PIEZO2

Summary

PIEZO2 (piezo type mechanosensitive ion channel component 2, HGNC:26270) is a protein-coding gene on chromosome 18p11.22-p11.21, encoding Piezo-type mechanosensitive ion channel component 2 (Q9H5I5). 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 contains more than thirty transmembrane domains and likely functions as part of mechanically-activated (MA) cation channels. These channels serve to connect mechanical forces to biological signals. The encoded protein quickly adapts MA currents in somatosensory neurons. Defects in this gene are a cause of type 5 distal arthrogryposis. Several alternatively spliced transcript variants of this gene have been described, but their full-length nature is not known.

Source: NCBI Gene 63895 — RefSeq curated summary.

At a glance

• Gene–disease (curated): arthrogryposis, distal, with impaired proprioception and touch (Definitive, GenCC) — +4 more curated relationships
• GWAS associations: 11
• Clinical variants (ClinVar): 1,566 total — 60 pathogenic, 78 likely-pathogenic (top 2% of genes corpus-wide)
• Expression (HPA): Low tissue specificity — highest in parieto-temporal junction (white matter), temporal white matter, corpus callosum, splenium (white matter)
• GTEx eGene: eQTL in 15 tissues, sQTL in 5 (q < 0.05)
• Phenotypes (HPO): 175
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 0.56 (moderately constrained)
• MANE Select transcript: NM_001378183

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26270
Approved symbol	PIEZO2
Name	piezo type mechanosensitive ion channel component 2
Location	18p11.22-p11.21
Locus type	gene with protein product
Status	Approved
Aliases	FLJ23403, FLJ23144, HsT748, HsT771, FLJ34907
Ensembl gene	ENSG00000154864
Ensembl biotype	protein_coding
OMIM	613629
Entrez	63895

Gene structure

Transcript identifiers

Ensembl transcripts: 24 — 11 protein_coding, 5 retained_intron, 4 nonsense_mediated_decay, 4 protein_coding_CDS_not_defined

MANE Select: ENST00000674853

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 2: 2, TSL 3: 3, TSL 4: 2, TSL 5: 6

ENST00000674853, ENST00000302079, ENST00000383408, ENST00000503781, ENST00000538948, ENST00000578145, ENST00000579112, ENST00000579151, ENST00000579899, ENST00000579949, ENST00000580640, ENST00000581680, ENST00000582913, ENST00000582937, ENST00000583325, ENST00000643712, ENST00000685517, ENST00000686869, ENST00000688929, ENST00000691469, ENST00000693743, ENST00001108831, ENST00001108832, ENST00001132632

RefSeq mRNA: 3 — MANE Select: NM_001378183 NM_001378183, NM_001410871, NM_022068

CCDS: CCDS11850, CCDS92435, CCDS92436

Canonical transcript exons

ENST00000674853 — 56 exons

Exon	Start	End
ENSE00001018194	10857001	10857211
ENSE00001111048	10855353	10855566
ENSE00001163259	10807112	10807274
ENSE00001184001	10797374	10797522
ENSE00001184006	10800337	10800475
ENSE00001184010	10803875	10803994
ENSE00001184045	10759482	10759583
ENSE00001184051	10759705	10759909
ENSE00001184058	10760911	10761111
ENSE00001184066	10762500	10762625
ENSE00001184080	10762922	10763098
ENSE00001283817	10801390	10801428
ENSE00001286051	10770148	10770308
ENSE00001286059	10773412	10773629
ENSE00001286064	10774006	10774038
ENSE00001286070	10780325	10780366
ENSE00001286075	10784784	10784957
ENSE00001411604	10794772	10795002
ENSE00002269737	10911186	10911228
ENSE00002270003	10787036	10787184
ENSE00002272763	10979535	10979660
ENSE00002303866	11066127	11066222
ENSE00003461890	10715650	10715816
ENSE00003480241	10704394	10704652
ENSE00003480887	10701989	10702171
ENSE00003492997	10791201	10791324
ENSE00003494154	10697748	10697880
ENSE00003499937	10696392	10696539
ENSE00003503802	10705336	10705746
ENSE00003511599	10741031	10741102
ENSE00003524632	10672690	10672873
ENSE00003540092	10789079	10789365
ENSE00003549734	10681661	10681753
ENSE00003555484	10736604	10736710
ENSE00003577942	10714764	10714930
ENSE00003584668	10675209	10675288
ENSE00003587542	10680199	10680371
ENSE00003592021	10718200	10718259
ENSE00003614146	10871253	10871415
ENSE00003616530	10696074	10696288
ENSE00003663770	10682104	10682292
ENSE00003672398	10677747	10677875
ENSE00003676374	10698925	10699177
ENSE00003677775	10731407	10731521
ENSE00003688817	10689655	10689802
ENSE00003691399	10691225	10691383
ENSE00003710058	10742494	10742615
ENSE00003718201	10757969	10758134
ENSE00003718615	10750091	10750187
ENSE00003731742	10748471	10748630
ENSE00003743148	10752636	10752879
ENSE00003749768	10744142	10744231
ENSE00003821711	10708275	10708439
ENSE00003899335	10735232	10735330
ENSE00003900582	11148525	11149569
ENSE00003903018	10670247	10671779

Expression profiles

Bgee: expression breadth ubiquitous, 237 present calls, max score 97.57.

FANTOM5 (CAGE): breadth broad, TPM avg 3.6775 / max 108.5483, expressed in 676 samples.

Highest expression (Bgee): sural nerve, corpus callosum, dorsal root ganglion, visceral pleura, inferior vagus X ganglion.

Genetic regulation across tissues (GTEx eQTL / sQTL)

PIEZO2 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 15 tissues and its splicing (sQTL) in 5 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

20 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Cells EBV-transformed lymphocytes	eqtl	1.2e-16	+0.52	18:10947497:A:T
Nerve Tibial	eqtl	2.7e-13	-0.18	18:10892953:A:C
Pancreas	eqtl	6.8e-09	+0.43	18:11020485:C:T
Spleen	eqtl	8.8e-06	+0.78	18:10697494:C:T
Testis	sqtl	1.5e-05	+0.54	18:10701592:A:G
Lung	sqtl	7.4e-04	+0.84	18:10769017:C:T
Brain Spinal cord cervical c-1	eqtl	3.1e-03	+0.93	18:11740200:C:G
Adrenal Gland	eqtl	4.7e-03	+0.46	18:11005558:A:C
Colon Sigmoid	eqtl	5.3e-03	+0.15	18:10923478:G:A
Skin Sun Exposed Lower leg	eqtl	7.3e-03	+0.35	18:10681316:A:G
Esophagus Mucosa	eqtl	1.5e-02	+0.38	18:10719449:G:A
Esophagus Muscularis	eqtl	1.6e-02	-0.45	18:10920221:T:C
Thyroid	eqtl	1.7e-02	+0.48	18:10685781:C:A
Artery Coronary	eqtl	1.8e-02	+1.35	18:10249164:A:C
Artery Tibial	eqtl	1.9e-02	+0.25	18:10668069:T:C
Spleen	sqtl	2.3e-02	+0.44	18:10993597:C:T
Artery Aorta	eqtl	2.7e-02	-0.34	18:11557129:A:C
Esophagus Mucosa	sqtl	3.8e-02	+0.40	18:11093927:C:T
Cells EBV-transformed lymphocytes	sqtl	4.1e-02	-1.10	18:10774538:G:T
Colon Transverse	eqtl	4.9e-02	+0.35	18:11178423:G:A

