ANO2
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Summary
ANO2 (anoctamin 2, HGNC:1183) is a protein-coding gene on chromosome 12p13.31, encoding Anoctamin-2 (Q9NQ90). Calcium-activated chloride channel (CaCC) which may play a role in olfactory signal transduction.
ANO2 belongs to a family of calcium-activated chloride channels (CaCCs) (reviewed by Hartzell et al., 2009 [PubMed 19015192]).
Source: NCBI Gene 57101 — RefSeq curated summary.
At a glance
- GWAS associations: 9
- Clinical variants (ClinVar): 30 total — 2 pathogenic
- GTEx eGene: eQTL in 27 tissues, sQTL in 7 (q < 0.05)
- Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.02 (unconstrained)
- MANE Select transcript:
NM_001364791
Identifiers
Gene identifiers
| Field | Value |
|---|---|
| HGNC ID | HGNC:1183 |
| Approved symbol | ANO2 |
| Name | anoctamin 2 |
| Location | 12p13.31 |
| Locus type | gene with protein product |
| Status | Approved |
| Ensembl gene | ENSG00000047617 |
| Ensembl biotype | protein_coding |
| OMIM | 610109 |
| Entrez | 57101 |
Gene structure
Transcript identifiers
Ensembl transcripts: 13 — 7 protein_coding_CDS_not_defined, 6 protein_coding
MANE Select: ENST00000682330
Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 3: 4, TSL 4: 2, TSL 5: 3
ENST00000682330, ENST00000356134, ENST00000536751, ENST00000538154, ENST00000540543, ENST00000541487, ENST00000541874, ENST00000542326, ENST00000544988, ENST00000545860, ENST00000650848, ENST00001129547, ENST00001136573
RefSeq mRNA: 3 — MANE Select: NM_001364791
NM_001278596, NM_001278597, NM_001364791
CCDS: CCDS44807, CCDS91642, CCDS91643
Canonical transcript exons
ENST00000682330 — 25 exons
| Exon | Start | End |
|---|---|---|
| ENSE00000369645 | 5575834 | 5576015 |
| ENSE00000714392 | 5565558 | 5565663 |
| ENSE00000714393 | 5577955 | 5578007 |
| ENSE00000714395 | 5599484 | 5599629 |
| ENSE00000714434 | 5615186 | 5615297 |
| ENSE00000714440 | 5744157 | 5744317 |
| ENSE00000714441 | 5750836 | 5750970 |
| ENSE00000714442 | 5799507 | 5799571 |
| ENSE00000714454 | 5806052 | 5806093 |
| ENSE00001043579 | 5635152 | 5635347 |
| ENSE00001167065 | 5807313 | 5807368 |
| ENSE00001296413 | 5921040 | 5921366 |
| ENSE00001302307 | 5827769 | 5827820 |
| ENSE00001314561 | 5922620 | 5922804 |
| ENSE00001649282 | 5578366 | 5578518 |
| ENSE00003475792 | 5647727 | 5647801 |
| ENSE00003483300 | 5612656 | 5612756 |
| ENSE00003506281 | 5732520 | 5732630 |
| ENSE00003548353 | 5612901 | 5612958 |
| ENSE00003559502 | 5830435 | 5830489 |
| ENSE00003563197 | 5739317 | 5739399 |
| ENSE00003656372 | 5854043 | 5854141 |
| ENSE00003671636 | 5832452 | 5832603 |
| ENSE00003720946 | 5945196 | 5945259 |
| ENSE00003919205 | 5562655 | 5563568 |
Expression profiles
Bgee: expression breadth ubiquitous, 165 present calls, max score 89.19.
FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.3565 / max 122.5880, expressed in 101 samples.
Highest expression (Bgee): sural nerve, testis, calcaneal tendon, male germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad.
Genetic regulation across tissues (GTEx eQTL / sQTL)
ANO2 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 27 tissues and its splicing (sQTL) in 7 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.
showing 20 of 34 significant tissue × QTL associations:
| Tissue | QTL | q-value | Slope | Lead variant |
|---|---|---|---|---|
| Testis | sqtl | 3.7e-16 | +0.65 | 12:5600399:G:A |
| Skin Sun Exposed Lower leg | eqtl | 1.2e-15 | -0.26 | 12:5937460:ACTT:A |
| Adipose Subcutaneous | eqtl | 6.5e-14 | +0.28 | 12:5953687:C:T |
| Muscle Skeletal | eqtl | 3.9e-13 | -0.33 | 12:5938554:C:T |
| Skin Not Sun Exposed Suprapubic | eqtl | 9.0e-13 | +0.27 | 12:5962603:T:C |
| Nerve Tibial | eqtl | 5.4e-12 | -0.27 | 12:5936095:T:C |
| Esophagus Mucosa | eqtl | 1.3e-11 | -0.39 | 12:5947326:T:C |
| Thyroid | eqtl | 2.0e-11 | -0.28 | 12:5924756:T:C |
| Colon Transverse | eqtl | 3.5e-11 | -0.25 | 12:5936095:T:C |
| Adipose Visceral Omentum | eqtl | 1.1e-09 | -0.23 | 12:5936095:T:C |
| Heart Atrial Appendage | eqtl | 2.1e-09 | -0.25 | 12:5940870:A:C |
| Colon Sigmoid | eqtl | 2.2e-09 | -0.26 | 12:5936095:T:C |
| Esophagus Muscularis | eqtl | 9.9e-09 | -0.25 | 12:5927515:G:A |
| Artery Aorta | eqtl | 1.8e-08 | -0.28 | 12:5924756:T:C |
| Breast Mammary Tissue | eqtl | 3.3e-08 | +0.19 | 12:5948745:A:G |
| Lung | eqtl | 1.1e-07 | -0.23 | 12:5937460:ACTT:A |
| Spleen | eqtl | 4.0e-07 | -0.69 | 12:6176637:G:A |
| Adipose Subcutaneous | sqtl | 5.7e-07 | +0.41 | 12:5609057:C:T |
| Brain Cerebellum | eqtl | 8.0e-07 | -0.31 | 12:5930247:A:G |
| Heart Left Ventricle | eqtl | 5.4e-06 | -0.26 | 12:5947284:G:T |
FANTOM5 promoters
3 alternative TSS:
| Promoter ID | TPM avg | Samples expressed |
|---|---|---|
| 129038 | 0.2155 | 75 |
| 129039 | 0.1116 | 23 |
| 129035 | 0.0294 | 11 |
Top tissues by expression
showing 100 of 285 tissues by Bgee expression score (0-100, higher = more expressed):
| Tissue | Anatomy ID | Expression score | Quality |
|---|---|---|---|
| sural nerve | UBERON:0015488 | 89.19 | gold quality |
| left testis | UBERON:0004533 | 86.43 | gold quality |
| calcaneal tendon | UBERON:0003701 | 86.17 | gold quality |
| right testis | UBERON:0004534 | 85.94 | gold quality |
| male germ line stem cell (sensu Vertebrata) in testis | CL:0000089 ∩ UBERON:0000473 | 82.84 | gold quality |
| primordial germ cell in gonad | CL:0000670 ∩ UBERON:0000991 | 82.77 | gold quality |
| testis | UBERON:0000473 | 82.37 | gold quality |
| apex of heart | UBERON:0002098 | 82.21 | gold quality |
| omental fat pad | UBERON:0010414 | 81.91 | gold quality |
| peritoneum | UBERON:0002358 | 81.80 | gold quality |
