SLC26A9

Summary

SLC26A9 (solute carrier family 26 member 9, HGNC:14469) is a protein-coding gene on chromosome 1q32.1, encoding Solute carrier family 26 member 9 (Q7LBE3). Ion transporter that can act both as an ion channel and anion exchanger.

This gene is one member of a family of sulfate/anion transporter genes. Family members are well conserved in their genomic (number and size of exons) and protein (aa length among species) structures yet have markedly different tissue expression patterns. The product of this gene is a highly selective chloride ion channel regulated by WNK kinases. Alternative splicing results in multiple transcript variants encoding differing isoforms.

Source: NCBI Gene 115019 — RefSeq curated summary.

At a glance

• Gene–disease (curated): cystic fibrosis (Supportive, GenCC)
• GWAS associations: 5
• Clinical variants (ClinVar): 158 total
• Phenotypes (HPO): 35
• Druggable target: yes
• MANE Select transcript: NM_052934

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14469
Approved symbol	SLC26A9
Name	solute carrier family 26 member 9
Location	1q32.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000174502
Ensembl biotype	protein_coding
OMIM	608481
Entrez	115019

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 4 protein_coding, 3 retained_intron

ENST00000340781, ENST00000367134, ENST00000367135, ENST00000461505, ENST00000469392, ENST00000491127, ENST00000865095

RefSeq mRNA: 2 — MANE Select: NM_052934 NM_052934, NM_134325

CCDS: CCDS30989, CCDS30990

Canonical transcript exons

ENST00000367135 — 21 exons

Exon	Start	End
ENSE00001040649	205935696	205935838
ENSE00001193665	205929892	205930056
ENSE00001193671	205931860	205932035
ENSE00001193675	205932702	205932812
ENSE00001193680	205932945	205933084
ENSE00001910538	205913052	205915404
ENSE00003477881	205918840	205918985
ENSE00003487120	205926535	205926630
ENSE00003495133	205917283	205917354
ENSE00003501721	205927902	205928049
ENSE00003505097	205929204	205929356
ENSE00003540045	205928827	205928909
ENSE00003540752	205924383	205924489
ENSE00003545356	205923082	205923195
ENSE00003606395	205921566	205921847
ENSE00003633669	205927211	205927288
ENSE00003634375	205923544	205923613
ENSE00003640686	205923335	205923427
ENSE00003647126	205920176	205920230
ENSE00003667455	205927492	205927605
ENSE00003847749	205943365	205943456

Expression profiles

Bgee: expression breadth ubiquitous, 151 present calls, max score 93.90.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.6676 / max 344.3153, expressed in 61 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
17052	0.5038	33
17044	0.0996	22
17048	0.0335	1
17050	0.0195	5
17051	0.0077	3
17047	0.0035	1

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
parotid gland	UBERON:0001831	93.90	gold quality
left ventricle myocardium	UBERON:0006566	90.37	gold quality
cardiac muscle of right atrium	UBERON:0003379	89.80	gold quality
pancreatic ductal cell	CL:0002079	89.61	silver quality
apex of heart	UBERON:0002098	85.95	gold quality
myocardium	UBERON:0002349	85.14	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.43	silver quality
heart left ventricle	UBERON:0002084	82.86	gold quality
cardiac ventricle	UBERON:0002082	82.68	gold quality
body of stomach	UBERON:0001161	82.57	gold quality
cardiac atrium	UBERON:0002081	82.28	gold quality
right atrium auricular region	UBERON:0006631	81.92	gold quality
stomach	UBERON:0000945	80.82	gold quality
kidney epithelium	UBERON:0004819	80.24	gold quality
epithelium of nasopharynx	UBERON:0001951	80.20	gold quality
pylorus	UBERON:0001166	80.02	gold quality
saliva-secreting gland	UBERON:0001044	79.41	gold quality
upper lobe of lung	UBERON:0008948	79.21	gold quality
upper lobe of left lung	UBERON:0008952	78.90	gold quality
lower lobe of lung	UBERON:0008949	78.83	gold quality
cardia of stomach	UBERON:0001162	78.43	gold quality
heart	UBERON:0000948	77.51	gold quality
epithelial cell of pancreas	CL:0000083	75.42	silver quality
lung	UBERON:0002048	75.18	gold quality
minor salivary gland	UBERON:0001830	75.09	gold quality
right lung	UBERON:0002167	74.52	gold quality
heart right ventricle	UBERON:0002080	74.35	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	74.16	gold quality
mouth mucosa	UBERON:0003729	73.30	gold quality
fundus of stomach	UBERON:0001160	72.86	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	15.78
E-CURD-114	yes	11.96