FANTOM5 promoters

2 alternative TSS:

Promoter ID	TPM avg	Samples expressed
171205	3.6415	675
171202	0.0360	10

Top tissues by expression

showing 100 of 282 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
sural nerve	UBERON:0015488	97.57	gold quality
corpus callosum	UBERON:0002336	91.06	gold quality
dorsal root ganglion	UBERON:0000044	88.33	gold quality
visceral pleura	UBERON:0002401	87.29	gold quality
inferior vagus X ganglion	UBERON:0005363	87.26	gold quality
trigeminal ganglion	UBERON:0001675	87.05	gold quality
adrenal tissue	UBERON:0018303	86.45	gold quality
pleura	UBERON:0000977	85.60	gold quality
parietal pleura	UBERON:0002400	85.21	gold quality
cranial nerve II	UBERON:0000941	85.13	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	84.98	gold quality
calcaneal tendon	UBERON:0003701	84.00	gold quality
spinal cord	UBERON:0002240	83.99	gold quality
inferior olivary complex	UBERON:0002127	83.80	gold quality
lower lobe of lung	UBERON:0008949	82.86	silver quality
colonic epithelium	UBERON:0000397	82.47	gold quality
lung	UBERON:0002048	81.07	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.04	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	80.31	gold quality
subthalamic nucleus	UBERON:0001906	80.17	gold quality
globus pallidus	UBERON:0001875	79.92	gold quality
CA1 field of hippocampus	UBERON:0003881	79.83	gold quality
Brodmann (1909) area 46	UBERON:0006483	79.47	gold quality
substantia nigra	UBERON:0002038	79.43	gold quality
medial globus pallidus	UBERON:0002477	79.43	gold quality
upper lobe of lung	UBERON:0008948	79.34	gold quality
midbrain	UBERON:0001891	78.94	gold quality
cartilage tissue	UBERON:0002418	78.92	gold quality
upper lobe of left lung	UBERON:0008952	78.82	gold quality
right lung	UBERON:0002167	78.66	gold quality
tendon	UBERON:0000043	78.10	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	77.95	gold quality
gall bladder	UBERON:0002110	77.76	gold quality
lateral globus pallidus	UBERON:0002476	77.53	gold quality
muscle layer of sigmoid colon	UBERON:0035805	77.28	gold quality
skin of hip	UBERON:0001554	77.15	gold quality
substantia nigra pars reticulata	UBERON:0001966	76.56	gold quality
epithelial cell of pancreas	CL:0000083	76.52	silver quality
germinal epithelium of ovary	UBERON:0001304	76.44	gold quality
tibial nerve	UBERON:0001323	75.81	gold quality
olfactory bulb	UBERON:0002264	75.59	silver quality
type B pancreatic cell	CL:0000169	75.48	gold quality
Ammon’s horn	UBERON:0001954	75.23	gold quality
layer of synovial tissue	UBERON:0007616	75.22	gold quality
hair follicle	UBERON:0002073	74.97	silver quality
dorsal plus ventral thalamus	UBERON:0001897	74.82	gold quality
urinary bladder	UBERON:0001255	74.40	gold quality
medulla oblongata	UBERON:0001896	74.19	gold quality
liver	UBERON:0002107	74.04	gold quality
tibia	UBERON:0000979	73.87	gold quality
mucosa of paranasal sinus	UBERON:0005030	73.80	gold quality
tendon of biceps brachii	UBERON:0008188	73.51	gold quality
bronchial epithelial cell	CL:0002328	73.47	gold quality
right lobe of liver	UBERON:0001114	73.37	gold quality
mucosa of urinary bladder	UBERON:0001259	73.17	gold quality
epithelium of bronchus	UBERON:0002031	72.87	gold quality
bronchus	UBERON:0002185	72.31	gold quality
postcentral gyrus	UBERON:0002581	72.26	gold quality
amygdala	UBERON:0001876	71.92	gold quality
smooth muscle tissue	UBERON:0001135	71.89	gold quality
parietal lobe	UBERON:0001872	71.84	gold quality
synovial joint	UBERON:0002217	71.79	gold quality
substantia nigra pars compacta	UBERON:0001965	71.77	gold quality
ventral tegmental area	UBERON:0002691	71.64	gold quality
corpus epididymis	UBERON:0004359	71.53	gold quality
prostate gland	UBERON:0002367	71.46	gold quality
ventricular zone	UBERON:0003053	71.40	gold quality
prefrontal cortex	UBERON:0000451	71.03	gold quality
lower esophagus mucosa	UBERON:0035834	70.85	gold quality
body of pancreas	UBERON:0001150	70.70	gold quality
Brodmann (1909) area 9	UBERON:0013540	70.63	gold quality
orbitofrontal cortex	UBERON:0004167	70.40	gold quality
buccal mucosa cell	CL:0002336	70.23	gold quality
pons	UBERON:0000988	70.20	gold quality
temporal lobe	UBERON:0001871	69.99	gold quality
pancreas	UBERON:0001264	69.85	gold quality
hypothalamus	UBERON:0001898	69.72	gold quality
putamen	UBERON:0001874	69.53	gold quality
trabecular bone tissue	UBERON:0002483	69.50	gold quality
islet of Langerhans	UBERON:0000006	69.13	gold quality
frontal cortex	UBERON:0001870	69.03	gold quality
frontal lobe	UBERON:0016525	69.03	gold quality
colon	UBERON:0001155	68.80	gold quality
upper leg skin	UBERON:0004262	68.42	gold quality
cerebral cortex	UBERON:0000956	68.41	gold quality
telencephalon	UBERON:0001893	68.34	gold quality
mammary duct	UBERON:0001765	68.11	gold quality
large intestine	UBERON:0000059	68.06	gold quality
forebrain	UBERON:0001890	67.89	gold quality
entorhinal cortex	UBERON:0002728	67.87	gold quality
occipital lobe	UBERON:0002021	67.82	gold quality
neocortex	UBERON:0001950	67.71	gold quality
ganglionic eminence	UBERON:0004023	67.58	gold quality
superior vestibular nucleus	UBERON:0007227	67.52	gold quality
rectum	UBERON:0001052	67.51	gold quality
superior frontal gyrus	UBERON:0002661	67.44	gold quality
vermiform appendix	UBERON:0001154	67.40	gold quality
pylorus	UBERON:0001166	67.37	gold quality
right frontal lobe	UBERON:0002810	67.17	gold quality
caput epididymis	UBERON:0004358	67.14	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-ANND-2	yes	590.48
E-CURD-119	yes	11.33
E-MTAB-9067	yes	7.32
E-ANND-3	yes	7.15