| right lung | UBERON:0002167 | 80.66 | gold quality |
| adipose tissue of abdominal region | UBERON:0007808 | 79.84 | gold quality |
| upper lobe of left lung | UBERON:0008952 | 77.91 | gold quality |
| right atrium auricular region | UBERON:0006631 | 76.51 | gold quality |
| heart left ventricle | UBERON:0002084 | 76.29 | gold quality |
| upper lobe of lung | UBERON:0008948 | 75.84 | gold quality |
| endocervix | UBERON:0000458 | 75.41 | gold quality |
| subcutaneous adipose tissue | UBERON:0002190 | 75.21 | gold quality |
| cardiac ventricle | UBERON:0002082 | 75.15 | gold quality |
| tendon | UBERON:0000043 | 75.14 | gold quality |
| ectocervix | UBERON:0012249 | 74.69 | gold quality |
| cardiac atrium | UBERON:0002081 | 74.31 | gold quality |
| heart | UBERON:0000948 | 73.47 | gold quality |
| mucosa of stomach | UBERON:0001199 | 72.91 | gold quality |
| left coronary artery | UBERON:0001626 | 72.52 | gold quality |
| body of uterus | UBERON:0009853 | 72.51 | gold quality |
| lower esophagus muscularis layer | UBERON:0035833 | 72.41 | gold quality |
| lower esophagus | UBERON:0013473 | 72.34 | gold quality |
| right coronary artery | UBERON:0001625 | 72.26 | gold quality |
| adipose tissue | UBERON:0001013 | 71.92 | gold quality |
| muscle of leg | UBERON:0001383 | 71.84 | gold quality |
| gastrocnemius | UBERON:0001388 | 71.83 | gold quality |
| tibial nerve | UBERON:0001323 | 71.48 | gold quality |
| colonic epithelium | UBERON:0000397 | 71.31 | gold quality |
| ventricular zone | UBERON:0003053 | 71.25 | gold quality |
| esophagogastric junction muscularis propria | UBERON:0035841 | 71.23 | gold quality |
| connective tissue | UBERON:0002384 | 71.06 | gold quality |
| coronary artery | UBERON:0001621 | 70.75 | gold quality |
| tibial artery | UBERON:0007610 | 70.35 | gold quality |
| popliteal artery | UBERON:0002250 | 70.29 | gold quality |
| right ovary | UBERON:0002118 | 70.11 | gold quality |
| left uterine tube | UBERON:0001303 | 70.09 | gold quality |
| hindlimb stylopod muscle | UBERON:0004252 | 70.02 | gold quality |
| vagina | UBERON:0000996 | 69.67 | gold quality |
| aorta | UBERON:0000947 | 69.65 | gold quality |
| pigmented layer of retina | UBERON:0001782 | 69.28 | gold quality |
| ascending aorta | UBERON:0001496 | 69.24 | gold quality |
| thoracic aorta | UBERON:0001515 | 69.21 | gold quality |
| esophagus | UBERON:0001043 | 69.14 | gold quality |
| placenta | UBERON:0001987 | 69.03 | gold quality |
| descending thoracic aorta | UBERON:0002345 | 68.82 | gold quality |
| left lobe of thyroid gland | UBERON:0001120 | 68.51 | gold quality |
| muscle layer of sigmoid colon | UBERON:0035805 | 68.49 | gold quality |
| lower esophagus mucosa | UBERON:0035834 | 68.49 | gold quality |
| caudate nucleus | UBERON:0001873 | 68.40 | gold quality |
| right lobe of thyroid gland | UBERON:0001119 | 68.25 | gold quality |
| body of stomach | UBERON:0001161 | 68.19 | gold quality |
| nucleus accumbens | UBERON:0001882 | 68.10 | gold quality |
| spleen | UBERON:0002106 | 67.73 | gold quality |
| C1 segment of cervical spinal cord | UBERON:0006469 | 67.56 | gold quality |
| thyroid gland | UBERON:0002046 | 67.49 | gold quality |
| putamen | UBERON:0001874 | 67.37 | gold quality |
| right frontal lobe | UBERON:0002810 | 67.21 | gold quality |
| left ovary | UBERON:0002119 | 67.13 | gold quality |
| stomach | UBERON:0000945 | 67.01 | gold quality |
| esophagus mucosa | UBERON:0002469 | 66.64 | gold quality |
| muscle organ | UBERON:0001630 | 66.59 | gold quality |
| smooth muscle tissue | UBERON:0001135 | 66.08 | gold quality |
| olfactory segment of nasal mucosa | UBERON:0005386 | 66.08 | gold quality |
| lung | UBERON:0002048 | 65.86 | gold quality |
| ganglionic eminence | UBERON:0004023 | 65.69 | gold quality |
| fundus of stomach | UBERON:0001160 | 65.33 | gold quality |
| gall bladder | UBERON:0002110 | 65.08 | gold quality |
| spinal cord | UBERON:0002240 | 64.93 | gold quality |
| uterine cervix | UBERON:0000002 | 64.87 | gold quality |
| anterior cingulate cortex | UBERON:0009835 | 64.70 | gold quality |
| amygdala | UBERON:0001876 | 64.68 | gold quality |
| cingulate cortex | UBERON:0003027 | 64.64 | gold quality |
| minor salivary gland | UBERON:0001830 | 64.60 | gold quality |
| metanephros cortex | UBERON:0010533 | 64.40 | gold quality |
| skin of abdomen | UBERON:0001416 | 64.10 | gold quality |
| skin of leg | UBERON:0001511 | 63.92 | gold quality |
| transverse colon | UBERON:0001157 | 63.83 | gold quality |
| small intestine Peyer’s patch | UBERON:0003454 | 63.77 | gold quality |
| ovary | UBERON:0000992 | 63.02 | gold quality |
| cerebellar hemisphere | UBERON:0002245 | 62.93 | gold quality |
| right hemisphere of cerebellum | UBERON:0014890 | 62.92 | gold quality |
| pancreatic ductal cell | CL:0002079 | 62.73 | silver quality |
| cerebellar cortex | UBERON:0002129 | 62.69 | gold quality |
| hypothalamus | UBERON:0001898 | 62.58 | gold quality |
| anatomical system | UBERON:0000467 | 62.57 | gold quality |
| small intestine | UBERON:0002108 | 62.51 | gold quality |
| prefrontal cortex | UBERON:0000451 | 62.47 | gold quality |
| multicellular organism | UBERON:0000468 | 62.38 | gold quality |
| material anatomical entity | UBERON:0000465 | 62.35 | gold quality |
| prostate gland | UBERON:0002367 | 62.20 | gold quality |
| colon | UBERON:0001155 | 62.19 | gold quality |
| myometrium | UBERON:0001296 | 61.98 | gold quality |
| female reproductive system | UBERON:0000474 | 61.75 | gold quality |
| right uterine tube | UBERON:0001302 | 61.75 | gold quality |
Single-cell (SCXA)
Detected in 3 experiment(s), a significant marker in 3.
