Description: Homo sapiens transient receptor potential cation channel, subfamily V, member 4 (TRPV4), transcript variant 1, mRNA. RefSeq Summary (NM_021625): This gene encodes a member of the OSM9-like transient receptor potential channel (OTRPC) subfamily in the transient receptor potential (TRP) superfamily of ion channels. The encoded protein is a Ca2+-permeable, nonselective cation channel that is thought to be involved in the regulation of systemic osmotic pressure. Mutations in this gene are the cause of spondylometaphyseal and metatropic dysplasia and hereditary motor and sensory neuropathy type IIC. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2010]. Transcript (Including UTRs) Position: hg19 chr12:110,220,892-110,271,212 Size: 50,321 Total Exon Count: 16 Strand: - Coding Region Position: hg19 chr12:110,221,426-110,252,601 Size: 31,176 Coding Exon Count: 15
ID:TRPV4_HUMAN DESCRIPTION: RecName: Full=Transient receptor potential cation channel subfamily V member 4; Short=TrpV4; AltName: Full=Osm-9-like TRP channel 4; Short=OTRPC4; AltName: Full=Transient receptor potential protein 12; Short=TRP12; AltName: Full=Vanilloid receptor-like channel 2; AltName: Full=Vanilloid receptor-like protein 2; Short=VRL-2; AltName: Full=Vanilloid receptor-related osmotically-activated channel; Short=VR-OAC; FUNCTION: Non-selective calcium permeant cation channel probably involved in osmotic sensitivity and mechanosensitivity. Activation by exposure to hypotonicity within the physiological range exhibits an outward rectification. Also activated by low pH, citrate and phorbol esters. Increase of intracellular Ca(2+) potentiates currents. Channel activity seems to be regulated by a calmodulin-dependent mechanism with a negative feedback mechanism. Promotes cell-cell junction formation in skin keratinocytes and plays an important role in the formation and/or maintenance of functional intercellular barriers. Acts as a regulator of intracellular Ca(2+) in synoviocytes. Plays an obligatory role as a molecular component in the nonselective cation channel activation induced by 4-alpha-phorbol 12,13-didecanoate and hypotonic stimulation in synoviocytes and also regulates production of IL-8. SUBUNIT: Homotetramer (Probable). Self-associates in a isoform- specific manner. Isoforms 1/A and 5/D but not isoform 2/B, 4/C and 6/E can oligomerize. Interacts with calmodulin. Interacts with Map7 and Src family Tyr protein kinases LYN, SRC, FYN, HCK, LCK and YES. Interacts with CTNNB1. The TRPV4 and CTNNB1 complex can interact with CDH1 (By similarity). Part of a complex containing MLC1, AQP4, HEPACAM and ATP1B1. SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein (By similarity). Cell junction, adherens junction (By similarity). Note=Assembly of the putative homotetramer occurs primarily in the endoplasmic reticulum. SUBCELLULAR LOCATION: Isoform 1: Cell membrane. SUBCELLULAR LOCATION: Isoform 5: Cell membrane. TISSUE SPECIFICITY: Found in the synoviocytes from patients with (RA) and without (CTR) rheumatoid arthritis (at protein level). PTM: Phosphorylation results in enhancement of its channel function. POLYMORPHISM: Genetic variations in TRPV4 determine the sodium serum level quantitative trait locus 1 (SSQTL1) [MIM:613508]. In some populations, variant Pro19Ser has been shown to be significantly associated with hyponatremia defined as serum sodium concentration below or equal to 135 mEq/L. DISEASE: Defects in TRPV4 are the cause of brachyolmia type 3 (BRAC3) [MIM:113500]; also known as brachyrachia. The brachyolmias constitute a clinically and genetically heterogeneous group of skeletal dysplasias characterized by a short trunk, scoliosis and mild short stature. BRAC3 is an autosomal dominant form with severe kyphoscoliosis and flattened, irregular cervical vertebrae. DISEASE: Defects in TRPV4 are the cause of spondylometaphyseal dysplasia Kozlowski type (SMDK) [MIM:184252]. The spondylometaphyseal dysplasias (SMDs) are a group of