PIEZO1

Summary

PIEZO1 (piezo type mechanosensitive ion channel component 1 (Er blood group), HGNC:28993) is a protein-coding gene on chromosome 16q24.3, encoding Piezo-type mechanosensitive ion channel component 1 (Q92508). Pore-forming subunit of the mechanosensitive non-specific cation Piezo channel required for rapidly adapting mechanically activated (MA) currents and has a key role in sensing touch and tactile pain.

The protein encoded by this gene is a mechanically-activated ion channel that links mechanical forces to biological signals. The encoded protein contains 36 transmembrane domains and functions as a homotetramer. Defects in this gene have been associated with dehydrated hereditary stomatocytosis.

Source: NCBI Gene 9780 — RefSeq curated summary.

At a glance

• Gene–disease (curated): obsolete PIEZO1-related generalized lymphatic dysplasia with non-immune hydrops fetalis (Definitive, ClinGen) — +4 more curated relationships
• GWAS associations: 80
• Clinical variants (ClinVar): 1,848 total — 29 pathogenic, 48 likely-pathogenic
• Phenotypes (HPO): 66
• Druggable target: yes
• MANE Select transcript: NM_001142864

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28993
Approved symbol	PIEZO1
Name	piezo type mechanosensitive ion channel component 1 (Er blood group)
Location	16q24.3
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0233
Ensembl gene	ENSG00000103335
Ensembl biotype	protein_coding
OMIM	611184
Entrez	9780

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 9 retained_intron, 6 protein_coding, 1 nonsense_mediated_decay

ENST00000301015, ENST00000327397, ENST00000419505, ENST00000466823, ENST00000472168, ENST00000474606, ENST00000475586, ENST00000484567, ENST00000490756, ENST00000491917, ENST00000495568, ENST00000497793, ENST00000518793, ENST00000521877, ENST00000566414, ENST00000938928

RefSeq mRNA: 1 — MANE Select: NM_001142864 NM_001142864

CCDS: CCDS54058

Canonical transcript exons

ENST00000301015 — 51 exons

Exon	Start	End
ENSE00001262457	88720069	88720283
ENSE00001262461	88720385	88720532
ENSE00001262465	88720616	88720748
ENSE00001262469	88721166	88721430
ENSE00001262473	88721538	88721726
ENSE00001262478	88721808	88722066
ENSE00001262487	88722218	88722397
ENSE00001262494	88722583	88722689
ENSE00001262515	88723871	88723971
ENSE00001262521	88725009	88725080
ENSE00001262544	88726547	88726643
ENSE00001262549	88726715	88726958
ENSE00001262554	88727039	88727192
ENSE00001262561	88727557	88727661
ENSE00001262569	88731706	88731910
ENSE00001262575	88732335	88732535
ENSE00001290610	88733588	88733745
ENSE00001290763	88732607	88732732
ENSE00001291928	88736148	88736408
ENSE00001292699	88734875	88735053
ENSE00001294442	88734356	88734538
ENSE00001311141	88734650	88734798
ENSE00001312139	88733906	88734054
ENSE00001314842	88735135	88735246
ENSE00001330151	88733278	88733454
ENSE00001504122	88725595	88725684
ENSE00001504123	88726284	88726455
ENSE00001711076	88737728	88737814
ENSE00001744712	88736639	88736739
ENSE00001770599	88737559	88737646
ENSE00002092290	88738227	88738440
ENSE00002100605	88737934	88738105
ENSE00002109808	88742053	88742095
ENSE00002121832	88738568	88738736
ENSE00002125197	88741478	88741616
ENSE00002252508	88749384	88749479
ENSE00002289455	88784901	88785220
ENSE00002304284	88742300	88742422
ENSE00003495325	88719802	88719960
ENSE00003505674	88725416	88725519
ENSE00003506639	88722837	88723009
ENSE00003542956	88719574	88719721
ENSE00003556453	88717023	88717211
ENSE00003577783	88716198	88716277
ENSE00003612043	88715933	88716119
ENSE00003620855	88723226	88723328
ENSE00003627999	88723095	88723151
ENSE00003655415	88716806	88716898
ENSE00003658195	88716559	88716731
ENSE00003676551	88716361	88716483
ENSE00003826213	88715338	88715854

Expression profiles

Bgee: expression breadth ubiquitous, 142 present calls, max score 98.56.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 30.5440 / max 309.2865, expressed in 1799 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
158576	25.2033	1783
158575	5.3407	1638

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
muscle layer of sigmoid colon	UBERON:0035805	98.56	gold quality
lower esophagus mucosa	UBERON:0035834	98.47	gold quality
upper lobe of left lung	UBERON:0008952	98.10	gold quality
granulocyte	CL:0000094	98.06	gold quality
lower esophagus	UBERON:0013473	98.01	gold quality
lower esophagus muscularis layer	UBERON:0035833	98.01	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	97.99	gold quality
omental fat pad	UBERON:0010414	97.94	gold quality
adipose tissue	UBERON:0001013	97.88	gold quality
spleen	UBERON:0002106	97.88	gold quality
subcutaneous adipose tissue	UBERON:0002190	97.87	gold quality
right lung	UBERON:0002167	97.71	gold quality
mucosa of stomach	UBERON:0001199	97.63	gold quality
prostate gland	UBERON:0002367	97.63	gold quality
skin of leg	UBERON:0001511	97.51	gold quality
left uterine tube	UBERON:0001303	97.50	gold quality
metanephros cortex	UBERON:0010533	97.45	gold quality
mammary gland	UBERON:0001911	97.43	gold quality
thoracic mammary gland	UBERON:0005200	97.43	gold quality
zone of skin	UBERON:0000014	97.26	gold quality
body of uterus	UBERON:0009853	97.11	gold quality
skin of abdomen	UBERON:0001416	97.06	gold quality
sural nerve	UBERON:0015488	97.04	gold quality
myometrium	UBERON:0001296	96.98	gold quality
esophagus	UBERON:0001043	96.97	gold quality
ectocervix	UBERON:0012249	96.89	gold quality
vagina	UBERON:0000996	96.78	gold quality
colon	UBERON:0001155	96.67	gold quality
transverse colon	UBERON:0001157	96.54	gold quality
stromal cell of endometrium	CL:0002255	96.53	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.89

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 40)