| Experiment | Marker? | Max mean expression |
|---|---|---|
| E-MTAB-11268 | yes | 2693.27 |
| E-HCAD-35 | yes | 22.03 |
| E-ANND-3 | no | 0.00 |
HPA expression
RNA tissue specificity: Tissue enriched
showing 60 of 69 HPA tissues / cells by nTPM:
| Tissue / cell | Axis | nTPM | Protein (IHC) |
|---|---|---|---|
| Retina | tissue | 190.9 | low |
| Basal ganglia | tissue | 19.6 | not detected |
| Septum | tissue | 19.6 | |
| Caudate putamen | tissue | 17.8 | |
| Choroid plexus | tissue | 9.0 | |
| Testis | tissue | 8.6 | not detected |
| Ventral forebrain | tissue | 7.1 | |
| Nucleus accumbens | tissue | 6.3 | |
| Putamen | tissue | 5.8 | |
| Medulla oblongata | tissue | 5.7 | |
| Substantia nigra | tissue | 5.1 | |
| Spinal cord | tissue | 5.0 | |
| Amygdala | tissue | 4.6 | |
| Locus coeruleus | tissue | 3.7 | |
| Hippocampus | tissue | 3.4 | not detected |
| Tongue | tissue | 3.0 | |
| Placenta | tissue | 2.9 | not detected |
| Entorhinal cortex | tissue | 2.6 | |
| Retrosplenial cortex | tissue | 2.6 | |
| Adipose tissue | tissue | 2.4 | not detected |
| Postcentral gyrus | tissue | 2.1 | |
| Heart muscle | tissue | 2.0 | not detected |
| Pons | tissue | 1.7 | |
| Hippocampal formation | tissue | 1.7 | |
| Lung | tissue | 1.5 | not detected |
| Skeletal muscle | tissue | 1.4 | not detected |
| Cervix | tissue | 1.3 | not detected |
| Cerebral cortex | tissue | 1.1 | not detected |
| Smooth muscle | tissue | 1.1 | not detected |
| Frontal cortex | tissue | 1.1 | |
| Spleen | tissue | 1.1 | not detected |
| Corpus callosum | tissue | 1.1 | |
| Breast | tissue | 1.0 | not detected |
| Parathyroid gland | tissue | 1.0 | not detected |
| Endometrium 1 | tissue | 0.9 | not detected |
| Epididymis | tissue | 0.9 | not detected |
| Fallopian tube | tissue | 0.9 | high |
| Thalamus | tissue | 0.8 | |
| Seminal vesicle | tissue | 0.7 | not detected |
| Thyroid gland | tissue | 0.7 | not detected |
| Occipital cortex | tissue | 0.7 | |
| Ovary | tissue | 0.6 | not detected |
| Urinary bladder | tissue | 0.6 | not detected |
| Hypothalamus | tissue | 0.6 | |
| Small intestine | tissue | 0.6 | not detected |
| Gallbladder | tissue | 0.6 | not detected |
| Esophagus | tissue | 0.5 | not detected |
| Stomach 1 | tissue | 0.4 | not detected |
| Rectum | tissue | 0.4 | not detected |
| Colon | tissue | 0.4 | not detected |
| Prostate | tissue | 0.4 | not detected |
| Skin 1 | tissue | 0.3 | not detected |
| Vagina | tissue | 0.3 | not detected |
| Salivary gland | tissue | 0.3 | not detected |
| Kidney | tissue | 0.3 | not detected |
| Duodenum | tissue | 0.3 | not detected |
| Somatosensory cortex | tissue | 0.3 | |
| Appendix | tissue | 0.3 | not detected |
| Pancreas | tissue | 0.2 | not detected |
| Thymus | tissue | 0.2 |
Brain sub-regions (HPA Brain Atlas): detected in 185; highest nTPM — Nucleus basalis of Meynert (7.6), Posterior thalamic nucleus (7.3), Lateral amygdala (6.6), Caudate nucleus (6.4), Motor trigeminal nucleus (6.2).
Regulation
Is transcription factor: no
Upstream regulators (CollecTRI, top): FOXA2, MYCN
Functional genomics
gnomAD constraint: pLI 1.03e-30, LOEUF 1.02, missense Z -0.0956 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD
Regional missense constraint (gnomAD RMC): no regional variation along ENST00000682330 — one region, missense o/e 1.01.
Literature-anchored findings (GeneRIF, showing 13)
- C12orf3, FLJ10261 (ORAOV2), C11orf25 and FLJ34272 constitute a family of eight-transmembrane proteins with N- and C-terminal tails facing the cytoplasm. (PMID:12739008)
- VWF and TMEM16B deletions may have a role in severe von Willebrand disease type 3 (PMID:17371490)
- This study suggested that TMEM16B to be a strong candidate for the long sought-after Ca(2+)-dependent chloride channel in the photoreceptor synapse. (PMID:19474308)
- Ano2 likely amplifies the odor-induced generator potential in olfactory sensory neuron cilia by sensing elevated calcium levels, permitting the outward flow of chloride ions from the cell. (PMID:19561302)
- The third intracellular loop of TMEM16B is the site involved in calcium ion sensitivity, whereas the C-terminal part affects the rate of transition between the open and the closed state of the channel. (PMID:23570556)
- ANO2 is present in human myometrium. (PMID:24928056)
- results reveal multidimensional regulation of TMEM16A/16B by preassociated apoCaM and introduce ChIMP as a versatile tool to probe the macromolecular complex and function of Ca(2+)-activated chloride channels (PMID:25489088)
- Olfactory function impairment in Italian patients with type 3 von Willebrand disease with partial deletion of TMEM16B. (PMID:25635880)
- data revealed prominently increased autoantibody reactivity against the chloride-channel protein anoctamin 2 (ANO2) in multiple sclerosis cases compared with controls (PMID:26862169)
- residues facing the putative channel pore are responsible both for controlling the ion selectivity and the gating of the channel, providing an initial understanding of molecular mechanism of ion permeation in TMEM16B (PMID:28046119)
- a hypothesis where immune reactivity toward EBNA1 through molecular mimicry with ANO2 contributes to the etiopathogenesis of Multiple sclerosis. (PMID:31375628)
- Anoctamin 2-chloride channels reduce simple spike activity and mediate inhibition at elevated calcium concentration in cerebellar Purkinje cells. (PMID:33651839)
- Modulation of TMEM16B channel activity by the calcium-activated chloride channel regulator 4 (CLCA4) in human cells. (PMID:38825009)
Cross-species orthologs
5 orthologs
| Organism | Symbol | Gene ID |
|---|---|---|
| danio_rerio | ano2a | ENSDARG00000003210 |
| danio_rerio | ano2b | ENSDARG00000101363 |
| danio_rerio | ENSDARG00000112349 | |
| mus_musculus | Ano2 | ENSMUSG00000038115 |
| rattus_norvegicus | Ano2 | ENSRNOG00000023561 |
Paralogs (10): ANO8 (ENSG00000074855), PPP1R7 (ENSG00000115685), ANO1 (ENSG00000131620), ANO3 (ENSG00000134343), ANO7 (ENSG00000146205), ANO4 (ENSG00000151572), ANO10 (ENSG00000160746), ANO5 (ENSG00000171714), ANO6 (ENSG00000177119), ANO9 (ENSG00000185101)
Mouse-model phenotypes
Observed phenotypes of the mouse ortholog (MGI:2387214) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 10 distinct phenotype terms.
| Mouse phenotype (MP) | Records |
|---|---|
| enlarged lymph nodes | 1 |
| abnormal thymus morphology | 1 |
| enlarged thymus | 1 |
| decreased anxiety-related response | 1 |
| hyperactivity | 1 |
| abnormal olfactory system physiology | 1 |
| abnormal digit morphology | 1 |
| abnormal lymph node morphology | 1 |
| abnormal behavior | 1 |
| decreased thigmotaxis | 1 |
Additional cross-species homologs
Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.
| Organism | UniProt | Identity | Method |
|---|---|---|---|
| Bos taurus | A6QLE6 | 95.0% | Diamond |
Genomic neighbors (locus context)
Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).
| Symbol | Type | Entrez |
|---|---|---|
| SNORA120 | snoRNA | 109729112 |
| NTF3 | protein-coding | 4908 |
| VWF | protein-coding | 7450 |
| LINC02443 | ncRNA | 101929584 |
Protein
Protein identifiers
Anoctamin-2 — Q9NQ90 (reviewed: Q9NQ90)
Alternative names: Transmembrane protein 16B
All UniProt accessions (3): A0A804HIY3, F5H806, Q9NQ90
UniProt curated annotations — full annotation on UniProt →
Function. Calcium-activated chloride channel (CaCC) which may play a role in olfactory signal transduction. Odorant molecules bind to odor-sensing receptors (OSRs), leading to an increase in calcium entry that activates CaCC current which amplifies the depolarization of the OSR cells, ANO2 seems to be the underlying chloride channel involved in this process. May mediate light perception amplification in retina.
