Details for: ANO1

Gene ID: 55107

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: ANO1

Ensembl ID: ENSG00000131620

Description: anoctamin 1

Cell Significance Landscape

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • perivascular cell CL4033054
    CSI 3.62
    rCSI 4.95%
    PRS 88.03
  • hepatocyte CL0000182
    CSI 3.53
    rCSI 6.32%
    PRS 83
  • alveolar type 1 fibroblast cell CL4028004
    CSI 3.31
    rCSI 3.63%
    PRS 85.57
  • intestine goblet cell CL0019031
    CSI 3.09
    rCSI 2.74%
    PRS 81.59
  • mucus secreting cell CL0000319
    CSI 3.07
    rCSI 4.88%
    PRS 90.8
  • basal-myoepithelial cell of mammary gland CL0002324
    CSI 3.02
    rCSI 5.71%
    PRS 92
  • fibroblast of lung CL0002553
    CSI 2.97
    rCSI 2.77%
    PRS 84.7
  • midzonal region hepatocyte CL0019028
    CSI 2.93
    rCSI 6.89%
    PRS 82.9
  • keratinocyte CL0000312
    CSI 2.66
    rCSI 2.23%
    PRS 85.81
  • hepatic stellate cell CL0000632
    CSI 2.5
    rCSI 9.35%
    PRS 76.94
  • basal cell CL0000646
    CSI 2.29
    rCSI 3.06%
    PRS 81.86
  • renal interstitial pericyte CL1001318
    CSI 2.23
    rCSI 6.13%
    PRS 79.46
  • centrilobular region hepatocyte CL0019029
    CSI 2.22
    rCSI 5.78%
    PRS 81.44
  • tracheobronchial smooth muscle cell CL0019019
    CSI 1.99
    rCSI 3.51%
    PRS 88.18
  • periportal region hepatocyte CL0019026
    CSI 1.91
    rCSI 7.41%
    PRS 82.26
  • contractile cell CL0000183
    CSI 1.86
    rCSI 5.48%
    PRS 83.02
  • epithelial cell CL0000066
    CSI 1.85
    rCSI 2.85%
    PRS 72.79
  • pericyte CL0000669
    CSI 1.8
    rCSI 4.8%
    PRS 61.16
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 1.73
    rCSI 2.15%
    PRS 65.05
  • duct epithelial cell CL0000068
    CSI 1.71
    rCSI 2.5%
    PRS 88.31
  • myoepithelial cell CL0000185
    CSI 1.65
    rCSI 4.17%
    PRS 87.8
  • luminal epithelial cell of mammary gland CL0002326
    CSI 1.63
    rCSI 2.96%
    PRS 91.79
  • vascular associated smooth muscle cell CL0000359
    CSI 1.62
    rCSI 5.25%
    PRS 82.01
  • VIP GABAergic cortical interneuron CL4023016
    CSI 1.49
    rCSI 1.77%
    PRS 67.2
  • mural cell CL0008034
    CSI 1.41
    rCSI 4.77%
    PRS 79.41
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 1.38
    rCSI 2.31%
    PRS 67.09
  • fallopian tube secretory epithelial cell CL4030006
    CSI 1.36
    rCSI 1.31%
    PRS 83.23
  • colon goblet cell CL0009039
    CSI 1.29
    rCSI 3.08%
    PRS 87.75
  • enteric smooth muscle cell CL0002504
    CSI 1.29
    rCSI 1.83%
    PRS 84.5
  • sncg GABAergic cortical interneuron CL4023015
    CSI 1.16
    rCSI 1.86%
    PRS 68.55
  • foveolar cell of stomach CL0002179
    CSI 1.14
    rCSI 2.43%
    PRS 88.64
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 1.12
    rCSI 1.98%
    PRS 66.68
  • cholangiocyte CL1000488
    CSI 0.94
    rCSI 5.62%
    PRS 84.94
  • mesangial cell CL0000650
    CSI 0.93
    rCSI 3.81%
    PRS 90.88
  • blood vessel smooth muscle cell CL0019018
    CSI 0.93
    rCSI 7.58%
    PRS 78.87
  • GABAergic neuron CL0000617
    CSI 0.88
    rCSI 2.95%
    PRS 68.25
  • fibroblast of cardiac tissue CL0002548
    CSI 0.78
    rCSI 3.75%
    PRS 83.91
  • microcirculation associated smooth muscle cell CL0008035
    CSI 0.78
    rCSI 2.25%
    PRS 83.05
  • pancreatic stellate cell CL0002410
    CSI 0.67
    rCSI 3.92%
    PRS 86.8
  • mesenchymal cell CL0008019
    CSI 0.62
    rCSI 1.57%
    PRS 77.61
  • chandelier pvalb GABAergic cortical interneuron CL4023036
    CSI 0.54
    rCSI 1.69%
    PRS 70.96