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 79 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Nucleus accumbens	tissue	20.1
Locus coeruleus	tissue	12.4
Hippocampus	tissue	12.2	low
Postcentral gyrus	tissue	6.8
Lung	tissue	5.3	medium
Gallbladder	tissue	4.4	high
Choroid plexus	tissue	4.3
Spinal cord	tissue	4.3
Esophagus	tissue	4.1	low
Urinary bladder	tissue	4.1	medium
Hippocampal formation	tissue	3.0
Olfactory bulb	tissue	2.5
Seminal vesicle	tissue	2.3	low
Liver	tissue	2.3	not detected
Prostate	tissue	2.1	medium
Spleen	tissue	2.0	not detected
Smooth muscle	tissue	1.8	medium
Amygdala	tissue	1.3
Breast	tissue	1.1	high
Stomach 1	tissue	1.1	medium
Thyroid gland	tissue	1.1	low
Appendix	tissue	1.1	medium
Rectum	tissue	1.0	medium
Epididymis	tissue	1.0	low
Cerebellum	tissue	1.0	low
Septum	tissue	1.0
Testis	tissue	0.9	medium
Medulla oblongata	tissue	0.9
Small intestine	tissue	0.9	high
Skin 1	tissue	0.8	low
Adipose tissue	tissue	0.8	not detected
Hypothalamus	tissue	0.8
Substantia nigra	tissue	0.8
Kidney	tissue	0.8	medium
Fallopian tube	tissue	0.8	low
Ovary	tissue	0.7	medium
Colon	tissue	0.7	medium
Cervix	tissue	0.6	not detected
Lymph node	tissue	0.6	medium
Midbrain	tissue	0.6
Cerebral cortex	tissue	0.5	low
Endometrium 1	tissue	0.5	low
Superior colliculi	tissue	0.5
Thymus	tissue	0.5
Retrosplenial cortex	tissue	0.5
Pituitary gland	tissue	0.4
Pons	tissue	0.4
Vagina	tissue	0.4	not detected
Motor cortex	tissue	0.4
Putamen	tissue	0.4
Thalamus	tissue	0.4
Tonsil	tissue	0.4	medium
Retrosplenial and cingulate cortex	tissue	0.4
Periaqueductal gray	tissue	0.4
Temporal cortex	tissue	0.4
Prefrontal cortex	tissue	0.3
Parathyroid gland	tissue	0.3	medium
Adrenal gland	tissue	0.3	high
Bone marrow	tissue	0.3	low
Entorhinal cortex	tissue	0.3

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Parieto-temporal junction (white matter) (111.7), Temporal white matter (91.0), Corpus callosum, splenium (white matter) (76.0), Corpus callosum, genu (white matter) (70.1), Cerebellar white matter (64.6).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting PIEZO2 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 104 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-574-5P	100.00	66.01	989
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-613	99.91	71.50	1710
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-380-3P	99.89	70.18	1978
HSA-MIR-129-5P	99.88	70.26	3273

Functional genomics

gnomAD constraint: pLI 2.18e-15, LOEUF 0.563, missense Z 3.03 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000674853 splits into 5 regions with different missense tolerance; 0 are missense-constrained. Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
18:10,671,530–10,682,120	332 / 363.8	0.91	no
18:10,682,121–10,696,272	179 / 281.8	0.64	no
18:10,696,273–10,794,814	1925 / 2051.9	0.94	no
18:10,794,815–10,797,396	50 / 88.2	0.57	no
18:10,797,397–11,148,588	542 / 605.6	0.89	no

Literature-anchored findings (GeneRIF, showing 40)