Subunit / interactions. Homodimer. Component of a presynaptic protein complex recruited to specialized plasma membrane domains of photoreceptors. Interacts with DLG4 by its C-terminal region.
Subcellular location. Cell membrane.
Tissue specificity. Retina, especially in the photoreceptor synaptic terminals.
Activity regulation. Channel activity is repressed by chloride inhibitors; strongly by niflumic acid (NFA), partially by flufenamic acid (FFA), and only slightly by meclofenamic acid (MFA), 5-Nitro-2-(3-phenylpropylamino)benzoic acid (NPPB), 4-acetamido-4’-isothiocyanato-stilben-2,2’-disulfonate (SITS), and 4,4’-diisothiocyanatostilbene-2,2’-disulfonic acid (DIDS).
Miscellaneous. The term ‘anoctamin’ was coined because these channels are anion selective and 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. Splice site between exons 4 and 5 is non-canonical. Splice site between exons 4 and 5 is non-canonical. A molecular mimicry between ANO2 and Epstein-Barr virus EBNA1 could possibly be linked to multiple sclerosis in the host.
Similarity. Belongs to the anoctamin family.
Isoforms (3)
| UniProt ID | Names | Canonical? |
|---|---|---|
| Q9NQ90-4 | 1 | yes |
| Q9NQ90-1 | 2 | |
| Q9NQ90-2 | 3 |
RefSeq proteins (3): NP_001265525, NP_001265526, NP_001351720* (*=MANE)
Domains & families (InterPro)
| ID | Name | Type |
|---|---|---|
| IPR007632 | Anoctamin | Family |
| IPR032394 | Anoct_dimer | Domain |
| IPR049452 | Anoctamin_TM | Domain |
Pfam: PF04547, PF16178
Catalyzed reactions (Rhea)
- chloride(in) = chloride(out) (RHEA:29823)
UniProt features (34 total): topological domain 9, transmembrane region 8, glycosylation site 4, sequence variant 4, splice variant 3, region of interest 2, compositionally biased region 2, chain 1, short sequence motif 1
Structure
Predicted structure (AlphaFold)
| Model | pLDDT | Fraction very-high |
|---|---|---|
| AF-Q9NQ90-F1 | 74.81 | 0.26 |
Human Protein Atlas
Protein class: Transporters, Transporter channels and pores, Predicted membrane proteins
Protein evidence: Evidence at protein level
Subcellular location (HPA, imaging): plasma membrane; nucleoplasm
Antibody reliability (HPA): IH enhanced · IF supported
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 (4)
| Type | Positions |
|---|---|
| N-linked (glcnac…) asparagine | 421, 836, 844, 851 |
Function
Pathways and Gene Ontology
Reactome pathways
2 curated (TAS) of 12; 7 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).
12 pathways:
| ID | Pathway | Evidence |
|---|---|---|
| R-HSA-9733458 | Induction of Cell-Cell Fusion ⚕ | curated |
| R-HSA-2672351 | Stimuli-sensing channels | curated |
| R-HSA-1643685 | Disease ⚕ | — |
| R-HSA-5663205 | Infectious disease ⚕ | — |
| R-HSA-9772573 | Late SARS-CoV-2 Infection Events ⚕ | — |
| R-HSA-9679506 | SARS-CoV Infections ⚕ | — |
| R-HSA-9694516 | SARS-CoV-2 Infection ⚕ | — |
| R-HSA-9824446 | Viral Infection Pathways ⚕ | — |
| R-HSA-983712 | Ion channel transport | — |
| R-HSA-381753 | Olfactory Signaling Pathway | electronic |
| R-HSA-9709957 | Sensory Perception | — |
| R-HSA-382551 | Transport of small molecules | — |
MSigDB gene sets: 76 (showing top):
GSE18804_BRAIN_VS_COLON_TUMORAL_MACROPHAGE_UP, GOBP_INORGANIC_ANION_TRANSPORT, GOBP_CHLORIDE_TRANSPORT, GOBP_TRANSMEMBRANE_TRANSPORT, SHEN_SMARCA2_TARGETS_DN, SENESE_HDAC3_TARGETS_DN, GOCC_CHLORIDE_CHANNEL_COMPLEX, GOCC_TRANSPORTER_COMPLEX, GOCC_MEMBRANE_PROTEIN_COMPLEX, GOMF_PROTEIN_DIMERIZATION_ACTIVITY, GOMF_GATED_CHANNEL_ACTIVITY, GOMF_PASSIVE_TRANSMEMBRANE_TRANSPORTER_ACTIVITY, GOMF_MONOATOMIC_ANION_CHANNEL_ACTIVITY, GOMF_MONOATOMIC_ANION_TRANSMEMBRANE_TRANSPORTER_ACTIVITY, GOMF_TRANSPORTER_ACTIVITY
GO Biological Process (4): monoatomic ion transmembrane transport (GO:0034220), chloride transmembrane transport (GO:1902476), monoatomic ion transport (GO:0006811), chloride transport (GO:0006821)
GO Molecular Function (4): intracellularly calcium-gated chloride channel activity (GO:0005229), chloride channel activity (GO:0005254), protein dimerization activity (GO:0046983), protein binding (GO:0005515)
GO Cellular Component (3): plasma membrane (GO:0005886), chloride channel complex (GO:0034707), membrane (GO:0016020)
Reactome top-level categories
9 top-level categories:
| Category | Pathways |
|---|---|
| Ion channel transport | 1 |
| Sensory Perception | 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
18 GO namespaces:
| Category | Terms |
|---|---|
| monoatomic ion transport | 1 |
| transmembrane transport | 1 |
| chloride transport | 1 |
| monoatomic anion transmembrane transport | 1 |
| transport | 1 |
| monoatomic anion transport | 1 |
| inorganic anion transport | 1 |
| chloride channel activity | 1 |
| ligand-gated monoatomic anion channel activity | 1 |
| intracellularly calcium-gated channel activity | 1 |
| monoatomic anion channel activity | 1 |
| chloride transmembrane transporter activity | 1 |
| protein binding | 1 |
| binding | 1 |
| membrane | 1 |
| cell periphery | 1 |
| monoatomic ion channel complex | 1 |
| cellular anatomical structure | 1 |
Experimentally-supported GO annotations
GO terms backed by direct experimental evidence (ECO experimental codes) — 3 of 11 annotations. The rest are phylogenetic / computational / electronic (IEA).
3 experimentally-supported GO terms:
| GO term | NS | Evidence |
|---|---|---|
| plasma membrane | CC | direct assay |
| intracellularly calcium-gated chloride channel activity | MF | direct assay |
| protein dimerization activity | MF | direct assay |
Protein interactions and networks
STRING
showing 15 of 662 interactions by confidence (×1000):
| Protein A | Protein B | Partner UniProt | Score |
|---|---|---|---|
| ANO2 | CLCA4 | Q14CN2 | 971 |
| ANO2 | CLCA2 | Q9UQC9 | 953 |
| ANO2 | CLCA1 | A8K7I4 | 893 |
| ANO2 | CNGA2 | Q16280 | 773 |
| ANO2 | CNGA4 | Q8IV77 | 699 |
| ANO2 | RTP2 | Q5QGT7 | 595 |
| ANO2 | ADCY3 | O60266 | 529 |
| ANO2 | OMP | P47874 | 499 |
| ANO2 | HEPACAM | Q14CZ8 | 490 |
| ANO2 | GNAL | P38405 | 484 |
| ANO2 | RTP1 | P59025 | 443 |
| ANO2 | OR4D2 | P58180 | 441 |
| ANO2 | FAM162B | Q5T6X4 | 433 |
| ANO2 | OR2Y1 | Q8NGV0 | 432 |
| ANO2 | ZNF70 | Q9UC06 | 431 |
IntAct
Human interaction partners of ANO2 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).