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
SLC26A9	Activation

Upstream regulators (CollecTRI, top): HMX2, SLC26A9

miRNA regulators (miRDB)

126 targeting SLC26A9, 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-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-4487	99.96	64.58	1252
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-22-3P	99.93	68.13	917
HSA-MIR-12133	99.92	71.82	2006
HSA-MIR-1271-5P	99.91	71.99	1972
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-7162-3P	99.89	68.16	1682
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-12119	99.87	68.35	1653
HSA-MIR-6857-5P	99.87	65.32	985
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-609	99.82	64.26	505

Literature-anchored findings (GeneRIF, showing 28)

• Slc26a9 functions as an electrogenic nCl-/HCO3- exchanger, suggesting a role in pulmonary and gastric HCO3- secretion and/or CO2 transport. (PMID:17120765)
• SLC26A9 is a highly selective Cl(-) channel with minimal OH(-)/HCO(3)(-) permeability that is regulated by the WNK kinases. (PMID:17673510)
• The transport properties of human SLC26A9 was studied to determine its functional and pharmacological characteristics. (PMID:18769029)
• Functions as an anion conductance in the apical membranes of bronchial epithelium; contributes to transepithelial chloride currents under basal and cyclic AMP/protein kinase A-stimulated conditions. (PMID:19289574)
• These results imply that Slc26-STAS domains may all interact with (R)CFTR but that the physiological outcome is specific to differing Slc26 proteins, allowing for dynamic and acute fine tuning of ion transport for various epithelia. (PMID:19643730)
• The interactions between SLC26A9 and CFTR were studied, and an alternative hypothesis to their known interactions is presented. (PMID:20658517)
• the L683P mutation of SLC26A9 was found to reduce Cl(-) transport through SLC26A9 as well as the positive interaction exerted by SLC26A9 on CFTR ion transport activity (PMID:21439353)
• Report functional interaction between CFTR and SLC26A9 in polarized airway epithelial cells and in non-polarized HEK293 cells. (PMID:21809345)
• Single nucleotide polymorphism in SLC26A9 gene is associated with cystic fibrosis. (PMID:22466613)
• SLC26A9 polymorphisms lead to several function modifications (increased activity, decreased activity, altered protein expression), which could lead to a spectrum of pathophysiologies. (PMID:22544634)
• Several SNPs in the 3’ UTR of SLC26A9 (rs12031234, rs2282429, rs2282430)were associated with asthma in children with asthma. (PMID:22945630)
• SLC26A9 is an epithelial chloride/bicarbonate channel that can interact with the CF transmembrane regulator (CFTR), the protein mutated in CF (PMID:23670970)
• We have identified two SLC26A9 mutations decreasing Cl- channel transport in patients with a CF-like lung disease. (PMID:24272871)
• SLC26A9 single nucleotide polymorphisms modify prenatal exocrine pancreatic damage in cystic fibrosis (PMID:25771386)
• Treatment response to ivacaftor, which aims to improve CFTR-channel opening probability in cystic fibrosis patients with gating mutations, shows substantial variability in response, 28% of which can be explained by rs7512462 in SLC26A9. (PMID:28171547)
• when SLC26A9 is coexpressed with F508del CFTR, its trafficking defect leads to a PDZ motif-sensitive intracellular retention of SLC26A9. (PMID:28360110)
• findings indicate that an increase in SLC26A9 expression in ductal cells of the pancreas delays the age at onset of diabetes, suggesting a CFTR-agnostic treatment for a major complication of CF. (PMID:31581148)
• The anion-conducting transporter solute carrier family 26 member 9 (SLC26A9) localizes to the tight junction in well-differentiated bronchi epithelial cell from non-cystic fibrosis (CF) patients, suggesting that F508del-CF transmembrane conductance regulator (CFTR) enhances proteasomal SLC26A9 degradation. (PMID:31645438)
• SLC26A9 SNP rs7512462 is not associated with lung disease severity or lung function response to ivacaftor in cystic fibrosis patients with G551D-CFTR. (PMID:33674211)
• SLC26A9 is selected for endoplasmic reticulum associated degradation (ERAD) via Hsp70-dependent targeting of the soluble STAS domain. (PMID:34821356)
• Synergy in Cystic Fibrosis Therapies: Targeting SLC26A9. (PMID:34884866)
• Alterations in SLC4A2, SLC26A7 and SLC26A9 Drive Acid-Base Imbalance in Gastric Neuroendocrine Tumors and Uncover a Novel Mechanism for a Co-Occurring Polyautoimmune Scenario. (PMID:34944008)
• Expression of SLC26A9 in Airways and Its Potential Role in Asthma. (PMID:35328418)
• SLC26A9 deficiency causes gastric intraepithelial neoplasia in mice and aggressive gastric cancer in humans. (PMID:35426084)
• Identification of single nucleotide variants in SLC26A9 gene in patients with cystic fibrosis (p.Phe508del homozygous) and its association to Orkambi(R) (Lumacaftor and Ivacaftor) response in vitro. (PMID:37068695)
• Pathogenic Relationships in Cystic Fibrosis and Renal Diseases: CFTR, SLC26A9 and Anoctamins. (PMID:37686084)
• The role of the STAS domain in SLC26A9 for chloride ion transporter function. (PMID:38773769)
• The solute carrier family 26 member 9 modifies rapidly progressing cystic fibrosis associated with homozygous F508del CFTR mutation. (PMID:38852790)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Slc26a9	ENSMUSG00000042268
rattus_norvegicus	Slc26a9	ENSRNOG00000029514

