by acidic pH.

Similarity. Belongs to the SLC26A/SulP transporter (TC 2.A.53) family.

RefSeq proteins (1): NP_000102* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001902	SLC26A/SulP_fam	Family
IPR002645	STAS_dom	Domain
IPR011547	SLC26A/SulP_dom	Domain
IPR018045	S04_transporter_CS	Conserved_site
IPR036513	STAS_dom_sf	Homologous_superfamily

Pfam: PF00916, PF01740

Catalyzed reactions (Rhea), 1 shown:

• hydrogencarbonate(in) + 2 chloride(out) = hydrogencarbonate(out) + 2 chloride(in) (RHEA:72203)

UniProt features (129 total): helix 36, sequence variant 34, strand 18, turn 13, topological domain 11, transmembrane region 10, glycosylation site 3, chain 1, domain 1, short sequence motif 1, mutagenesis site 1

Structure

Experimental structures (PDB)

13 structures.

PDB	Method	Resolution (Å)
8X1U	ELECTRON MICROSCOPY	2.21
8X1Q	ELECTRON MICROSCOPY	2.29
8X1S	ELECTRON MICROSCOPY	2.37
8X1T	ELECTRON MICROSCOPY	2.47
8X1R	ELECTRON MICROSCOPY	2.72
7XUH	ELECTRON MICROSCOPY	2.76
7XUJ	ELECTRON MICROSCOPY	2.8
7XUL	ELECTRON MICROSCOPY	3.16
8X2N	ELECTRON MICROSCOPY	3.18
8YR9	ELECTRON MICROSCOPY	3.18
8IET	ELECTRON MICROSCOPY	3.5
8YRA	ELECTRON MICROSCOPY	3.78
8YS8	ELECTRON MICROSCOPY	3.79

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P40879-F1	84.91	0.58

Functional residue map

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

Glycosylation sites (3): 153, 161, 165

Mutagenesis-validated functional residues (1):

Position	Phenotype
761–764	loss of interaction with nherf4. no effect on localization to cell membrane or its exchanger activity.

Function

Pathways and Gene Ontology

Reactome pathways

8 pathways

ID	Pathway
R-HSA-427601	Inorganic anion exchange by SLC26 transporters
R-HSA-5619085	Defective SLC26A3 causes congenital secretory chloride diarrhea 1 (DIAR1)
R-HSA-1643685	Disease
R-HSA-382551	Transport of small molecules
R-HSA-425393
R-HSA-425407	SLC-mediated transmembrane transport
R-HSA-5619102	SLC transporter disorders
R-HSA-5619115	Disorders of transmembrane transporters

MSigDB gene sets: 205 (showing top): GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_INORGANIC_ANION_TRANSPORT, TGACCTY_ERR1_Q2, GOBP_MALE_GAMETE_GENERATION, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_ORGANIC_ACID_TRANSPORT, COUP_01, GOBP_SPERM_CAPACITATION, GOBP_ANATOMICAL_STRUCTURE_MATURATION, GOBP_CHLORIDE_TRANSPORT, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM4, GOBP_RESPONSE_TO_CAMP, GOBP_CELL_MATURATION, TGCTGAY_UNKNOWN, GOBP_CELLULAR_RESPONSE_TO_CAMP

GO Biological Process (11): monoatomic ion transport (GO:0006811), monoatomic anion transport (GO:0006820), sperm capacitation (GO:0048240), intracellular pH elevation (GO:0051454), membrane hyperpolarization (GO:0060081), cellular response to cAMP (GO:0071320), sulfate transmembrane transport (GO:1902358), chloride transmembrane transport (GO:1902476), bicarbonate transport (GO:0015701), oxalate transport (GO:0019532), transmembrane transport (GO:0055085)

GO Molecular Function (9): solute:inorganic anion antiporter activity (GO:0005452), secondary active sulfate transmembrane transporter activity (GO:0008271), bicarbonate transmembrane transporter activity (GO:0015106), chloride transmembrane transporter activity (GO:0015108), sulfate transmembrane transporter activity (GO:0015116), oxalate transmembrane transporter activity (GO:0019531), chloride:bicarbonate antiporter activity (GO:0140900), protein binding (GO:0005515), antiporter activity (GO:0015297)