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

Comma-separated if multiple.
Comma-separated if multiple.
Legend:
  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [ANO1](/details-gene/55107) (Anoctamin-1), also known as TMEM16A, is a protein-coding gene located on chromosome 11q13.3. It encodes a calcium-activated chloride channel that plays a fundamental role in ion transport across the plasma membrane. This function is critical for a variety of physiological processes, including fluid and mucus secretion, smooth muscle contraction, and sensory perception. **Overall**, the expression profile of [ANO1](/details-gene/55107) indicates its high significance in secretory epithelial cells, such as [intestine goblet cell](/details-cell/CL0019031) and [mucus secreting cell](/details-cell/CL0000319), as well as in stromal and parenchymal cells like [perivascular cell](/details-cell/CL4033054), [hepatocyte](/details-cell/CL0000182), and various fibroblasts. Its established role in both normal physiology and disease, particularly in cancer and channelopathies, makes it a subject of significant research interest ([Link](https://doi.org/10.1242/jcs.109553), [Link](https://doi.org/10.1016/s0002-9440(10)63279-8)). ## Cellular Roles and Expression Landscape The expression pattern of [ANO1](/details-gene/55107) highlights its importance in cells responsible for secretion, structural support, and metabolic functions. **Overall**, its significance is highest in mesenchymal and stromal cell types, including [perivascular cell](/details-cell/CL4033054) (CSI: 3.62), [alveolar type 1 fibroblast cell](/details-cell/CL4028004) (CSI: 3.31), and [fibroblast of lung](/details-cell/CL0002553) (CSI: 2.97), suggesting a role in tissue architecture and maintenance. A second major functional cluster is secretory epithelial cells. [ANO1](/details-gene/55107) shows high significance in [intestine goblet cell](/details-cell/CL0019031) (CSI: 3.09) and [mucus secreting cell](/details-cell/CL0000319) (CSI: 3.07), which is consistent with its function in driving chloride and fluid secretion, a process essential for mucosal hydration ([Link](https://doi.org/10.1074/jbc.m109.065367)). Its expression in [basal-myoepithelial cell of mammary gland](/details-cell/CL0002324) (CSI: 3.02) and [keratinocyte](/details-cell/CL0000312) (CSI: 2.66) further underscores its broad role in epithelial biology. Finally, [ANO1](/details-gene/55107) is a significant gene in [hepatocyte](/details-cell/CL0000182) populations (CSI: 3.53), including [midzonal](/details-cell/CL0019028) and [centrilobular](/details-cell/CL0019029) region hepatocytes, as well as [hepatic stellate cell](/details-cell/CL0000632) (CSI: 2.50). This suggests its involvement in liver-specific functions, potentially related to bile secretion or metabolic homeostasis. ## Pathways and Molecular Function The molecular functions and biological pathways associated with [ANO1](/details-gene/55107) are centered on its identity as an ion channel. It is primarily annotated with [calcium-activated chloride channel activity](/gene-ontology/GO:0005229) and is a key component of the [chloride channel complex](/gene-ontology/GO:0034707), located at the [plasma membrane](/gene-ontology/GO:0005886). Its activity is integral to [chloride transmembrane transport](/gene-ontology/GO:1902476) and [iodide transport](/gene-ontology/GO:0015705). The function of [ANO1](/details-gene/55107) in driving ion flux directly enables higher-order biological processes. Its role in [mucus secretion](/gene-ontology/GO:0070254) is consistent with its high expression in goblet and mucus-secreting