TRPV4 Gene: Structure, Function, and Clinical Significance
A comprehensive overview of the TRPV4 gene, its protein product, associated diseases, expression patterns, and mutation spectrum.
Gene Information Card
| Symbol | TRPV4 |
|---|---|
| Full Name | Transient Receptor Potential Cation Channel Subfamily V Member 4 |
| Gene Type | Protein coding |
| Chromosomal Location | 12q24.11 |
| NCBI Gene ID | 59341 ncbi.nlm.nih.gov/gene/59341 |
| Ensembl ID | ENSG00000111181 |
| UniProt ID | Q9HBA0 |
| OMIM ID | 605427 |
| HGNC ID | 18083 |
| Aliases | TRP12, VRL2, OTRPC4, VR-OAC, CMT2C, HMSN2C, SPSMA, SSQTL1 |
Description
The TRPV4 gene encodes a calcium-permeable non-selective cation channel belonging to the transient receptor potential (TRP) family. TRPV4 is widely expressed in various tissues and participates in multiple physiological processes including osmoregulation, mechanosensation, thermosensation, and vascular tone regulation. Mutations in TRPV4 are associated with a spectrum of skeletal dysplasias and neuropathies, reflecting its critical role in development and cellular signaling.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Spinal Muscular Atrophy, Distal, Congenital Non-Progressive (SMA-DCNP) | Missense mutations in TRPV4 lead to altered channel activity, affecting motor neuron function. | ClinVar, OMIM |
| Charcot-Marie-Tooth Disease Type 2C (CMT2C) | Dominant mutations cause gain-of-function effects, leading to neuronal degeneration. | ClinVar, OMIM |
| Hereditary Motor and Sensory Neuropathy Type IIC (HMSN2C) | Same as CMT2C; mutations disrupt axonal transport and calcium homeostasis. | ClinVar, OMIM |
| Spondyloepiphyseal Dysplasia, Maroteaux Type (SEDM) | Mutations in TRPV4 impair chondrocyte differentiation and bone development. | OMIM, ClinVar |
| Metatropic Dysplasia (MTD) | Gain-of-function mutations increase channel activity, causing skeletal abnormalities. | OMIM, ClinVar |
| Parastremmatic Dysplasia | TRPV4 mutations lead to abnormal calcium signaling in bone growth plates. | OMIM, ClinVar |
| Kozlowski Type Spondylometaphyseal Dysplasia (SMDK) | Mutations affect TRPV4 channel gating, disrupting skeletal development. | OMIM, ClinVar |
| Osteoarthritis Susceptibility | TRPV4 variants may influence chondrocyte mechanotransduction, contributing to joint degeneration. | ClinVar, literature |
| Hyponatremia (in some contexts) | TRPV4 participates in osmosensing; variants may affect renal water balance. | Literature, ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lung | 9.8 | Medium |
| Kidney | 8.5 | Medium |
| Trachea | 7.9 | Medium |
| Esophagus | 6.2 | Low |
| Skin | 5.4 | Low |
| Brain | 4.1 | Low |
| Heart | 3.0 | Low |
| Liver | 1.2 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 12.5 | Overexpressed in studies |
| A549 (Lung carcinoma) | 8.3 | Endogenous expression |
| HUVEC (Endothelial) | 7.1 | Endothelial function |
| U2OS (Osteosarcoma) | 5.6 | Bone-related expression |
| SH-SY5Y (Neuroblastoma) | 4.2 | Neuronal expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| p.Arg269Cys | Missense | Rare | Gain-of-function; associated with CMT2C |
| p.Arg616Gln | Missense | Rare | Gain-of-function; associated with metatropic dysplasia |
| p.Arg775Lys | Missense | Rare | Gain-of-function; associated with skeletal dysplasias |
| p.Leu596Pro | Missense | Rare | Loss-of-function; associated with distal SMA |
| p.Gly20Asp | Missense | Rare | Gain-of-function; associated with SMDK |
| p.Val620Ile | Missense | Rare | Gain-of-function; associated with CMT2C |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in TRPV4 are less common and typically associated with distal spinal muscular atrophy (SMA). These mutations reduce channel activity, impairing calcium influx and neuronal survival.
Gain of Function (GOF)
Most pathogenic TRPV4 mutations are gain-of-function, leading to increased channel activity and elevated intracellular calcium. This is observed in CMT2C, metatropic dysplasia, and other skeletal dysplasias, causing cellular toxicity and developmental defects.
Dominant Negative (DN)
Dominant-negative effects have been reported for some TRPV4 mutations, where the mutant subunit co-assembles with wild-type subunits, reducing overall channel function. This mechanism is implicated in certain neuropathies.
View complete mutation data：
Gene Ontology (GO)
| • Calcium ion binding | • Calcium channel activity |
| • Ion channel activity | • Mechanosensitive ion channel activity |
| • Response to heat | • Cellular response to osmotic stress |
| • Positive regulation of cytosolic calcium ion concentration | • Integral component of plasma membrane |
Pathways
• Calcium signaling pathway
• TRP channels in inflammatory response
• Mechanotransduction pathway
• Osmosensory signaling
• VEGF signaling pathway (in endothelial cells)
Protein Summary
The TRPV4 protein is a calcium-permeable cation channel that forms tetramers and is activated by various stimuli including heat, mechanical stretch, hypotonicity, and phorbol esters. It plays a role in multiple tissues: in the kidney, it regulates osmolarity; in the vasculature, it mediates vasodilation; in chondrocytes, it responds to mechanical load; and in neurons, it contributes to pain sensation and motor function. The channel has six transmembrane domains, a pore-forming loop, and intracellular N- and C-termini with regulatory domains. Mutations that alter channel gating or trafficking lead to disease phenotypes.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TRPV4 Overexpression HEK293 Stable Cell Line | EDJ-GQ77 | Human | 59341 | Details Get a Quote |
| TRPV4 Knockout HEK293 Cell Line | EDJ-KQ1035 | Human | 59341 | Details Get a Quote |
| TRPV4 Knockout HeLa Cell Line | EDJ-KQ56968 | Human | 59341 | Details Get a Quote |
| TRPV4 Knockout A-549 Cell Line | EDJ-KQ65471 | Human | 59341 | Details Get a Quote |
| TRPV4 Knockout HCT 116 Cell Line | EDJ-KQ73909 | Human | 59341 | Details Get a Quote |
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