GO Cellular Component (5): plasma membrane (GO:0005886), membrane (GO:0016020), brush border membrane (GO:0031526), sperm midpiece (GO:0097225), apical plasma membrane (GO:0016324)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
SLC-mediated transport of inorganic anions	1
SLC transporter disorders	1
Transport of small molecules	1
Disorders of transmembrane transporters	1
Disease	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transport	3
secondary active transmembrane transporter activity	2
cellular anatomical structure	2
monoatomic ion transport	1
developmental process involved in reproduction	1
spermatid development	1
cellular process involved in reproduction in multicellular organism	1
cell maturation	1
regulation of intracellular pH	1
regulation of membrane potential	1
response to cAMP	1
cellular response to nitrogen compound	1
cellular response to oxygen-containing compound	1
inorganic anion transport	1
transmembrane transport	1
sulfur compound transport	1
chloride transport	1
monoatomic anion transmembrane transport	1
dicarboxylic acid transport	1
cellular process	1
antiporter activity	1
sulfate transmembrane transporter activity	1
bicarbonate transport	1
transmembrane transporter activity	1
monoatomic anion transmembrane transporter activity	1
chloride transmembrane transport	1
sulfur compound transmembrane transporter activity	1
sulfate transmembrane transport	1
dicarboxylic acid transmembrane transporter activity	1
oxalate transport	1
solute:inorganic anion antiporter activity	1
chloride transmembrane transporter activity	1
bicarbonate:monoatomic anion antiporter activity	1
binding	1
membrane	1
cell periphery	1
brush border	1
apical plasma membrane	1
cell projection membrane	1
sperm flagellum	1

Protein interactions and networks

STRING

1682 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLC26A3	NHERF1	O14745	939
SLC26A3	PDZK1	Q5T2W1	903
SLC26A3	SLC9A3	P48764	902
SLC26A3	CFTR	P13569	878
SLC26A3	MBP	P02686	861
SLC26A3	NHERF2	Q15599	829
SLC26A3	SLC13A1	Q9BZW2	816
SLC26A3	Q5Y7H0	Q5Y7H0	784
SLC26A3	HLA-DRB1	P01911	769
SLC26A3	SLC13A4	Q9UKG4	753
SLC26A3	SLC9A2	Q9UBY0	716
SLC26A3	SLC13A2	Q13183	716
SLC26A3	CA2	P00918	670
SLC26A3	HLA-DPB1	P01916	666
SLC26A3	MYO5B	Q9ULV0	639

IntAct

123 interactions, top by confidence:

A	B	Type	Score
SLC26A3	NHERF2	psi-mi:“MI:0407”(direct interaction)	0.720
SLC26A3	NHERF2	psi-mi:“MI:0915”(physical association)	0.720
NHERF2	SLC26A3	psi-mi:“MI:0407”(direct interaction)	0.720
SLC26A3	PDZK1	psi-mi:“MI:0407”(direct interaction)	0.440
SLC26A3	MAST2	psi-mi:“MI:0407”(direct interaction)	0.440
SLC26A3	SNX27	psi-mi:“MI:0407”(direct interaction)	0.440
SLC26A3	MAST1	psi-mi:“MI:0407”(direct interaction)	0.440
SLC26A3	PTPN3	psi-mi:“MI:0407”(direct interaction)	0.440
SLC26A3	SHANK1	psi-mi:“MI:0407”(direct interaction)	0.440
SLC26A3	SCRIB	psi-mi:“MI:0407”(direct interaction)	0.440
SLC26A3	WHRN	psi-mi:“MI:0407”(direct interaction)	0.440
SLC26A3	LIN7B	psi-mi:“MI:0407”(direct interaction)	0.440
SLC26A3	PICK1	psi-mi:“MI:0407”(direct interaction)	0.440
SLC26A3	PARD3B	psi-mi:“MI:0407”(direct interaction)	0.440
SLC26A3	DLG3	psi-mi:“MI:0407”(direct interaction)	0.440
SLC26A3	RHPN1	psi-mi:“MI:0407”(direct interaction)	0.440
SLC26A3	TJP2	psi-mi:“MI:0407”(direct interaction)	0.440
SLC26A3	LIN7C	psi-mi:“MI:0407”(direct interaction)	0.440
SLC26A3	MAGI2	psi-mi:“MI:0407”(direct interaction)	0.440
SLC26A3	TIAM2	psi-mi:“MI:0407”(direct interaction)	0.440
APBA3	SLC26A3	psi-mi:“MI:0407”(direct interaction)	0.440
SLC26A3	PDZRN4	psi-mi:“MI:0407”(direct interaction)	0.440
SLC26A3	MPP2	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (26): SLC9A3R2 (Reconstituted Complex), ABCB1 (Affinity Capture-MS), ATP11B (Affinity Capture-MS), ATP6V0A1 (Affinity Capture-MS), ATP6V0A2 (Affinity Capture-MS), ATP6V0C (Affinity Capture-MS), ATP6V0D1 (Affinity Capture-MS), ATP6V1A (Affinity Capture-MS), ATP6V1B2 (Affinity Capture-MS), ATP6V1E1 (Affinity Capture-MS), CACNA2D1 (Affinity Capture-MS), CD55 (Affinity Capture-MS), ERLIN2 (Affinity Capture-MS), FLOT1 (Affinity Capture-MS), FLOT2 (Affinity Capture-MS)