• The MIB index was strongly correlated with disease progression in papillary urothelial neoplasms in the urinary bladder. (PMID:18311491)
• siRNA knockdown in epithelial cells inactivates endogenous beta1 integrin, reducing cell adhesion (PMID:20016066)
• Data show that the transmission of PIEZO1 mutations and cosegregation with the disease phenotype in all affected persons in both kindreds. (PMID:22529292)
• Piezo1 responses in a patch emulate many of the responses seen in whole-cell mode, there are significant differences, presumably in the force transfer structures. (PMID:22790451)
• Loss of Fam38A expression may cause increased cell migration and metastasis in lung tumours. (PMID:22792288)
• R2456H and R2488Q mutations in PIEZO1 alter mechanosensitive channel regulation, leading to increased cation transport in erythroid cells. (PMID:23479567)
• Xerocytosis is caused by mutations that alter the kinetics of the mechanosensitive channel PIEZO1. (PMID:23487776)
• study reports two unrelated families with hereditary xerocytosis where probands presented fetal hydrops for which the same heterozygous mutation in PIEZO1 was identified (PMID:23581886)
• The gain-of-function PIEZO1 phenotype provides insight that helps to explain the increased permeability of cations in red blood cells of dehydrated hereditary stomatocytosis patients. (PMID:23695678)
• gating and inactivation as a function of pressure (PMID:23972840)
• PIEZO1 stretch sensitivity is modulated by polycystin-2. (PMID:24157948)
• Hereditary xerocytosis and familial haemolysis due to mutation in the PIEZO1 gene have been found in a Danish pedigree. (PMID:24314002)
• Piezo1 is a novel TFF1 binding protein that is important for TFF1-mediated cell migration in gastric cancer cells. (PMID:24798994)
• family of mechanically activated channels that counts only two members in human, piezo1 and 2, has emerged recently. [review] (PMID:25037583)
• The R2488Q PIEZO1 mutation is an apparent major cause of familial hereditary xerocytosis. (PMID:25044010)
• the mechanically gated ion channel Piezo1 is an important determinant of mechanosensitive lineage choice in neural stem cells and may play similar roles in other multipotent stem cells. (PMID:25349416)
• Protonation of the human PIEZO1 ion channel stabilizes inactivation. (PMID:25561736)
• a possible role of Piezo1 in invasion and metastatic propagation. (PMID:25666479)
• PIEZO1 is permeable to monovalent ions (K+, Na+, Cs+, Li+) and most divalent ions (Ba2+, Ca2+ and Mg2+), but not to Mn2+. (PMID:25955826)
• Mechanically activated Piezo1 plays an essential role in red blood cell volume homeostasis. (PMID:26001274)
• Piezo1 is amenable to chemical activation and thus there is a possibility that endogenous Piezo1 agonists might exist. (PMID:26001275)
• Homozygous and compound heterozygous mutations in PIEZO1, result in an autosomal recessive form of generalized lymphatic dysplasia with a high incidence of non-immune hydrops fetalis and childhood onset of facial and four limb lymphoedema. (PMID:26333996)
• Piezo1 channels are likely to function in normal RBCs and suggest a previously unidentified mechanotransductive pathway in ATP release. (PMID:26351678)
• Mutations in PIEZO1 is associated with persistent lymphoedema caused by congenital lymphatic dysplasia. (PMID:26387913)
• Piezo1 responds to lateral membrane tension with exquisite sensitivity as compared to other mechanically activated channels and that resting tension can drive channel inactivation, thereby tuning overall mechanical sensitivity of Piezo1. (PMID:26646186)
• When the “split protein” is coexpressed, the parts associate to form a normal channel. (PMID:26963637)
• correlation between HPCHA and PIEZO1-gene mutated findings raise an important question as to whether any of the high phosphatidylcholine hemolytic anemia cases previously diagnosed in Japan may have in fact been the form of hemolytic anemia known as hereditary xerocytosis or dehydrated hereditary stomatocytosis with PIEZO1 gene mutation (PMID:26971963)
• differential regulation of PKA and cell stiffness in unconfined versus confined cells is abrogated by dual, but not individual, inhibition of Piezo1 and myosin II. (PMID:27160899)
• MiR-103a might be a potential biomarker of myocardium infarction and could be used as an index for the diagnosis of AMI. It may be involved in the development of HBP and onset of AMI through regulating the Piezo1 expression. (PMID:27515482)
• analysis of Piezo1 domains by using localized force on magnetic nanoparticles (PMID:27694883)
• The Piezo1 convert a variety of mechanical stimuli into channel activation and subsequent inactivation, and what molecules and mechanisms modulate Piezo function. (PMID:27743844)
• data demonstrate that PIEZO1 is required for the regulation of NO formation, vascular tone, and blood pressure. (PMID:27797339)
• In the absence of extracellular matrix (ECM) proteins Piezo1 receptors are relatively insensitive to mechanical forces pushing the cellular membrane, whereas they can hardly be activated by mechanically pulling the membrane. Yet, if conjugated with Matrigel, a mix of ECM proteins, the receptors become sensitized. (PMID:28164706)
• Because Piezo1 senses both mechanical crowding and stretch, it may act as a homeostatic sensor to control epithelial cell numbers, triggering extrusion and apoptosis in crowded regions and cell division in sparse regions. (PMID:28199303)
• platelets and Meg-01 cells express the MS cation channel Piezo1, which may contribute to Ca(2+) entry and thrombus formation under arterial shear. (PMID:28416610)
• present study was designed to evaluate in hereditary xerocytosis the functional link between mutated Piezo1 and KCNN4 (PMID:28619848)
• Results find that Ucn1 exerts its chondroprotective effect by maintaining Piezo1 in a closed conformation. (PMID:28698554)
• Additional alterations in mutant PIEZO1 channel kinetics, differences in response to osmotic stress, and altered membrane protein trafficking, predicting variant alleles that worsen or ameliorate erythrocyte hydration. (PMID:28716860)
• The structural dynamics of the PIEZO1 channel activation and inactivation by coarse-grained modeling has been reported. (PMID:28905417)
• Piezo1-shRNA could inhibit the invasion of the osteosarcoma cells. (PMID:29065102)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	piezo1	ENSDARG00000076870
mus_musculus	Piezo1	ENSMUSG00000014444
rattus_norvegicus	Piezo1	ENSRNOG00000056786
drosophila_melanogaster	Piezo	FBGN0264953
caenorhabditis_elegans		WBGENE00007505

Paralogs (1): PIEZO2 (ENSG00000154864)

Protein

Protein identifiers

Piezo-type mechanosensitive ion channel component 1 — Q92508 (reviewed: Q92508)

Alternative names: Membrane protein induced by beta-amyloid treatment, Protein FAM38A

All UniProt accessions (6): Q92508, E7EUT2, H0YB49, H3BRR7, H3BSF6, H7C2J5

UniProt curated annotations — full annotation on UniProt →

Function. Pore-forming subunit of the mechanosensitive non-specific cation Piezo channel required for rapidly adapting mechanically activated (MA) currents and has a key role in sensing touch and tactile pain. Piezo channels are homotrimeric three-blade propeller-shaped structures that utilize a cap-motion and plug-and-latch mechanism to gate their ion-conducting pathways. Generates currents characterized by a linear current-voltage relationship that are sensitive to ruthenium red and gadolinium. Conductance to monovalent alkali ions is highest for K(+), intermediate for Na(+) and lowest for Li(+). Divalent ions except for Mn(2+) permeate the channel but more slowly than the monovalent ions and they also reduce K(+) currents. Plays a key role in epithelial cell adhesion by maintaining integrin activation through R-Ras recruitment to the ER, most probably in its activated state, and subsequent stimulation of calpain signaling. In inner ear hair cells, PIEZO1/2 subunits may constitute part of the mechanotransducer (MET) non-selective cation channel complex where they may act as pore-forming ion-conducting component in the complex. In the kidney, may contribute to the detection of intraluminal pressure changes and to urine flow sensing. Acts as a shear-stress sensor that promotes endothelial cell organization and alignment in the direction of blood flow through calpain activation. Plays a key role in blood vessel formation and vascular structure in both development and adult physiology. Acts as a sensor of phosphatidylserine (PS) flipping at the plasma membrane and governs morphogenesis of muscle cells. In myoblasts, flippase-mediated PS enrichment at the inner leaflet of plasma membrane triggers channel activation and Ca2+ influx followed by Rho GTPases signal transduction, leading to assembly of cortical actomyosin fibers and myotube formation.