cells. Furthermore, its involvement in the [phospholipase c-activating g protein-coupled receptor signaling pathway](/gene-ontology/GO:0007200) suggests it acts downstream of signaling cascades that elevate intracellular calcium, which in turn gates the channel. Reactome pathway analysis highlights its role in the transport of small molecules, specifically through [ion channel transport](/reactome-pathway/R-HSA-983712), and also implicates it in various disease states, including [viral infections](/reactome-pathway/R-HSA-9824446) such as [SARS-CoV-2 infection](/reactome-pathway/R-HSA-9694516), possibly by facilitating viral entry or replication processes. ## Research Directions The widespread expression of [ANO1](/details-gene/55107) in secretory and stromal cells, combined with its fundamental role as an ion channel, opens several avenues for future research. **Proposed Hypotheses:** 1. Given its high significance in multiple fibroblast subtypes ([alveolar type 1 fibroblast cell](/details-cell/CL4028004), [fibroblast of lung](/details-cell/CL0002553)) and [hepatic stellate cell](/details-cell/CL0000632), dysregulation of [ANO1](/details-gene/55107)-mediated ion transport may be a key driver of pathological fibrosis. We hypothesize that increased [ANO1](/details-gene/55107) activity in these cells promotes their activation and excessive deposition of extracellular matrix in diseases like idiopathic pulmonary fibrosis or liver cirrhosis. 2. The established co-expression and functional relationship between [ANO1](/details-gene/55107) and CFTR ([Link](https://doi.org/10.1159/000335765)) suggests that variations in [ANO1](/details-gene/55107) expression or function could act as a disease modifier in cystic fibrosis (CF). We hypothesize that individuals with CF who have higher baseline [ANO1](/details-gene/55107) activity in airway epithelial cells experience milder disease phenotypes due to partial compensation for the defective CFTR-mediated chloride transport. **Experimental Approach:** To test the hypothesis regarding the role of [ANO1](/details-gene/55107) in fibrosis, one could utilize an in vitro model of fibroblast activation. Primary human lung fibroblasts could be cultured and stimulated with TGF-beta, a potent pro-fibrotic cytokine. One group of cells would be concurrently treated with a specific pharmacological inhibitor of [ANO1](/details-gene/55107). The effect of inhibition would be assessed by measuring the expression of myofibroblast markers (e.g., alpha-smooth muscle actin) via immunofluorescence and Western blot, and by quantifying collagen production using a Sirius Red assay. A significant reduction in these fibrotic markers in the inhibitor-treated group would support the hypothesis. **Therapeutic Potential:** [ANO1](/details-gene/55107) presents a dual therapeutic potential. In diseases characterized by its overexpression, such as certain cancers like gastrointestinal stromal tumors (GISTs) where it serves as a diagnostic marker ([Link](https://doi.org/10.1016/s0002-9440(10)63279-8)), [ANO1](/details-gene/55107) is a promising target for **inhibition**. Small molecule inhibitors could potentially reduce tumor growth and proliferation. Conversely, in conditions of deficient chloride secretion like cystic fibrosis or Sjögren's syndrome, [ANO1](/details-gene/55107) is a candidate for pharmacological **activation**. Potentiating its activity could provide an alternative pathway for chloride transport, thereby alleviating symptoms like mucus obstruction and dry mouth. Its nature as a cell-surface ion channel makes it a particularly accessible target for small molecule drugs.

