ANO1

Summary

ANO1 (anoctamin 1, HGNC:21625) is a protein-coding gene on chromosome 11q13.3, encoding Anoctamin-1 (Q5XXA6). Calcium-activated chloride channel (CaCC).

Enables identical protein binding activity; iodide transmembrane transporter activity; and ligand-gated monoatomic ion channel activity. Involved in several processes, including monoatomic anion transport; mucus secretion; and positive regulation of insulin secretion involved in cellular response to glucose stimulus. Located in apical plasma membrane and nucleoplasm. Implicated in Moyamoya disease.

Source: NCBI Gene 55107 — RefSeq curated summary.

At a glance

• Gene–disease (curated): intestinal dysmotility syndrome (Moderate, GenCC) — +1 more curated relationship
• GWAS associations: 18
• Clinical variants (ClinVar): 207 total — 3 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 27
• Druggable target: yes — 2 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_018043

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21625
Approved symbol	ANO1
Name	anoctamin 1
Location	11q13.3
Locus type	gene with protein product
Status	Approved
Aliases	TAOS2, FLJ10261, DOG1
Ensembl gene	ENSG00000131620
Ensembl biotype	protein_coding
OMIM	610108
Entrez	55107

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 8 protein_coding, 3 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000316296, ENST00000355303, ENST00000525494, ENST00000529636, ENST00000529913, ENST00000530676, ENST00000531300, ENST00000531349, ENST00000531604, ENST00000689710, ENST00000930664, ENST00000930665

RefSeq mRNA: 7 — MANE Select: NM_018043 NM_001378092, NM_001378093, NM_001378094, NM_001378095, NM_001378096, NM_001378097, NM_018043

CCDS: CCDS44663, CCDS91524

Canonical transcript exons

ENST00000355303 — 26 exons

Exon	Start	End
ENSE00000737880	70161161	70161362
ENSE00000737913	70156947	70157021
ENSE00000992053	70153057	70153128
ENSE00001064305	70126061	70126195
ENSE00001165274	70161622	70161733
ENSE00001235937	70124350	70124414
ENSE00001235944	70116458	70116499
ENSE00001235996	70131919	70132079
ENSE00001336001	70163283	70163340
ENSE00001470960	70155911	70155988
ENSE00001614847	70165470	70165570
ENSE00002143830	70187738	70189530
ENSE00002183067	70078317	70078714
ENSE00002444031	70152450	70152461
ENSE00002449881	70103066	70103164
ENSE00002464828	70103999	70104150
ENSE00003479961	70185590	70185695
ENSE00003484117	70105734	70105788
ENSE00003533817	70149710	70149792
ENSE00003535366	70180004	70180056
ENSE00003539674	70108353	70108404
ENSE00003556435	70167242	70167387
ENSE00003563988	70182502	70182686
ENSE00003595082	70087752	70088084
ENSE00003645458	70111707	70111762
ENSE00003654272	70170887	70171039

Expression profiles

Bgee: expression breadth ubiquitous, 214 present calls, max score 98.11.

FANTOM5 (CAGE): breadth broad, TPM avg 2.9355 / max 395.2815, expressed in 384 samples.

FANTOM5 promoters (14 alternative TSS)

Promoter ID	TPM avg	Samples expressed
115629	0.7073	149
115634	0.5140	127
115627	0.4971	78
115630	0.2991	101
115635	0.2425	108
115622	0.2286	83
115632	0.1416	62
115628	0.1021	25
115631	0.0819	40
115633	0.0743	34

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
caput epididymis	UBERON:0004358	98.11	gold quality
seminal vesicle	UBERON:0000998	97.95	gold quality
corpus epididymis	UBERON:0004359	97.93	gold quality
parotid gland	UBERON:0001831	97.76	gold quality
ascending aorta	UBERON:0001496	96.54	gold quality
thoracic aorta	UBERON:0001515	96.52	gold quality
gall bladder	UBERON:0002110	96.08	gold quality
descending thoracic aorta	UBERON:0002345	96.01	gold quality
mucosa of stomach	UBERON:0001199	95.57	gold quality
cauda epididymis	UBERON:0004360	94.29	gold quality
right coronary artery	UBERON:0001625	93.85	gold quality
mammary duct	UBERON:0001765	93.67	gold quality
right uterine tube	UBERON:0001302	93.26	gold quality
blood vessel layer	UBERON:0004797	92.23	gold quality
epithelium of mammary gland	UBERON:0003244	92.11	gold quality
upper leg skin	UBERON:0004262	92.10	gold quality
saliva-secreting gland	UBERON:0001044	92.09	gold quality
aorta	UBERON:0000947	91.82	gold quality
right lobe of liver	UBERON:0001114	91.66	gold quality
urethra	UBERON:0000057	91.65	gold quality
skin of abdomen	UBERON:0001416	91.63	gold quality
saphenous vein	UBERON:0007318	91.61	gold quality
lower esophagus muscularis layer	UBERON:0035833	91.59	gold quality
lower esophagus	UBERON:0013473	91.50	gold quality
sural nerve	UBERON:0015488	90.87	gold quality
minor salivary gland	UBERON:0001830	90.56	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	90.38	gold quality
left uterine tube	UBERON:0001303	90.32	gold quality
left coronary artery	UBERON:0001626	90.32	gold quality
skin of leg	UBERON:0001511	90.25	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-2	yes	3085.63
E-ANND-3	yes	16.38

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

101 targeting ANO1, 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-9-5P	100.00	72.28	2361
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-4262	100.00	73.26	3931
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-548C-3P	99.99	74.01	7587
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-548AW	99.99	72.57	3559
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-548BB-3P	99.86	70.58	4354

Literature-anchored findings (GeneRIF, showing 40)