1 partners by confidence:
| Partner | Interaction type | MIscore | Records |
|---|---|---|---|
| DLG1 | direct interaction | 0.440 | 2 |
BioGRID (8 interactions; top human partners by supporting records): CLIC1 (Affinity Capture-MS), KIAA1429 (Affinity Capture-RNA), KIF14 (Affinity Capture-MS), PARP1 (Proximity Label-MS), PARP12 (Proximity Label-MS), PARP2 (Proximity Label-MS), PARP9 (Proximity Label-MS), TIPARP (Proximity Label-MS)
Disease & clinical
Genetic variants
Variant evidence for ANO2: 30 ClinVar records (2 pathogenic / likely pathogenic); 18 PharmGKB clinical annotations; 9 GWAS associations. Per-variant detail is on Sugi Variant.
ClinVar
30 variants total. Per-class counts are floors (≥ shown; pagination cap):
| Classification | Count (floor) |
|---|---|
| Pathogenic | 2 |
| Likely pathogenic | 0 |
| Uncertain significance | 4 |
| Likely benign | 4 |
| Benign | 2 |
Top pathogenic / likely-pathogenic (2)
Showing all 2 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.
| Variant ID | HGVS | Classification | Review | Submitters |
|---|---|---|---|---|
| 1330180 | GRCh37/hg19 12p13.33-13.31(chr12:146240-8330229)x3 | Pathogenic | criteria provided, single submitter | 1 |
| 1527679 | GRCh37/hg19 12p13.31(chr12:6024262-6276970)x1 | Pathogenic | criteria provided, single submitter | 1 |
Per-variant reference — Sugi Variant
Explore ANO2’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.
SpliceAI
Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 41 predictions of 3,037):
| Position(s) | Effect | Δscore | Sites |
|---|---|---|---|
| 12:5563569–5563570 | acceptor_loss | 1.0000 | 6 |
| 12:5563573 | acceptor_gain | 1.0000 | |
| 12:5599487–5599489 | donor_gain | 1.0000 | 2 |
| 12:5599630–5599631 | acceptor_loss | 1.0000 | 4 |
| 12:5612757–5612758 | acceptor_loss | 1.0000 | 6 |
| 12:5615184–5615185 | donor_loss | 1.0000 | 5 |
| 12:5615188 | donor_gain | 1.0000 | |
| 12:5615298–5615299 | acceptor_loss | 1.0000 | 6 |
| 12:5732518–5732519 | donor_loss | 1.0000 | 4 |
| 12:5732631–5732632 | acceptor_loss | 1.0000 | 6 |
AlphaMissense
2,520 missense substitutions predicted likely pathogenic (of 6,620 scored), across 598 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:
| Residue | Likely-pathogenic substitutions | Mean am_pathogenicity | Max am_pathogenicity |
|---|---|---|---|
| M749 | 9 | 0.898 | 0.986 |
| M448 | 9 | 0.865 | 0.987 |
| D781 | 8 | 0.997 | 0.998 |
| D100 | 8 | 0.993 | 0.997 |
| H316 | 8 | 0.993 | 0.998 |
| D733 | 8 | 0.986 | 0.996 |
| F759 | 8 | 0.986 | 0.998 |
| F273 | 8 | 0.984 | 0.997 |
| H190 | 8 | 0.982 | 0.999 |
| F364 | 8 | 0.981 | 0.999 |
| N693 | 8 | 0.977 | 0.997 |
| F763 | 8 | 0.974 | 0.994 |
| F256 | 8 | 0.970 | 0.999 |
| N774 | 8 | 0.953 | 0.999 |
| F92 | 8 | 0.951 | 0.991 |
| D437 | 8 | 0.951 | 0.981 |
| F356 | 8 | 0.948 | 0.997 |
| F455 | 8 | 0.948 | 0.997 |
| F909 | 8 | 0.947 | 0.992 |
| N773 | 8 | 0.946 | 0.998 |
HPA cancer prognostics
RNA cancer specificity: Cancer enhanced (Testicular Germ Cell Tumor)
Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.
1 prognostic cancer types:
| Cancer | Prognostic | p-value |
|---|---|---|
| Kidney Renal Clear Cell Carcinoma (validation) | favorable | 0.000364 |
Disease associations
OMIM: gene MIM:610109 | disease phenotypes:
GWAS associations
9 associations:
| Study | Trait | p-value |
|---|---|---|
| GCST000320_7 | Panic disorder | 4e-9 |
| GCST002925_5 | Sex hormone levels | 2e-8 |
| GCST010703_195 | Brain morphology (MOSTest) | 3e-8 |
| GCST001762_753 | Obesity-related traits | 3e-6 |
| GCST003133_3 | Plasma clusterin levels | 3e-6 |
| GCST009391_1299 | Metabolite levels | 5e-6 |
| GCST011038_7 | Parkinson’s disease progression (motor) | 6e-6 |
| GCST004751_25 | Serum uric acid levels in response to allopurinol in gout | 7e-6 |
| GCST009542_1 | Cleft lip with or without cleft palate x maternal periconceptional alcohol use interaction (parent of origin effect) | 7e-6 |
EFO canonical traits (from GWAS)
11 canonical traits:
| EFO ID | Trait name |
|---|---|
| EFO:0003940 | physical activity |
| EFO:0004697 | estradiol measurement |
| EFO:0004730 | hormone measurement |
| EFO:0007656 | plasma clusterin measurement |
| EFO:0004761 | uric acid measurement |
| EFO:0010523 | phosphoglyceric acid measurement |
| EFO:0003959 | cleft lip |
| EFO:0005939 | parental genotype effect measurement |
| EFO:0009113 | alcohol exposure measurement |
| EFO:0004346 | neuroimaging measurement |
| EFO:0008336 | disease progression measurement |
Drugs & pharmacology
Drug and pharmacology data
Is drug target: yes
ChEMBL targets (1): CHEMBL4105767 (SINGLE PROTEIN)
PharmGKB: 1 entry (CPIC guideline: no)
PharmGKB clinical annotations
18 annotations by evidence level (1 strongest → 4):
| Variant | Association | Level | Drugs | Phenotypes |
|---|---|---|---|---|
| rs17724452 | Efficacy | 3 | duloxetine | Major Depressive Disorder |
| rs17724464 | Efficacy | 3 | duloxetine | Major Depressive Disorder |
| rs17724494 | Efficacy | 3 | duloxetine | Major Depressive Disorder |
| rs17786394 | Efficacy | 3 | duloxetine | Major Depressive Disorder |
| rs17786400 | Efficacy | 3 | duloxetine | Major Depressive Disorder |
| rs17786412 | Efficacy | 3 | duloxetine | Major Depressive Disorder |
| rs61908402 | Efficacy | 3 | duloxetine | Major Depressive Disorder |
| rs61908403 | Efficacy | 3 | duloxetine | Major Depressive Disorder |
| rs61908404 | Efficacy | 3 | duloxetine | Major Depressive Disorder |
| rs61908405 | Efficacy | 3 | duloxetine | Major Depressive Disorder |
| rs61908406 | Efficacy | 3 | duloxetine | Major Depressive Disorder |
| rs61908407 | Efficacy | 3 | duloxetine | Major Depressive Disorder |
| rs61908408 | Efficacy | 3 | duloxetine | Major Depressive Disorder |
| rs61908409 | Efficacy | 3 | duloxetine | Major Depressive Disorder |
| rs61908410 | Efficacy | 3 | duloxetine | Major Depressive Disorder |
| rs61908411 | Efficacy | 3 | duloxetine | Major Depressive Disorder |
| rs78482393 | Efficacy | 3 | duloxetine | Major Depressive Disorder |
| rs78615940 | Efficacy | 3 | duloxetine | Major Depressive Disorder |
PharmGKB variants
18 variants:
| Variant | Genes | Level | Score | #Clin annots | Drugs |
|---|---|---|---|---|---|
| rs17724452 | ANO2 | 3 | 0.00 | 1 | duloxetine |
| rs17724464 | ANO2 | 3 | 0.00 | 1 | duloxetine |
| rs17724494 | ANO2 | 3 | 0.00 | 1 | duloxetine |
| rs17786394 | ANO2 | 3 | 0.00 | 1 | duloxetine |
| rs17786400 | ANO2 | 3 | 0.00 | 1 | duloxetine |
| rs17786412 | ANO2 | 3 | 0.00 | 1 | duloxetine |
| rs61908402 | ANO2 | 3 | 0.00 | 1 | duloxetine |
| rs61908403 | ANO2 | 3 | 0.00 | 1 | duloxetine |
| rs61908404 | ANO2 | 3 | 0.00 | 1 | duloxetine |
| rs61908405 | ANO2 | 3 | 0.00 | 1 | duloxetine |
| rs61908406 | ANO2 | 3 | 0.00 | 1 | duloxetine |
| rs61908407 | ANO2 | 3 | 0.00 | 1 | duloxetine |
| rs61908408 | ANO2 | 3 | 0.00 | 1 | duloxetine |
| rs61908409 | ANO2 | 3 | 0.00 | 1 | duloxetine |
| rs61908410 | ANO2 | 3 | 0.00 | 1 | duloxetine |
| rs61908411 | ANO2 | 3 | 0.00 | 1 | duloxetine |
| rs78482393 | ANO2 | 3 | 0.00 | 1 | duloxetine |
| rs78615940 | ANO2 | 3 | 0.00 | 1 | duloxetine |
PharmGKB variant annotations
Per-publication pharmacogenomic findings for this gene (significant associations).
