Gene: TRPV4
Alternate names for this Gene: BCYM3|CMT2C|HMSN2C|OTRPC4|SMAL|SPSMA|SSQTL1|TRP12|VRL2|VROAC
Gene Summary: 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.
Gene is located in Chromosome: 12
Location in Chromosome : 12q24.11
Description of this Gene: transient receptor potential cation channel subfamily V member 4
Type of Gene: protein-coding
rs121912632 in
TRPV4 gene and
Brachyolmia Type 3
PMID 18587396 2008 Gain-of-function mutations in TRPV4 cause autosomal dominant brachyolmia.
rs267607144 in
TRPV4 gene and
Congenital clubfoot
PMID 22702953 2012 Structural and biochemical consequences of disease-causing mutations in the ankyrin repeat domain of the human TRPV4 channel.
PMID 20037588 2010 Alterations in the ankyrin domain of TRPV4 cause congenital distal SMA, scapuloperoneal SMA and HMSN2C.
PMID 20037586 2010 Mutations in TRPV4 cause Charcot-Marie-Tooth disease type 2C.
PMID 24789864 2014 Phenotypic spectrum and incidence of TRPV4 mutations in patients with inherited axonal neuropathy.
rs7971845 in
TRPV4 gene and
Creatinine measurement, serum (procedure)
PMID 29403010 2018 Genetic analysis of quantitative traits in the Japanese population links cell types to complex human diseases.
rs387907219 in
TRPV4 gene and
Digital Arthropathy-Brachydactyly, Familial
PMID 21964574 2011 Mutations in TRPV4 cause an inherited arthropathy of hands and feet.
rs1555208063 in
TRPV4 gene and
Dysmorphic features
PMID 22791502 2012 TRPV4-associated skeletal dysplasias.
PMID 20577006 2010 Novel and recurrent TRPV4 mutations and their association with distinct phenotypes within the TRPV4 dysplasia family.
PMID 26249260 2015 A mutation in TRPV4 results in altered chondrocyte calcium signaling in severe metatropic dysplasia.
PMID 21288981 2011 TRPV4 mutations and cytotoxic hypercalcemia in axonal Charcot-Marie-Tooth neuropathies.
PMID 24677493 2014 Autosomal dominant brachyolmia in a large Swedish family: phenotypic spectrum and natural course.
PMID 4056805 1985 A dominantly inherited lower motor neuron disorder presenting at birth with associated arthrogryposis.
PMID 22851605 2012 Comprehensive analysis of the TRPV4 gene in a large series of inherited neuropathies and controls.
PMID 20460441 2010 Dominant mutations in the cation channel gene transient receptor potential vanilloid 4 cause an unusual spectrum of neuropathies.
PMID 27330106 2016 Gain-of-function mutation in TRPV4 identified in patients with osteonecrosis of the femoral head.
PMID 1520078 1992 A large New England kindred with autosomal dominant neurogenic scapuloperoneal amyotrophy with unique features.
PMID 21115951 2010 CMT2C with vocal cord paresis associated with short stature and mutations in the TRPV4 gene.
PMID 20503319 2010 Spondylo-epiphyseal dysplasia, Maroteaux type (pseudo-Morquio syndrome type 2), and parastremmatic dysplasia are caused by TRPV4 mutations.
PMID 28898540 2017 Compound heterozygous TRPV4 mutations in two siblings with a complex phenotype including severe intellectual disability and neuropathy.
PMID 20037588 2010 Alterations in the ankyrin domain of TRPV4 cause congenital distal SMA, scapuloperoneal SMA and HMSN2C.
PMID 21964574 2011 Mutations in TRPV4 cause an inherited arthropathy of hands and feet.
PMID 18587396 2008 Gain-of-function mutations in TRPV4 cause autosomal dominant brachyolmia.
PMID 20425821 2010 Dominant TRPV4 mutations in nonlethal and lethal metatropic dysplasia.
PMID 20037586 2010 Mutations in TRPV4 cause Charcot-Marie-Tooth disease type 2C.
PMID 14755468 2004 Spondyloepimetaphyseal dysplasia of Maroteaux (pseudo-Morquio type II syndrome): report of a new patient and review of the literature.
PMID 25900305 2015 Phenotypic variability of TRPV4 related neuropathies.
PMID 11891693 2002 Familial digital arthropathy-brachydactyly.
PMID 19232556 2009 Mutations in the gene encoding the calcium-permeable ion channel TRPV4 produce spondylometaphyseal dysplasia, Kozlowski type and metatropic dysplasia.
PMID 956253 1976 Parastremmatic dwarfism.
PMID 20037587 2010 Scapuloperoneal spinal muscular atrophy and CMT2C are allelic disorders caused by alterations in TRPV4.
rs387906905 in
TRPV4 gene and
Gait abnormality
PMID 21288981 2011 TRPV4 mutations and cytotoxic hypercalcemia in axonal Charcot-Marie-Tooth neuropathies.
rs10850813 in
TRPV4 gene and
Glomerular Filtration Rate
PMID 29403010 2018 Genetic analysis of quantitative traits in the Japanese population links cell types to complex human diseases.
rs121912637 in
TRPV4 gene and
HEREDITARY MOTOR AND SENSORY NEUROPATHY, TYPE IIC (disorder)
PMID 21573172 2011 Increased basal activity is a key determinant in the severity of human skeletal dysplasia caused by TRPV4 mutations.