ESM2 similar proteins: A0FKN5, D7PC76, O00341, O04289, O35874, O43511, O57321, O70531, P24942, P31597, P40879, P43003, P43005, P46411, P50443, P51906, P51907, P53391, P53392, P56564, P58743, Q62273, Q65AC2, Q69DJ1, Q7SYH5, Q7T2C4, Q8BYF6, Q8CIW6, Q8GYH8, Q8JZR4, Q8N695, Q924C9, Q94LW6, Q95135, Q99NH7, Q9BEG8, Q9BXS9, Q9EPH0, Q9FEP7, Q9FY46

Diamond homologs: A0FKN5, A4IIF2, A8J6J0, D7PC76, O43511, O70531, P40879, P45380, P50443, P53391, P53392, P58735, P58743, Q5EBI0, Q5RAL2, Q62273, Q65AC2, Q69DJ1, Q7LBE3, Q7T2C4, Q8BU91, Q8CIW6, Q8GYH8, Q8HY59, Q8NG04, Q8R2Z3, Q8TE54, Q924C9, Q99NH7, Q9BEG8, Q9BXS9, Q9EPH0, Q9FY46, Q9GJY3, Q9H2B4, Q9JKQ2, Q9R154, Q9R155, Q9SAY1, Q9WVC8

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
ETS1	“up-regulates quantity by expression”	SLC26A3	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 79 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	51.9×	1e-06
Unblocking of NMDA receptors, glutamate binding and activation	5	49.4×	1e-06
Negative regulation of NMDA receptor-mediated neuronal transmission	5	49.4×	1e-06
Assembly and cell surface presentation of NMDA receptors	10	46.1×	9e-13
Dopamine Neurotransmitter Release Cycle	5	45.1×	2e-06
Long-term potentiation	5	43.3×	2e-06
Neurexins and neuroligins	11	39.4×	5e-13
Protein-protein interactions at synapses	7	33.8×	8e-08

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	11	84.1×	1e-16
protein localization to synapse	6	60.5×	6e-08
receptor clustering	7	57.5×	6e-09
regulation of postsynaptic membrane neurotransmitter receptor levels	7	45.6×	2e-08
protein-containing complex assembly	9	13.5×	1e-06
cell-cell adhesion	10	13.4×	3e-07
protein localization to plasma membrane	7	10.0×	3e-04
Golgi organization	5	8.8×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	62
Likely pathogenic	60
Uncertain significance	246
Likely benign	424
Benign	48

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1071195	NM_000111.3(SLC26A3):c.614del (p.Leu205fs)	Pathogenic
1074649	NM_000111.3(SLC26A3):c.1414del (p.Trp472fs)	Pathogenic
16754	NM_000111.3(SLC26A3):c.951_953del (p.Val318del)	Pathogenic
16755	NM_000111.3(SLC26A3):c.371A>T (p.His124Leu)	Pathogenic
16757	NM_000111.3(SLC26A3):c.735+708_971+1514del	Pathogenic
16759	NM_000111.3(SLC26A3):c.559G>T (p.Gly187Ter)	Pathogenic
16761	NM_000111.3(SLC26A3):c.1386G>A (p.Trp462Ter)	Pathogenic
1803226	NM_000111.3(SLC26A3):c.1514+1G>A	Pathogenic
2506951	NM_000111.3(SLC26A3):c.1679T>A (p.Val560Asp)	Pathogenic
2702415	NM_000111.3(SLC26A3):c.1021G>T (p.Gly341Ter)	Pathogenic
2705280	NM_000111.3(SLC26A3):c.76A>T (p.Lys26Ter)	Pathogenic
2709449	NM_000111.3(SLC26A3):c.67dup (p.Glu23fs)	Pathogenic
2710688	NM_000111.3(SLC26A3):c.839_840insACACTATGTTGAATAGGAGCGGTGAGAGAGGGCATCCCTGTCTTGTGCCGGTTTTCAAAGGGAATGCTTCCAGNNNNNNNNNNAAAAAAAAAAAAAAAAAAAAAAAGAAATAAATCA (p.Gln280_Arg281insHisTyrValGluTer)	Pathogenic
2713332	NM_000111.3(SLC26A3):c.1735C>T (p.Arg579Ter)	Pathogenic
2732780	NM_000111.3(SLC26A3):c.118A>T (p.Lys40Ter)	Pathogenic
2735075	NM_000111.3(SLC26A3):c.735+4_735+7del	Pathogenic
2738372	NM_000111.3(SLC26A3):c.1743_1744delinsAT (p.Gln582Ter)	Pathogenic
2743332	NM_000111.3(SLC26A3):c.240del (p.Ile81fs)	Pathogenic
2744753	NM_000111.3(SLC26A3):c.594del (p.Ile198fs)	Pathogenic
2745038	NM_000111.3(SLC26A3):c.2092G>T (p.Glu698Ter)	Pathogenic
2753284	NM_000111.3(SLC26A3):c.1407T>A (p.Cys469Ter)	Pathogenic
2758913	NM_000111.3(SLC26A3):c.2017G>T (p.Glu673Ter)	Pathogenic
2760071	NM_000111.3(SLC26A3):c.1281del (p.Ile428fs)	Pathogenic
2765459	NM_000111.3(SLC26A3):c.885del (p.Ile295_Met296insTer)	Pathogenic
2784196	NM_000111.3(SLC26A3):c.23_24del (p.Gln8fs)	Pathogenic
2786763	NM_000111.3(SLC26A3):c.1750C>T (p.Gln584Ter)	Pathogenic
2816311	NM_000111.3(SLC26A3):c.1740_1752del (p.Leu581fs)	Pathogenic
2825281	NM_000111.3(SLC26A3):c.1562del (p.Lys521fs)	Pathogenic
2834470	NM_000111.3(SLC26A3):c.1718_1719del (p.Lys573fs)	Pathogenic
2835525	NM_000111.3(SLC26A3):c.1066del (p.Ser356fs)	Pathogenic