Genular Protein ID: 3770625937

Symbol: ANO1_HUMAN

Name: Anoctamin-1

UniProtKB Accession Codes:

Q5XXA6 A0A2H4Y9B2 A8KAM3 E9PNA7 Q8IYY8 Q8N7V3

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BindingDB 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 2 CTD 1 ChEBI 10 ChEMBL 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 DrugBank 1 DrugCentral 1 EMBL 7 Ensembl 4 ExpressionAtlas 1 GO 28 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 GuidetoPHARMACOLOGY 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 3 KEGG 1 MANE-Select 1 MIM 5 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRO 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 2 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 4 RNAct 1 Reactome 2 RefSeq 3 Rhea 1 SMR 1 STRING 1 SignaLink 1 SwissPalm 1 TCDB 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 16906560

Title: Comprehensive genome and transcriptome analysis of the 11q13 amplicon in human oral cancer and synteny to the 7F5 amplicon in murine oral carcinoma.

PubMed ID: 16906560

DOI: 10.1002/gcc.20371

PubMed ID: 26359375

Title: A novel exon in the human Ca2+-activated Cl- channel Ano1 imparts greater sensitivity to intracellular Ca2.

PubMed ID: 26359375

DOI: 10.1152/ajpgi.00074.2015

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 16554811

Title: Human chromosome 11 DNA sequence and analysis including novel gene identification.

PubMed ID: 16554811

DOI: 10.1038/nature04632

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 12739008

Title: FLJ10261 gene, located within the CCND1-EMS1 locus on human chromosome 11q13, encodes the eight-transmembrane protein homologous to C12orf3, C11orf25 and FLJ34272 gene products.

PubMed ID: 12739008

PubMed ID: 15215166

Title: The novel marker, DOG1, is expressed ubiquitously in gastrointestinal stromal tumors irrespective of KIT or PDGFRA mutation status.

PubMed ID: 15215166

DOI: 10.1016/s0002-9440(10)63279-8

PubMed ID: 20056604

Title: Expression and function of epithelial anoctamins.

PubMed ID: 20056604

DOI: 10.1074/jbc.m109.065367

PubMed ID: 21269460

Title: Initial characterization of the human central proteome.

PubMed ID: 21269460

DOI: 10.1186/1752-0509-5-17

PubMed ID: 22178883

Title: CFTR and TMEM16A are separate but functionally related Cl-channels.

PubMed ID: 22178883

DOI: 10.1159/000335765

PubMed ID: 21056985

Title: Characterization of the oligomeric structure of the Ca(2+)-activated Cl- channel Ano1/TMEM16A.

PubMed ID: 21056985

DOI: 10.1074/jbc.m110.174847

PubMed ID: 22946059

Title: Anoctamins are a family of Ca2+ activated Cl- channels.

PubMed ID: 22946059

DOI: 10.1242/jcs.109553

PubMed ID: 24913262

Title: TMEM16A is a Ca(2+) -activated Cl(-) channel expressed in the renal collecting duct.

PubMed ID: 24913262

DOI: 10.1111/apha.12323

PubMed ID: 25220078

Title: A novel TMEM16A splice variant lacking the dimerization domain contributes to calcium-activated chloride secretion in human sweat gland epithelial cells.

PubMed ID: 25220078

DOI: 10.1111/exd.12543

PubMed ID: 24275569

Title: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.

PubMed ID: 24275569

DOI: 10.1016/j.jprot.2013.11.014

PubMed ID: 28559167

Title: The stoichiometry of the TMEM16A ion channel determined in intact plasma membranes of COS-7 cells using liquid-phase electron microscopy.

PubMed ID: 28559167

DOI: 10.1016/j.jsb.2017.05.009

PubMed ID: 28963502

Title: Epithelial Chloride Transport by CFTR Requires TMEM16A.

PubMed ID: 28963502

DOI: 10.1038/s41598-017-10910-0

PubMed ID: 31732694

Title: TMEM16A chloride channel does not drive mucus production.

PubMed ID: 31732694

DOI: 10.26508/lsa.201900462

PubMed ID: 33026825

Title: TMEM16A Mediates Mucus Production in Human Airway Epithelial Cells.

PubMed ID: 33026825

DOI: 10.1165/rcmb.2019-0442oc

PubMed ID: 32487539

Title: TMEM16A deficiency: a potentially fatal neonatal disease resulting from impaired chloride currents.

PubMed ID: 32487539

DOI: 10.1136/jmedgenet-2020-106978

PubMed ID: 37253099

Title: Rare variants in ANO1, encoding a calcium-activated chloride channel, predispose to moyamoya disease.