• This gene, located within the CCND1-EMS1 locus on human chromosome 11q13, encodes the eight-transmembrane protein homologous to C12orf3, C11orf25 and FLJ34272 gene products and is amplified in various cancers (PMID:12739008)
• Based on four cases, the DOG1 gene was found not to be mutated in gastrointestinal stromal tumors. (PMID:18648740)
• results indicate that TMEM16A is an intrinsic constituent of the calcium-dependent chloride channel (PMID:18772398)
• DOG1.1 is a sensitive immunohistochemical marker for gastrointestinal stromal tumors (PMID:19011564)
• Ano1 labels all classes of interstitial cells of Cajal (ICC) and represents a highly specific marker for studying the distribution of ICC in mouse and human gastrointestinal tissues. (PMID:19372102)
• DOG1 should be added into the diagnostic panel evaluating GI and other abdominal tumors, but limitations in its sensitivity and specificity should be recognized. (PMID:19606013)
• TMEM16 proteins appear to be a crucial component of epithelial volume-regulated Cl(-) channels and may also have a function during proliferation and apoptotic cell death (PMID:19654323)
• Anoctin 1 (Ano1) was observed in specialized populations of cells with the morphologies of all classes of Interstitial cells of Cajal. Data suggest a novel role for ANO1 Cl- channels in the generation of slow waves in gastrointestinal muscles. (PMID:19687122)
• Data show that alternative splicing appears as an important mechanism to regulate the voltage and Ca(2+) dependence of the TMEM16A-dependent Cl(-) channels in a tissue-specific manner. (PMID:19819874)
• Data demonstrate that bestrophin 1 is localized in the endoplasmic reticulum (ER), where it interacts with the ER-Ca(2+) sensor and can enhance Ca(2+) signaling and activation of Ca(2+)-dependent Cl(-) (TMEM16A) and K(+) (SK4) channels. (PMID:19823864)
• Compared with CD117, DOG1 (using the K9 antibody) is a more specific marker, whereas PKC theta (using the clone 27 antibody) is a considerably less specific immunohistochemical marker for GIST. (PMID:20716167)
• In the majority of histologically suspected GISTs a combination of CD117 and DOG1 immunostaining is sufficient to confirm the histological diagnosis. (PMID:20716168)
• TMEM16A is the operative channel and contributes to Ca(2+)-activated Cl(-) secretion in response to extracellular nucleotides (PMID:21041307)
• TMEM16A inhibitors reveal TMEM16A as a minor component of calcium-activated chloride channel conductance in airway and intestinal epithelial cells. (PMID:21084298)
• variant was a leucine-to-arginine substitution in the DUF 590 domain of a 16K transmembrane protein, a putative calcium-activated chloride channel encoded by anoctamin 10 (PMID:21092923)
• Discovered on gastrointestinal stromal tumor 1 (DOG1) is expressed in pancreatic centroacinar cells and in solid-pseudopapillary neoplasms. (PMID:21295818)
• important changes in expression and splicing of Ano1 in patients with diabetic gastroparesis that alter the electrophysiological properties of the channel. (PMID:21349842)
• DOG1 antibody is a highly sensitive and specific marker for gastrointestinal stromal tumors in cytology cell blocks. (PMID:21350101)
• Both DOG1 and PKC-theta; can be used in the diagnosis of KIT-negative GISTs. (PMID:21358619)
• Data suggest that Ano1 is a reliable and sensitive marker for interstitial cells of Cajal, and that labeling with antibodies selective for Ano1 reproducibly detects depletion of Kit-positive cells in patients with slow transit constipation. (PMID:21585622)
• an isoform of the TMEM16A protein is associated with chloride channel activity (PMID:21645494)
• The expression of DOG-1 was elevated in gastrointestinal stromal tumors. (PMID:21756825)
• Ano1 regulates proliferation at the G(1)/S transition of the cell cycle and may play a role in tumorigenesis. (PMID:21940901)
• Findings indicate that ANO1 Ca2+-activated Cl- channels of ICC are activated during cholinergic neurotransmission and contribute to the excitatory motor control of motility in the jejunum. (PMID:21965629)
• TMEM16A-currents were attenuated by additional expression of CFTR, and were completely abrogated when additionally expressed CFTR was activated by IBMX and forskolin. (PMID:22178883)
• The most sensitive marker for gastrointestinal stromal tumors was CD117, followed by DOG-1 and PKCtheta. (PMID:22197035)
• demonstrated nests of membranous DOG1(+) chondroblasts located within cellular portions of chondroblastoma containing diffuse heterogeneous infiltrates of mostly DOG1(-) chondroblasts, CD163(+) macrophages and multinucleated osteoclastic giant cells (PMID:22335248)
• TMEM16A mRNA and protein expression was increased by EGF to 256 +/- 38% (n = 7; P < 0.01) and 297 +/- 46% (n = 9, P < 0.001) of control levels, respectively. (PMID:22351639)
• c-KIT, PKC-theta; and DOG-1 antigens are the most sensitive and specific immunomarkers for confirming EGISTs (PMID:22399613)
• the regulation of anion fluxes in insulin-producing cells may involve both SLC4A4 and TMEM16A (PMID:22415075)
• DOG1 staining is a marker of salivary acinar and to a lesser extent intercalated duct differentiation. (PMID:22460810)
• seldom expressed and not useful in the evaluation of pancreatic neoplasms (PMID:22495382)
• [REVIEW] The human ANO1 gene contains four alternatively spliced segments (designated a, b, c and d) which are not predicted to alter the overall membrane topology but change the biophysical properties of the resulting channels. (PMID:22526416)
• TMEM16A-induced cancer cell proliferation and tumor growth were accompanied by an increase in extracellular signal-regulated kinase (ERK)1/2 activation and cyclin D1 induction (PMID:22564524)
• DOG-1 is a highly sensitive and specific marker for GISTs and also highlights hitherto unrecognized and unusual patterns of expression in non-mesenchymal neoplasms. (PMID:22571292)
• Ano1, ezrin, and moesin/radixin colocalize apically in salivary gland epithelial cells, and overexpression of moesin and Ano1 in HEK cells alters the subcellular localization of both proteins (PMID:22685202)
• Aberrant expression of TMEM16A occurs in the majority of gastric carcinoma cases. (PMID:22699056)
• Enhanced expression of ANO1 in head and neck squamous cell carcinoma causes cell migration and correlates with poor prognosis. (PMID:22912841)
• These data provide evidence for a functional role of TMEM16A in the vasoconstrictor responses of murine thoracic aorta and mesenteric artery as well as human resistance vessels. (PMID:22946562)
• These data indicate that TMEM16A is the target for INO-4995, although the mode of action appears different for overexpressed and endogenous channels. INO-4995 may be useful for the treatment of CF lung disease. (PMID:22946960)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio		ENSDARG00000099362
danio_rerio	ano1a	ENSDARG00000102335
mus_musculus	Ano1	ENSMUSG00000031075
rattus_norvegicus	Ano1	ENSRNOG00000020865

Paralogs (10): ANO2 (ENSG00000047617), ANO8 (ENSG00000074855), PPP1R7 (ENSG00000115685), ANO3 (ENSG00000134343), ANO7 (ENSG00000146205), ANO4 (ENSG00000151572), ANO10 (ENSG00000160746), ANO5 (ENSG00000171714), ANO6 (ENSG00000177119), ANO9 (ENSG00000185101)

Protein

Protein identifiers

Anoctamin-1 — Q5XXA6 (reviewed: Q5XXA6)

Alternative names: Discovered on gastrointestinal stromal tumors protein 1, Oral cancer overexpressed protein 2, Transmembrane protein 16A, Tumor-amplified and overexpressed sequence 2

All UniProt accessions (3): E9PP68, E9PS90, Q5XXA6

UniProt curated annotations — full annotation on UniProt →

Function. Calcium-activated chloride channel (CaCC). Plays a role in transepithelial anion transport and smooth muscle contraction. Required for the normal functioning of the interstitial cells of Cajal (ICCs) which generate electrical pacemaker activity in gastrointestinal smooth muscles. Acts as a major contributor to basal and stimulated chloride conductance in airway epithelial cells and plays an important role in tracheal cartilage development. Required for CFTR activation by enhancing endoplasmic reticulum Ca(2+) store release and is also required for CFTR membrane expression. Required for basal and ATP-dependent mucus secretion in airways and intestine, probably by controlling exocytosis of mucus-filled granules by providing Ca(2+) to an apical signaling compartment. Contributes to airway mucus expression induced by interleukins IL3 and IL8 and by the asthma-associated protein CLCA1 and is required for expression of mucin MUC5AC. However, was shown in another study not to be required for MUC5AC expression. Plays a role in the propagation of Ca(2+) waves in Kolliker’s organ in the cochlea and contributes to the refinement of auditory brainstem circuitries prior to hearing onset. In vomeronasal sensory neurons, modulates spontaneous firing patterns in the absence of stimuli as well as the firing pattern of pheromone-evoked activity. Responsible for calcium-activated chloride channel activity in type I taste cells of the vallate papillae. Acts as a heat sensor in nociceptive neurons. In dorsal root ganglion neurons, plays a role in mediating non-histaminergic Mas-related G-protein coupled receptor (MRGPR)-dependent itching, acting as a downstream effector of MRGPRs. In the developing brain, required for the Ca(2+)-dependent process extension of radial glial cells. Calcium-activated chloride channel (CaCC). Contributes to calcium-activated chloride secretion in human sweat gland epithelial cells. Shows increased basal chloride permeability and decreased Ca(2+)-induced chloride permeability. Calcium-activated chloride channel (CaCC). Shows increased sensitivity to intracellular Ca(2+).

Subunit / interactions. Homodimer. Interacts with CFTR. Interacts with TRPV4.

Subcellular location. Apical cell membrane. Presynapse.