• piezo2 sensitization may contribute to PKA- and PKC-mediated mechanical hyperalgesia. (PMID:22921401)
• Gain-of-function mutations in the mechanically activated ion channel PIEZO2 cause a subtype of Distal Arthrogryposis. (PMID:23487782)
• this study used exome sequencing to discover that mutations in PIEZO2 cause Gordon syndrome, Marden-Walker syndrome, and distal arthrogryposis type 5. (PMID:24726473)
• family of mechanically activated channels that counts only two members in human, piezo1 and 2, has emerged recently. [review] (PMID:25037583)
• we demonstrate that the mechanosensitivity of human embryonic stem cell-derived touch receptors depends on PIEZO2 (PMID:25469543)
• Whole-exome sequencing revealed a novel heterozygous mutation c.4456G>C (p.A1486P) of PIEZO2. (PMID:25712306)
• Transgenic mouse lines lacking Piezo2 in proprioceptive neurons showed severely uncoordinated body movements. (PMID:26551544)
• Enterochromaffin cells in the human and mouse small bowel GI epithelium selectively express the mechanosensitive ion channel Piezo2, and also that activation of Piezo2 by force leads to inward currents, 5-HT release and an increase in mucosal secretion (PMID:27392819)
• we report a consanguineous family with three siblings who showed short stature, scoliosis, gross motor impairment, and a progressive form of contractures involving the distal joints that is distinct from that found in patients with domina Recessive mutations in PIEZO2 thus appear to cause a progressive phenotype that overlaps with, while being mostly distinct from that associated with dominant mutations in the same gene (PMID:27607563)
• Our results show that PIEZO2 is a determinant of mechanosensation in humans. (PMID:27653382)
• we report the developmental phenotypic spectrum of familial Gordon syndrome in one family due to the previously characterized PIEZO2 mutation c.8057G>A. (PMID:27714920)
• The Piezo2 convert a variety of mechanical stimuli into channel activation and subsequent inactivation, and what molecules and mechanisms modulate Piezo function. (PMID:27743844)
• We identified homozygous loss of function variants in PIEZO2 as the underlying cause for an autosomal-recessive distal muscular atrophy with arthrogryposis, kyphoscoliosis, and neonatal respiratory insufficiency distinct from previously described dominant PIEZO2 diseases. (PMID:27843126)
• Sensory ataxia and proprioception defect with dorsal column involvement together with arthrogryposis, myopathy, scoliosis and progressive respiratory failure may represent a distinct clinical phenotype, and indicate recessive mutations in PIEZO2 (PMID:27974811)
• The present results demonstrate the occurrence of Piezo2 in cutaneous sensory nerve formations that functionally work as slowly adapting (Merkel cells) and rapidly adapting (Meissner’s corpuscles) low-threshold mechanoreceptors and are related to fine and discriminative touch but not to vibration or hard touch (PMID:28905996)
• Study demonstrate the splicing of Piezo2 to be cell type specific. Biophysical characterization revealed substantial differences in ion permeability, sensitivity to calcium modulation, and inactivation kinetics among Piezo2 splice variants. (PMID:29212024)
• This study identified Piezo2 mechanosensitive cationic channel as a transducer of environmental physical cues into mechanobiological responses. (PMID:29432180)
• The molecular defects identified through clinical exome sequencing in this study expands the phenotypic spectra of CHD7-associated disorders and implicate PIEZO2 as a candidate gene for major eye developmental defects. (PMID:30181649)
• Novel mutations in TPM2 and PIEZO2 are responsible for distal arthrogryposis (DA) 2B and mild DA in two Chinese families. (PMID:30285720)
• individuals with loss-of-function mutations in PIEZO2 completely failed to develop sensitization and painful reactions to touch after skin inflammation. (PMID:30305456)
• the presence of both Piezo1 and 2 in enteric neurons throughout the gastrointestinal tract from guinea pigs, mice and humans, were studied. (PMID:30324494)
• identify a functionally conserved inactivation gate in the pore-lining inner helix of mouse Piezo1 and Piezo2 that is distinct from the two constrictions (PMID:30628892)
• Results indicate the critical prognostic values of the piezo type mechanosensitive ion channel components PIEZO1 and PIEZO2 in non-small cell lung cancer (NSCLC). (PMID:30745454)
• we present a 3-generation family affected with DA5, who all carry a variant of unknown clinical significance c.8068A>C (p.Ser2690Arg) in the PIEZO2 gene. DA5 is a very rare condition with less than 20 cases previously reported. Our report expands the phenotype and contributes to evidence of this variant’s pathogenicity. (PMID:30938034)
• The Piezo2 ion channel is mechanically activated by low-threshold positive pressure. (PMID:31015490)
• Studied role of piezo type mechanosensitive ion channel component 2 (PIEZO2) expression in development of adolescent idiopathic scoliosis. (PMID:31513102)
• A neuromuscular disorder with homozygosity for PIEZO2 gene variants: an important differential diagnosis for kyphoscoliotic Ehlers-Danlos Syndrome. (PMID:31609726)
• A dietary fatty acid counteracts neuronal mechanical sensitization. (PMID:32561714)
• Glans clitoris innervation: PIEZO2 and sexual mechanosensitivity. (PMID:32996126)
• PIEZO2 in sensory neurons and urothelial cells coordinates urination. (PMID:33057202)
• Confirming the involvement of PIEZO2 in the etiology of Marden-Walker syndrome. (PMID:33369052)
• The Form and Function of PIEZO2. (PMID:34153212)
• Piezo2 downregulation via the Cre-lox system affects aqueous humor dynamics in mice. (PMID:34220183)
• Molecular Sensors of Temperature, Pressure, and Pain with Special Focus on TRPV1, TRPM8, and PIEZO2 Ion Channels. (PMID:34825354)
• Is the Sex Difference a Clue to the Pathomechanism of Dry Eye Disease? Watch out for the NGF-TrkA-Piezo2 Signaling Axis and the Piezo2 Channelopathy. (PMID:35507012)
• Piezo2 is not an indispensable mechanosensor in murine cardiomyocytes. (PMID:35581325)
• PIEZO2 ion channels in proprioception. (PMID:35689908)
• Distal Arthrogryposis type 5 in an Italian family due to an autosomal dominant gain-of-function mutation of the PIEZO2 gene. (PMID:35906671)
• Loss of lung microvascular endothelial Piezo2 expression impairs NO synthesis, induces EndMT, and is associated with pulmonary hypertension. (PMID:36149769)
• The role of PIEZO ion channels in the musculoskeletal system. (PMID:36717101)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	piezo2a	ENSDARG00000076005
danio_rerio		ENSDARG00000107086
danio_rerio	piezo2b	ENSDARG00000112723
mus_musculus	Piezo2	ENSMUSG00000041482
rattus_norvegicus	Piezo2	ENSRNOG00000038784
drosophila_melanogaster	Piezo	FBGN0264953
caenorhabditis_elegans		WBGENE00007505

Paralogs (1): PIEZO1 (ENSG00000103335)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1918781) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 4 distinct phenotype terms.

Mouse phenotype (MP)	Records
increased circulating triglyceride level	1
abnormal embryo size	1
increased vertical activity	1
preweaning lethality, complete penetrance	1

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
MIR6788	ncRNA	102466735
LINC01928	ncRNA	105371994
LINC01887	ncRNA	102724470

Protein

Protein identifiers

Piezo-type mechanosensitive ion channel component 2 — Q9H5I5 (reviewed: Q9H5I5)

Alternative names: Protein FAM38B

All UniProt accessions (10): A0A2H4UKA7, A0A2R8Y3N5, A0A2R8YG64, A0A8I5KT39, E7EVM7, J3KRQ5, J3KRW1, J3QLJ9, Q9H5I5, V9GZ18

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. Expressed in sensory neurons, is essential for diverse physiological processes, including respiratory control, systemic metabolism, urinary function, and proprioception. Mediates airway stretch sensing, enabling efficient respiration at birth and maintaining normal breathing in adults. It regulates brown and beige adipose tissue morphology and function, preventing systemic hypermetabolism. In the lower urinary tract, acts as a sensor in both the bladder urothelium and innervating sensory neurons being required for bladder-stretch sensing and urethral micturition reflexes, ensuring proper urinary function. Additionally, PIEZO2 serves as the principal mechanotransducer in proprioceptors, facilitating proprioception and coordinated body movements. 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. Required for Merkel-cell mechanotransduction. Plays a major role in light-touch mechanosensation. In kidney, during blood volume challenges, regulates calcium dynamics and maintains renin production, thereby serving as an essential regulator of the renin-angiotensin-aldosterone system (RAAS) and systemic blood volume control.

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 STOML3. Interacts with TMC7; the interaction inhibits PIEZO2-conducted mechanically activated currents. Interacts with TMC1; 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. Cell membrane.