short-stature disorders distinguished by abnormalities in the vertebrae and the metaphyses of the tubular bones. SMDK is an autosomal dominant disorder characterized by significant scoliosis and mild metaphyseal abnormalities in the pelvis. The vertebrae exhibit platyspondyly and overfaced pedicles. DISEASE: Defects in TRPV4 are the cause of metatropic dysplasia (MTD) [MIM:156530]; also called metatropic dwarfism. Metatropic dysplasia is a severe spondyloepimetaphyseal dysplasia characterized by short limbs with limitation and enlargement of joints and usually severe kyphoscoliosis. Radiologic features include severe platyspondyly, severe metaphyseal enlargement and shortening of long bones. DISEASE: Defects in TRPV4 are the cause of distal spinal muscular atrophy congenital non-progressive (DSMAC) [MIM:600175]; a clinically variable, neuromuscular disorder characterized by congenital lower motor neuron disorder restricted to the lower part of the body. Clinical manifestations include non-progressive muscular atrophy, thigh muscle atrophy, weak thigh adductors, weak knee and foot extensors, minimal jaw muscle and neck flexor weakness, flexion contractures of knees and pes equinovarus. Tendon reflexes are normal. DISEASE: Defects in TRPV4 are the cause of Charcot-Marie-Tooth disease type 2C (CMT2C) [MIM:606071]; an axonal form of Charcot- Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies (designated CMT1 when they are dominantly inherited) and primary peripheral axonal neuropathies (CMT2). Neuropathies of the CMT2 group are characterized by signs of axonal regeneration in the absence of obvious myelin alterations, normal or slightly reduced nerve conduction velocities, and progressive distal muscle weakness and atrophy. Nerve conduction velocities are normal or slightly reduced. DISEASE: Defects in TRPV4 are the cause of Scapuloperoneal spinal muscular atrophy (SPSMA) [MIM:181405]. It is a clinically variable neuromuscular disorder characterized by neurogenic scapuloperoneal amyotrophy, laryngeal palsy, congenital absence of muscles, progressive scapuloperoneal atrophy and progressive distal weakness and amyotrophy. DISEASE: Defects in TRPV4 are the cause of spondyloepiphyseal dysplasia Maroteaux type (SEDM) [MIM:184095]. It is a clinically variable spondyloepiphyseal dysplasia with manifestations limited to the musculoskeletal system. Clinical features include short stature, brachydactyly, platyspondyly, short and stubby hands and feet, epiphyseal hypoplasia of the large joints, and iliac hypoplasia. Intelligence is normal. DISEASE: Defects in TRPV4 are the cause of parastremmatic dwarfism (PSTD) [MIM:168400]. It is a bone dysplasia characterized by severe dwarfism, kyphoscoliosis, distortion and bowing of the extremities, and contractures of the large joints. Radiographically, the disease is characterized by a combination of decreased bone density, bowing of the long bones, platyspondyly and striking irregularities of endochondral ossification with areas of calcific stippling and streaking in radiolucent epiphyses, metaphyses and apophyses. DISEASE: Defects in TRPV4 are the cause of digital arthropathy- brachydactyly, familial (FDAB) [MIM:606835]. A disorder characterized by irregularities in the proximal articular surfaces of the distal interphalangeal joints of the hand. Individuals appear normal at birth, with no clinical or radiographic evidence of a developmental skeletal dysplasia. The earliest changes appear during the first decade of life. By adulthood, all interphalangeal, metacarpophalangeal, and metatarsophalangeal joints are affected by a deforming, painful osteoarthritis. The remainder of the skeleton is clinically and radiographically unaffected. SIMILARITY: Belongs to the transient receptor (TC 1.A.4) family. TrpV subfamily. TRPV4 sub-subfamily. SIMILARITY: Contains 3 ANK repeats.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q9HBA0
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
US Server