Tissue specificity. Expressed in nasal epithelial cells (at protein level). In the kidney, expressed in the collecting duct (at protein level). Broadly expressed with higher levels in liver, skeletal muscle and gastrointestinal muscles. Expressed in eccrine sweat glands.

Disease relevance. Intestinal dysmotility syndrome (IDMTS) [MIM:620045] An autosomal recessive disorder characterized by impaired intestinal peristalsis, recurrent episodes of haemorrhagic diarrhea, and distention of intestinal loops. Intestinal and hepatic portal venous gas, dysmorphic features, and developmental delay may also be present. The disease may be caused by variants affecting the gene represented in this entry. Moyamoya disease 7 (MYMY7) [MIM:620687] A form of Moyamoya disease, a progressive cerebral angiopathy characterized by bilateral intracranial carotid artery stenosis and telangiectatic vessels in the region of the basal ganglia. The abnormal vessels resemble a ‘puff of smoke’ (moyamoya) on cerebral angiogram. Affected individuals can develop transient ischemic attacks and/or cerebral infarction, and rupture of the collateral vessels can cause intracranial hemorrhage. Hemiplegia of sudden onset and epileptic seizures constitute the prevailing presentation in childhood, while subarachnoid bleeding occurs more frequently in adults. MYMY7 inheritance can be autosomal dominant or autosomal recessive. The disease may be caused by variants affecting the gene represented in this entry.

Activity regulation. ATP and calmodulin are essential for its activation. Channel activity is inhibited by CFTR protein and by chloride inhibitors such as niflumic acid (NFA) and 4,4’-diisothiocyanatostilbene-2,2’-disulfonic acid (DIDS). Activated by heat with activation seen at temperatures above 44 degrees Celsius. Activated by BDNF in radial glial cells.

Domain organisation. The region spanning the fifth and sixth transmembrane domains probably forms the pore-forming region.

Induction. By IL13. By IL4, likely as a result of IL4-induced cell proliferation. By wounding in airway epithelial cells with levels decreasing significantly during the healing process.

Miscellaneous. The term ‘anoctamin’ was coined because these channels are anion selective and are predicted to have eight (OCT) transmembrane segments. There is some dissatisfaction in the field with the Ano nomenclature because it is not certain that all the members of this family are anion channels or have the 8-transmembrane topology.

Similarity. Belongs to the anoctamin family.

Isoforms (5)

UniProt ID	Names	Canonical?
Q5XXA6-1	1, TMEM16A(ac)	yes
Q5XXA6-2	2
Q5XXA6-3	3
Q5XXA6-4	4, TMEM16A(ac-delta-e3)
Q5XXA6-5	5, Ano1(+0)

RefSeq proteins (7): NP_001365021, NP_001365022, NP_001365023, NP_001365024, NP_001365025, NP_001365026, NP_060513* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007632	Anoctamin	Family
IPR032394	Anoct_dimer	Domain
IPR049452	Anoctamin_TM	Domain

Pfam: PF04547, PF16178

Catalyzed reactions (Rhea), 1 shown:

• chloride(in) = chloride(out) (RHEA:29823)

UniProt features (63 total): topological domain 10, transmembrane region 10, splice variant 10, binding site 9, sequence variant 9, disulfide bond 4, sequence conflict 3, region of interest 2, modified residue 2, chain 1, compositionally biased region 1, site 1, glycosylation site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5XXA6-F1	77.20	0.29

Functional residue map

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

Catalytic / active sites (1): 428 (unlikely to bind calcium but may play an important structural role)

Ligand- & substrate-binding residues (9): 425; 677; 680; 728; 731; 760; 764; 909; 914

Post-translational modifications (2): 107, 196

Disulfide bonds (4): 370–395, 379–862, 382–386, 651–656

Glycosylation sites (1): 832

Function

Pathways and Gene Ontology

Reactome pathways

10 pathways

ID	Pathway
R-HSA-2672351	Stimuli-sensing channels
R-HSA-9733458	Induction of Cell-Cell Fusion
R-HSA-1643685	Disease
R-HSA-382551	Transport of small molecules
R-HSA-5663205	Infectious disease
R-HSA-9679506	SARS-CoV Infections
R-HSA-9694516	SARS-CoV-2 Infection
R-HSA-9772573	Late SARS-CoV-2 Infection Events
R-HSA-9824446	Viral Infection Pathways
R-HSA-983712	Ion channel transport

MSigDB gene sets: 264 (showing top): GOBP_SENSORY_PERCEPTION_OF_TEMPERATURE_STIMULUS, BERTUCCI_MEDULLARY_VS_DUCTAL_BREAST_CANCER_DN, GOBP_RESPONSE_TO_PEPTIDE, GOBP_GLIAL_CELL_DEVELOPMENT, GOBP_INORGANIC_ANION_TRANSPORT, GOBP_NEUROGENESIS, MAHADEVAN_IMATINIB_RESISTANCE_DN, chr11q13, ONDER_CDH1_TARGETS_3_DN, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_SENSORY_PERCEPTION_OF_PAIN, GOBP_DETECTION_OF_TEMPERATURE_STIMULUS, GOBP_CHLORIDE_TRANSPORT, MCBRYAN_PUBERTAL_BREAST_3_4WK_UP, CAIRO_HEPATOBLASTOMA_DN

GO Biological Process (13): chloride transport (GO:0006821), phospholipase C-activating G protein-coupled receptor signaling pathway (GO:0007200), iodide transport (GO:0015705), monoatomic ion transmembrane transport (GO:0034220), cellular response to heat (GO:0034605), detection of temperature stimulus involved in sensory perception of pain (GO:0050965), mucus secretion (GO:0070254), protein localization to membrane (GO:0072657), glial cell projection elongation (GO:0106091), cellular response to peptide (GO:1901653), chloride transmembrane transport (GO:1902476), monoatomic ion transport (GO:0006811), monoatomic cation transmembrane transport (GO:0098655)

GO Molecular Function (11): signaling receptor binding (GO:0005102), calcium-activated cation channel activity (GO:0005227), intracellularly calcium-gated chloride channel activity (GO:0005229), voltage-gated chloride channel activity (GO:0005247), chloride channel activity (GO:0005254), iodide transmembrane transporter activity (GO:0015111), identical protein binding (GO:0042802), protein homodimerization activity (GO:0042803), metal ion binding (GO:0046872), protein binding (GO:0005515), protein dimerization activity (GO:0046983)

GO Cellular Component (9): nucleoplasm (GO:0005654), plasma membrane (GO:0005886), apical plasma membrane (GO:0016324), chloride channel complex (GO:0034707), extracellular exosome (GO:0070062), presynapse (GO:0098793), membrane (GO:0016020), cell projection (GO:0042995), synapse (GO:0045202)

Reactome top-level categories

Rollup of top-8 pathways:

Category	Pathways
Ion channel transport	1
Late SARS-CoV-2 Infection Events	1
Disease	1
Viral Infection Pathways	1
SARS-CoV Infections	1
SARS-CoV-2 Infection	1
Infectious disease	1
Transport of small molecules	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
protein binding	3
monoatomic anion transport	2
inorganic anion transport	2
chloride channel activity	2
G protein-coupled receptor signaling pathway	1
phospholipase C activator activity	1
monoatomic ion transport	1
transmembrane transport	1
response to heat	1
cellular response to stress	1
sensory perception of pain	1
detection of temperature stimulus involved in sensory perception	1
body fluid secretion	1
secretion by tissue	1
intracellular protein localization	1
localization within membrane	1
glial cell development	1
cell projection morphogenesis	1
cellular response to chemical stimulus	1
response to peptide	1
chloride transport	1
monoatomic anion transmembrane transport	1
transport	1
monoatomic cation transport	1
monoatomic ion transmembrane transport	1
monoatomic ion-gated channel activity	1
ligand-gated monoatomic cation channel activity	1
ligand-gated monoatomic anion channel activity	1
intracellularly calcium-gated channel activity	1
voltage-gated monoatomic anion channel activity	1
monoatomic anion channel activity	1
chloride transmembrane transporter activity	1
monoatomic anion transmembrane transporter activity	1
iodide transport	1
identical protein binding	1
protein dimerization activity	1
cation binding	1
binding	1
nuclear lumen	1