Subunit / interactions. Homotrimer; the homotrimer forms a propeller-shaped Piezo channel with a cation-ion conducting pore. Heterotrimeric interaction may occur between PIEZO1 and PIEZO2. Interacts with PKD2. Interacts with STOML3. Interacts with TMC1, TMC2, PCDH15 and CIB2; the interaction may be part of the MET complex. Interacts with MDFIC (via C-terminus); the interaction prolongs Piezo channel inactivation. Interacts with MDFI (via C-terminus); the interaction prolongs Piezo channel inactivation.

Subcellular location. Endoplasmic reticulum membrane. Endoplasmic reticulum-Golgi intermediate compartment membrane. Cell membrane. Cell projection. Lamellipodium membrane.

Tissue specificity. Expressed in numerous tissues. In normal brain, expressed exclusively in neurons, not in astrocytes. In Alzheimer disease brains, expressed in about half of the activated astrocytes located around classical senile plaques. In Parkinson disease substantia nigra, not detected in melanin-containing neurons nor in activated astrocytes. Expressed in erythrocytes (at protein level). Expressed in myoblasts (at protein level).

Disease relevance. Dehydrated hereditary stomatocytosis 1 with or without pseudohyperkalemia and/or perinatal edema (DHS1) [MIM:194380] An autosomal dominant hemolytic anemia characterized by primary erythrocyte dehydration. DHS erythrocytes exhibit decreased total cation and potassium content that are not accompanied by a proportional net gain of sodium and water. DHS patients typically exhibit mild to moderate compensated hemolytic anemia, with an increased erythrocyte mean corpuscular hemoglobin concentration and a decreased osmotic fragility, both of which reflect cellular dehydration. Patients may also show perinatal edema and pseudohyperkalemia due to loss of potassium from red cells stored at room temperature. A minor proportion of red cells appear as stomatocytes on blood films. Complications such as splenomegaly and cholelithiasis, resulting from increased red cell trapping in the spleen and elevated bilirubin levels, respectively, may occur. The course of DHS is frequently associated with iron overload, which may lead to hepatosiderosis. The disease is caused by variants affecting the gene represented in this entry. All disease-causing mutations characterized so far produce a gain-of-function phenotype, mutated channels exhibiting increased cation transport in erythroid cells, that could be due to slower channel inactivation rate compared to the wild-type protein. Lymphatic malformation 6 (LMPHM6) [MIM:616843] A form of primary lymphedema, a disease characterized by swelling of body parts due to developmental anomalies and functional defects of the lymphatic system. Patients with lymphedema may suffer from recurrent local infections. LMPHM6 is an autosomal recessive, severe form manifesting as generalized lymphatic dysplasia. It is characterized by uniform, widespread swelling of all segments of the body, with systemic involvement such as intestinal and/or pulmonary lymphangiectasia, pleural effusions, chylothoraces and/or pericardial effusions, and with a high incidence of non- immune hydrops fetalis. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Regulated by auxillary subunits MDFIC and MDFI. Down-regulated by phosphatidylserines exposed on the cell surface. Divalent ions decrease the single-channel permeability of K(+).

Polymorphism. PIEZO1 is responsible for the Er blood group system (ER) [MIM:620207]. At least five antigens have been identified: Er(a), Er(b), Er(3), Er(4), and Er(5). The molecular basis of the Er(a)/Er(b) polymorphism is a single variation at position 2394; Gly-2394 corresponds to Er(a) and Ser-2394 to Er(b), while the Er(3) antigen is recognized by antibodies produced by Er(a-b-) individuals. The Er(4) and Er(5) antigens are defined by Glu-2407 and Arg-2245, respectively. Alloantibodies against Er(4) and Er(5) are associated with hemolytic disease of the fetus and newborn.

Miscellaneous. Piezo comes from the Greek ‘piesi’ meaning pressure.

Similarity. Belongs to the PIEZO (TC 1.A.75) family.

RefSeq proteins (1): NP_001136336* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR027272	Piezo	Family
IPR031334	Piezo_cap_dom	Domain
IPR031805	Piezo_TM25-28	Domain
IPR056768	THU_Piezo	Domain
IPR056769	Piezo_TM1-24	Domain
IPR056770	Piezo_THU9_anchor	Domain

Pfam: PF12166, PF15917, PF23188, PF24871, PF24874

Catalyzed reactions (Rhea), 4 shown:

• K(+)(in) = K(+)(out) (RHEA:29463)
• Ca(2+)(in) = Ca(2+)(out) (RHEA:29671)
• Mg(2+)(in) = Mg(2+)(out) (RHEA:29827)
• Na(+)(in) = Na(+)(out) (RHEA:34963)

UniProt features (228 total): helix 60, topological domain 39, transmembrane region 38, sequence variant 26, strand 24, turn 15, compositionally biased region 7, modified residue 7, region of interest 5, glycosylation site 2, chain 1, disulfide bond 1, mutagenesis site 1, sequence conflict 1, coiled-coil region 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
8ZU3	ELECTRON MICROSCOPY	3.1
8YFC	ELECTRON MICROSCOPY	3.2
9VMX	ELECTRON MICROSCOPY	3.2
8YEZ	ELECTRON MICROSCOPY	3.3
8ZU8	ELECTRON MICROSCOPY	3.9
8YFG	ELECTRON MICROSCOPY	4.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q92508-F1	72.74	0.13

Functional residue map

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

Post-translational modifications (7): 734, 758, 1391, 1396, 1636, 1646, 1854

Disulfide bonds (1): 2411–2415

Glycosylation sites (2): 295, 2294

Mutagenesis-validated functional residues (1):

Position	Phenotype
2456	does not inactivate the protein. gives rise to mechanically activated currents that inactivate more slowly than wild-typ

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-9856530	High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells
R-HSA-9856532	Mechanical load activates signaling by PIEZO1 and integrins in osteocytes
R-HSA-9860927	Turbulent (oscillatory, disturbed) flow shear stress activates signaling by PIEZO1 and integrins in endothelial cells

MSigDB gene sets: 364 (showing top): GOBP_POSITIVE_REGULATION_OF_MYOTUBE_DIFFERENTIATION, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, GOBP_CELLULAR_RESPONSE_TO_EXTERNAL_STIMULUS, GOBP_POSITIVE_REGULATION_OF_MUSCLE_CELL_DIFFERENTIATION, GOBP_STRIATED_MUSCLE_CELL_DIFFERENTIATION, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, GOBP_REGULATION_OF_STRIATED_MUSCLE_CELL_DIFFERENTIATION, TGACCTY_ERR1_Q2, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_POSITIVE_REGULATION_OF_CELL_ADHESION, GOBP_CELL_CELL_ADHESION, GOBP_DETECTION_OF_MECHANICAL_STIMULUS, NIKOLSKY_BREAST_CANCER_16Q24_AMPLICON, GOBP_POSITIVE_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS

GO Biological Process (10): monoatomic cation transport (GO:0006812), positive regulation of myotube differentiation (GO:0010831), positive regulation of integrin activation (GO:0033625), positive regulation of cell-cell adhesion mediated by integrin (GO:0033634), regulation of membrane potential (GO:0042391), detection of mechanical stimulus (GO:0050982), cellular response to mechanical stimulus (GO:0071260), monoatomic ion transport (GO:0006811), monoatomic ion transmembrane transport (GO:0034220), monoatomic cation transmembrane transport (GO:0098655)

GO Molecular Function (4): monoatomic cation channel activity (GO:0005261), mechanosensitive monoatomic ion channel activity (GO:0008381), mechanosensitive monoatomic cation channel activity (GO:0140135), protein binding (GO:0005515)

GO Cellular Component (9): endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), plasma membrane (GO:0005886), lamellipodium membrane (GO:0031258), stereocilium (GO:0032420), cuticular plate (GO:0032437), endoplasmic reticulum-Golgi intermediate compartment membrane (GO:0033116), membrane (GO:0016020), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Response of endothelial cells to shear stress	2
Cellular responses to mechanical stimuli	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
monoatomic ion transport	2
monoatomic ion transmembrane transport	2
response to mechanical stimulus	2
monoatomic ion channel activity	2
regulation of myotube differentiation	1
myotube differentiation	1
positive regulation of striated muscle cell differentiation	1
positive regulation of protein-containing complex assembly	1
integrin activation	1
regulation of integrin activation	1
positive regulation of cell-cell adhesion	1
positive regulation of cell adhesion mediated by integrin	1
cell-cell adhesion mediated by integrin	1
regulation of cell-cell adhesion mediated by integrin	1
regulation of biological quality	1
detection of external stimulus	1
detection of abiotic stimulus	1
cellular response to abiotic stimulus	1
cellular response to external stimulus	1
transport	1
transmembrane transport	1
monoatomic cation transport	1
monoatomic cation transmembrane transporter activity	1
gated channel activity	1
monoatomic cation channel activity	1
mechanosensitive monoatomic ion channel activity	1
binding	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
membrane	1
cell periphery	1
lamellipodium	1
cell projection membrane	1
leading edge membrane	1
stereocilium bundle	1

Protein interactions and networks

STRING

2117 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PIEZO1	TRPV4	Q9HBA0	782
PIEZO1	TMC2	Q8TDI7	726
PIEZO1	KCNK4	Q9NYG8	715
PIEZO1	TRPC1	P48995	713
PIEZO1	KCNK2	O95069	710
PIEZO1	ATP2A2	P16614	682
PIEZO1	TMEM150C	B9EJG8	667
PIEZO1	STOML3	Q8TAV4	667
PIEZO1	TMC1	Q8TDI8	630
PIEZO1	PANX1	Q96RD7	625
PIEZO1	PKD1	P98161	621
PIEZO1	TRPA1	O75762	611
PIEZO1	KCNN4	O15554	609
PIEZO1	COPB1	P53618	608
PIEZO1	TRPV1	Q8NER1	604

IntAct

78 interactions, top by confidence:

A	B	Type	Score
NIPAL1	ESYT2	psi-mi:“MI:0914”(association)	0.640
TRDN	TMEM223	psi-mi:“MI:0914”(association)	0.640
TFF1	PIEZO1	psi-mi:“MI:0915”(physical association)	0.600
PIEZO1	TFF1	psi-mi:“MI:0915”(physical association)	0.600
TFF1	PIEZO1	psi-mi:“MI:0403”(colocalization)	0.600
CYP20A1	PIEZO1	psi-mi:“MI:0915”(physical association)	0.590
CXCR4	TMEM120B	psi-mi:“MI:0914”(association)	0.530
YIPF3	TMEM120B	psi-mi:“MI:0914”(association)	0.530
FBXO2	TMEM131L	psi-mi:“MI:0914”(association)	0.530
LGALS1	PODXL	psi-mi:“MI:0914”(association)	0.530
PIEZO1	CLGN	psi-mi:“MI:0914”(association)	0.530
TSPAN5	SC5D	psi-mi:“MI:0914”(association)	0.530
SLC39A4	TMEM120B	psi-mi:“MI:0914”(association)	0.530
LGALS3	PODXL	psi-mi:“MI:0914”(association)	0.530
LGALS1	LAMA5	psi-mi:“MI:0914”(association)	0.530
ANKRD22	ESYT2	psi-mi:“MI:0914”(association)	0.530
PIEZO1	CHRNA5	psi-mi:“MI:0915”(physical association)	0.400
	TK2	psi-mi:“MI:0915”(physical association)	0.400
Rab5c		psi-mi:“MI:0914”(association)	0.350
GJB2	SNX3	psi-mi:“MI:0914”(association)	0.350
RAB5C	GCA	psi-mi:“MI:0914”(association)	0.350
RAB7A		psi-mi:“MI:0914”(association)	0.350
VAPA		psi-mi:“MI:0914”(association)	0.350
GOLT1B		psi-mi:“MI:0914”(association)	0.350

BioGRID (71): PIEZO1 (Affinity Capture-MS), PIEZO1 (Affinity Capture-MS), PIEZO1 (Affinity Capture-MS), PIEZO1 (Affinity Capture-MS), PIEZO1 (Affinity Capture-MS), PIEZO1 (Affinity Capture-MS), PIEZO1 (Affinity Capture-MS), PIEZO1 (Affinity Capture-MS), PIEZO1 (Affinity Capture-MS), PIEZO1 (Affinity Capture-MS), PIEZO1 (Affinity Capture-RNA), PIEZO1 (Biochemical Activity), PIEZO1 (Affinity Capture-MS), PIEZO1 (Affinity Capture-RNA), PIEZO1 (Proximity Label-MS)

ESM2 similar proteins: A0JN53, A0PJX8, A1L1L2, A1L3T7, A4FV45, B0BMG8, E2JF22, G3HQ82, O15360, O43299, O70491, P60330, Q0KL00, Q0V8E7, Q17Q97, Q24JP3, Q3U829, Q49LS3, Q4QR83, Q562E7, Q5ND34, Q5R7B4, Q5T1A1, Q5XG04, Q6NUQ4, Q6PH58, Q6UX68, Q7L4E1, Q7Z412, Q8BGI5, Q8BM55, Q8BSD4, Q8BXV2, Q8C3R1, Q8C7B8, Q8IXR5, Q8K0R6, Q8N6S5, Q8R115, Q8VCA6

Diamond homologs: E2JF22, Q0KL00, Q8CD54, Q92508, Q9H5I5

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
PIEZO1	“form complex”	“Hair cells mechanotransduction channel”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 87 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

GO biological processes:

GO term	Partners	Fold	FDR
adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway	5	14.2×	7e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

1848 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	29
Likely pathogenic	48
Uncertain significance	818
Likely benign	430
Benign	161

