PIEZO1

piezo type mechanosensitive ion channel component 1, the group of MicroRNA protein coding host genes

Basic information

Region (hg38): 16:88715337-88785220

Previous symbols: [ "FAM38A" ]

Links

ENSG00000103335 ∙ NCBI:9780 ∙ OMIM:611184 ∙ HGNC:28993 ∙ Uniprot:Q92508 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• dehydrated hereditary stomatocytosis with or without pseudohyperkalemia and/or perinatal edema (Strong), mode of inheritance: AD
• dehydrated hereditary stomatocytosis with or without pseudohyperkalemia and/or perinatal edema (Strong), mode of inheritance: AD
• lymphatic malformation 6 (Strong), mode of inheritance: AR
• dehydrated hereditary stomatocytosis (Supportive), mode of inheritance: AD
• lymphatic malformation 6 (Strong), mode of inheritance: AR
• dehydrated hereditary stomatocytosis with or without pseudohyperkalemia and/or perinatal edema (Strong), mode of inheritance: AD
• PIEZO1-related generalized lymphatic dysplasia with non-immune hydrops fetalis (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Dehydrated hereditary stomatocytosis 1 with or without pseudohyperkalemia and/or perinatal edema; ER blood group system	AD/BG	Hematologic	Dehydrated hereditary stomatocytosis 1 with or without pseudohyperkalemia and/or perinatal edema is highly variable, and can involve moderately symptomatic hemolysis, severe iron overload requiring hepatic transplantation, and life-threatening thromboembolic disease after splenectomy, and awareness may allow early medical management; Variants associated with a blood group may be important in specific situations (eg, related to transfusion)	Dermatologic; Hematologic	22529292; 23479567; 23695678; 26333996; 36122374

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PIEZO1 gene.

• not provided (1186 variants)
• Inborn genetic diseases (248 variants)
• not specified (69 variants)
• Lymphatic malformation 6 (69 variants)
• Dehydrated hereditary stomatocytosis with or without pseudohyperkalemia and/or perinatal edema (59 variants)
• PIEZO1-related condition (54 variants)
• Lymphatic malformation 6;Dehydrated hereditary stomatocytosis with or without pseudohyperkalemia and/or perinatal edema (13 variants)
• Dehydrated hereditary stomatocytosis with or without pseudohyperkalemia and/or perinatal edema;Lymphatic malformation 6 (7 variants)
• Blood group, ER (5 variants)
• Non-immune hydrops fetalis (4 variants)
• ER BLOOD GROUP SYSTEM, ER(a-b-) (2 variants)
• Thickened nuchal skin fold;Hydrops fetalis (2 variants)
• - (2 variants)
• Hemolytic anemia (2 variants)
• Hydrops fetalis (2 variants)
• Thickened nuchal skin fold;Hydrops fetalis;Polyhydramnios (1 variants)
• Congenital isolated adrenocorticotropic hormone deficiency (1 variants)
• Hydrops fetalis;Thickened nuchal skin fold;Polyhydramnios (1 variants)
• Familial hemolytic anemia (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PIEZO1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			10	207	58	275
missense	1	12	551	50	46	660
nonsense	14	11				25
start loss						0
frameshift	5	13	1			19
inframe indel	1	2	23	1	4	31
splice donor/acceptor (+/-2bp)	2	3	2	2		9
splice region			24	39	11	74
non coding			17	73	122	212
Total	23	41	604	333	230