SpliceAI

2647 predictions. Top by Δscore:

Variant	Effect	Δscore
7:107766678:C:CT	donor_gain	1.0000
7:107767574:CTTA:C	donor_loss	1.0000
7:107767575:TTA:T	donor_loss	1.0000
7:107767576:TACC:T	donor_loss	1.0000
7:107767577:A:C	donor_loss	1.0000
7:107767642:TTCC:T	acceptor_loss	1.0000
7:107767644:CCTGA:C	acceptor_loss	1.0000
7:107767645:C:CC	acceptor_gain	1.0000
7:107772047:CACTT:C	donor_loss	1.0000
7:107772048:ACTTA:A	donor_loss	1.0000
7:107772049:CTTAC:C	donor_loss	1.0000
7:107772050:TTA:T	donor_loss	1.0000
7:107772051:TAC:T	donor_loss	1.0000
7:107772053:C:A	donor_loss	1.0000
7:107772053:CCAT:C	donor_gain	1.0000
7:107773936:A:AC	donor_gain	1.0000
7:107773937:C:CC	donor_gain	1.0000
7:107774775:A:AC	donor_gain	1.0000
7:107774776:C:CC	donor_gain	1.0000
7:107774776:CTG:C	donor_gain	1.0000
7:107776450:A:AC	donor_gain	1.0000
7:107776451:C:CC	donor_gain	1.0000
7:107776451:CAG:C	donor_gain	1.0000
7:107776540:TACAT:T	acceptor_gain	1.0000
7:107776542:CAT:C	acceptor_gain	1.0000
7:107776542:CATCT:C	acceptor_loss	1.0000
7:107776543:ATCTG:A	acceptor_loss	1.0000
7:107776544:TCTGT:T	acceptor_loss	1.0000
7:107776545:C:CC	acceptor_gain	1.0000
7:107776546:T:G	acceptor_loss	1.0000

AlphaMissense

5000 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:107774838:C:G	R571P	0.996
7:107778216:A:C	S491R	0.996
7:107778216:A:T	S491R	0.996
7:107778218:T:G	S491R	0.996
7:107783031:A:C	S394R	0.995
7:107783031:A:T	S394R	0.995
7:107783033:T:G	S394R	0.995
7:107789609:G:T	A217D	0.995
7:107791216:A:C	S134R	0.995
7:107791216:A:T	S134R	0.995
7:107791218:T:G	S134R	0.995
7:107791930:A:C	F94L	0.995
7:107791930:A:T	F94L	0.995
7:107791932:A:G	F94L	0.995
7:107767825:C:G	A716P	0.994
7:107793786:T:G	D76A	0.994
7:107791898:C:T	G105E	0.993
7:107791899:C:A	G105W	0.993
7:107793787:C:G	D76H	0.993
7:107778275:A:G	W472R	0.992
7:107778275:A:T	W472R	0.992
7:107773981:A:G	L649P	0.991
7:107778230:C:G	G487R	0.991
7:107789582:A:G	L226P	0.991
7:107789606:G:T	A218D	0.991
7:107789607:C:G	A218P	0.991
7:107789620:G:C	F213L	0.991
7:107789620:G:T	F213L	0.991
7:107789622:A:G	F213L	0.991
7:107767824:G:T	A716D	0.990

dbSNP variants (sampled 300 via entrez): RS1000050117 (7:107783762 A>G,T), RS1000060881 (7:107778678 C>A), RS1000133766 (7:107799021 A>C), RS1000151286 (7:107790675 A>G), RS1000201976 (7:107771695 C>G,T), RS1000244515 (7:107772443 T>A), RS1000268959 (7:107772719 G>A), RS1000276112 (7:107777572 A>G,T), RS1000341640 (7:107784415 A>G), RS1000350860 (7:107800872 C>T), RS1000512960 (7:107796146 C>A,T), RS1000518447 (7:107790446 A>G), RS1000646280 (7:107765833 A>G,T), RS1000814243 (7:107795473 G>A), RS1000837997 (7:107783511 G>T)