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1323447	NM_001142864.4(PIEZO1):c.6616C>T (p.Gln2206Ter)	Pathogenic
1330705	NM_001142864.4(PIEZO1):c.5404-1G>C	Pathogenic
1330992	NM_001142864.4(PIEZO1):c.5632_5633delinsG (p.Lys1878fs)	Pathogenic
1344888	NM_001142864.4(PIEZO1):c.307C>T (p.Arg103Ter)	Pathogenic
1997542	NM_001142864.4(PIEZO1):c.4666C>T (p.Gln1556Ter)	Pathogenic
2195015	NM_001142864.4(PIEZO1):c.145C>T (p.Arg49Ter)	Pathogenic
223127	NM_001142864.4(PIEZO1):c.2263G>T (p.Glu755Ter)	Pathogenic
223128	NM_001142864.4(PIEZO1):c.4888G>T (p.Glu1630Ter)	Pathogenic
223129	NM_001142864.4(PIEZO1):c.6682C>T (p.Gln2228Ter)	Pathogenic
223130	NM_001142864.4(PIEZO1):c.3796+1G>A	Pathogenic
223133	NM_001142864.4(PIEZO1):c.7289C>T (p.Pro2430Leu)	Pathogenic
2444346	NM_001142864.4(PIEZO1):c.4058+1G>C	Pathogenic
2506015	NM_001142864.4(PIEZO1):c.4914C>G (p.Tyr1638Ter)	Pathogenic
2646989	NM_001142864.4(PIEZO1):c.6073_6074del (p.Lys2025fs)	Pathogenic
2705448	NM_001142864.4(PIEZO1):c.3585C>A (p.Tyr1195Ter)	Pathogenic
280281	NM_001142864.4(PIEZO1):c.2035G>T (p.Glu679Ter)	Pathogenic
3342620	NM_001142864.4(PIEZO1):c.5006_5010dup (p.Leu1673fs)	Pathogenic
3581334	NM_001142864.4(PIEZO1):c.3367G>T (p.Glu1123Ter)	Pathogenic
4080838	NM_001142864.4(PIEZO1):c.7117C>T (p.Gln2373Ter)	Pathogenic
418948	NM_001142864.4(PIEZO1):c.7477CTGGAG[3] (p.2493LE[3])	Pathogenic
449461	NM_001142864.4(PIEZO1):c.1264C>T (p.Gln422Ter)	Pathogenic
4771255	NM_001142864.4(PIEZO1):c.4285dup (p.Glu1429fs)	Pathogenic
4795115	NM_001142864.4(PIEZO1):c.5242C>T (p.Gln1748Ter)	Pathogenic
4820297	NM_001142864.4(PIEZO1):c.6763C>T (p.Gln2255Ter)	Pathogenic
55806	NM_001142864.4(PIEZO1):c.7367G>A (p.Arg2456His)	Pathogenic
55808	NM_001142864.4(PIEZO1):c.4073G>C (p.Arg1358Pro)	Pathogenic
962685	NM_001142864.4(PIEZO1):c.4453C>T (p.Gln1485Ter)	Pathogenic
973951	NM_001142864.4(PIEZO1):c.6964G>T (p.Glu2322Ter)	Pathogenic
985646	NM_001142864.4(PIEZO1):c.4275_4278del (p.Ser1425fs)	Pathogenic
1065481	NM_001142864.4(PIEZO1):c.5716_5738del (p.Pro1906fs)	Likely pathogenic

SpliceAI

8840 predictions. Top by Δscore:

Variant	Effect	Δscore
16:88715850:TGATG:T	acceptor_gain	1.0000
16:88715852:ATG:A	acceptor_gain	1.0000
16:88715853:TG:T	acceptor_gain	1.0000
16:88715853:TGC:T	acceptor_loss	1.0000
16:88715854:GCT:G	acceptor_loss	1.0000
16:88715855:C:A	acceptor_loss	1.0000
16:88715855:C:CC	acceptor_gain	1.0000
16:88715856:T:G	acceptor_loss	1.0000
16:88715931:AC:A	donor_gain	1.0000
16:88715932:CC:C	donor_gain	1.0000
16:88716115:CTCAT:C	acceptor_gain	1.0000
16:88716116:TCAT:T	acceptor_gain	1.0000
16:88716117:CAT:C	acceptor_gain	1.0000
16:88716117:CATC:C	acceptor_gain	1.0000
16:88716118:AT:A	acceptor_gain	1.0000
16:88716120:C:CC	acceptor_gain	1.0000
16:88716120:CTGG:C	acceptor_loss	1.0000
16:88716125:A:AC	acceptor_gain	1.0000
16:88716125:A:C	acceptor_gain	1.0000
16:88716190:ATACT:A	donor_loss	1.0000
16:88716191:TACT:T	donor_loss	1.0000
16:88716194:TCACT:T	donor_loss	1.0000
16:88716195:CACT:C	donor_loss	1.0000
16:88716196:A:AC	donor_gain	1.0000
16:88716197:C:CT	donor_gain	1.0000
16:88716197:CT:C	donor_gain	1.0000
16:88716197:CTG:C	donor_gain	1.0000
16:88716197:CTGGG:C	donor_gain	1.0000
16:88716276:CC:C	acceptor_gain	1.0000
16:88716277:CC:C	acceptor_gain	1.0000

AlphaMissense

16322 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:88715625:A:G	W2516R	0.999
16:88715625:A:T	W2516R	0.999
16:88715663:A:G	L2503P	0.999
16:88716572:A:G	W2305R	0.999
16:88716572:A:T	W2305R	0.999
16:88716651:C:A	W2278C	0.999
16:88716651:C:G	W2278C	0.999
16:88716653:A:G	W2278R	0.999
16:88716653:A:T	W2278R	0.999
16:88717121:A:G	W2188R	0.999
16:88717121:A:T	W2188R	0.999
16:88719675:A:G	W2124R	0.999
16:88719675:A:T	W2124R	0.999
16:88715648:C:G	R2508P	0.998
16:88715654:A:G	L2506P	0.998
16:88715759:A:G	L2471P	0.998
16:88715847:C:G	G2442R	0.998
16:88715847:C:T	G2442R	0.998
16:88716039:A:G	W2404R	0.998
16:88716039:A:T	W2404R	0.998
16:88716642:A:C	S2281R	0.998
16:88716642:A:T	S2281R	0.998
16:88716644:T:G	S2281R	0.998
16:88717048:A:T	V2212D	0.998
16:88717054:A:T	V2210D	0.998
16:88717114:G:C	P2190R	0.998
16:88719587:C:G	R2153P	0.998
16:88719639:A:G	W2136R	0.998
16:88719639:A:T	W2136R	0.998
16:88719677:T:A	D2123V	0.998

dbSNP variants (sampled 300 via entrez): RS1000034932 (16:88729847 G>A,C), RS1000102634 (16:88768230 C>T), RS1000132183 (16:88726114 T>C), RS1000154153 (16:88773269 G>A,C), RS1000160076 (16:88741300 G>A,C,T), RS1000164278 (16:88773443 C>T), RS1000316438 (16:88746272 C>A,T), RS1000343931 (16:88723897 T>G), RS1000361330 (16:88777093 C>T), RS1000431822 (16:88726807 G>C), RS1000476808 (16:88723964 G>A,C,T), RS1000553808 (16:88718897 G>A,C), RS1000604219 (16:88720487 G>A,C), RS1000626703 (16:88736880 C>T), RS1000630465 (16:88759063 T>C)

Disease associations

OMIM: gene MIM:611184 | disease phenotypes: MIM:616843, MIM:194380, MIM:236750, MIM:153100