Highest pathogenic variant AF is 0.0000788

Variants in PIEZO1

This is a list of pathogenic ClinVar variants found in the PIEZO1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
16-88715383-A-C			Benign (Jul 09, 2018)
16-88715442-C-T			Benign (Jul 09, 2018)
16-88715610-C-G		Inborn genetic diseases	Conflicting classifications of pathogenicity (Jan 11, 2024)
16-88715613-T-C			Conflicting classifications of pathogenicity (Oct 28, 2023)
16-88715616-C-T		Inborn genetic diseases	Uncertain significance (Jun 11, 2021)
16-88715618-C-G		Lymphatic malformation 6	Uncertain significance (Sep 15, 2023)
16-88715618-C-T		Dehydrated hereditary stomatocytosis with or without pseudohyperkalemia and/or perinatal edema	Uncertain significance (Apr 06, 2020)
16-88715621-G-C			Uncertain significance (-)
16-88715631-T-G			Uncertain significance (Jun 02, 2021)
16-88715641-C-T			Benign (Jan 13, 2024)
16-88715642-G-A		not specified	Conflicting classifications of pathogenicity (Jan 24, 2024)
16-88715647-G-A			Likely benign (Apr 26, 2023)
16-88715649-G-T			Uncertain significance (Mar 29, 2023)
16-88715664-G-A			Uncertain significance (Oct 10, 2022)
16-88715666-T-C		not specified • PIEZO1-related disorder	Conflicting classifications of pathogenicity (Jan 26, 2024)
16-88715670-C-T		Inborn genetic diseases	Uncertain significance (Aug 16, 2022)
16-88715671-G-A		not specified	Benign (Jan 29, 2024)
16-88715673-A-ACAACT			Likely pathogenic (Dec 01, 2016)
16-88715676-A-G		Dehydrated hereditary stomatocytosis with or without pseudohyperkalemia and/or perinatal edema;Lymphatic malformation 6	Benign/Likely benign (Nov 22, 2023)
16-88715682-CCTCCAG-C		Inborn genetic diseases	Likely pathogenic (Feb 12, 2018)
16-88715683-C-G		Lymphatic malformation 6	Likely pathogenic (Jan 01, 2022)
16-88715682-C-CCTCCAG		Dehydrated hereditary stomatocytosis with or without pseudohyperkalemia and/or perinatal edema • Lymphatic malformation 6	Pathogenic (Feb 06, 2024)
16-88715690-T-C		PIEZO1-related disorder	Uncertain significance (Sep 30, 2022)
16-88715693-A-AGCTCCC		Dehydrated hereditary stomatocytosis with or without pseudohyperkalemia and/or perinatal edema;Lymphatic malformation 6	Conflicting classifications of pathogenicity (Dec 28, 2023)
16-88715700-G-A		not specified • PIEZO1-related disorder	Conflicting classifications of pathogenicity (Feb 06, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PIEZO1	protein_coding	protein_coding	ENST00000301015	51	69869

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.94e-21	1.00	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-3.43	1905	1.53e+3	1.25	0.000108	16079
Missense in Polyphen		661	610.63	1.0825		6740
Synonymous	-12.1	1086	685	1.59	0.0000502	5211
Loss of Function	5.40	55	118	0.464	0.00000554	1331

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Pore-forming subunit of a mechanosensitive non-specific cation channel (PubMed:23479567, PubMed:23695678). Generates currents characterized by a linear current-voltage relationship that are sensitive to ruthenium red and gadolinium. 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 (PubMed:20016066). In the kidney, may contribute to the detection of intraluminal pressure changes and to urine flow sensing. Acts as shear-stress sensor that promotes endothelial cell organization and alignment in the direction of blood flow through calpain activation (PubMed:25119035). Plays a key role in blood vessel formation and vascular structure in both development and adult physiology (By similarity). {ECO:0000250|UniProtKB:E2JF22, ECO:0000269|PubMed:20016066, ECO:0000269|PubMed:23479567, ECO:0000269|PubMed:23695678, ECO:0000269|PubMed:25119035}.
• Disease: DISEASE: 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. {ECO:0000269|PubMed:22529292, ECO:0000269|PubMed:23479567, ECO:0000269|PubMed:23487776, ECO:0000269|PubMed:23581886, ECO:0000269|PubMed:23695678, ECO:0000269|PubMed:23973043}. Note=The disease is caused by mutations 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.; DISEASE: Lymphedema, hereditary, 3 (LMPH3) [MIM:616843]: A severe form of lymphedema, a chronic disabling condition which results in swelling of the extremities due to altered lymphatic flow. Patients with lymphedema suffer from recurrent local infections, and physical impairment. LMPH3 manifests as generalized lymphatic dysplasia, characterized by uniform, widespread lymphedema affecting 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. {ECO:0000269|PubMed:26333996}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Intolerance Scores

• rvis_EVS: 3.75
• rvis_percentile_EVS: 99.6

Haploinsufficiency Scores

• pHI: 0.276
• hipred: N
• hipred_score: 0.231

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.114

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High

Mouse Genome Informatics

• Gene name: Piezo1
• Phenotype: homeostasis/metabolism phenotype; growth/size/body region phenotype; embryo phenotype; immune system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan)

Zebrafish Information Network

• Gene name: piezo1
• Affected structure: nucleate erythrocyte
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: cation transport;positive regulation of integrin activation;positive regulation of cell-cell adhesion mediated by integrin;regulation of membrane potential;detection of mechanical stimulus;cellular response to mechanical stimulus;cation transmembrane transport
• Cellular component: endoplasmic reticulum;endoplasmic reticulum membrane;plasma membrane;integral component of membrane;lamellipodium membrane;endoplasmic reticulum-Golgi intermediate compartment membrane
• Molecular function: cation channel activity;mechanosensitive ion channel activity