Protein interactions and networks

STRING

1312 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ANO1	CLCA4	Q14CN2	946
ANO1	CLCA2	Q9UQC9	925
ANO1	KIT	P10721	891
ANO1	CLCA1	A8K7I4	876
ANO1	RTEL1	Q9NZ71	871
ANO1	CFTR	P13569	841
ANO1	PDGFRA	P16234	804
ANO1	BRIP1	Q9BX63	785
ANO1	CD34	P28906	773
ANO1	CALD1	Q05682	720
ANO1	LRRC8A	Q8IWT6	718
ANO1	RDX	P35241	711
ANO1	EZR	P15311	698
ANO1	CALML4	Q96GE6	689
ANO1	CALML3	P27482	672

IntAct

7 interactions, top by confidence:

A	B	Type	Score
LGALS3	PODXL	psi-mi:“MI:0914”(association)	0.530
CFTR	ANO1	psi-mi:“MI:0403”(colocalization)	0.460
ANO1	CFTR	psi-mi:“MI:0915”(physical association)	0.460
ANO1	H2BC9	psi-mi:“MI:0915”(physical association)	0.400
WDR59	HDAC3	psi-mi:“MI:0914”(association)	0.350
	ACTN4	psi-mi:“MI:0914”(association)	0.350

BioGRID (25): ANO1 (Proximity Label-MS), HIST1H2BH (Proximity Label-MS), TRIM23 (Two-hybrid), TRIM23 (Reconstituted Complex), ANO1 (Reconstituted Complex), TRIM23 (Affinity Capture-Western), ANO1 (Affinity Capture-Western), TRIM21 (Reconstituted Complex), TRIM21 (Affinity Capture-Western), ANO1 (Affinity Capture-Western), ANO1 (Biochemical Activity), ANO1 (Affinity Capture-MS), ANO1 (Affinity Capture-MS), ANO1 (Affinity Capture-MS), COPB1 (Co-localization)

ESM2 similar proteins: A0A0R4IQZ2, A0MFS9, A2WV32, A2YMH5, A5WVX9, A8Y2U2, F1RAX4, F4HVJ3, F4JIN3, G5ECD6, G5ED05, O13621, O17386, O18304, O45363, O48947, O62136, O74737, P0C5E7, P34319, P34389, P34577, Q0JJZ6, Q10287, Q10436, Q21412, Q22566, Q23027, Q23369, Q4KMQ2, Q4R690, Q5JN63, Q5NVB9, Q5XXA6, Q6ZF85, Q84JA6, Q8BHY3, Q8CFW1, Q8IUH4, Q8L778

Diamond homologs: A1A5B4, A2AHL1, A6QLE6, P86044, Q14AT5, Q32M45, Q4KMQ2, Q5XXA6, Q6IFT6, Q6IWH7, Q6P9J9, Q75UR0, Q75V66, Q8BHY3, Q8C5H1, Q8CFW1, Q9BYT9, Q9NQ90, Q6PB70, Q9HCE9, A0MFS9, O13621

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	1
Uncertain significance	133
Likely benign	30
Benign	4

Top pathogenic / likely-pathogenic (4)

Variant ID	HGVS	Classification
1340992	GRCh37/hg19 11q13.3-13.4(chr11:69214835-70821137)x1	Pathogenic
2691755	NM_018043.7(ANO1):c.1972A>G (p.Met658Val)	Pathogenic
2691757	NM_018043.7(ANO1):c.2219C>T (p.Thr740Ile)	Pathogenic
1526099	NM_018043.7(ANO1):c.1273G>T (p.Glu425Ter)	Likely pathogenic

SpliceAI

4283 predictions. Top by Δscore:

Variant	Effect	Δscore
11:70078710:GCACG:G	donor_gain	1.0000
11:70078711:CACGG:C	donor_loss	1.0000
11:70078714:GGT:G	donor_loss	1.0000
11:70078715:G:C	donor_loss	1.0000
11:70078715:G:GG	donor_gain	1.0000
11:70078716:T:G	donor_loss	1.0000
11:70087750:A:AG	acceptor_gain	1.0000
11:70087751:G:GA	acceptor_gain	1.0000
11:70087751:GCTGC:G	acceptor_gain	1.0000
11:70088081:GGAC:G	donor_gain	1.0000
11:70088082:G:GT	donor_gain	1.0000
11:70088082:G:T	donor_gain	1.0000
11:70103061:TCCAG:T	acceptor_loss	1.0000
11:70103062:CCAGA:C	acceptor_loss	1.0000
11:70103063:CAGAC:C	acceptor_loss	1.0000
11:70103064:A:AG	acceptor_gain	1.0000
11:70103064:AGAC:A	acceptor_loss	1.0000
11:70103065:G:GG	acceptor_gain	1.0000
11:70103065:GAC:G	acceptor_gain	1.0000
11:70103065:GACT:G	acceptor_gain	1.0000
11:70103065:GACTA:G	acceptor_gain	1.0000
11:70104146:CATCT:C	donor_gain	1.0000
11:70104147:ATCT:A	donor_gain	1.0000
11:70104148:TCT:T	donor_gain	1.0000
11:70104149:CT:C	donor_gain	1.0000
11:70104150:TG:T	donor_loss	1.0000
11:70104151:G:A	donor_loss	1.0000
11:70104151:G:GG	donor_gain	1.0000
11:70104152:TAAG:T	donor_loss	1.0000
11:70105720:C:A	acceptor_gain	1.0000

AlphaMissense

6564 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:70103129:G:C	A169P	1.000
11:70108404:G:C	G267R	1.000
11:70111719:T:C	L271P	1.000
11:70124365:T:A	W305R	1.000
11:70124365:T:C	W305R	1.000
11:70126143:G:A	G349R	1.000
11:70126143:G:C	G349R	1.000
11:70165498:T:C	L660P	1.000
11:70165510:T:C	L664P	1.000
11:70170898:G:C	G737R	1.000
11:70170913:T:C	F742L	1.000
11:70170915:T:A	F742L	1.000
11:70170915:T:G	F742L	1.000
11:70170957:C:A	N756K	1.000
11:70170957:C:G	N756K	1.000
11:70170960:C:A	N757K	1.000
11:70170960:C:G	N757K	1.000
11:70170977:T:C	L763P	1.000
11:70087840:T:C	L66P	0.999
11:70088047:T:A	L135H	0.999
11:70088047:T:C	L135P	0.999
11:70088062:T:C	L140P	0.999
11:70103103:C:A	A160D	0.999
11:70103130:C:A	A169D	0.999
11:70105778:G:C	R246P	0.999
11:70108354:T:A	V250D	0.999
11:70108373:A:C	R256S	0.999
11:70108373:A:T	R256S	0.999
11:70111707:G:A	G267D	0.999
11:70111707:G:T	G267V	0.999

dbSNP variants (sampled 300 via entrez): RS1000004795 (11:70169155 C>A,T), RS1000020511 (11:70032733 G>A), RS1000031498 (11:70038104 A>G), RS1000040531 (11:70094942 C>T), RS1000042313 (11:70020934 C>G,T), RS1000060195 (11:70162923 C>G,T), RS1000067803 (11:69966073 A>G), RS1000068150 (11:70069917 G>A,C), RS1000072242 (11:70103498 G>T), RS1000089573 (11:70170225 G>A,T), RS1000120529 (11:70145798 G>A,T), RS1000155420 (11:70160737 C>T), RS1000173107 (11:70125936 G>A), RS1000173405 (11:70097389 A>G), RS1000178330 (11:70141225 G>A,T)