19 published findings:
| Variant | Drug(s) | Category | Finding | PMID |
|---|---|---|---|---|
| rs17724452 | duloxetine | Efficacy | Allele C is associated with decreased response to duloxetine in people with Depressive Disorder, Major as compared to allele A. | PMID:29407288 |
| rs17724464 | duloxetine | Efficacy | Allele G is associated with decreased response to duloxetine in people with Depressive Disorder, Major as compared to allele C. | PMID:29407288 |
| rs17724494 | duloxetine | Efficacy | Allele C is associated with decreased response to duloxetine in people with Depressive Disorder, Major as compared to allele T. | PMID:29407288 |
| rs17786394 | duloxetine | Efficacy | Allele T is associated with decreased response to duloxetine in people with Depressive Disorder, Major as compared to allele C. | PMID:29407288 |
| rs17786400 | duloxetine | Efficacy | Allele A is associated with decreased response to duloxetine in people with Depressive Disorder, Major as compared to allele G. | PMID:29407288 |
| rs17786412 | duloxetine | Efficacy | Allele G is associated with decreased response to duloxetine in people with Depressive Disorder, Major as compared to allele A. | PMID:29407288 |
| rs61908402 | duloxetine | Efficacy | Allele T is associated with decreased response to duloxetine in people with Depressive Disorder, Major as compared to allele C. | PMID:29407288 |
| rs61908403 | duloxetine | Efficacy | Allele G is associated with decreased response to duloxetine in people with Depressive Disorder, Major as compared to allele A. | PMID:29407288 |
| rs61908404 | duloxetine | Efficacy | Allele C is associated with decreased response to duloxetine in people with Depressive Disorder, Major as compared to allele T. | PMID:29407288 |
| rs61908405 | duloxetine | Efficacy | Allele C is associated with decreased response to duloxetine in people with Depressive Disorder, Major as compared to allele A. | PMID:29407288 |
| rs61908406 | duloxetine | Efficacy | Allele G is associated with decreased response to duloxetine in people with Depressive Disorder, Major as compared to allele A. | PMID:29407288 |
| rs61908407 | duloxetine | Efficacy | Allele A is associated with decreased response to duloxetine in people with Depressive Disorder, Major as compared to allele G. | PMID:29407288 |
| rs61908408 | duloxetine | Efficacy | Allele A is associated with decreased response to duloxetine in people with Depressive Disorder, Major as compared to allele G. | PMID:29407288 |
| rs61908409 | duloxetine | Efficacy | Allele C is associated with decreased response to duloxetine in people with Depressive Disorder, Major as compared to allele G. | PMID:29407288 |
| rs61908410 | duloxetine | Efficacy | Allele T is associated with decreased response to duloxetine in people with Depressive Disorder, Major as compared to allele A. | PMID:29407288 |
| rs61908411 | duloxetine | Efficacy | Allele C is associated with decreased response to duloxetine in people with Depressive Disorder, Major as compared to allele T. | PMID:29407288 |
| rs78482393 | duloxetine | Efficacy | Allele G is associated with decreased response to duloxetine in people with Depressive Disorder, Major as compared to allele A. | PMID:29407288 |
| rs78615940 | duloxetine | Efficacy | Allele A is associated with decreased response to duloxetine in people with Depressive Disorder, Major as compared to allele C. | PMID:29407288 |
| rs2110166 | aflibercept, ranibizumab | Efficacy | Genotype TT is associated with increased clinical benefit to aflibercept or ranibizumab in people with Macular Degeneration as compared to genotypes CC + CT. | PMID:38980270 |
Binding affinities (BindingDB)
20 measured of 30 human assays (30 total across all organisms); most potent 20 below. Values come from heterogeneous assays and are not directly comparable.
| Ligand | Measure | Value | Patent |
|---|---|---|---|
| CHEMBL5186789 | IC50 | 24 nM | |
| CHEMBL4074929 | IC50 | 30 nM | |
| 2-(4-chloro-2-methylphenoxy)-N-[(E)-(2-methoxyphenyl)methylideneamino]acetamide | IC50 | 110 nM | US-11274074: Pharmaceutical composition for ANO1 antagonist with anticancer activity |
| CHEMBL3134585 | IC50 | 130 nM | |
| CHEMBL4104024 | IC50 | 150 nM | |
| CHEMBL4071143 | IC50 | 180 nM | |
| CHEMBL1444023 | IC50 | 260 nM | |
| 2-(4-chloro-2-methylphenoxy)-N-[(E)-1-[2-(trifluoromethoxy)phenyl]ethylideneamino]acetamide | IC50 | 300 nM | US-11274074: Pharmaceutical composition for ANO1 antagonist with anticancer activity |
| CHEMBL4085154 | IC50 | 600 nM | |
| CHEMBL1299863 | IC50 | 1000 nM | |
| CHEMBL4086165 | IC50 | 1600 nM | |
| 2-(4-chloro-2-methylphenoxy)-N’-[(2-methoxyphenyl)methyl]acetohydrazide | IC50 | 10700 nM | US-11274074: Pharmaceutical composition for ANO1 antagonist with anticancer activity |
| ethyl 2-[[2-(4-chloro-2-methylphenoxy)acetyl]amino]-1,3-thiazole-4-carboxylate | IC50 | 14800 nM | US-11274074: Pharmaceutical composition for ANO1 antagonist with anticancer activity |
| ethyl 2-[2-[(E)-[[2-(4-chloro-2-methylphenoxy)acetyl]hydrazinylidene]methyl]phenoxy]-2-fluoroacetate | IC50 | 15700 nM | US-11274074: Pharmaceutical composition for ANO1 antagonist with anticancer activity |
| 2-[(4-chloro-2-methylphenoxy)methyl]-5-(2-methoxyphenyl)-1,3,4-oxadiazole | IC50 | 19400 nM | US-11274074: Pharmaceutical composition for ANO1 antagonist with anticancer activity |
| 2-(4-chloro-2-methylphenoxy)-N-[(2-methoxyphenyl)methyl]acetamide | IC50 | 20600 nM | US-11274074: Pharmaceutical composition for ANO1 antagonist with anticancer activity |
| 2-[(4-chloro-2-methylphenoxy)methyl]-5-(2-fluorophenyl)-1,3,4-oxadiazole | IC50 | 21200 nM | US-11274074: Pharmaceutical composition for ANO1 antagonist with anticancer activity |
| 2-(4-chloro-2-methylphenoxy)-N-[(E)-pyridin-2-ylmethylideneamino]acetamide | IC50 | 31300 nM | US-11274074: Pharmaceutical composition for ANO1 antagonist with anticancer activity |
| 2-(4-chloro-2-methylphenoxy)-N-[(3-methoxyphenyl)methyl]acetamide | IC50 | 53700 nM | US-11274074: Pharmaceutical composition for ANO1 antagonist with anticancer activity |
| 2-[(4-chloro-2-methylphenoxy)methyl]-5-(furan-2-yl)-1,3,4-oxadiazole | IC50 | 63800 nM | US-11274074: Pharmaceutical composition for ANO1 antagonist with anticancer activity |
ChEMBL bioactivities
8 potent at pChembl≥5 of 14 total, top 8 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).
