PIEZO2

piezo type mechanosensitive ion channel component 2, the group of Armadillo like helical domain containing|MicroRNA protein coding host genes

Basic information

Region (hg38): 18:10666483-11149569

Previous symbols: [ "FAM38B2", "C18orf30", "C18orf58", "FAM38B" ]

Links

ENSG00000154864 ∙ NCBI:63895 ∙ OMIM:613629 ∙ HGNC:26270 ∙ Uniprot:Q9H5I5 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Gordon syndrome (Definitive), mode of inheritance: AD
• Marden-Walker syndrome (Moderate), mode of inheritance: AR
• connective tissue disorder (Moderate), mode of inheritance: AR
• Marden-Walker syndrome (Moderate), mode of inheritance: AD
• Gordon syndrome (Moderate), mode of inheritance: AD
• arthrogryposis- oculomotor limitation-electroretinal anomalies syndrome (Moderate), mode of inheritance: AD
• arthrogryposis, distal, with impaired proprioception and touch (Moderate), mode of inheritance: AR
• arthrogryposis, distal, with impaired proprioception and touch (Definitive), mode of inheritance: AR
• arthrogryposis- oculomotor limitation-electroretinal anomalies syndrome (Supportive), mode of inheritance: AD
• Gordon syndrome (Supportive), mode of inheritance: AD
• Marden-Walker syndrome (Supportive), mode of inheritance: AR
• arthrogryposis, distal, with impaired proprioception and touch (Strong), mode of inheritance: AR
• arthrogryposis, distal, with impaired proprioception and touch (Definitive), mode of inheritance: AR
• Gordon syndrome (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Arthrogryposis, distal, type 3; Arthrogryposis, distal, type 5; Marden-Walker syndrome; Arthrogryposis, distal, with impaired proprioception and touch	AD/AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic	23487782; 24726473; 27607563; 27653382

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PIEZO2 gene.

• not provided (21 variants)
• Arthrogryposis, distal, with impaired proprioception and touch (15 variants)
• Arthrogryposis- oculomotor limitation-electroretinal anomalies syndrome (6 variants)
• Inborn genetic diseases (5 variants)
• Gordon syndrome (4 variants)
• Fetal akinesia deformation sequence 1;Arthrogryposis multiplex congenita (2 variants)
• Abnormality of the skeletal system (1 variants)
• Gordon syndrome;Arthrogryposis- oculomotor limitation-electroretinal anomalies syndrome (1 variants)
• Distal arthrogryposis (1 variants)
• Marden-Walker syndrome (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PIEZO2 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			9	126	20	155
missense	3	8	289	26	20	346
nonsense	16	13	4			33
start loss						0
frameshift	14	12	1	1		28
inframe indel	1	1	1			3
splice donor/acceptor (+/-2bp)	6	17	2			25
splice region			7	11	4	22
non coding			1	93	216	310
Total	40	51	307	246	256

Highest pathogenic variant AF is 0.0000263

Variants in PIEZO2

This is a list of pathogenic ClinVar variants found in the PIEZO2 region.

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

Position	Type	Phenotype	Significance	ClinVar
18-10671540-TCTCTAGTC-T		Gordon syndrome	Pathogenic (Jun 04, 2014)
18-10671544-T-C			Uncertain significance (Jun 05, 2022)
18-10671570-G-A		Arthrogryposis- oculomotor limitation-electroretinal anomalies syndrome	Likely pathogenic (-)
18-10671571-A-G		Arthrogryposis- oculomotor limitation-electroretinal anomalies syndrome	Pathogenic (Jun 04, 2014)
18-10671577-AT-A		Arthrogryposis- oculomotor limitation-electroretinal anomalies syndrome	Pathogenic (Jun 04, 2014)
18-10671590-T-C		Congenital contracture • PIEZO2-related disorder	Likely benign (Jan 02, 2024)
18-10671598-A-G			Uncertain significance (Jan 13, 2024)
18-10671602-ATCT-A		Arthrogryposis- oculomotor limitation-electroretinal anomalies syndrome • Distal arthrogryposis • Gordon syndrome • Inborn genetic diseases	Pathogenic (Jun 18, 2024)
18-10671604-C-T			Uncertain significance (Nov 27, 2023)
18-10671620-T-C			Likely benign (Jun 05, 2018)
18-10671633-C-A		Arthrogryposis- oculomotor limitation-electroretinal anomalies syndrome	Pathogenic (Jun 04, 2014)
18-10671633-C-G		Arthrogryposis- oculomotor limitation-electroretinal anomalies syndrome	Pathogenic (Jun 04, 2014)
18-10671633-C-T		Gordon syndrome	Likely pathogenic (Sep 13, 2022)
18-10671634-G-A			Uncertain significance (Sep 23, 2021)
18-10671638-T-TA			Likely pathogenic (Dec 28, 2023)
18-10671645-A-G			Uncertain significance (Nov 04, 2019)
18-10671658-A-G			Likely benign (May 01, 2024)
18-10671669-C-T			Likely benign (Dec 01, 2023)
18-10671713-C-T			Likely benign (Jul 05, 2022)
18-10671729-C-T		Gordon syndrome • Arthrogryposis- oculomotor limitation-electroretinal anomalies syndrome • Inborn genetic diseases • Fetal akinesia deformation sequence 1;Arthrogryposis multiplex congenita • Gordon syndrome;Arthrogryposis- oculomotor limitation-electroretinal anomalies syndrome • Arthrogryposis, distal, with impaired proprioception and touch	Pathogenic (Mar 12, 2024)
18-10671730-G-A		Marden-Walker syndrome • Gordon syndrome	Pathogenic/Likely pathogenic (Nov 29, 2022)
18-10671730-G-C		Arthrogryposis- oculomotor limitation-electroretinal anomalies syndrome	Pathogenic/Likely pathogenic (Dec 09, 2022)
18-10671739-T-C		Gordon syndrome	Uncertain significance (Feb 01, 2022)
18-10671739-T-G			Uncertain significance (Apr 16, 2023)
18-10671741-C-A			Uncertain significance (Sep 04, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PIEZO2	protein_coding	protein_coding	ENST00000503781	52	482108