Disease associations

OMIM: gene MIM:610108 | disease phenotypes: MIM:620687, MIM:620045

GenCC curated gene-disease

Disease	Classification	Inheritance
moyamoya disease 7	Moderate	Autosomal dominant
intestinal dysmotility syndrome	Moderate	Autosomal recessive

Mondo (2): moyamoya disease 7 (MONDO:0958202), intestinal dysmotility syndrome (MONDO:0859289)

Orphanet (0):

HPO phenotypes

27 total (27 of 27 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000218	High palate
HP:0000289	Broad philtrum
HP:0000369	Low-set ears
HP:0000518	Cataract
HP:0001252	Hypotonia
HP:0001269	Hemiparesis
HP:0001297	Stroke
HP:0001508	Failure to thrive
HP:0001561	Polyhydramnios
HP:0001824	Weight loss
HP:0002014	Diarrhea
HP:0002076	Migraine
HP:0002315	Headache
HP:0002326	Transient ischemic attack
HP:0002587	Projectile vomiting
HP:0003270	Abdominal distention
HP:0003577	Congenital onset
HP:0003581	Adult onset
HP:0003623	Neonatal onset
HP:0008081	Pes valgus
HP:0011463	Childhood onset
HP:0011968	Feeding difficulties
HP:0012495	Posterior cerebral artery stenosis
HP:0030897	Decreased intestinal transit time
HP:0100546	Carotid artery stenosis

GWAS associations

18 associations (top):

Study	Trait	p-value
GCST002821_16	Survival in rectal cancer	8.000000e-06
GCST003991_9	Childhood ear infection	3.000000e-09
GCST003996_10	Monobrow	5.000000e-12
GCST004651_2	Aortic root size	2.000000e-09
GCST005013_44	Childhood ear infection	3.000000e-09
GCST006630_28	Diastolic blood pressure	8.000000e-16
GCST007267_114	Systolic blood pressure	7.000000e-11
GCST008362_5	Birth weight	5.000000e-10
GCST90000025_168	Appendicular lean mass	5.000000e-23
GCST90000025_169	Appendicular lean mass	1.000000e-14
GCST90000025_170	Appendicular lean mass	7.000000e-21
GCST90002379_90	Basophil count	6.000000e-09
GCST90002381_515	Eosinophil count	5.000000e-13
GCST90002382_388	Eosinophil percentage of white cells	9.000000e-11
GCST90014033_100	Haemorrhoidal disease	4.000000e-08
GCST90020024_416	A body shape index	3.000000e-09
GCST90020025_873	Waist-to-hip ratio adjusted for BMI	8.000000e-10
GCST90020027_1625	Waist-hip index	8.000000e-10

EFO canonical traits (12, from GWAS)

EFO ID	Trait name
EFO:0000409	disease free survival
EFO:0007904	susceptibility to childhood ear infection measurement
EFO:0007906	synophrys measurement
EFO:0006336	diastolic blood pressure
EFO:0006335	systolic blood pressure
EFO:0004344	birth weight
EFO:0004980	appendicular lean mass
EFO:0005090	basophil count
EFO:0004842	eosinophil count
EFO:0007991	eosinophil percentage of leukocytes
EFO:0007789	BMI-adjusted waist circumference
EFO:0007788	BMI-adjusted waist-hip ratio

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2046267 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

2 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 23,826 (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
CHEMBL1401	NITAZOXANIDE	4	9,504
CHEMBL1448	NICLOSAMIDE	4	14,322

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: other ic — Calcium activated chloride channel (CaCC)

Most potent curated ligand interactions (6 total), top 6:

Ligand	Action	Affinity	Parameter
PAM_16A	Activation	8.44	pEC50
TMinh-23	Inhibition	7.52	pIC50
MONNA	Inhibition	7.1	pIC50
Ani9	Inhibition	6.97	pIC50
T16Ainh-A01	Inhibition	6.0	pIC50
crofelemer	Inhibition	5.19	pIC50

Binding affinities (BindingDB)

3 measured of 3 human assays (3 total across all organisms); most potent 3 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
N-(1-adamantyl)-4-[[2-(5-chloro-2-hydroxyphenyl)acetyl]amino]pyridine-2-carboxamide	EC50	240 nM	US-20200361871: COMPOUNDS
N-(1-adamantyl)-3-[[2-(5-chloro-2-hydroxyphenyl)acetyl]amino]benzamide	EC50	540 nM	US-20200361871: COMPOUNDS
4-[[2-(2-adamantyl)acetyl]amino]-N-tert-butylpyridine-2-carboxamide	EC50	870 nM	US-20200361871: COMPOUNDS

ChEMBL bioactivities

576 potent at pChembl≥5 of 620 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.00	EC50	10	nM	CHEMBL5818335
8.00	EC50	10	nM	CHEMBL5987751
8.00	EC50	10	nM	CHEMBL5748528
8.00	EC50	10	nM	CHEMBL5944799
7.70	EC50	20	nM	CHEMBL5923346
7.70	EC50	20	nM	CHEMBL5888912
7.70	EC50	20	nM	CHEMBL6035973
7.70	EC50	20	nM	CHEMBL6063625
7.70	EC50	20	nM	CHEMBL6027216
7.68	IC50	21	nM	CHEMBL4445544
7.66	IC50	22	nM	CHEMBL4445544
7.62	IC50	24	nM	CHEMBL5186789
7.55	IC50	28	nM	NICLOSAMIDE
7.54	IC50	29	nM	CHEMBL5206041
7.52	IC50	30	nM	CHEMBL4074929
7.40	EC50	40	nM	CHEMBL5886634
7.40	EC50	40	nM	CHEMBL5751293
7.40	EC50	40	nM	CHEMBL5867107
7.40	EC50	40	nM	CHEMBL5794087
7.30	EC50	50	nM	CHEMBL5875064
7.30	EC50	50	nM	CHEMBL5854301
7.30	EC50	50	nM	CHEMBL5793913
7.30	EC50	50	nM	CHEMBL5924873
7.30	EC50	50	nM	CHEMBL5874757
7.22	IC50	60	nM	CHEMBL4080525
7.22	EC50	60	nM	CHEMBL5974117
7.22	EC50	60	nM	CHEMBL5758425
7.22	EC50	60	nM	CHEMBL5911037
7.22	EC50	60	nM	CHEMBL6039401
7.16	EC50	70	nM	CHEMBL5869137
7.16	EC50	70	nM	CHEMBL6057591
7.11	IC50	77	nM	CHEMBL4080525
7.10	IC50	80	nM	CHEMBL4086165
7.10	EC50	80	nM	CHEMBL5965278
7.08	IC50	83	nM	CHEMBL4074929
7.05	EC50	90	nM	CHEMBL5789360
7.05	EC50	90	nM	CHEMBL5957346
7.05	EC50	90	nM	CHEMBL6028707
7.01	IC50	97	nM	CHEMBL4080525
7.00	EC50	100	nM	CHEMBL6061522
7.00	EC50	100	nM	CHEMBL5769067
7.00	EC50	100	nM	CHEMBL5979945
7.00	EC50	100	nM	CHEMBL6043593
7.00	EC50	100	nM	CHEMBL6040254
6.96	IC50	110	nM	CHEMBL4080525
6.96	EC50	110	nM	CHEMBL5912840
6.96	EC50	110	nM	CHEMBL5985276
6.96	EC50	110	nM	CHEMBL6055475
6.92	EC50	120	nM	CHEMBL5822025
6.92	EC50	120	nM	CHEMBL5947400