Disease associations

OMIM: gene MIM:126650 | disease phenotypes: MIM:214700

GenCC curated gene-disease

Disease	Classification	Inheritance
congenital secretory chloride diarrhea 1	Definitive	Autosomal recessive

Mondo (4): congenital secretory chloride diarrhea 1 (MONDO:0008964), intestinal obstruction (MONDO:0004565), polyhydramnios (MONDO:0004585), hydrops fetalis (MONDO:0015193)

Orphanet (2): Congenital chloride diarrhea (Orphanet:53689), Hydrops fetalis (Orphanet:1041)

HPO phenotypes

21 total (22 of 21 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000841	Hyperactive renin-angiotensin system
HP:0000848	Increased circulating renin concentration
HP:0000859	Increased circulating aldosterone concentration
HP:0001507	Growth abnormality
HP:0001508	Failure to thrive
HP:0001510	Growth delay
HP:0001561	Polyhydramnios
HP:0001622	Premature birth
HP:0001944	Dehydration
HP:0001948	Alkalosis
HP:0002900	Hypokalemia
HP:0002902	Hyponatremia
HP:0003113	Hypochloremia
HP:0003270	Abdominal distention
HP:0003593	Infantile onset
HP:0003621	Juvenile onset
HP:0005208	Secretory diarrhea
HP:0032067	Elevated serum bicarbonate concentration
HP:0034470	Elevated stool chloride content
HP:0200114	Metabolic alkalosis
HP:0001789	Hydrops fetalis

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST000311_10	Ulcerative colitis	7.000000e-06
GCST000311_5	Ulcerative colitis	1.000000e-06
GCST000311_6	Ulcerative colitis	9.000000e-06
GCST000529_6	Ulcerative colitis	1.000000e-07
GCST004131_45	Inflammatory bowel disease	8.000000e-16
GCST004133_10	Ulcerative colitis	9.000000e-21
GCST005537_214	Chronic inflammatory diseases (ankylosing spondylitis, Crohn’s disease, psoriasis, primary sclerosing cholangitis, ulcerative colitis) (pleiotropy)	5.000000e-11
GCST005956_26	Waist-to-hip ratio adjusted for BMI	2.000000e-08
GCST005962_48	Waist-to-hip ratio adjusted for BMI x sex x age interaction (4df test)	2.000000e-06
GCST006146_1	Behavioural changes in frontotemporal lobe dementia	2.000000e-06

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D015160	Hydrops Fetalis	C12.050.703.277.060.480; C15.378.295.480; C15.378.420.826.100.350; C16.300.060.480; C16.320.365.826.100.350; C20.306.480; C23.888.277.395
D007415	Intestinal Obstruction	C06.405.469.531
D006831	Polyhydramnios	C12.050.703.610
C536210	Congenital chloride diarrhea (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4523223 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: transporter — Chloride/bicarbonate exchangers

ChEMBL bioactivities

22 potent at pChembl≥5 of 22 total, top 22 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.60	IC50	25	nM	CHEMBL4436134
7.60	IC50	25	nM	CHEMBL5574882
7.57	IC50	27	nM	CHEMBL5569871
7.40	IC50	40	nM	CHEMBL4464849
7.30	IC50	50	nM	CHEMBL4464849
7.17	IC50	67	nM	CHEMBL5565580
7.11	IC50	78	nM	CHEMBL5567239
7.07	IC50	86	nM	CHEMBL5569246
7.06	IC50	87	nM	CHEMBL5592078
7.06	IC50	87	nM	CHEMBL5575580
6.88	IC50	132	nM	CHEMBL5575646
6.88	IC50	131	nM	CHEMBL5563274
6.85	IC50	140	nM	CHEMBL4544784
6.67	IC50	212	nM	CHEMBL5567359
6.60	IC50	250	nM	CHEMBL4544784
6.56	IC50	274	nM	CHEMBL5563491
6.50	IC50	320	nM	CHEMBL5575409
6.46	IC50	345	nM	CHEMBL5592217
6.30	IC50	500	nM	CHEMBL5566195
6.25	IC50	560	nM	CHEMBL5574665
6.08	IC50	829	nM	CHEMBL5573707
6.05	IC50	900	nM	CHEMBL5563533