PubMed ID: 37253099

DOI: 10.1093/brain/awad172

Sequence Information:

  • Length: 986
  • Mass: 114078
  • Checksum: E30A02F91EF36FC2
  • Sequence:
    • MRVNEKYSTL PAEDRSVHII NICAIEDIGY LPSEGTLLNS LSVDPDAECK YGLYFRDGRR 
KVDYILVYHH KRPSGNRTLV RRVQHSDTPS GARSVKQDHP LPGKGASLDA GSGEPPMDYH 
EDDKRFRREE YEGNLLEAGL ELERDEDTKI HGVGFVKIHA PWNVLCREAE FLKLKMPTKK 
MYHINETRGL LKKINSVLQK ITDPIQPKVA EHRPQTMKRL SYPFSREKQH LFDLSDKDSF 
FDSKTRSTIV YEILKRTTCT KAKYSMGITS LLANGVYAAA YPLHDGDYNG ENVEFNDRKL 
LYEEWARYGV FYKYQPIDLV RKYFGEKIGL YFAWLGVYTQ MLIPASIVGI IVFLYGCATM 
DENIPSMEMC DQRHNITMCP LCDKTCSYWK MSSACATARA SHLFDNPATV FFSVFMALWA 
ATFMEHWKRK QMRLNYRWDL TGFEEEEEAV KDHPRAEYEA RVLEKSLKKE SRNKEKRRHI 
PEESTNKWKQ RVKTAMAGVK LTDKVKLTWR DRFPAYLTNL VSIIFMIAVT FAIVLGVIIY 
RISMAAALAM NSSPSVRSNI RVTVTATAVI INLVVIILLD EVYGCIARWL TKIEVPKTEK 
SFEERLIFKA FLLKFVNSYT PIFYVAFFKG RFVGRPGDYV YIFRSFRMEE CAPGGCLMEL 
CIQLSIIMLG KQLIQNNLFE IGIPKMKKLI RYLKLKQQSP PDHEECVKRK QRYEVDYNLE 
PFAGLTPEYM EMIIQFGFVT LFVASFPLAP LFALLNNIIE IRLDAKKFVT ELRRPVAVRA 
KDIGIWYNIL RGIGKLAVII NAFVISFTSD FIPRLVYLYM YSKNGTMHGF VNHTLSSFNV 
SDFQNGTAPN DPLDLGYEVQ ICRYKDYREP PWSENKYDIS KDFWAVLAAR LAFVIVFQNL 
VMFMSDFVDW VIPDIPKDIS QQIHKEKVLM VELFMREEQD KQQLLETWME KERQKDEPPC 
NHHNTKACPD SLGSPAPSHA YHGGVL

Genular Protein ID: 1133799003

Symbol: Q9NW72_HUMAN

Name: N/A

UniProtKB Accession Codes:

Q9NW72

Database IDs:

ARBA 5 AlphaFoldDB 1 BioGRID-ORCS 1 CTD 1 DNASU 1 DisGeNET 1 EMBL 2 GO 2 InterPro 2 KEGG 1 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 PeptideAtlas 1 Pfam 2 PharmGKB 1 RefSeq 1 RuleBase 1 SAM 1

Citations:

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

Sequence Information:

  • Length: 594
  • Mass: 68928
  • Checksum: 3E66AE3FEA245917
  • Sequence:
    • MEMCDQRHNI TMCPLCDKTC SYWKMSSACA TARASHLFDN PATVFFSVFM ALWAATFMEH 
WKRKQMRLNY RWDLTGFEEE EEAVKDHPRA EYEARVLEKS LKKESRNKET DKVKLTWRDR 
FPAYLTNLVS IIFMIAVTFA IVLGVIIYRI SMAAALAMNS SPSVRSNIRV TVTATAVIIN 
LVVIILLDEV YGCIARWLTK IEVPKTEKSF EERLIFKAFL LKFVNSYTPI FYVAFFKGRF 
VGRPGDYVYI FRSFRMEECA PGGCLMELCI QLSIIMLGKQ LIQNNLFEIG IPKMKKLIRY 
LKLKQQSPPD HEECVKRKQR YEVDYNLEPF AGLTPEYMEM IIQFGFVTLF VASFPLAPLF 
ALLNNIIEIR LDAKKFVTEL RRPVAVRAKD IGIWYNILRG IGKLAVIINA FVISFTSDFI 
PRLVYLYMYS KNGTMHGFVN HTLSSFNVSD FQNGTAPNDP LDLGYEVQIC RYKDYREPPW 
SENKYDISKD FWAVLAARLA FVIVFQNLVM FMSDFVDWVI PDIPKDISQQ IHKEKVLMVE 
LFMREEQDKQ QLLETWMEKE RQKDEPPCNH HNTKACPDSL GSPAPSHAYH GGVL