Paralogs (9): SLC26A4 (ENSG00000091137), SLC26A3 (ENSG00000091138), SLC26A8 (ENSG00000112053), SLC26A1 (ENSG00000145217), SLC26A7 (ENSG00000147606), SLC26A2 (ENSG00000155850), SLC26A5 (ENSG00000170615), SLC26A11 (ENSG00000181045), SLC26A6 (ENSG00000225697)

Protein

Protein identifiers

Solute carrier family 26 member 9 — Q7LBE3 (reviewed: Q7LBE3)

Alternative names: Anion transporter/exchanger protein 9

All UniProt accessions (1): Q7LBE3

UniProt curated annotations — full annotation on UniProt →

Function. Ion transporter that can act both as an ion channel and anion exchanger. Mainly acts as a chloride channel, which mediate uncoupled chloride anion transport in an alternate-access mechanism where a saturable binding site is alternately exposed to either one or the other side of the membrane. Also acts as a DIDS- and thiosulfate- sensitive anion exchanger the exchange of chloride for bicarbonate ions across the cell membrane.

Subunit / interactions. Homodimer.

Subcellular location. Cell membrane. Endomembrane system.

Tissue specificity. Predominantly expressed in lung at the luminal side of the bronchiolar and alveolar epithelium of lung. To a lower extent, also expressed in pancreas and prostate.

Activity regulation. Inhibited by ammonium and thiosulfate.

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

Isoforms (2)

UniProt ID	Names	Canonical?
Q7LBE3-1	1	yes
Q7LBE3-2	2

RefSeq proteins (2): NP_443166, NP_599152 (=MANE)

Domains & families (InterPro)

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

Pfam: PF00916, PF01740

Catalyzed reactions (Rhea), 2 shown:

• chloride(in) = chloride(out) (RHEA:29823)
• hydrogencarbonate(in) + chloride(out) = hydrogencarbonate(out) + chloride(in) (RHEA:72363)

UniProt features (109 total): helix 34, topological domain 16, transmembrane region 14, turn 10, strand 9, mutagenesis site 9, sequence variant 8, sequence conflict 2, compositionally biased region 2, chain 1, intramembrane region 1, domain 1, region of interest 1, splice variant 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
7CH1	ELECTRON MICROSCOPY	2.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q7LBE3-F1	79.93	0.48

Functional residue map

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

Mutagenesis-validated functional residues (9):