PubChem BioAssay actives

21 with measured affinity, of 22 total; 20 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
2-[4,8-dimethyl-2-oxo-7-[[3-(trifluoromethyl)phenyl]methoxy]chromen-3-yl]acetic acid	2094008: Inhibition of DRA (unknown origin) expressed in FRT cells coexpressing iodide-sensitive YFP assessed as reduction in iodine flux measured after 10 mins by fluorescence based assay	ic50	0.0250	uM
2-[8-chloro-4-methyl-2-oxo-7-[[3-(trifluoromethyl)phenyl]methoxy]chromen-3-yl]acetic acid	2094008: Inhibition of DRA (unknown origin) expressed in FRT cells coexpressing iodide-sensitive YFP assessed as reduction in iodine flux measured after 10 mins by fluorescence based assay	ic50	0.0250	uM
2-[8-chloro-7-[(3-iodophenyl)methoxy]-4-methyl-2-oxochromen-3-yl]acetic acid	2094008: Inhibition of DRA (unknown origin) expressed in FRT cells coexpressing iodide-sensitive YFP assessed as reduction in iodine flux measured after 10 mins by fluorescence based assay	ic50	0.0270	uM
2-[7-[(3-iodophenyl)methoxy]-4,8-dimethyl-2-oxochromen-3-yl]acetic acid	2094009: Inhibition of DRA (unknown origin)	ic50	0.0400	uM
2-[8-fluoro-7-[(3-iodophenyl)methoxy]-4-methyl-2-oxochromen-3-yl]acetic acid	2094008: Inhibition of DRA (unknown origin) expressed in FRT cells coexpressing iodide-sensitive YFP assessed as reduction in iodine flux measured after 10 mins by fluorescence based assay	ic50	0.0670	uM
2-[7-[(3-bromophenyl)methoxy]-8-fluoro-4-methyl-2-oxochromen-3-yl]acetic acid	2094008: Inhibition of DRA (unknown origin) expressed in FRT cells coexpressing iodide-sensitive YFP assessed as reduction in iodine flux measured after 10 mins by fluorescence based assay	ic50	0.0780	uM
2-[7-[(3-bromophenyl)methoxy]-8-chloro-4-methyl-2-oxochromen-3-yl]acetic acid	2094008: Inhibition of DRA (unknown origin) expressed in FRT cells coexpressing iodide-sensitive YFP assessed as reduction in iodine flux measured after 10 mins by fluorescence based assay	ic50	0.0860	uM
2-[8-bromo-7-[(3-bromophenyl)methoxy]-4-methyl-2-oxochromen-3-yl]acetic acid	2094008: Inhibition of DRA (unknown origin) expressed in FRT cells coexpressing iodide-sensitive YFP assessed as reduction in iodine flux measured after 10 mins by fluorescence based assay	ic50	0.0870	uM
2-[8-fluoro-4-methyl-2-oxo-7-[[3-(trifluoromethyl)phenyl]methoxy]chromen-3-yl]acetic acid	2094008: Inhibition of DRA (unknown origin) expressed in FRT cells coexpressing iodide-sensitive YFP assessed as reduction in iodine flux measured after 10 mins by fluorescence based assay	ic50	0.0870	uM
2-[8-bromo-4-methyl-2-oxo-7-[[3-(trifluoromethyl)phenyl]methoxy]chromen-3-yl]acetic acid	2094008: Inhibition of DRA (unknown origin) expressed in FRT cells coexpressing iodide-sensitive YFP assessed as reduction in iodine flux measured after 10 mins by fluorescence based assay	ic50	0.1310	uM
2-[8-bromo-7-[(3-iodophenyl)methoxy]-4-methyl-2-oxochromen-3-yl]acetic acid	2094008: Inhibition of DRA (unknown origin) expressed in FRT cells coexpressing iodide-sensitive YFP assessed as reduction in iodine flux measured after 10 mins by fluorescence based assay	ic50	0.1320	uM
2-[7-[(3-bromophenyl)methoxy]-4,8-dimethyl-2-oxochromen-3-yl]acetic acid	2094008: Inhibition of DRA (unknown origin) expressed in FRT cells coexpressing iodide-sensitive YFP assessed as reduction in iodine flux measured after 10 mins by fluorescence based assay	ic50	0.1400	uM
2-[8-chloro-7-[[3-(difluoromethyl)phenyl]methoxy]-4-methyl-2-oxochromen-3-yl]acetic acid	2094008: Inhibition of DRA (unknown origin) expressed in FRT cells coexpressing iodide-sensitive YFP assessed as reduction in iodine flux measured after 10 mins by fluorescence based assay	ic50	0.2120	uM
2-[7-[[3-(difluoromethyl)phenyl]methoxy]-8-fluoro-4-methyl-2-oxochromen-3-yl]acetic acid	2094008: Inhibition of DRA (unknown origin) expressed in FRT cells coexpressing iodide-sensitive YFP assessed as reduction in iodine flux measured after 10 mins by fluorescence based assay	ic50	0.2740	uM
2-[7-[[3-(difluoromethyl)phenyl]methoxy]-4,8-dimethyl-2-oxochromen-3-yl]acetic acid	2094008: Inhibition of DRA (unknown origin) expressed in FRT cells coexpressing iodide-sensitive YFP assessed as reduction in iodine flux measured after 10 mins by fluorescence based assay	ic50	0.3200	uM
2-[8-bromo-7-[[3-(difluoromethyl)phenyl]methoxy]-4-methyl-2-oxochromen-3-yl]acetic acid	2094008: Inhibition of DRA (unknown origin) expressed in FRT cells coexpressing iodide-sensitive YFP assessed as reduction in iodine flux measured after 10 mins by fluorescence based assay	ic50	0.3450	uM
2-[7-[(3-iodophenyl)methoxy]-4,5-dimethyl-2-oxochromen-3-yl]acetic acid	2094008: Inhibition of DRA (unknown origin) expressed in FRT cells coexpressing iodide-sensitive YFP assessed as reduction in iodine flux measured after 10 mins by fluorescence based assay	ic50	0.5000	uM
2-[7-[(3-bromophenyl)methoxy]-4,5-dimethyl-2-oxochromen-3-yl]acetic acid	2094008: Inhibition of DRA (unknown origin) expressed in FRT cells coexpressing iodide-sensitive YFP assessed as reduction in iodine flux measured after 10 mins by fluorescence based assay	ic50	0.5600	uM
2-[7-[[3-(difluoromethyl)phenyl]methoxy]-4,5-dimethyl-2-oxochromen-3-yl]acetic acid	2094008: Inhibition of DRA (unknown origin) expressed in FRT cells coexpressing iodide-sensitive YFP assessed as reduction in iodine flux measured after 10 mins by fluorescence based assay	ic50	0.8290	uM
2-[4,5-dimethyl-2-oxo-7-[[3-(trifluoromethyl)phenyl]methoxy]chromen-3-yl]acetic acid	2094008: Inhibition of DRA (unknown origin) expressed in FRT cells coexpressing iodide-sensitive YFP assessed as reduction in iodine flux measured after 10 mins by fluorescence based assay	ic50	0.9000	uM