GenCC curated gene-disease

Disease	Classification	Inheritance
dehydrated hereditary stomatocytosis with or without pseudohyperkalemia and/or perinatal edema	Strong	Autosomal dominant
lymphatic malformation 6	Strong	Autosomal recessive
PIEZO1-related generalized lymphatic dysplasia with non-immune hydrops fetalis	Strong	Autosomal recessive
dehydrated hereditary stomatocytosis	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (2)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
dehydrated hereditary stomatocytosis with or without pseudohyperkalemia and/or perinatal edema	Strong	AD
obsolete PIEZO1-related generalized lymphatic dysplasia with non-immune hydrops fetalis	Definitive	AR

Mondo (11): lymphatic malformation 6 (MONDO:0014797), dehydrated hereditary stomatocytosis with or without pseudohyperkalemia and/or perinatal edema (MONDO:0008689), non-immune hydrops fetalis (MONDO:0009369), lymphatic malformation (MONDO:0019313), hemolytic anemia (MONDO:0003664), polyhydramnios (MONDO:0004585), hydrops fetalis (MONDO:0015193), diffuse lymphatic malformation (MONDO:0015408), familial hemolytic anemia (MONDO:0003689), dehydrated hereditary stomatocytosis (MONDO:0017910), (MONDO:0035474)

Orphanet (5): PIEZO1-related generalized lymphatic dysplasia with non-immune hydrops fetalis (Orphanet:568062), Dehydrated hereditary stomatocytosis (Orphanet:3202), Non-immune hydrops fetalis (Orphanet:363999), Hydrops fetalis (Orphanet:1041), Diffuse lymphatic malformation (Orphanet:141209)

HPO phenotypes

66 total (30 of 66 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000034	Hydrocele testis
HP:0000282	Facial edema
HP:0000286	Epicanthus
HP:0000347	Micrognathia
HP:0000365	Hearing impairment
HP:0000377	Abnormal pinna morphology
HP:0000378	Cupped ear
HP:0000465	Webbed neck
HP:0000767	Pectus excavatum
HP:0000821	Hypothyroidism
HP:0000952	Jaundice
HP:0000969	Edema
HP:0000980	Pallor
HP:0001004	Lymphedema
HP:0001046	Intermittent jaundice
HP:0001081	Cholelithiasis
HP:0001263	Global developmental delay
HP:0001541	Ascites
HP:0001561	Polyhydramnios
HP:0001631	Atrial septal defect
HP:0001744	Splenomegaly
HP:0001790	Nonimmune hydrops fetalis
HP:0001878	Hemolytic anemia
HP:0001900	Increased circulating hemoglobin concentration
HP:0001901	Polycythemia
HP:0001907	Thromboembolism
HP:0001923	Reticulocytosis
HP:0001930	Nonspherocytic hemolytic anemia

GWAS associations

80 associations (top):

Study	Trait	p-value
GCST001765_20	Red blood cell traits	2.000000e-22
GCST003479_9	Hair color	1.000000e-07
GCST003998_5	Joint mobility (Beighton score)	6.000000e-12
GCST004329_4	Mean corpuscular hemoglobin concentration	4.000000e-14
GCST004601_141	Red blood cell count	9.000000e-28
GCST004602_284	Mean corpuscular volume	2.000000e-09
GCST004602_285	Mean corpuscular volume	4.000000e-15
GCST004603_244	Platelet count	2.000000e-11
GCST004605_17	Mean corpuscular hemoglobin concentration	9.000000e-11
GCST004605_18	Mean corpuscular hemoglobin concentration	9.000000e-29
GCST004605_19	Mean corpuscular hemoglobin concentration	5.000000e-81
GCST004611_210	High light scatter reticulocyte count	5.000000e-16
GCST004611_211	High light scatter reticulocyte count	1.000000e-09
GCST004612_202	High light scatter reticulocyte percentage of red cells	5.000000e-09
GCST004615_106	Hemoglobin concentration	4.000000e-09
GCST004619_156	Reticulocyte fraction of red cells	4.000000e-09
GCST004622_42	Reticulocyte count	4.000000e-11
GCST004622_43	Reticulocyte count	3.000000e-18
GCST005992_21	Mean corpuscular hemoglobin concentration	7.000000e-56
GCST006001_15	Hemoglobin A1c levels	1.000000e-12
GCST006011_46	Mean corpuscular volume	2.000000e-19
GCST006479_15	Diverticular disease	8.000000e-06
GCST006979_641	Heel bone mineral density	2.000000e-15
GCST006979_642	Heel bone mineral density	2.000000e-14
GCST006979_643	Heel bone mineral density	2.000000e-27
GCST008163_452	Height	4.000000e-07
GCST008839_430	Height	3.000000e-08
GCST010083_290	Hemoglobin levels	7.000000e-91
GCST011528_2	Response to antidepressants (symptom improvement)	9.000000e-06
GCST011531_3	Remission after antidepressant treatment in major depression	1.000000e-06

EFO canonical traits (23, from GWAS)

EFO ID	Trait name
EFO:0004528	mean corpuscular hemoglobin concentration
EFO:0007905	joint hypermobility measurement
EFO:0004305	erythrocyte count
EFO:0004309	platelet count
EFO:0007986	reticulocyte count
EFO:0004509	hemoglobin measurement
EFO:0004541	HbA1c measurement
EFO:0009959	diverticular disease
EFO:0009270	heel bone mineral density
EFO:0007006	depressive symptom measurement
EFO:0009785	remission
EFO:0004530	triglyceride measurement
EFO:0009473	hemolysis
EFO:0007789	BMI-adjusted waist circumference
EFO:0004980	appendicular lean mass
EFO:0004348	hematocrit
EFO:0004587	lymphocyte count
EFO:0005091	monocyte count
EFO:0007989	monocyte percentage of leukocytes
EFO:0010701	mean reticulocyte volume
EFO:0007985	platelet crit
EFO:0009188	Red cell distribution width
EFO:0008039	BMI-adjusted hip circumference

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D000743	Anemia, Hemolytic	C15.378.050.141
D000745	Anemia, Hemolytic, Congenital	C15.378.050.141.150; C16.320.070
D015160	Hydrops Fetalis	C12.050.703.277.060.480; C15.378.295.480; C15.378.420.826.100.350; C16.300.060.480; C16.320.365.826.100.350; C20.306.480; C23.888.277.395
D006831	Polyhydramnios	C12.050.703.610

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5169186 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: other ic — Piezo channels

Most potent curated ligand interactions (11 total), top 11:

Ligand	Action	Affinity	Parameter
Yoda2b	Activation	6.9	pEC50
Yoda2	Activation	6.82	pEC50
Yaddle1	Activation	6.4	pEC50
salvianolic acid B	Inhibition	5.9	pIC50
Dooku1	Inhibition	5.82	pIC50
escin	Inhibition	5.8	pIC50
benzbromarone	Inhibition	5.4	pIC50
GsMTx-4	Inhibition	5.4	pIC50
Yoda1	Activation	4.58	pEC50
Jedi2	Activation	3.8	pEC50
Jedi1	Activation	3.8	pEC50