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
8.10e-7	1.00	125714	0	34	125748	0.000135

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.44	1081	1.45e+3	0.745	0.0000804	18140
Missense in Polyphen		288	501.68	0.57407		6409
Synonymous	2.31	481	550	0.875	0.0000330	5044
Loss of Function	7.85	40	140	0.285	0.00000749	1749

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000120	0.000119
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.0000925	0.0000924
European (Non-Finnish)	0.000221	0.000211
Middle Eastern	0.000109	0.000109
South Asian	0.00	0.00
Other	0.000490	0.000489

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Component of a mechanosensitive channel required for rapidly adapting mechanically activated (MA) currents. Required for Merkel-cell mechanotransduction. Plays a major role in light- touch mechanosensation. {ECO:0000250|UniProtKB:Q8CD54}.
• Disease: DISEASE: Arthrogryposis, distal, 5 (DA5) [MIM:108145]: A form of distal arthrogryposis, a disease characterized by congenital joint contractures that mainly involve two or more distal parts of the limbs, in the absence of a primary neurological or muscle disease. DA5 features include ocular abnormalities, typically ptosis, ophthalmoplegia and/or strabismus, in addition to contractures of the skeletal muscles. Some patients have pulmonary hypertension as a result of restrictive lung disease. {ECO:0000269|PubMed:23487782, ECO:0000269|PubMed:24726473}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Arthrogryposis, distal, 3 (DA3) [MIM:114300]: A form of distal arthrogryposis, a disease characterized by congenital joint contractures that mainly involve two or more distal parts of the limbs, in the absence of a primary neurological or muscle disease. DA3 features include short stature and cleft palate. {ECO:0000269|PubMed:24726473}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Marden-Walker syndrome (MWKS) [MIM:248700]: A syndrome characterized by a mask-like face with blepharophimosis, micrognathia, cleft or high-arched palate, low-set ears, congenital joint contractures, kyphoscoliosis, pectus excavatum or carinatum, and arachnodactyly. Additional features include decreased muscular mass, failure to thrive, renal anomalies, hypoplastic corpus callosum, cerebellar vermis hypoplasia, enlarged cisterna magna, and psychomotor retardation. {ECO:0000269|PubMed:24726473}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Arthrogryposis, distal, with impaired proprioception and touch (DAIPT) [MIM:617146]: A form of distal arthrogryposis, a disease characterized by congenital joint contractures that mainly involve two or more distal parts of the limbs, in the absence of a primary neurological or muscle disease. DAIPT is an autosomal recessive disease characterized by selective loss of discriminative touch perception, ataxia, difficulty walking, dysmetria, and progressive skeletal contractures. {ECO:0000269|PubMed:27607563, ECO:0000269|PubMed:27653382}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.106

Haploinsufficiency Scores

• pHI: 0.488
• hipred: Y
• hipred_score: 0.659
• ghis: 0.447

Essentials

• 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: Piezo2
• Phenotype: behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan)

Zebrafish Information Network

• Gene name: piezo2b
• Affected structure: thigmotropism
• Phenotype tag: abnormal
• Phenotype quality: decreased occurrence

Gene ontology

• Biological process: cation transport;response to mechanical stimulus;regulation of membrane potential;detection of mechanical stimulus involved in sensory perception;detection of mechanical stimulus;cellular response to mechanical stimulus;cation transmembrane transport
• Cellular component: plasma membrane;integral component of membrane
• Molecular function: cation channel activity;mechanosensitive ion channel activity