CTD chemical–gene interactions

27 total (human), top 27 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Cyclosporine	decreases expression	4
Benzo(a)pyrene	decreases expression, increases methylation, increases mutagenesis	3
Tetrachlorodibenzodioxin	affects expression, decreases expression	3
Aflatoxin B1	affects expression, decreases expression, decreases methylation	3
Estradiol	decreases expression	2
Nickel	decreases expression	2
methyleugenol	decreases expression	1
propionaldehyde	decreases expression	1
sodium arsenite	decreases expression	1
morniflumate	decreases activity	1
vanadyl sulfate	decreases expression	1
tenidap	decreases activity	1
CGP 52608	affects binding, increases reaction	1
Capecitabine	increases expression	1
Decitabine	increases expression, affects cotreatment	1
Bicarbonates	affects transport	1
Calcitriol	increases expression, affects cotreatment	1
Chlorides	affects transport	1
Folic Acid	increases expression	1
Methotrexate	decreases expression	1
Quercetin	decreases expression	1
Dihydrotestosterone	increases expression	1
Testosterone	affects cotreatment, increases expression	1
Zidovudine	decreases expression	1
Isotretinoin	decreases expression	1
Palmitic Acid	decreases expression	1
Okadaic Acid	decreases expression	1

ChEMBL screening assays

6 unique, capped per target: 6 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4418146	Binding	Inhibition of human SLC26A3 expressed in COS7 co-expressing EYFP-HIF assessed as reduction in SCN gradient	Small molecule inhibitors of pendrin ion exchange and pharmaceutical compositions