ChEMBL bioactivities

14 potent at pChembl≥5 of 16 total, top 14 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.40	EC50	400	nM	CHEMBL5557661
6.34	EC50	460	nM	CHEMBL5517966
6.30	EC50	500	nM	CHEMBL4303374
6.26	EC50	550	nM	CHEMBL5557001
6.24	EC50	570	nM	CHEMBL5559656
6.22	EC50	600	nM	CHEMBL5559157
6.06	EC50	880	nM	CHEMBL5523571
6.00	EC50	1000	nM	CHEMBL5568319
5.98	EC50	1040	nM	CHEMBL5562183
5.96	EC50	1090	nM	CHEMBL5560993
5.87	EC50	1340	nM	CHEMBL5567510
5.69	EC50	2060	nM	CHEMBL5542789
5.68	EC50	2100	nM	CHEMBL5549987
5.00	EC50	9900	nM	CHEMBL5564574

PubChem BioAssay actives

14 with measured affinity, of 205 total; 14 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-chloro-6-(trifluoromethyl)phenyl]methylsulfanyl]-5-pyrazin-2-yl-1,3,4-oxadiazole	2071361: Agonist activity at human PIEZO1 overexpressing HEK293-A cells co-expressing mCherry-piezo1 assessed as induction of calcium influx by fluo-3 based real-time flow cytometric analysis	ec50	0.4000	uM
2-[[2-bromo-6-(trifluoromethyl)phenyl]methylsulfanyl]-5-pyrazin-2-yl-1,3,4-oxadiazole	2071361: Agonist activity at human PIEZO1 overexpressing HEK293-A cells co-expressing mCherry-piezo1 assessed as induction of calcium influx by fluo-3 based real-time flow cytometric analysis	ec50	0.4600	uM
2-[(2,6-dichlorophenyl)methylsulfanyl]-5-pyrazin-2-yl-1,3,4-thiadiazole	2071361: Agonist activity at human PIEZO1 overexpressing HEK293-A cells co-expressing mCherry-piezo1 assessed as induction of calcium influx by fluo-3 based real-time flow cytometric analysis	ec50	0.5000	uM
2-[[5-chloro-2-(trifluoromethyl)phenyl]methylsulfanyl]-5-pyrazin-2-yl-1,3,4-oxadiazole	2071361: Agonist activity at human PIEZO1 overexpressing HEK293-A cells co-expressing mCherry-piezo1 assessed as induction of calcium influx by fluo-3 based real-time flow cytometric analysis	ec50	0.5500	uM
2-[(2,5-dichlorophenyl)methylsulfanyl]-5-pyrazin-2-yl-1,3,4-oxadiazole	2071361: Agonist activity at human PIEZO1 overexpressing HEK293-A cells co-expressing mCherry-piezo1 assessed as induction of calcium influx by fluo-3 based real-time flow cytometric analysis	ec50	0.5700	uM
2-[[2-bromo-5-(trifluoromethyl)phenyl]methylsulfanyl]-5-pyrazin-2-yl-1,3,4-oxadiazole	2071361: Agonist activity at human PIEZO1 overexpressing HEK293-A cells co-expressing mCherry-piezo1 assessed as induction of calcium influx by fluo-3 based real-time flow cytometric analysis	ec50	0.6000	uM
2-[[2-chloro-5-(trifluoromethyl)phenyl]methylsulfanyl]-5-pyrazin-2-yl-1,3,4-oxadiazole	2071361: Agonist activity at human PIEZO1 overexpressing HEK293-A cells co-expressing mCherry-piezo1 assessed as induction of calcium influx by fluo-3 based real-time flow cytometric analysis	ec50	0.8800	uM
2-[[2,5-bis(trifluoromethyl)phenyl]methylsulfanyl]-5-pyrazin-2-yl-1,3,4-oxadiazole	2071361: Agonist activity at human PIEZO1 overexpressing HEK293-A cells co-expressing mCherry-piezo1 assessed as induction of calcium influx by fluo-3 based real-time flow cytometric analysis	ec50	1.0000	uM
2-[(2-bromo-6-chlorophenyl)methylsulfanyl]-5-pyrazin-2-yl-1,3,4-oxadiazole	2071361: Agonist activity at human PIEZO1 overexpressing HEK293-A cells co-expressing mCherry-piezo1 assessed as induction of calcium influx by fluo-3 based real-time flow cytometric analysis	ec50	1.0400	uM
2-[(2-chloro-6-fluorophenyl)methylsulfanyl]-5-pyrazin-2-yl-1,3,4-oxadiazole	2071361: Agonist activity at human PIEZO1 overexpressing HEK293-A cells co-expressing mCherry-piezo1 assessed as induction of calcium influx by fluo-3 based real-time flow cytometric analysis	ec50	1.0900	uM
2-[(2,6-dichlorophenyl)methylsulfanyl]-5-pyrazin-2-yl-1,3,4-oxadiazole	2071361: Agonist activity at human PIEZO1 overexpressing HEK293-A cells co-expressing mCherry-piezo1 assessed as induction of calcium influx by fluo-3 based real-time flow cytometric analysis	ec50	1.3400	uM
2-pyrazin-2-yl-5-[[2-(trifluoromethyl)phenyl]methylsulfanyl]-1,3,4-oxadiazole	2071361: Agonist activity at human PIEZO1 overexpressing HEK293-A cells co-expressing mCherry-piezo1 assessed as induction of calcium influx by fluo-3 based real-time flow cytometric analysis	ec50	2.0600	uM
2-[(2,6-dibromophenyl)methylsulfanyl]-5-pyrazin-2-yl-1,3,4-oxadiazole	2071361: Agonist activity at human PIEZO1 overexpressing HEK293-A cells co-expressing mCherry-piezo1 assessed as induction of calcium influx by fluo-3 based real-time flow cytometric analysis	ec50	2.1000	uM
2-[(2,5-dibromophenyl)methylsulfanyl]-5-pyrazin-2-yl-1,3,4-oxadiazole	2071361: Agonist activity at human PIEZO1 overexpressing HEK293-A cells co-expressing mCherry-piezo1 assessed as induction of calcium influx by fluo-3 based real-time flow cytometric analysis	ec50	9.9000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, increases expression, increases methylation	4
sodium arsenite	affects methylation, increases expression	3
Acetaminophen	decreases expression, increases expression	3
belinostat	decreases expression, affects cotreatment	2
Air Pollutants	affects methylation, increases abundance, decreases expression	2
Estradiol	affects cotreatment, increases expression	2
Tunicamycin	increases expression	2
Cyclosporine	increases expression	2
Palmitic Acid	increases expression, increases phosphorylation	2
FR900359	affects phosphorylation	1
dicrotophos	increases expression	1
bisphenol A	affects cotreatment, increases methylation, decreases methylation	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, increases expression	1
arsenite	affects binding, decreases reaction	1
cobaltous chloride	decreases expression	1
2-bromopalmitate	decreases reaction, increases abundance, increases palmitoylation	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
monomethylarsonous acid	decreases expression, increases methylation	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	increases expression	1
Grape Seed Proanthocyanidins	decreases expression, affects cotreatment	1
dorsomorphin	affects cotreatment, decreases expression	1
bisphenol S	affects expression	1
(+)-JQ1 compound	decreases expression	1
3-(2-hydroxy-4-(2-methylnonan-2-yl)phenyl)cyclohexan-1-ol	decreases expression	1
Sunitinib	increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Arsenic	affects methylation	1
Atrazine	increases expression	1