PubChem BioAssay actives

106 with measured affinity, of 237 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
2-(4-chloro-2-methylphenoxy)-N-[(E)-[2-(trifluoromethoxy)phenyl]methylideneamino]acetamide	1514133: Inhibition of YFP-fused ANO1 (unknown origin) expressed in FRT cells after 20 mins by fluorescence quenching method	ic50	0.0210	uM
4-(4-chlorophenyl)-2-[(2,5-difluorobenzoyl)amino]thiophene-3-carboxylic acid	1868416: Inhibition of YFP tagged ANO1 (unknown origin) expressed in FRT cells incubated for 24 hrs by fluorescence plate reader assay	ic50	0.0240	uM
5-chloro-N-(2-chloro-4-nitrophenyl)-2-hydroxybenzamide	1868416: Inhibition of YFP tagged ANO1 (unknown origin) expressed in FRT cells incubated for 24 hrs by fluorescence plate reader assay	ic50	0.0280	uM
2-[(2-bromo-5-chlorobenzoyl)amino]-4-(4-chlorophenyl)thiophene-3-carboxylic acid	1868416: Inhibition of YFP tagged ANO1 (unknown origin) expressed in FRT cells incubated for 24 hrs by fluorescence plate reader assay	ic50	0.0290	uM
2-[(2-bromo-2,2-difluoroacetyl)amino]-N-(2-methylphenyl)-5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophene-3-carboxamide	1448055: Inhibition of human TMEM16A expressed in FRT cells assessed as reduction of ATP-induced in chloride conductance preincubated for 5 mins followed by ATP addition by short-circuit current assay	ic50	0.0300	uM
2-(4-chloro-2-methylphenoxy)-N-[(E)-(2-methoxyphenyl)methylideneamino]acetamide	1705412: Inhibition of human ANO1 channel expressed in HEK293 cells incubated for 10 mins by FLIPR assay	ic50	0.0600	uM
2-[(4-methoxynaphthalen-2-yl)amino]-5-nitrobenzoic acid	1448060: Inhibition of TMEM16A (unknown origin) expressed in Xenopus laevis oocytes at -60 mV holding potential by voltage-clamp assay	ic50	0.0800	uM
N-phenyl-2-[(2,2,2-trifluoroacetyl)amino]-5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophene-3-carboxamide	1448055: Inhibition of human TMEM16A expressed in FRT cells assessed as reduction of ATP-induced in chloride conductance preincubated for 5 mins followed by ATP addition by short-circuit current assay	ic50	0.1300	uM
2-[(2,2-difluoro-2-iodoacetyl)amino]-N-(4-fluorophenyl)-5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophene-3-carboxamide	1448054: Inhibition of human TMEM16A expressed in FRT cells co-expressing iodide sensitive fluorescent protein YFP-H148Q/I152L/F46L assessed as reduction in ATP-induced Ca2+ activation-mediated chloride current by measuring decrease in iodide influx preincubated for 10 mins followed by ATP/iodide addition by fluorescence assay	ic50	0.1500	uM
N-(2-methylphenyl)-2-[(2,2,2-trifluoroacetyl)amino]-4,5,6,7-tetrahydro-1-benzothiophene-3-carboxamide	1448054: Inhibition of human TMEM16A expressed in FRT cells co-expressing iodide sensitive fluorescent protein YFP-H148Q/I152L/F46L assessed as reduction in ATP-induced Ca2+ activation-mediated chloride current by measuring decrease in iodide influx preincubated for 10 mins followed by ATP/iodide addition by fluorescence assay	ic50	0.1700	uM
2-[(2-chloro-2,2-difluoroacetyl)amino]-N-(2-methylphenyl)-5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophene-3-carboxamide	1448054: Inhibition of human TMEM16A expressed in FRT cells co-expressing iodide sensitive fluorescent protein YFP-H148Q/I152L/F46L assessed as reduction in ATP-induced Ca2+ activation-mediated chloride current by measuring decrease in iodide influx preincubated for 10 mins followed by ATP/iodide addition by fluorescence assay	ic50	0.1800	uM
2-(4-chloro-2-methylphenoxy)-N-[(E)-[2-(trifluoromethyl)phenyl]methylideneamino]acetamide	1514133: Inhibition of YFP-fused ANO1 (unknown origin) expressed in FRT cells after 20 mins by fluorescence quenching method	ic50	0.2100	uM
N-(4-methylphenyl)-2-[(2,2,2-trifluoroacetyl)amino]-4,5,6,7-tetrahydro-1-benzothiophene-3-carboxamide	1448054: Inhibition of human TMEM16A expressed in FRT cells co-expressing iodide sensitive fluorescent protein YFP-H148Q/I152L/F46L assessed as reduction in ATP-induced Ca2+ activation-mediated chloride current by measuring decrease in iodide influx preincubated for 10 mins followed by ATP/iodide addition by fluorescence assay	ic50	0.2200	uM
2-[(2,2-difluoro-2-iodoacetyl)amino]-N-phenyl-5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophene-3-carboxamide	1448054: Inhibition of human TMEM16A expressed in FRT cells co-expressing iodide sensitive fluorescent protein YFP-H148Q/I152L/F46L assessed as reduction in ATP-induced Ca2+ activation-mediated chloride current by measuring decrease in iodide influx preincubated for 10 mins followed by ATP/iodide addition by fluorescence assay	ic50	0.2300	uM
2-[(2-bromo-2,2-difluoroacetyl)amino]-N-phenyl-5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophene-3-carboxamide	1448054: Inhibition of human TMEM16A expressed in FRT cells co-expressing iodide sensitive fluorescent protein YFP-H148Q/I152L/F46L assessed as reduction in ATP-induced Ca2+ activation-mediated chloride current by measuring decrease in iodide influx preincubated for 10 mins followed by ATP/iodide addition by fluorescence assay	ic50	0.2300	uM
N-(2-methylphenyl)-2-[(2,2,2-trifluoroacetyl)amino]-5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophene-3-carboxamide	1448055: Inhibition of human TMEM16A expressed in FRT cells assessed as reduction of ATP-induced in chloride conductance preincubated for 5 mins followed by ATP addition by short-circuit current assay	ic50	0.2600	uM
4-(4-chlorophenyl)-2-[(2,5-dichlorobenzoyl)amino]thiophene-3-carboxylic acid	1868416: Inhibition of YFP tagged ANO1 (unknown origin) expressed in FRT cells incubated for 24 hrs by fluorescence plate reader assay	ic50	0.2700	uM
2-(4-chloro-2-methylphenoxy)-N-[(E)-1-[2-(trifluoromethoxy)phenyl]ethylideneamino]acetamide	1514133: Inhibition of YFP-fused ANO1 (unknown origin) expressed in FRT cells after 20 mins by fluorescence quenching method	ic50	0.3000	uM
N-(4-fluorophenyl)-2-[(2,2,2-trifluoroacetyl)amino]-5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophene-3-carboxamide	1448054: Inhibition of human TMEM16A expressed in FRT cells co-expressing iodide sensitive fluorescent protein YFP-H148Q/I152L/F46L assessed as reduction in ATP-induced Ca2+ activation-mediated chloride current by measuring decrease in iodide influx preincubated for 10 mins followed by ATP/iodide addition by fluorescence assay	ic50	0.3200	uM
N-phenyl-2-[(2,2,2-trifluoroacetyl)amino]-4,5,6,7-tetrahydro-1-benzothiophene-3-carboxamide	1448054: Inhibition of human TMEM16A expressed in FRT cells co-expressing iodide sensitive fluorescent protein YFP-H148Q/I152L/F46L assessed as reduction in ATP-induced Ca2+ activation-mediated chloride current by measuring decrease in iodide influx preincubated for 10 mins followed by ATP/iodide addition by fluorescence assay	ic50	0.3700	uM