Position	Phenotype
88	reduced chloride ion flux.
131	reduced chloride ion flux.
132	reduced chloride ion flux.
166	reduced chloride ion flux.
201	increased current; when associated with a-781.
775–782	increased current.
775–776	increased current.
781	increased current; when associated with k-201.
783	increased current.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-427601	Inorganic anion exchange by SLC26 transporters
R-HSA-382551	Transport of small molecules
R-HSA-425393
R-HSA-425407	SLC-mediated transmembrane transport

MSigDB gene sets: 249 (showing top): MYAATNNNNNNNGGC_UNKNOWN, YAATNRNNNYNATT_UNKNOWN, CCAWYNNGAAR_UNKNOWN, LFA1_Q6, GOCC_CELL_SURFACE, GOBP_INORGANIC_ANION_TRANSPORT, GTTAAAG_MIR302B, GOBP_ORGANIC_ACID_TRANSPORT, EVI1_05, TCF4_Q5, AP1_Q4_01, GATA3_01, GOBP_CHLORIDE_TRANSPORT, BACH2_01, MARTIN_NFKB_TARGETS_UP

GO Biological Process (8): monoatomic ion transport (GO:0006811), monoatomic anion transport (GO:0006820), chloride transport (GO:0006821), positive regulation of gene expression (GO:0010628), sulfate transmembrane transport (GO:1902358), chloride transmembrane transport (GO:1902476), oxalate transport (GO:0019532), transmembrane transport (GO:0055085)

GO Molecular Function (7): chloride channel activity (GO:0005254), solute:inorganic anion antiporter activity (GO:0005452), sulfate transmembrane transporter activity (GO:0015116), oxalate transmembrane transporter activity (GO:0019531), ATPase binding (GO:0051117), chloride:bicarbonate antiporter activity (GO:0140900), protein binding (GO:0005515)

GO Cellular Component (9): Golgi membrane (GO:0000139), endoplasmic reticulum membrane (GO:0005789), plasma membrane (GO:0005886), cell surface (GO:0009986), endosome membrane (GO:0010008), apical plasma membrane (GO:0016324), extracellular exosome (GO:0070062), endomembrane system (GO:0012505), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
SLC-mediated transport of inorganic anions	1
Transport of small molecules	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
transport	2
inorganic anion transport	2
chloride transmembrane transporter activity	2
bounding membrane of organelle	2
monoatomic ion transport	1
monoatomic anion transport	1
gene expression	1
regulation of gene expression	1
positive regulation of macromolecule biosynthetic process	1
transmembrane transport	1
sulfur compound transport	1
chloride transport	1
monoatomic anion transmembrane transport	1
dicarboxylic acid transport	1
cellular process	1
monoatomic anion channel activity	1
antiporter activity	1
sulfur compound transmembrane transporter activity	1
sulfate transmembrane transport	1
dicarboxylic acid transmembrane transporter activity	1
oxalate transport	1
enzyme binding	1
solute:inorganic anion antiporter activity	1
bicarbonate:monoatomic anion antiporter activity	1
binding	1
Golgi apparatus	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
membrane	1
cell periphery	1
endosome	1
cytoplasmic vesicle membrane	1
apical part of cell	1
plasma membrane region	1
extracellular vesicle	1
vacuole	1
plasma membrane	1

Protein interactions and networks

STRING

1204 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLC26A9	CFTR	P13569	874
SLC26A9	SLC6A14	Q9UN76	652
SLC26A9	ANO1	Q5XXA6	611
SLC26A9	SLC4A4	Q9Y6R1	611
SLC26A9	SLC4A9	Q96Q91	596
SLC26A9	SLC9A3	P48764	592
SLC26A9	SLC4A3	P48751	581
SLC26A9	SLC4A8	Q2Y0W8	553
SLC26A9	SLC4A5	Q9BY07	544
SLC26A9	SLC4A7	Q9Y6M7	518
SLC26A9	CA2	P00918	513
SLC26A9	SLC26A8	Q96RN1	498
SLC26A9	SLC4A2	P04920	482
SLC26A9	WNK3	Q9BYP7	467
SLC26A9	CLCA1	A8K7I4	463

IntAct

6 interactions, top by confidence:

A	B	Type	Score
CFTR	NHERF1	psi-mi:“MI:0407”(direct interaction)	0.940
CFTR	NHERF2	psi-mi:“MI:0407”(direct interaction)	0.940
	SLC26A9	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (2): SLC26A9 (Affinity Capture-MS), SLC26A9 (Affinity Capture-MS)

ESM2 similar proteins: A4IIF2, A8J6J0, B0JZG0, D7PC76, E9Q3M5, G3X939, G5EBK1, O04722, O13134, O88343, P02730, P04919, P23562, P26433, P32847, P58743, P92946, Q02920, Q11180, Q21751, Q22682, Q28362, Q2Y0W8, Q32LP4, Q4R445, Q4U116, Q5DTL9, Q5RAL2, Q6RI88, Q6RVG2, Q6U841, Q7LBE3, Q80ZA5, Q8BU91, Q8JZR6, Q8R2Z3, Q8T5S1, Q8TE54, Q94225, Q99NH7

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

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	133
Likely benign	6
Benign	6

Top pathogenic / likely-pathogenic (0)

SpliceAI

3225 predictions. Top by Δscore:

Variant	Effect	Δscore
1:205917277:GCTCA:G	donor_loss	1.0000
1:205917278:CTCA:C	donor_loss	1.0000
1:205917279:TCA:T	donor_loss	1.0000
1:205917280:CACCT:C	donor_loss	1.0000
1:205917281:A:C	donor_loss	1.0000
1:205917282:C:CA	donor_loss	1.0000
1:205917282:CCTG:C	donor_gain	1.0000
1:205918838:ACC:A	donor_gain	1.0000
1:205918839:CCC:C	donor_gain	1.0000
1:205921560:CCTCA:C	donor_loss	1.0000
1:205921561:CTCAC:C	donor_loss	1.0000
1:205921562:TCACC:T	donor_loss	1.0000
1:205921563:CA:C	donor_loss	1.0000
1:205921564:A:AC	donor_gain	1.0000
1:205921564:A:C	donor_loss	1.0000
1:205921565:C:CC	donor_gain	1.0000
1:205921565:C:T	donor_loss	1.0000
1:205921843:ACAGT:A	acceptor_gain	1.0000
1:205921844:CAGT:C	acceptor_gain	1.0000
1:205921844:CAGTC:C	acceptor_gain	1.0000
1:205923105:T:TA	donor_gain	1.0000
1:205923624:C:CT	acceptor_gain	1.0000
1:205923625:A:T	acceptor_gain	1.0000
1:205924381:A:AC	donor_gain	1.0000
1:205924382:C:CC	donor_gain	1.0000
1:205924382:CAA:C	donor_gain	1.0000
1:205926529:ACTT:A	donor_loss	1.0000
1:205926530:CTTA:C	donor_loss	1.0000
1:205926531:TTACA:T	donor_loss	1.0000
1:205926532:TA:T	donor_loss	1.0000

AlphaMissense

5213 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:205923372:G:T	A541D	0.999
1:205924472:G:C	S469R	0.999
1:205924472:G:T	S469R	0.999
1:205924474:T:G	S469R	0.999
1:205932016:G:C	S132R	0.999
1:205932016:G:T	S132R	0.999
1:205932018:T:G	S132R	0.999
1:205918899:C:G	A733P	0.998
1:205921586:C:G	G679R	0.998
1:205921594:T:A	D676V	0.998
1:205923345:A:T	V550D	0.998
1:205923368:G:C	N542K	0.998
1:205923368:G:T	N542K	0.998
1:205924426:C:G	G485R	0.998
1:205924483:A:G	W466R	0.998
1:205924483:A:T	W466R	0.998
1:205926599:A:G	L442P	0.998
1:205929977:G:T	A211D	0.998
1:205929992:C:T	G206D	0.998
1:205929993:C:G	G206R	0.998
1:205932026:G:T	A129D	0.998
1:205932802:A:C	F92L	0.998
1:205932802:A:T	F92L	0.998
1:205932804:A:G	F92L	0.998
1:205918895:A:T	V734D	0.997
1:205918898:G:T	A733E	0.997
1:205921585:C:T	G679D	0.997
1:205921594:T:G	D676A	0.997
1:205921599:G:C	F674L	0.997
1:205921599:G:T	F674L	0.997