Disease relevance. 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. The disease is caused by variants affecting the gene represented in this entry. 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. The disease is caused by variants affecting the gene represented in this entry. 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. The disease is caused by variants affecting the gene represented in this entry. 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. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Regulated by auxillary subunits MDFIC and MDFI. Channel activity is inhibited by TMEM120A. Phosphatidic acid and lysophosphatidic acid inhibit PIEZO2 channel activity.

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

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

Isoforms (4)

UniProt ID	Names	Canonical?
Q9H5I5-1	1	yes
Q9H5I5-2	2
Q9H5I5-3	3
Q9H5I5-4	4

RefSeq proteins (3): NP_001365112, NP_001397800, NP_071351 (=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)

• Ca(2+)(in) = Ca(2+)(out) (RHEA:29671)

UniProt features (117 total): topological domain 39, transmembrane region 38, sequence variant 11, region of interest 8, compositionally biased region 7, sequence conflict 5, splice variant 3, glycosylation site 2, chain 1, coiled-coil region 1, modified residue 1, disulfide bond 1

Structure

Experimental structures (PDB)

2 structures by resolution:

PDB	Title	Method	Resolution (Å)
9VEE	The cryo-EM structure of human Piezo2-MDFIC2 complex (composite map)	ELECTRON MICROSCOPY	3.36
9VEF	The cryo-EM structure of human Piezo2-MDFIC complex (composite map)	ELECTRON MICROSCOPY	3.75

Predicted structure (AlphaFold)

No AlphaFold model available for Q9H5I5 — AlphaFold DB does not currently provide models for proteins above ~3000 aa.

Human Protein Atlas

Protein class: Transporters, Transporter channels and pores, Predicted membrane proteins, Predicted intracellular proteins, Disease related genes, Potential drug targets, Human disease related genes, Congenital malformations, Other congenital malformations

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): plasma membrane; cytosol; vesicles

Antibody reliability (HPA): IH approved · IF approved

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 (1)

Type	Positions
Phosphoserine	838

Disulfide bonds (1)

Type	Positions
Disulfide bond	1014–1192

Glycosylation sites (2)

Type	Positions
N-linked (glcnac…) asparagine	95, 1013

Function

Pathways and Gene Ontology

Reactome pathways

0 curated (TAS) of 0; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

MSigDB gene sets: 491 (showing top): VALK_AML_WITH_FLT3_ITD, GSE45365_NK_CELL_VS_CD8A_DC_DN, GOBP_SENSORY_PERCEPTION_OF_MECHANICAL_STIMULUS, GOBP_CELLULAR_RESPONSE_TO_EXTERNAL_STIMULUS, GOBP_DETECTION_OF_MECHANICAL_STIMULUS_INVOLVED_IN_SENSORY_PERCEPTION, GOBP_MONOATOMIC_CATION_TRANSPORT, PATIL_LIVER_CANCER, GOBP_DETECTION_OF_MECHANICAL_STIMULUS, SMID_BREAST_CANCER_LUMINAL_B_UP, RIGGI_EWING_SARCOMA_PROGENITOR_DN, HNF4_DR1_Q3, GOBP_RESPONSE_TO_ABIOTIC_STIMULUS, GOBP_DETECTION_OF_ABIOTIC_STIMULUS, CAIRO_HEPATOBLASTOMA_UP, GOBP_DETECTION_OF_STIMULUS

GO Biological Process (10): monoatomic cation transport (GO:0006812), response to mechanical stimulus (GO:0009612), regulation of membrane potential (GO:0042391), detection of mechanical stimulus involved in sensory perception (GO:0050974), detection of mechanical stimulus (GO:0050982), cellular response to mechanical stimulus (GO:0071260), detection of renal blood flow (GO:0002000), monoatomic ion transport (GO:0006811), monoatomic ion transmembrane transport (GO:0034220), monoatomic cation transmembrane transport (GO:0098655)

GO Molecular Function (3): monoatomic cation channel activity (GO:0005261), mechanosensitive monoatomic ion channel activity (GO:0008381), mechanosensitive monoatomic cation channel activity (GO:0140135)

GO Cellular Component (5): plasma membrane (GO:0005886), stereocilium (GO:0032420), cuticular plate (GO:0032437), neuronal cell body membrane (GO:0032809), membrane (GO:0016020)

GO top-level categories

32 GO namespaces:

Category	Terms
monoatomic ion transport	2
monoatomic ion transmembrane transport	2
detection of mechanical stimulus	2
response to mechanical stimulus	2
monoatomic ion channel activity	2
cellular anatomical structure	2
response to external stimulus	1
response to abiotic stimulus	1
regulation of biological quality	1
sensory perception	1
detection of stimulus involved in sensory perception	1
sensory perception of mechanical stimulus	1
detection of external stimulus	1
detection of abiotic stimulus	1
cellular response to abiotic stimulus	1
cellular response to external stimulus	1
renal response to blood flow involved in circulatory renin-angiotensin regulation of systemic arterial blood pressure	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
membrane	1
cell periphery	1
stereocilium bundle	1
neuron projection	1
actin-based cell projection	1
cortical actin cytoskeleton	1
neuronal cell body	1
cell body membrane	1

Protein interactions and networks

STRING

showing 15 of 1,611 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PIEZO2	TRPA1	O75762	732
PIEZO2	TRPV4	Q9HBA0	728
PIEZO2	TRPV1	Q8NER1	715
PIEZO2	STOML3	Q8TAV4	690
PIEZO2	TMEM150C	B9EJG8	672
PIEZO2	KCNK4	Q9NYG8	651
PIEZO2	KCNK2	O95069	650
PIEZO2	TMC2	Q8TDI7	642
PIEZO2	SCN10A	Q9Y5Y9	610
PIEZO2	TRPM8	Q7Z2W7	605
PIEZO2	ASIC3	Q9UHC3	604
PIEZO2	ASIC2	Q16515	599
PIEZO2	SCN9A	Q15858	586
PIEZO2	MRGPRD	Q8TDS7	574
PIEZO2	TMC1	Q8TDI8	566

IntAct

BioGRID (9 interactions; top human partners by supporting records): HIST1H3A (Cross-Linking-MS (XL-MS)), KIF20A (Affinity Capture-MS), KTN1 (Cross-Linking-MS (XL-MS)), LAYN (Proximity Label-MS), NRAS (Proximity Label-MS), PARP1 (Proximity Label-MS), PARP9 (Proximity Label-MS), PRKAA1 (Affinity Capture-MS), STMN1 (Cross-Linking-MS (XL-MS))

SIGNOR signaling

1 signaling interactions:

A	Effect	B	Mechanism
PIEZO2	“form complex”	“Hair cells mechanotransduction channel”	binding

Disease & clinical

Genetic variants

Variant evidence for PIEZO2: 1,566 ClinVar records (138 pathogenic / likely pathogenic); 11 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