2-[(2,2,2-trifluoroacetyl)amino]-N-[2-(trifluoromethoxy)phenyl]-5,6-dihydro-4H-cyclopenta[b]thiophene-3-carboxamide	1448054: Inhibition of human TMEM16A expressed in FRT cells co-expressing iodide sensitive fluorescent protein YFP-H148Q/I152L/F46L assessed as reduction in ATP-induced Ca2+ activation-mediated chloride current by measuring decrease in iodide influx preincubated for 10 mins followed by ATP/iodide addition by fluorescence assay	ic50	0.3700	uM
2-(2,2,3,3,4,4,4-heptafluorobutanoylamino)-N-(2-methylphenyl)-5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophene-3-carboxamide	1448054: Inhibition of human TMEM16A expressed in FRT cells co-expressing iodide sensitive fluorescent protein YFP-H148Q/I152L/F46L assessed as reduction in ATP-induced Ca2+ activation-mediated chloride current by measuring decrease in iodide influx preincubated for 10 mins followed by ATP/iodide addition by fluorescence assay	ic50	0.3800	uM
Nitazoxanide	1868416: Inhibition of YFP tagged ANO1 (unknown origin) expressed in FRT cells incubated for 24 hrs by fluorescence plate reader assay	ic50	0.4240	uM
2-[(2-bromo-2,2-difluoroacetyl)amino]-N-(4-fluorophenyl)-5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophene-3-carboxamide	1448054: Inhibition of human TMEM16A expressed in FRT cells co-expressing iodide sensitive fluorescent protein YFP-H148Q/I152L/F46L assessed as reduction in ATP-induced Ca2+ activation-mediated chloride current by measuring decrease in iodide influx preincubated for 10 mins followed by ATP/iodide addition by fluorescence assay	ic50	0.4500	uM
N-(4-fluorophenyl)-2-[(2,2,2-trifluoroacetyl)amino]-4,5,6,7-tetrahydro-1-benzothiophene-3-carboxamide	1448054: Inhibition of human TMEM16A expressed in FRT cells co-expressing iodide sensitive fluorescent protein YFP-H148Q/I152L/F46L assessed as reduction in ATP-induced Ca2+ activation-mediated chloride current by measuring decrease in iodide influx preincubated for 10 mins followed by ATP/iodide addition by fluorescence assay	ic50	0.4900	uM
2-[(2,2-difluoro-2-iodoacetyl)amino]-N-(2-methylphenyl)-5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophene-3-carboxamide	1448054: Inhibition of human TMEM16A expressed in FRT cells co-expressing iodide sensitive fluorescent protein YFP-H148Q/I152L/F46L assessed as reduction in ATP-induced Ca2+ activation-mediated chloride current by measuring decrease in iodide influx preincubated for 10 mins followed by ATP/iodide addition by fluorescence assay	ic50	0.6000	uM
N-(2-chlorophenyl)-2-[(2,2,2-trifluoroacetyl)amino]-5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophene-3-carboxamide	1448054: Inhibition of human TMEM16A expressed in FRT cells co-expressing iodide sensitive fluorescent protein YFP-H148Q/I152L/F46L assessed as reduction in ATP-induced Ca2+ activation-mediated chloride current by measuring decrease in iodide influx preincubated for 10 mins followed by ATP/iodide addition by fluorescence assay	ic50	0.6600	uM
2-[(2-bromo-2,2-difluoroacetyl)amino]-N-[2-(trifluoromethoxy)phenyl]-5,6-dihydro-4H-cyclopenta[b]thiophene-3-carboxamide	1448054: Inhibition of human TMEM16A expressed in FRT cells co-expressing iodide sensitive fluorescent protein YFP-H148Q/I152L/F46L assessed as reduction in ATP-induced Ca2+ activation-mediated chloride current by measuring decrease in iodide influx preincubated for 10 mins followed by ATP/iodide addition by fluorescence assay	ic50	0.7000	uM
4-(4-chlorophenyl)-2-(naphthalene-1-carbonylamino)thiophene-3-carboxylic acid	1868416: Inhibition of YFP tagged ANO1 (unknown origin) expressed in FRT cells incubated for 24 hrs by fluorescence plate reader assay	ic50	0.7900	uM
2-[(2-chloro-2,2-difluoroacetyl)amino]-N-(4-fluorophenyl)-5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophene-3-carboxamide	1448054: Inhibition of human TMEM16A expressed in FRT cells co-expressing iodide sensitive fluorescent protein YFP-H148Q/I152L/F46L assessed as reduction in ATP-induced Ca2+ activation-mediated chloride current by measuring decrease in iodide influx preincubated for 10 mins followed by ATP/iodide addition by fluorescence assay	ic50	0.8400	uM
2-(4-chloro-2-methylphenoxy)-N-[(E)-(2-fluorophenyl)methylideneamino]acetamide	1514133: Inhibition of YFP-fused ANO1 (unknown origin) expressed in FRT cells after 20 mins by fluorescence quenching method	ic50	0.8900	uM
2-[(2-chloro-2,2-difluoroacetyl)amino]-N-phenyl-5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophene-3-carboxamide	1448054: Inhibition of human TMEM16A expressed in FRT cells co-expressing iodide sensitive fluorescent protein YFP-H148Q/I152L/F46L assessed as reduction in ATP-induced Ca2+ activation-mediated chloride current by measuring decrease in iodide influx preincubated for 10 mins followed by ATP/iodide addition by fluorescence assay	ic50	0.9250	uM
2-[(2-bromo-5-fluorobenzoyl)amino]-4-(4-chlorophenyl)thiophene-3-carboxylic acid	1868416: Inhibition of YFP tagged ANO1 (unknown origin) expressed in FRT cells incubated for 24 hrs by fluorescence plate reader assay	ic50	0.9600	uM
2-[(5-ethyl-4-methyl-6-oxo-1H-pyrimidin-2-yl)sulfanyl]-N-[4-(4-methoxyphenyl)-1,3-thiazol-2-yl]acetamide	1448055: Inhibition of human TMEM16A expressed in FRT cells assessed as reduction of ATP-induced in chloride conductance preincubated for 5 mins followed by ATP addition by short-circuit current assay	ic50	1.0000	uM
2-(4-chloro-2-methylphenoxy)-N-(2-methoxyphenyl)iminoacetamide	1868416: Inhibition of YFP tagged ANO1 (unknown origin) expressed in FRT cells incubated for 24 hrs by fluorescence plate reader assay	ic50	1.0700	uM
2-[(5-ethyl-4-methyl-6-oxo-1H-pyrimidin-2-yl)sulfanyl]-N-[5-(4-methoxyphenyl)-1,3-thiazol-2-yl]acetamide	1705443: Inhibition of human ANO1 expressed in FRT cells assessed as inhibition of ATP-induced channel current treated 20 mins prior to ATP challenge and measured by pacth-clamp technique	ic50	1.1000	uM
N-phenyl-2-(propanoylamino)-5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophene-3-carboxamide	1448054: Inhibition of human TMEM16A expressed in FRT cells co-expressing iodide sensitive fluorescent protein YFP-H148Q/I152L/F46L assessed as reduction in ATP-induced Ca2+ activation-mediated chloride current by measuring decrease in iodide influx preincubated for 10 mins followed by ATP/iodide addition by fluorescence assay	ic50	1.2000	uM
4-(4-chlorophenyl)-2-[(2,4-dichlorobenzoyl)amino]thiophene-3-carboxylic acid	1868416: Inhibition of YFP tagged ANO1 (unknown origin) expressed in FRT cells incubated for 24 hrs by fluorescence plate reader assay	ic50	1.2400	uM
N-(2-chlorophenyl)-2-[(2,2,2-trifluoroacetyl)amino]-5,6-dihydro-4H-cyclopenta[b]thiophene-3-carboxamide	1448054: Inhibition of human TMEM16A expressed in FRT cells co-expressing iodide sensitive fluorescent protein YFP-H148Q/I152L/F46L assessed as reduction in ATP-induced Ca2+ activation-mediated chloride current by measuring decrease in iodide influx preincubated for 10 mins followed by ATP/iodide addition by fluorescence assay	ic50	1.3000	uM