ChEMBL screening assays

17 unique, capped per target: 17 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5147864	Binding	Binding affinity to Piezo1 (unknown origin) transfected in human HEK293 cells assessed as equilibrium constant at 40 mmHg/+50 mV	Piezo-Type Mechanosensitive Ion Channel Component 1 (Piezo1): A Promising Therapeutic Target and Its Modulators. — J Med Chem

Cellosaurus cell lines

6 cell lines: 3 transformed cell line, 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D4Z8	HEK293T PIEZO1 KO	Transformed cell line	Female
CVCL_D7H7	Ubigene HEK293T PIEZO1 KO	Transformed cell line	Female
CVCL_D8EL	Ubigene BEAS-2B PIEZO1 KO	Transformed cell line	Male
CVCL_D9WJ	Ubigene HT-29 PIEZO1 KO	Cancer cell line	Female
CVCL_TD45	HAP1 PIEZO1 (-) 1	Cancer cell line	Male
CVCL_TD46	HAP1 PIEZO1 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05777993	PHASE4	ENROLLING_BY_INVITATION	A Study to Provide Continued Access to Mitapivat for Participants Who Previously Completed an Agios-Sponsored Mitapivat Study
NCT07285005	PHASE3	NOT_YET_RECRUITING	A Study to Investigate Efficacy and Safety of KP-001 Compared With Placebo in Patients Aged ≥2 Years With Common VM, Common LM, or KTS/CLOVES Syndrome
NCT00001729	PHASE3	COMPLETED	Combination Drug Therapy for Patients With Hepatitis C
NCT03548220	PHASE3	COMPLETED	A Study to Evaluate Efficacy and Safety of AG-348 in Not Regularly Transfused Adult Participants With Pyruvate Kinase Deficiency (PKD)
NCT03559699	PHASE3	COMPLETED	A Study Evaluating the Efficacy and Safety of AG-348 in Regularly Transfused Adult Participants With Pyruvate Kinase Deficiency (PKD)
NCT02335242	PHASE2	COMPLETED	Sildenafil for the Treatment of Lymphatic Malformations
NCT03243019	PHASE2	RECRUITING	Efficacy of Rapamycin in the Treatment of Cervico-facial Lymphatic Malformations
NCT03427619	PHASE2	COMPLETED	OK432 (Picibanil) in the Treatment of Lymphatic Malformations
NCT03972592	PHASE2	COMPLETED	Topical Sirolimus in Cutaneous Lymphatic Malformations
NCT04861064	PHASE2	RECRUITING	Weekly Sirolimus Therapy
NCT05871970	PHASE2	RECRUITING	Safety and Efficacy Study of Intracystic TARA-002 for the Treatment of Lymphatic Malformations in Participants 6 Months to Less Than 18 Years of Age
NCT05983159	PHASE2	RECRUITING	A Trial of Targeted Therapies for Patients With Slow-Flow or Fast-Flow Vascular Malformations
NCT06437158	PHASE2	RECRUITING	Use of Bleomycin in the Sclerotherapy of Lymphatic Malformations for Pediatric Patients
NCT06789913	PHASE2	RECRUITING	A Phase 2 Study of Mutant-selective PI3Kα Inhibitor, RLY-2608, in Adults and Children With PIK3CA Related Overgrowth Spectrum and Malformations Driven by PIK3CA Mutation
NCT00110617	PHASE2	COMPLETED	Study of Deferasirox Relative to Subcutaneous Deferoxamine in Sickle Cell Disease Patients
NCT01579110	PHASE2	UNKNOWN	Efficacy and Safety of Levamisole Combined With Standard Prednisolone in Warm Antibody Autoimmune Hemolytic Anemia.
NCT01642979	PHASE2	UNKNOWN	Safety and Efficacy of Levamisole Combined With Cyclosporine A in Patients With Classic Paroxysmal Nocturnal Hemoglobinuria
NCT01760096	PHASE2	UNKNOWN	Safety and Efficacy of Levamisole Combined With Cyclosporine A in Patients With Subclinical Paroxysmal Nocturnal Hemoglobinuria and PNH in the Setting of Another Bone Marrow Failure Syndromes(PNH-2013)
NCT01212965	PHASE1	TERMINATED	Selenium in the Treatment of Complicated Lymphatic Malformations
NCT04994002	PHASE1	WITHDRAWN	A Pharmacokinetic, Pharmacodynamic, Safety and Tolerability Study of CERC-006 in Adults With Complex Lymphatic Malformations
NCT05004259	PHASE1	COMPLETED	The Safety of Repurposing Daratumumab for Relapsed or Refractory Autoimmune Antibody Mediated Hemolytic Anemia
NCT06684041	PHASE1	COMPLETED	A Safety, Tolerability, Pharmacokinetic/Pharmacodynamic Study, and QT Interval Study of HRS-5965 Capsules in Healthy Subjects
NCT07040787	PHASE1	COMPLETED	Investigation of Drug-drug Interaction of HRS-5965 With Clopidogrel and Clarithromycin in Healthy Subjects
NCT02986698	PHASE1	TERMINATED	In Utero Hematopoietic Stem Cell Transplantation for Alpha-thalassemia Major (ATM)
NCT04372498	PHASE1/PHASE2	COMPLETED	Senicapoc and Dehydrated Stomatocytosis
NCT04308603	Not specified	COMPLETED	Multicentric Prospective Study to Screen Inborn Errors of Metabolism in Non-immune Hydrops (NIH) Fetalis by Massively Parallel Sequencing
NCT05528796	Not specified	ENROLLING_BY_INVITATION	Uncovering the Etiologies of Non-immune Hydrops Fetalis
NCT00010452	PHASE2/PHASE3	COMPLETED	Study of Picibanil (OK432) Sclerotherapy in Children With Macrocystic Lymphatic Malformations
NCT05948943	PHASE2/PHASE3	RECRUITING	Alpelisib in Pediatric and Adult Patients With Lymphatic Malformations Associated With a PIK3CA Mutation.
NCT06673290	PHASE2/PHASE3	RECRUITING	Different Doses of Sirolimus for the Treatment of Cystic Lymphatic Malformations
NCT04409145	PHASE1/PHASE2	TERMINATED	First in Human Trial of Topical VT30 in Pts With Venous/Lymphatic Malformations Assoc With PIK3CA or TEK Gene Mutations
NCT00577213	Not specified	COMPLETED	Diagnosis of Hemangiomas and Vascular Malformations
NCT00866827	Not specified	COMPLETED	Airway Vascular Lesions
NCT02399527	Not specified	RECRUITING	Lymphatic Anomalies Registry for the Assessment of Outcome Data
NCT04836884	Not specified	COMPLETED	Vascular Anomaly Pathology and Genomics Biopsy Study
NCT05563831	Not specified	COMPLETED	National Evaluation of Patients With PIK3CA-Related Overgrowth Spectrum (PROS)
NCT06257719	Not specified	COMPLETED	Clinical Characteristics of Lymphatic Malformations
NCT06275022	Not specified	RECRUITING	A Prospective Study on the Treatment of cLM Based on ICG Imaging
NCT06755905	Not specified	COMPLETED	Indocyanine Green Lymphography in Management of Lingual Lymphatic Malformation
NCT06892964	Not specified	RECRUITING	Institution of an Italian Registry and Biobank for Biological Sample Collection