1,566 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	60
Likely pathogenic	78
Uncertain significance	728
Likely benign	319
Benign	251

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 138 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
137629	NM_001378183.1(PIEZO2):c.8396G>A (p.Arg2799His)	Pathogenic	criteria provided, multiple submitters, no conflicts	19
235839	NM_001378183.1(PIEZO2):c.8514AGA[2] (p.Glu2840del)	Pathogenic	criteria provided, multiple submitters, no conflicts	11
489219	NM_001378183.1(PIEZO2):c.5257-1G>A	Pathogenic	criteria provided, multiple submitters, no conflicts	3
1033996	NM_001378183.1(PIEZO2):c.6614del (p.Thr2205fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
1033997	NM_001378183.1(PIEZO2):c.7807G>T (p.Glu2603Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
1339520	NM_001378183.1(PIEZO2):c.273_279del (p.Pro92fs)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	3
489220	NM_001378183.1(PIEZO2):c.1528-1G>A	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
978137	NM_001378183.1(PIEZO2):c.4708+2T>G	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
1324900	NM_001378183.1(PIEZO2):c.7686+1G>C	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
2571822	NM_001378183.1(PIEZO2):c.76C>T (p.Arg26Ter)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
3377454	NM_001378183.1(PIEZO2):c.7555G>A (p.Gly2519Arg)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
374902	NM_001378183.1(PIEZO2):c.5960del (p.Leu1987fs)	Pathogenic	criteria provided, single submitter	2
374904	NM_001378183.1(PIEZO2):c.3095_3105del (p.Pro1032fs)	Pathogenic	criteria provided, single submitter	2
632546	NM_001378183.1(PIEZO2):c.1384C>T (p.Arg462Ter)	Pathogenic	criteria provided, single submitter	2
638404	NM_001378183.1(PIEZO2):c.2170-2A>C	Pathogenic	criteria provided, single submitter	2

Per-variant reference — Sugi Variant

Explore PIEZO2’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 26 predictions of 5,339):

Position(s)	Effect	Δscore	Sites
18:10677745–10677746	donor_loss	1.0000	5
18:10677837	donor_gain	1.0000
18:10689653–10689654	donor_loss	1.0000	5
18:10731409	donor_gain	1.0000
18:10731522–10731523	acceptor_gain	1.0000	3
18:10731522–10731523	acceptor_loss	1.0000	2
18:10734037	donor_gain	1.0000
18:10742496	donor_gain	1.0000
18:10759910–10759911	acceptor_loss	1.0000	6
18:10759912	acceptor_gain	1.0000

AlphaMissense

6,100 missense substitutions predicted likely pathogenic (of 19,009 scored), across 1,224 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M1481	9	0.984	0.998
M1139	9	0.982	0.999
M2697	9	0.979	0.999
M2236	9	0.963	0.999
M2454	9	0.956	0.995
M2193	9	0.951	0.998
M2244	9	0.950	0.999
M2351	9	0.945	0.999
M2423	9	0.924	0.996
M2274	9	0.891	0.996
M1954	9	0.858	0.991
D1415	8	0.999	1.000
D2247	8	0.999	1.000
D2352	8	0.999	1.000
D2370	8	0.998	1.000
D2019	8	0.997	0.999
F1554	8	0.996	1.000
H2029	8	0.995	0.999
F2211	8	0.995	1.000
D2713	8	0.995	0.999

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

2 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	8.23e-06
Stomach Adenocarcinoma (TCGA)	unfavorable	8.15e-05

Disease associations

OMIM: gene MIM:613629 | disease phenotypes: MIM:108145 (Arthrogryposis, distal, type 5), MIM:114300 (Arthrogryposis, distal, type 3), MIM:248700 (Marden-Walker syndrome), MIM:617146 (Arthrogryposis, distal, with impaired proprioception and touch), MIM:617468 (Arthrogryposis multiplex congenita, neurogenic, with myelin defect), MIM:208150 (Fetal akinesia deformation sequence)

GenCC curated gene-disease

5 curated gene-disease records:

Disease	Classification	Inheritance	Records
Gordon syndrome	Definitive	Autosomal dominant	5
arthrogryposis, distal, with impaired proprioception and touch	Definitive	Autosomal recessive	6
arthrogryposis- oculomotor limitation-electroretinal anomalies syndrome	Strong	Autosomal dominant	3
Marden-Walker syndrome	Moderate	Autosomal dominant	3
connective tissue disorder	Moderate	Autosomal recessive

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (10 panels, 9 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

10 panels:

Panel	Rating
Arthrogryposis	green
Clefting	green
Congenital myopathy	green
DDG2P	green
Fetal anomalies	green
Hereditary neuropathy or pain disorder	green
Hypotonic infant	green
Other rare neuromuscular disorders	green
Paediatric disorders	green
Ehlers Danlos syndrome with a likely monogenic cause	amber

Mondo (7): arthrogryposis, distal, with impaired proprioception and touch (MONDO:0014941), Gordon syndrome (MONDO:0007252), arthrogryposis- oculomotor limitation-electroretinal anomalies syndrome (MONDO:0007158), Marden-Walker syndrome (MONDO:0009564), connective tissue disorder (MONDO:0003900), arthrogryposis multiplex congenita (MONDO:0015168), fetal akinesia deformation sequence 1 (MONDO:0100101)

Orphanet (5): Arthrogryposis-oculomotor limitation-electroretinal anomalies syndrome (Orphanet:1154), Gordon syndrome (Orphanet:376), Marden-Walker syndrome (Orphanet:2461), Arthrogryposis multiplex congenita (Orphanet:1037), Fetal akinesia deformation sequence (Orphanet:994)

HPO phenotypes

showing 60 of 175 phenotypes (HPO-id order):