| pChembl | Type | Value | Unit | Molecule |
|---|---|---|---|---|
| 6.40 | IC50 | 400 | nM | CHEMBL4071143 |
| 6.40 | IC50 | 400 | nM | CHEMBL4074929 |
| 5.96 | IC50 | 1100 | nM | CHEMBL4104024 |
| 5.85 | IC50 | 1400 | nM | CHEMBL1444023 |
| 5.85 | IC50 | 1400 | nM | CHEMBL4085154 |
| 5.40 | IC50 | 4000 | nM | CHEMBL1299863 |
| 5.34 | IC50 | 4600 | nM | CHEMBL3134585 |
| 5.06 | IC50 | 8700 | nM | CHEMBL5186789 |
PubChem BioAssay actives
8 with measured affinity, of 52 total; 8 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-[(2-bromo-2,2-difluoroacetyl)amino]-N-(2-methylphenyl)-5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophene-3-carboxamide | 1448056: Inhibition of human TMEM16B 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 | 0.4000 | uM |
| 2-[(2-chloro-2,2-difluoroacetyl)amino]-N-(2-methylphenyl)-5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophene-3-carboxamide | 1448056: Inhibition of human TMEM16B 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 | 0.4000 | uM |
| 2-[(2,2-difluoro-2-iodoacetyl)amino]-N-(4-fluorophenyl)-5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophene-3-carboxamide | 1448056: Inhibition of human TMEM16B 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 | 1.1000 | uM |
| N-(2-methylphenyl)-2-[(2,2,2-trifluoroacetyl)amino]-5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophene-3-carboxamide | 1448056: Inhibition of human TMEM16B 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 | 1.4000 | uM |
| 2-[(2,2-difluoro-2-iodoacetyl)amino]-N-(2-methylphenyl)-5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophene-3-carboxamide | 1448056: Inhibition of human TMEM16B 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 | 1.4000 | uM |
| 2-[(5-ethyl-4-methyl-6-oxo-1H-pyrimidin-2-yl)sulfanyl]-N-[4-(4-methoxyphenyl)-1,3-thiazol-2-yl]acetamide | 1448075: Inhibition of TMEM16B (unknown origin) expressed in FRT cells assessed as reduction of ATP-induced chloride conductance preincubated for 20 mins followed by ATP addition by short-circuit current assay | ic50 | 4.0000 | uM |
| N-phenyl-2-[(2,2,2-trifluoroacetyl)amino]-5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophene-3-carboxamide | 1448056: Inhibition of human TMEM16B 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 | 4.6000 | uM |
| 4-(4-chlorophenyl)-2-[(2,5-difluorobenzoyl)amino]thiophene-3-carboxylic acid | 1868466: Inhibition of human ANO2 expressed in HEK293 cells incubated for 5 mins by whole cell patch clamp electrophysiology | ic50 | 8.7000 | uM |
CTD chemical–gene interactions
17 total (human), top 17 by PubMed support.
| Chemical | Actions (top 5) | PubMed papers |
|---|---|---|
| sodium arsenite | affects methylation, decreases expression | 2 |
| Valproic Acid | decreases expression | 2 |
| bisphenol A | affects cotreatment, decreases methylation | 1 |
| sulforaphane | decreases expression | 1 |
| benzo(e)pyrene | increases methylation | 1 |
| aflatoxin B2 | increases methylation | 1 |
| nickel sulfate | decreases expression | 1 |
| CGP 52608 | affects binding, increases reaction | 1 |
| 2-palmitoylglycerol | increases expression | 1 |
| Fulvestrant | affects cotreatment, decreases methylation | 1 |
| Benzo(a)pyrene | increases methylation | 1 |
| Doxorubicin | decreases expression | 1 |
| Methapyrilene | increases methylation | 1 |
| Methotrexate | decreases expression | 1 |
| Smoke | decreases expression | 1 |
| Tretinoin | decreases expression | 1 |
| Aflatoxin B1 | affects methylation | 1 |
ChEMBL screening assays
8 unique, capped per target: 5 binding, 3 admet
Representative assays (with source publication via chembl_document):
| Assay ID | Type | Description | Source paper |
|---|---|---|---|
| CHEMBL4015869 | Binding | Inhibition of human TMEM16B 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 | Substituted 2-Acylaminocycloalkylthiophene-3-carboxylic Acid Arylamides as Inhibitors of the Calcium-Activated Chloride Channel Transmembrane Protein 16A (TMEM16A). — *J Med Chem* |
| CHEMBL4310425 | ADMET | Inhibition of YFP-fused ANO2 (unknown origin) expressed in FRT cells after 20 mins by fluorescence quenching method | Synthesis and biological evaluation of novel Ani9 derivatives as potent and selective ANO1 inhibitors. — *Eur J Med Chem* |
Clinical trials (associated diseases)
Via MONDO — disease-level, not drug-specific.