N-(2-methylphenyl)-2-(2,2,3,3,3-pentafluoropropanoylamino)-5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophene-3-carboxamide	1448054: Inhibition of human TMEM16A expressed in FRT cells co-expressing iodide sensitive fluorescent protein YFP-H148Q/I152L/F46L assessed as reduction in ATP-induced Ca2+ activation-mediated chloride current by measuring decrease in iodide influx preincubated for 10 mins followed by ATP/iodide addition by fluorescence assay	ic50	1.3000	uM
N-(2-chlorophenyl)-2-[(2,2,2-trifluoroacetyl)amino]-5,7-dihydro-4H-thieno[2,3-c]pyran-3-carboxamide	1448054: Inhibition of human TMEM16A expressed in FRT cells co-expressing iodide sensitive fluorescent protein YFP-H148Q/I152L/F46L assessed as reduction in ATP-induced Ca2+ activation-mediated chloride current by measuring decrease in iodide influx preincubated for 10 mins followed by ATP/iodide addition by fluorescence assay	ic50	1.3000	uM
N-(2-fluorophenyl)-2-[(2,2,2-trifluoroacetyl)amino]-5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophene-3-carboxamide	1448054: Inhibition of human TMEM16A expressed in FRT cells co-expressing iodide sensitive fluorescent protein YFP-H148Q/I152L/F46L assessed as reduction in ATP-induced Ca2+ activation-mediated chloride current by measuring decrease in iodide influx preincubated for 10 mins followed by ATP/iodide addition by fluorescence assay	ic50	1.3000	uM
2-[(2,2,2-trifluoroacetyl)amino]-N-[2-(trifluoromethoxy)phenyl]-5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophene-3-carboxamide	1448054: Inhibition of human TMEM16A expressed in FRT cells co-expressing iodide sensitive fluorescent protein YFP-H148Q/I152L/F46L assessed as reduction in ATP-induced Ca2+ activation-mediated chloride current by measuring decrease in iodide influx preincubated for 10 mins followed by ATP/iodide addition by fluorescence assay	ic50	1.3000	uM
N-(2-ethylphenyl)-2-[(2,2,2-trifluoroacetyl)amino]-5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophene-3-carboxamide	1448054: Inhibition of human TMEM16A expressed in FRT cells co-expressing iodide sensitive fluorescent protein YFP-H148Q/I152L/F46L assessed as reduction in ATP-induced Ca2+ activation-mediated chloride current by measuring decrease in iodide influx preincubated for 10 mins followed by ATP/iodide addition by fluorescence assay	ic50	1.3000	uM
6-tert-butyl-2-(furan-2-carbonylamino)-4,5,6,7-tetrahydro-1-benzothiophene-3-carboxylic acid	1705412: Inhibition of human ANO1 channel expressed in HEK293 cells incubated for 10 mins by FLIPR assay	ic50	1.3100	uM
4-(4-chlorophenyl)-2-[[5-chloro-2-(trifluoromethyl)benzoyl]amino]thiophene-3-carboxylic acid	1868416: Inhibition of YFP tagged ANO1 (unknown origin) expressed in FRT cells incubated for 24 hrs by fluorescence plate reader assay	ic50	1.5900	uM
N-(2-methylphenyl)-2-(2,2,3,3,3-pentafluoropropanoylamino)-5,7-dihydro-4H-thieno[2,3-c]pyran-3-carboxamide	1448054: Inhibition of human TMEM16A expressed in FRT cells co-expressing iodide sensitive fluorescent protein YFP-H148Q/I152L/F46L assessed as reduction in ATP-induced Ca2+ activation-mediated chloride current by measuring decrease in iodide influx preincubated for 10 mins followed by ATP/iodide addition by fluorescence assay	ic50	1.6000	uM
2-[(2-chloro-5-methylbenzoyl)amino]-4-(4-chlorophenyl)thiophene-3-carboxylic acid	1868416: Inhibition of YFP tagged ANO1 (unknown origin) expressed in FRT cells incubated for 24 hrs by fluorescence plate reader assay	ic50	1.7900	uM
2-[(2,2-difluoro-2-iodoacetyl)amino]-N-[2-(trifluoromethoxy)phenyl]-5,6-dihydro-4H-cyclopenta[b]thiophene-3-carboxamide	1448054: Inhibition of human TMEM16A expressed in FRT cells co-expressing iodide sensitive fluorescent protein YFP-H148Q/I152L/F46L assessed as reduction in ATP-induced Ca2+ activation-mediated chloride current by measuring decrease in iodide influx preincubated for 10 mins followed by ATP/iodide addition by fluorescence assay	ic50	1.8800	uM
4-(4-chlorophenyl)-2-[(2,3-dichlorobenzoyl)amino]thiophene-3-carboxylic acid	1868416: Inhibition of YFP tagged ANO1 (unknown origin) expressed in FRT cells incubated for 24 hrs by fluorescence plate reader assay	ic50	1.9400	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	increases expression, decreases reaction	4
(+)-JQ1 compound	affects cotreatment, decreases expression, increases expression	4
Benzo(a)pyrene	affects methylation, decreases expression, increases methylation	4
sodium arsenite	affects methylation, decreases expression, increases expression	3
Estradiol	increases reaction, affects cotreatment, increases expression, affects expression	3
Aflatoxin B1	decreases methylation, increases methylation, decreases expression	3
Genistein	increases expression	3
Fulvestrant	decreases reaction, increases expression, increases methylation	2
Valproic Acid	affects expression, increases methylation	2
bisphenol F	increases expression, decreases reaction	1
methyleugenol	decreases expression	1
beta-lapachone	increases expression	1
o,p’-DDT	increases expression	1
tobacco tar	decreases expression	1
benzo(e)pyrene	affects methylation	1
aflatoxin B2	increases methylation	1
9-phenanthrol	decreases reaction, increases activity	1
CGP 52608	affects binding, increases reaction	1
erucylphospho-N,N,N-trimethylpropylammonium	increases expression	1
abrine	increases expression	1
mirdametinib	affects cotreatment, decreases expression	1
bisphenol S	increases expression, decreases reaction	1
Resveratrol	increases expression	1
Air Pollutants	increases abundance, increases expression	1
Arsenic	increases methylation	1
Calcium	decreases reaction, increases activity	1
Diethylstilbestrol	increases expression	1
Doxorubicin	decreases expression	1
Endosulfan	increases expression	1
Ethinyl Estradiol	increases expression	1

ChEMBL screening assays

32 unique, capped per target: 32 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2050116	Binding	Inhibition of human TMEM16A transfected in FRT cells assessed as iodide influx using YFP-F46L/H148Q/I152L halide sensor after 10 mins by spectrofluorometric analysis	Novel 5-substituted benzyloxy-2-arylbenzofuran-3-carboxylic acids as calcium activated chloride channel inhibitors. — Bioorg Med Chem

Cellosaurus cell lines

8 cell lines: 6 induced pluripotent stem cell, 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_C4P8	MHHi001-A-1	Induced pluripotent stem cell	Female
CVCL_C4P9	MHHi001-A-2	Induced pluripotent stem cell	Female
CVCL_C4PA	MHHi002-A-4	Induced pluripotent stem cell	Male
CVCL_C4PB	MHHi002-A-5	Induced pluripotent stem cell	Male
CVCL_C4PC	MHHi002-A-6	Induced pluripotent stem cell	Male
CVCL_C4PD	MHHi002-A-7	Induced pluripotent stem cell	Male
CVCL_D1V8	Abcam A-549 ANO1 KO	Cancer cell line	Male
CVCL_D1ZV	Abcam HCT 116 ANO1 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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