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D4SU	HuH7-SLC26A3-KO-c3	Cancer cell line	Male
CVCL_D4SV	HuH7-SLC26A3-KO-c6	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01507220	PHASE4	TERMINATED	A Health Economic Trial in Adult Patients Undergoing Open Colectomy MA402S23B301
NCT01507233	PHASE4	TERMINATED	A Health Economic Trial in Adult Patients Undergoing Open Colectomy MA402S23B302
NCT01507246	PHASE4	COMPLETED	Adult Patients Undergoing Open Colectomy MA402S23B303
NCT02058290	PHASE4	TERMINATED	A Health Economic Trial in Adult Patients Undergoing Laparoscopic Colectomy
NCT02812186	PHASE4	COMPLETED	Deep Versus Moderate Neuromuscular Blockade During Laparoscopic Surgery
NCT03334578	PHASE4	WITHDRAWN	The Use of Gastrografin to Help Alleviate Bowel Obstruction in Gastroschisis Patients.
NCT06089551	PHASE4	UNKNOWN	Early vs Postponed Parenteral Nutrition After Emergency Abdominal Surgery
NCT00164879	PHASE3	UNKNOWN	Endolaparoscopic Versus Immediate Surgery for Obstructing Colorectal Cancers
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NCT00758186	PHASE3	COMPLETED	Randomized Trial of Colonic Stents as a Bridge to Surgery
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NCT02275338	PHASE2	COMPLETED	Study to Assess Efficacy and Safety of Lanreotide Autogel 120 MG in Treatment of Clinical Symptoms Associated With Inoperable Malignant Intestinal Obstruction
NCT02365584	PHASE2	TERMINATED	Quality of Life in Patients With Inoperable Malignant Bowel Obstruction
NCT01596764	PHASE1	COMPLETED	Effects of Methylnaltrexone in Comparison to Naloxone on Loperamide-induced Delay of the Oro-cecal, Whole-gut and Colon Transit Time.
NCT01596777	PHASE1	COMPLETED	Effects of 500 mg Immediate Release and Extended Release Methylnaltrexone on Loperamide-induced Delay of the Oro-cecal and Whole-gut Transit Time in Healthy Subjects
NCT02986698	PHASE1	TERMINATED	In Utero Hematopoietic Stem Cell Transplantation for Alpha-thalassemia Major (ATM)
NCT03655223	Not specified	ENROLLING_BY_INVITATION	Early Check: Expanded Screening in Newborns
NCT01083537	PHASE1/PHASE2	TERMINATED	Trial of Best Supportive Care and Either Cisplatin or Paclitaxel to Treat Patients With Primary Ovarian Cancer, Primary Peritoneal Cancer or Fallopian Tube Cancer and Inoperable Malignant Bowel Obstruction
NCT00130715	Not specified	COMPLETED	Seprafilm in the Reduction of Incidence of Bowel Obstruction in General Surgery
NCT00536523	Not specified	TERMINATED	Effect of Serotonin Level on Constipation Caused by Chemotherapy in Patients With Ovarian, Fallopian Tube, or Primary Peritoneal Cancer
NCT01040364	Not specified	COMPLETED	Internal Hernias After Laparoscopic Gastric Bypass
NCT01125280	Not specified	UNKNOWN	Prospective Multicenter Validation of a Severity Score of Strangulated Small Bowel Occlusion
NCT01196494	Not specified	TERMINATED	Study of Intraoperative Colonic Irrigation Versus Stent Placement in Obstructive Left-Sided Colonic Cancer
NCT01669044	Not specified	UNKNOWN	Comparison the Hemodynamics Effects Between Dexmedetomidine and Propofol in Major Abdominal Surgical Patients
NCT01899885	Not specified	COMPLETED	Acute High-risk Abdominal Surgery Study - an Optimized Perioperative Course
NCT01911793	Not specified	TERMINATED	Stoma Tube Decompression and Postoperative Ileus After Major Colorectal Surgery
NCT02116881	Not specified	TERMINATED	Incisional Hernia and Adhesion-Related Bowel Obstruction
NCT02639195	Not specified	UNKNOWN	The Impact of Small Bowel Obstruction (SBO) on Quality of Life (QOL)
NCT02928458	Not specified	WITHDRAWN	Clinical and Financial Impact of an Evidenced-Based Adhesive Small Bowel Obstruction Management Protocol
NCT03086304	Not specified	COMPLETED	Effects of Transcutaneous Acupoint Electrical Stimulation on Intestinal Obstruction After Gastrointestinal Surgery
NCT03150992	Not specified	UNKNOWN	EDMONd - Elemental Diet in Bowel Obstruction
NCT03202576	Not specified	COMPLETED	Nasogastric Tube Securement Comparison Study
NCT03350022	Not specified	COMPLETED	Sham Feeding Post-operative Infants
NCT03593252	Not specified	UNKNOWN	Bowel Preparation in Elective Pediatric Colorectal Surgery
NCT03663023	Not specified	COMPLETED	Band Adhesions in Relation to Previous Abdominal Surgery
NCT03773237	Not specified	COMPLETED	Intralipid Versus SMOFlipid in HPN Patients
NCT03997721	Not specified	COMPLETED	Pathophysiology of Perioperative Fluid Management in Emergency Laparotomy
NCT04020939	Not specified	COMPLETED	The Role of Indocyanine Green Angiography Fluorescence on Intestinal Resections in Pediatric Surgery.
NCT04213976	Not specified	UNKNOWN	Ostomy in Continuity or Conventional Ileostomy: a Retrospective Multicentric Analysis
NCT04403425	Not specified	UNKNOWN	Tissue Perfusion During Emergency Laparotomy