dbSNP variants (sampled 300 via entrez): RS1000280628 (1:205918405 C>T), RS1000293247 (1:205933653 G>A), RS1000337669 (1:205924058 G>C), RS1000446960 (1:205940706 T>C), RS1000526571 (1:205940996 C>T), RS1000601067 (1:205945456 G>T), RS1000677569 (1:205935142 A>C,G), RS1000714141 (1:205918043 G>A,T), RS1000750169 (1:205912992 G>C), RS1000909083 (1:205935382 C>A,T), RS1001137918 (1:205929509 G>A), RS1001224493 (1:205913356 G>A,T), RS1001345811 (1:205922880 C>A), RS1001389933 (1:205945403 T>C), RS1001604183 (1:205940214 G>A)

Disease associations

OMIM: gene MIM:608481 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
cystic fibrosis	Supportive	Autosomal recessive

Mondo (1): cystic fibrosis (MONDO:0009061)

Orphanet (0):

HPO phenotypes

35 total (30 of 35 shown, HPO-id order):

HPO	Term
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:0001738	Exocrine pancreatic insufficiency
HP:0002020	Gastroesophageal reflux
HP:0002024	Malabsorption
HP:0002035	Rectal prolapse
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:0004401	Meconium ileus
HP:0005376	Recurrent Haemophilus influenzae infections
HP:0006536	Airway obstruction
HP:0012236	Elevated sweat chloride

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST000884_2	Response to antipsychotic treatment	1.000000e-07
GCST002025_1	Cystic fibrosis-related diabetes	1.000000e-09
GCST002688_8	Very long-chain saturated fatty acid levels (fatty acid 22:0)	2.000000e-06
GCST002868_15	Response to serotonin reuptake inhibitors in major depressive disorder	3.000000e-06
GCST007367_7	Meconium ileus in cystic fibrosis	3.000000e-11

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0006796	very long-chain saturated fatty acid measurement
EFO:0005658	response to selective serotonin reuptake inhibitor

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): CHEMBL4523359 (SINGLE PROTEIN)

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs7512462	Efficacy	3	ivacaftor	Cystic Fibrosis

PharmGKB variants

2 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs11240594	SLC26A9		0.00	0
rs7512462	SLC26A9	3	2.00	1	ivacaftor

GtoPdb / IUPHAR curated pharmacology

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

Target class: transporter — Anion channels

CTD chemical–gene interactions

17 total (human), top 17 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression, decreases methylation, increases methylation	2
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
butyraldehyde	decreases expression	1
CGP 52608	affects binding, increases reaction	1
abrine	decreases expression	1
(+)-JQ1 compound	decreases expression	1
Doxorubicin	decreases expression	1
Oxalates	affects reaction, increases expression	1
Silicon Dioxide	decreases expression	1
Smoke	affects reaction, increases expression	1
Tobacco Smoke Pollution	increases expression	1
Triclosan	decreases expression	1
Valproic Acid	increases methylation	1
Zearalenone	decreases expression	1
Zidovudine	increases expression	1
Okadaic Acid	decreases expression	1
Lactic Acid	decreases expression	1

ChEMBL screening assays

4 unique, capped per target: 3 binding, 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4375443	Binding	Inhibition of human slc26a9 expressed in FRT cells co-expressing EYFP-H148Q/I152L/F46L assessed as reduction in protein-mediated chloride/iodide exchange at 10 uM preincubated for 10 mins followed by NaI-substituted PBS addition and measure	4,8-Dimethylcoumarin Inhibitors of Intestinal Anion Exchanger slc26a3 (Downregulated in Adenoma) for Anti-Absorptive Therapy of Constipation. — J Med Chem
CHEMBL5209598	Functional	Chloride uptake by the Anion Transporter/Exchanger Protein 9 (SLC26A9) as assessed by a Cl- sensitive FRET (Fluorescence Resonance Energy Transfer) sensor (SuperClomeleon) in HEK-293 cells stably transfected with SLC26A9 (PubChem AID: 17948	Superclomeleon biosensor-based assay for SLC26A9 using HEK293 SLC26A9 JumpIn OE cells

Clinical trials (associated diseases)

300 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