showing 60 of 300 trials:
| NCT | Phase | Status | Title |
|---|---|---|---|
| NCT00076362 | Phase 4 | COMPLETED | Pediatric Hypothalamic Obesity |
| NCT00079547 | Phase 4 | COMPLETED | The Safety and Effectiveness of Low and High Carbohydrate Diets |
| NCT00115063 | Phase 4 | TERMINATED | LOSS- Louisiana Obese Subjects Study |
| NCT00134303 | Phase 4 | COMPLETED | Trial Comparing Metformin Versus Placebo in Non Alcoholic Steatohepatitis (NASH) Patients Receiving Bariatric Surgery for Obesity |
| NCT00143936 | Phase 4 | COMPLETED | The Safety and Efficacy of Low and High Carbohydrate Diets |
| NCT00143962 | Phase 4 | COMPLETED | Comparison of Two Approaches to Weight Loss Follow-Up Study |
| NCT00152360 | Phase 4 | COMPLETED | The Effect of Xenical on Weight and Risk Factors |
| NCT00176306 | Phase 4 | COMPLETED | Levofloxacin Pharmacokinetics (PK) in the Severely Obese |
| NCT00203450 | Phase 4 | COMPLETED | Zonegran for the Treatment of Weight Gain Associated With Psychotropic Medication Use: A Placebo-Controlled Trial |
| NCT00205504 | Phase 4 | COMPLETED | Oral Contraceptives in the Metabolic Syndrome |
| NCT00229229 | Phase 4 | TERMINATED | Comparison of 4 Diets in the Management of Overweight Patients With Vascular Disease |
| NCT00234988 | Phase 4 | COMPLETED | A Phase IV, Multi-Center, Open-Label Trial of Sibutramine in Combination With a Hypocaloric Diet in Obese and Overweight Thai Subjects. |
| NCT00264589 | Phase 4 | COMPLETED | Exercise Training and Cardiovascular Function in Obesity and in Type 2 Diabetes |
| NCT00288873 | Phase 4 | COMPLETED | Characterization of Hyperparathyroidism and Vitamin D Deficiency in Obesity |
| NCT00298857 | Phase 4 | TERMINATED | A Pharmacokinetic Study to Compare the Dosing of Valproic Acid in Subjects With Different Body Weights |
| NCT00315146 | Phase 4 | COMPLETED | Optimizing Body Composition for Function in Older Adults |
| NCT00319202 | Phase 4 | TERMINATED | Clinical Trial to Assess the Effects of Candesartan on the Carbohydrate Metabolism of Obese Subjects |
| NCT00327912 | Phase 4 | UNKNOWN | Laparoscopic Roux-en-Y Gastric Bypass Versus Laparoscopic Biliopancreatic Diversion (BPD)- Duodenal Switch for Superobesity |
| NCT00352287 | Phase 4 | COMPLETED | Study to Determine the Effects of Human Growth Hormone and Pioglitazone in Overweight, Prediabetic Adults |
| NCT00353054 | Phase 4 | COMPLETED | Effect of Calcium/Vitamin D Supplementation on Body Weight and Fat Loss. |
| NCT00390637 | Phase 4 | COMPLETED | Diet, Obesity and Genes (DiOGenes) |
| NCT00415688 | Phase 4 | COMPLETED | Lifestyle Modification for Obesity-Related Type 2 Diabetes |
| NCT00433641 | Phase 4 | COMPLETED | Weight Loss in Response to Sibutramine (MERIDIA) is Influenced by the Inherited Genes |
| NCT00440375 | Phase 4 | COMPLETED | Effects of Rosiglitazone on Bone in Postmenopausal Diabetic Women |
| NCT00453557 | Phase 4 | COMPLETED | Mechanism of Growth Hormone Effects on Adipose Tissue |
| NCT00456885 | Phase 4 | COMPLETED | The Effect of Exenatide on Weight and Hunger in Obese, Healthy Women |
| NCT00463112 | Phase 4 | COMPLETED | Effect of Diet Plus Sibutramine on Hormonal and Metabolic Features in Overweight and Obese Women With PCOS |
| NCT00512187 | Phase 4 | COMPLETED | Moderate Weight Loss Makes Obese Patients With Severe Chronic Plaque Psoriasis Responsive to Sub-Optimal Dose of Cyclosporine: an Investigator Blinded, Controlled, Randomized Clinical Trial |
| NCT00516919 | Phase 4 | COMPLETED | Study of Behavioral Weight Loss Therapy for Obesity and Binge Eating in Monolingual Hispanic Persons |
| NCT00522470 | Phase 4 | COMPLETED | Effects of Rosiglitazone on Serum Ghrelin and Peptide YY Levels |
| NCT00537810 | Phase 4 | COMPLETED | Treatment of Binge Eating in Obese Patients in Primary Care |
| NCT00538486 | Phase 4 | COMPLETED | A Randomized, Double-Blind, Active Control Trial Comparing Effects of Telmisartan, Candesartan and Amlodipine, Alone or Plus Metformin, on Non-Diabetic, Obese Hypertensive Patients |
| NCT00584389 | Phase 4 | TERMINATED | The Effect of Rimonabant on Energy Expenditure, Fat Metabolism and Body Composition |
| NCT00585182 | Phase 4 | COMPLETED | Study to Evaluate Weight-based Enoxaparin Dosing in Obese Medical Patients at Risk for DVT |
| NCT00632840 | Phase 4 | COMPLETED | Pharmacological Regulation of Fat Transport in Metabolic Syndrome |
| NCT00636142 | Phase 4 | COMPLETED | Effects of Infliximab on Insulin Sensitivity and Beta Cell Function in Insulin Resistant Human Obesity |
| NCT00675987 | Phase 4 | COMPLETED | A Randomized Clinical Trial To Study Losartan On Endothelial Dysfunction and Insulin Resistance In Obese Patients |
| NCT00694811 | Phase 4 | COMPLETED | Effects of Re-Feeding Duration on Weight Maintenance After Weight Loss With Very-Low-Energy Diets (VLEDs) |
| NCT00699413 | Phase 4 | TERMINATED | Supplements for Controlling Resistance to Insulin |
| NCT00729963 | Phase 4 | COMPLETED | Sibutramine Versus Continuous Positive Airway Pressure (CPAP)in Obstructive Sleep Apnea (OSA) Patients |
| NCT00752726 | Phase 4 | COMPLETED | Effect of Orlistat in Body Composition |
| NCT00770328 | Phase 4 | COMPLETED | The Effects of Pentoxifylline on PAI-1 in an Obese Population |
| NCT00775164 | Phase 4 | WITHDRAWN | Pioglitazone Therapy in Obese Children With Insulin Resistance: A Randomized, Controlled Pilot Study |
| NCT00775814 | Phase 4 | COMPLETED | Efficacy of Candesartan on Reducing Blood Pressure in Insulin-Resistant, Obese Patients With Hypertension. |
| NCT00779844 | Phase 4 | TERMINATED | Anesthesic Propofol and Remifentanil Requirements in Obese Patients |
| NCT00788840 | Phase 4 | COMPLETED | Detemir Energy Expenditure Study |
| NCT00790946 | Phase 4 | UNKNOWN | Kagoshima Collaborate Trial in Metabolic Syndrome (KACT Study) |
| NCT00841217 | Phase 4 | COMPLETED | Regulation of Lipoprotein Transport in Metabolic Syndrome |
| NCT00845559 | Phase 4 | WITHDRAWN | The Effects of Exenatide on Post-Meal Sugar Peaks and Vascular Health in Obese/Pre-Diabetic Young Adults |
| NCT00847262 | Phase 4 | COMPLETED | Trial Comparing Metabolic Effects of Telmisartan and Amlodipine on Hypertensive Patients With Obesity and Diabetes |
| NCT00852384 | Phase 4 | COMPLETED | Non Invasive Pressure Support Ventilation (NIPPV) Versus Recruitment Maneuver (RM) and Preoxygenation |
| NCT00877123 | Phase 4 | COMPLETED | Effect of Vitamin D Supplementation on Fasting Glucose and Interleukin-10 (IL-10) in Arab Women With Impaired Fasting Glucose |
| NCT00883259 | Phase 4 | UNKNOWN | Metformin and Gestational Diabetes in High-risk Patients: a RCTs |
| NCT00917033 | Phase 4 | COMPLETED | Tracheal Intubation of Morbidly Obese Patients. GlideScope Versus Direct Laryngoscopy |
| NCT00928005 | Phase 4 | COMPLETED | Evaluating the Effects of a Diet and Exercise Program in People With Type 2 Diabetes or Prediabetes: (The SHAPE3 Study) |
| NCT00932022 | Phase 4 | COMPLETED | Trospium Chloride XR in Obese Female Patients With Overactive Bladder |
| NCT00934570 | Phase 4 | COMPLETED | Activity and Metformin Intervention in Obese Adolescents |
| NCT00943969 | Phase 4 | COMPLETED | Determinants of Oral Morphine Answer Among Obese Patients Before and After Gastric Bypass |
| NCT00959309 | Phase 4 | COMPLETED | Media Use in Preschooler Study (MUPS) |
| NCT00983970 | Phase 4 | COMPLETED | Effects of Interactive Video Game Cycling on Obese Adolescent Health |
Predicted chemistry — Sugi Predict
The predicted patent-compound landscape for ANO2 across ~30M SureChEMBL compounds — explore on Sugi Predict.
Related Atlas pages
- Disease cohort memberships (association, not causation — diseases whose associated-gene cohort lists this gene; a subset are also under Associated diseases): obesity disorder, panic disorder, Parkinson disease
- Pharmacogenomically associated drugs (drugs whose metabolism/response is associated with variants in this gene (PharmGKB) — not drugs that target it): Duloxetine