HPO	Term
HP:0000003	Multicystic kidney dysplasia
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000023	Inguinal hernia
HP:0000028	Cryptorchidism
HP:0000036	Abnormal penis morphology
HP:0000039	Epispadias
HP:0000047	Hypospadias
HP:0000054	Micropenis
HP:0000072	Hydroureter
HP:0000077	Abnormality of the kidney
HP:0000079	Abnormality of the urinary system
HP:0000089	Renal hypoplasia
HP:0000104	Renal agenesis
HP:0000110	Renal dysplasia
HP:0000126	Hydronephrosis
HP:0000160	Narrow mouth
HP:0000175	Cleft palate
HP:0000176	Submucous cleft hard palate
HP:0000193	Bifid uvula
HP:0000218	High palate
HP:0000219	Thin upper lip vermilion
HP:0000238	Hydrocephalus
HP:0000252	Microcephaly
HP:0000260	Wide anterior fontanel
HP:0000278	Retrognathia
HP:0000286	Epicanthus
HP:0000298	Mask-like facies
HP:0000316	Hypertelorism
HP:0000324	Facial asymmetry
HP:0000325	Triangular face
HP:0000343	Long philtrum
HP:0000347	Micrognathia
HP:0000358	Posteriorly rotated ears
HP:0000365	Hearing impairment
HP:0000369	Low-set ears
HP:0000400	Macrotia
HP:0000411	Protruding ear
HP:0000431	Wide nasal bridge
HP:0000463	Anteverted nares
HP:0000470	Short neck
HP:0000483	Astigmatism
HP:0000486	Strabismus
HP:0000490	Deeply set eye
HP:0000505	Visual impairment
HP:0000508	Ptosis
HP:0000512	Abnormal electroretinogram
HP:0000540	Hypermetropia
HP:0000563	Keratoconus
HP:0000568	Microphthalmia
HP:0000581	Blepharophimosis
HP:0000602	Ophthalmoplegia
HP:0000648	Optic atrophy
HP:0000766	Abnormal sternum morphology
HP:0000767	Pectus excavatum
HP:0000768	Pectus carinatum
HP:0000954	Single transverse palmar crease
HP:0001119	Keratoglobus
HP:0001166	Arachnodactyly
HP:0001193	Ulnar deviation of the hand or of fingers of the hand

GWAS associations

11 associations:

Study	Trait	p-value
GCST006630_33	Diastolic blood pressure	5e-17
GCST001859_37	Thiazide-induced adverse metabolic effects in hypertensive patients	3e-7
GCST002337_19	Amyotrophic lateral sclerosis (sporadic)	9e-7
GCST001210_1	Non-small cell lung cancer	1e-6
GCST003026_5	Yu-Zhi constitution type in type 2 diabetes	1e-6
GCST001850_27	Major depressive disorder	3e-6
GCST001850_8	Major depressive disorder	4e-6
GCST003263_46	Post bronchodilator FEV1 in COPD	4e-6
GCST003263_29	Post bronchodilator FEV1 in COPD	5e-6
GCST001821_9	Metabolite levels (5-HIAA/ MHPG Ratio)	8e-6
GCST001786_26	Dental caries	9e-6

EFO canonical traits (from GWAS)

6 canonical traits:

EFO ID	Trait name
EFO:0005132	5-HIAA measurement
EFO:0005133	MHPG measurement
EFO:0004530	triglyceride measurement
EFO:0007638	Yu-Zhi constitution type
EFO:0004314	forced expiratory volume
EFO:0006336	diastolic blood pressure

MeSH disease descriptors

3 disease descriptors:

Descriptor	Name	Tree numbers
D003240	Connective Tissue Diseases	C17.300
C537288	Gordon syndrome *(supp.)*
C535910	Marden-Walker syndrome *(supp.)*

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

GtoPdb / IUPHAR curated pharmacology

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

Target class: other ic — Piezo channels

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
GsMTx-4	Inhibition	5.3	pIC50

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, decreases expression, increases methylation	8
Benzo(a)pyrene	decreases expression, increases expression, affects expression, affects methylation	5
Aflatoxin B1	affects expression, decreases expression, decreases methylation, increases methylation	4
sodium arsenite	increases expression, decreases expression, increases abundance	3
Cyclosporine	decreases expression	3
bisphenol A	increases expression, affects cotreatment, decreases methylation	2
Acetaminophen	decreases expression, increases expression	2
Air Pollutants	decreases expression, increases abundance	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Tetrachlorodibenzodioxin	increases expression	2
FR900359	increases phosphorylation	1
sotorasib	affects cotreatment, increases expression	1
propionaldehyde	decreases expression	1
trichostatin A	increases expression	1
hydroxyhydroquinone	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
benzo(e)pyrene	decreases methylation	1
aflatoxin B2	decreases methylation	1
nickel sulfate	increases expression	1
diallyl trisulfide	decreases expression	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
perfluoro-n-nonanoic acid	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
bisphenol S	decreases methylation	1
trametinib	affects cotreatment, increases expression	1
NVP-BKM120	affects cotreatment, increases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Panobinostat	affects cotreatment, increases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_F1TH	HyCyte SH-SY5Y KO-hPIEZO2	Cancer cell line	Female

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

showing 60 of 383 trials:

NCT	Phase	Status	Title
NCT01042158	Phase 4	COMPLETED	A Clinical Trial of Ambrisentan and Tadalafil in Pulmonary Arterial Hypertension Associated With Systemic Sclerosis
NCT03688191	Phase 4	UNKNOWN	Study of Sirolimus in CTD-TP in China
NCT04169100	Phase 4	UNKNOWN	Novel Form of Acquired Long QT Syndrome
NCT04197050	Phase 4	UNKNOWN	Effect of Sacubitril/Valsartan on Reduced Right Ventricular Ejection Fraction in Patients With CTD
NCT04928586	Phase 4	UNKNOWN	Immunosuppressant Combined With Pirfenidone in CTD-ILD
NCT05440240	Phase 4	RECRUITING	Percutaneous Needle Fasciotomy +/- Corticosteroid Injection for Dupuytren’s Contracture
NCT05505409	Phase 4	UNKNOWN	Efficacy and Safety of Pirfenidone in CTD-ILD
NCT06499233	Phase 4	RECRUITING	Efficacy and Safety of Prophylactic Treatment for Pneumocystis Jirovecii Pneumonia in Patients With Autoimmune Inflammatory Rheumatic Disease
NCT00154830	Phase 4	COMPLETED	Alterations of Functional Activities and Leg Stiffness After Hamstring Lengthening in Cerebral Palsy Children
NCT00432055	Phase 4	COMPLETED	Effects of Botulinum Toxin Type A in Adults With Cerebral Palsy
NCT00549471	Phase 4	TERMINATED	Improvement After Botulinum Toxin Injections to the Arms in Children With Cerebral Palsy
NCT00752934	Phase 4	TERMINATED	Does Oral Baclofen Improve Care and Comfort in Spastic Children in Nursing Homes?
NCT00964639	Phase 4	COMPLETED	Postoperative Pain in Children With Cerebral Palsy After Pelvic and Femoral Osteotomies
NCT01386255	Phase 4	WITHDRAWN	Placebo Controlled Study of Baclofen for GERD in Children With Cerebral Palsy
NCT02546999	Phase 4	COMPLETED	Does Botulinum Toxin A Make Walking Easier in Children With Cerebral Palsy?
NCT02633241	Phase 4	COMPLETED	A Pilot Study of Dexmedetomidine-Propofol in Children Undergoing Magnetic Resonance Imaging
NCT03117322	Phase 4	COMPLETED	Synbiotic, Prebiotics and Probiotics in Children With Cerebral Palsy and Constipation
NCT03648658	Phase 4	UNKNOWN	Paracetamol Study in Patients With Low Muscle Mass
NCT04074265	Phase 4	COMPLETED	Peri-operative Use of a Pain Injection in Pediatric Patients With Cerebral Palsy
NCT04273737	Phase 4	TERMINATED	Amantadine in Treating Cognitive & Motor Impairments in Adolescents and Adults With Cerebral Palsy
NCT04523935	Phase 4	COMPLETED	Excessive Crying in Children With Cerebral Palsy and Communication Deficits
NCT05887765	Phase 4	COMPLETED	Effect of Systematic Dexamethasone on the Duration of Popliteal Nerve Block for Anesthesia After Pediatric Ankle Surgery
NCT06176430	Phase 4	UNKNOWN	Comparison of Twice Weekly Versus Daily Iron Therapy in Treating Anemia in Children With Cerebral Palsy
NCT06189781	Phase 4	RECRUITING	Pain Injection Versus Epidural Anesthesia for Hip Surgery in Pediatric Patients With Cerebral Palsy
NCT00864201	Phase 3	UNKNOWN	A Study to Evaluate the Use of Bosentan in Patients With Exercise Induced Pulmonary Arterial Hypertension Associated With Connective Tissue Disease
NCT01196091	Phase 3	COMPLETED	A Study of LY2127399 in Participants With Systemic Lupus Erythematosus
NCT01205438	Phase 3	COMPLETED	A Study of LY2127399 in Participants With Systemic Lupus Erythematosus
NCT01488708	Phase 3	TERMINATED	On Open-Label Study in Participants With Systemic Lupus Erythematosus
NCT03626688	Phase 3	COMPLETED	A Study Evaluating the Efficacy and Safety of Ralinepag to Improve Treatment Outcomes in PAH Patients
NCT03683186	Phase 3	ENROLLING_BY_INVITATION	A Study Evaluating the Long-Term Efficacy and Safety of Ralinepag in Subjects With PAH Via an Open-Label Extension
NCT06716606	Phase 3	RECRUITING	A Study to Investigate the Long-term Safety and Efficacy of Belimumab in Adults With Interstitial Lung Disease (ILD) Associated With Systemic Sclerosis (SSc) and Other Connective Tissue Diseases (CTD) (BLISSconneCTD-OLE)
NCT06917690	Phase 3	RECRUITING	A Study to Learn About the Safety and Efficacy of the Drug Oleogel-S10 in Japanese Patients With Epidermolysis Bullosa
NCT00014989	Phase 3	COMPLETED	Beneficial Effects of Antenatal Magnesium Sulfate (BEAM Trial)
NCT00065949	Phase 3	UNKNOWN	Magnesium Sulfate to Prevent Brain Injury in Premature Infants
NCT00367068	Phase 3	COMPLETED	Dutch National ITB Study in Children With Cerebral Palsy
NCT00491894	Phase 3	COMPLETED	Safety and Efficacy Study of Oral Glycopyrrolate Liquid for the Treatment of Pathologic (Chronic Moderate to Severe) Drooling in Pediatric Patients 3 to 18 Years of Age With Cerebral Palsy or Other Neurologic Conditions
NCT00632528	Phase 3	COMPLETED	MEOPA to Improve Physical Therapy Results After Multilevel Surgery
NCT00822029	Phase 3	TERMINATED	Use of Oral Bisphosphonates in the Treatment of Osteoporosis of Non-walking Children With Cerebral Palsy
NCT00922077	Phase 3	COMPLETED	Individualized Neurodevelopmental Treatment
NCT01249417	Phase 3	COMPLETED	Dysport® Pediatric Lower Limb Spasticity Study
NCT01251380	Phase 3	COMPLETED	Dysport® Pediatric Lower Limb Spasticity Follow-on Study
NCT01437644	Phase 3	COMPLETED	The Post-Operative Pain in Cerebral Palsy (POPPIES) Trial
NCT01492608	Phase 3	COMPLETED	Magnesium Sulphate for Preterm Birth (MASP Study)
NCT01603602	Phase 3	COMPLETED	BOTOX® Treatment in Pediatric Upper Limb Spasticity
NCT01603615	Phase 3	COMPLETED	BOTOX® Open-Label Treatment in Pediatric Upper Limb Spasticity
NCT01603628	Phase 3	COMPLETED	BOTOX® Treatment in Pediatric Lower Limb Spasticity
NCT01603641	Phase 3	COMPLETED	BOTOX® Open-Label Treatment in Pediatric Lower Limb Spasticity
NCT01633736	Phase 3	UNKNOWN	Targeted Hip Strength Training in Children With Cerebral Palsy (CP)
NCT01898520	Phase 3	COMPLETED	A Safety, Efficacy and Tolerability Study of Sativex for the Treatment of Spasticity in Children Aged 8 to 18 Years
NCT01929434	Phase 3	COMPLETED	Efficacy of Stem Cell Transplantation Compared to Rehabilitation Treatment of Patients With Cerebral Paralysis
NCT02002884	Phase 3	COMPLETED	Dose-response Study of Efficacy and Safety of Botulinum Toxin Type A to Treat Spasticity of the Arm(s) or of Arm(s) and Leg(s) in Cerebral Palsy
NCT02270736	Phase 3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT02839785	Phase 3	TERMINATED	Analgesia and Physiotherapy in Children With Cerebral Palsy (ANTALKINECP)
NCT03110341	Phase 3	UNKNOWN	Effect of Erythropoietin in Premature Infants on White Matter Lesions and Neurodevelopmental Outcome
NCT03302871	Phase 3	COMPLETED	Integrated Management Enhances Functional Gains in Children With Cerebral Palsy Treated by BoNT-A
NCT03306212	Phase 3	COMPLETED	Efficacy of Intermittent Serial Casting on Spastic Wrist Flexion Deformity
NCT03469999	Phase 3	COMPLETED	Effect of Dysport Injections on Energy Expenditure and Walking Efficiency in Children With Cerebral Palsy
NCT03472261	Phase 3	COMPLETED	Integrated Management of Pronation Deformity in Cerebral Palsy
NCT03616067	Phase 3	TERMINATED	Evaluation of the Efficacy of the Injection of Botulinum Toxin A vs Scopolamine Patches in the Treatment of Drooling in Children With Cerebral Palsy
NCT05206513	Phase 3	COMPLETED	Study to Assess the Efficacy, Safety, and Tolerability of Valbenazine for the Treatment of Dyskinesia Due to Cerebral Palsy