PMID 20577006 2010 Novel and recurrent TRPV4 mutations and their association with distinct phenotypes within the TRPV4 dysplasia family.
PMID 19232556 2009 Mutations in the gene encoding the calcium-permeable ion channel TRPV4 produce spondylometaphyseal dysplasia, Kozlowski type and metatropic dysplasia.
PMID 26249260 2015 A mutation in TRPV4 results in altered chondrocyte calcium signaling in severe metatropic dysplasia.
PMID 26170305 2015 A channelopathy mechanism revealed by direct calmodulin activation of TrpV4.
PMID 21658220 2011 TRPV4 related skeletal dysplasias: a phenotypic spectrum highlighted byclinical, radiographic, and molecular studies in 21 new families.
PMID 20503319 2010 Spondylo-epiphyseal dysplasia, Maroteaux type (pseudo-Morquio syndrome type 2), and parastremmatic dysplasia are caused by TRPV4 mutations.
PMID 20425821 2010 Dominant TRPV4 mutations in nonlethal and lethal metatropic dysplasia.
PMID 27066566 2015 Novel mutations highlight the key role of the ankyrin repeat domain in TRPV4-mediated neuropathy.
PMID 21454511 2011 Mutant TRPV4-mediated toxicity is linked to increased constitutive function in axonal neuropathies.
PMID 21115951 2010 CMT2C with vocal cord paresis associated with short stature and mutations in the TRPV4 gene.
PMID 20460441 2010 Dominant mutations in the cation channel gene transient receptor potential vanilloid 4 cause an unusual spectrum of neuropathies.
PMID 20037586 2010 Mutations in TRPV4 cause Charcot-Marie-Tooth disease type 2C.
PMID 21288981 2011 TRPV4 mutations and cytotoxic hypercalcemia in axonal Charcot-Marie-Tooth neuropathies.
PMID 20037587 2010 Scapuloperoneal spinal muscular atrophy and CMT2C are allelic disorders caused by alterations in TRPV4.
PMID 22702953 2012 Structural and biochemical consequences of disease-causing mutations in the ankyrin repeat domain of the human TRPV4 channel.
PMID 20037588 2010 Alterations in the ankyrin domain of TRPV4 cause congenital distal SMA, scapuloperoneal SMA and HMSN2C.
PMID 15668982 2005 Confirmation of a hereditary motor and sensory neuropathy IIC locus at chromosome 12q23-q24.
PMID 22065612 2011 Striking phenotypic variability in familial TRPV4-axonal neuropathy spectrum disorder.
PMID 25256292 2014 TRPV4 channel activity is modulated by direct interaction of the ankyrin domain to PI(4,5)P₂.
PMID 25900305 2015 Phenotypic variability of TRPV4 related neuropathies.
PMID 24575025 2014 Essential Tremor in a Charcot-Marie-Tooth Type 2C Kindred Does Not Segregate with the TRPV4 R269H Mutation.
PMID 21336783 2011 Reduced penetrance in hereditary motor neuropathy caused by TRPV4 Arg269Cys mutation.
PMID 24789864 2014 Phenotypic spectrum and incidence of TRPV4 mutations in patients with inherited axonal neuropathy.
PMID 24319099 2014 Mutations in CNTNAP1 and ADCY6 are responsible for severe arthrogryposis multiplex congenita with axoglial defects.
PMID 26110311 2015 Long-Term Observations in an Affected Family with Neurogenic Scapuloperoneal Syndrome Caused by Mutation R269C in the TRPV4 Gene.
PMID 26948711 2017 TRPV4 related scapuloperoneal spinal muscular atrophy: Report of an Italian family and review of the literature.
PMID 24963089 2014 Intrafamilial variable hearing loss in TRPV4 induced spinal muscular atrophy.
PMID 27751652 2016 A case of congenital spinal muscular atrophy with pain due to a mutation in TRPV4.
PMID 22419508 2012 TRPV4-pathy manifesting both skeletal dysplasia and peripheral neuropathy: a report of three patients.
PMID 26048687 2015 Charcot-Marie-Tooth disease type 2C and scapuloperoneal muscular atrophy overlap syndrome in a patient with the R232C TRPV4 mutation.
PMID 22526352 2012 TRPV4 mutations in children with congenital distal spinal muscular atrophy.
PMID 21288981 2011 The R316H is a novel de novo mutation found in a patient with CMT2C phenotype.
PMID 22675077 2012 Exome sequencing identifies a novel TRPV4 mutation in a CMT2C family.
PMID 27549087 2016 Improving diagnosis of inherited peripheral neuropathies through gene panel analysis.
rs121912636 in
TRPV4 gene and
Metatropic dwarfism
PMID 22702953 2012 Structural and biochemical consequences of disease-causing mutations in the ankyrin repeat domain of the human TRPV4 channel.
PMID 26249260 2015 A mutation in TRPV4 results in altered chondrocyte calcium signaling in severe metatropic dysplasia.
PMID 20425821 2010 Dominant TRPV4 mutations in nonlethal and lethal metatropic dysplasia.
PMID 19232556 2009 Mutations in the gene encoding the calcium-permeable ion channel TRPV4 produce spondylometaphyseal dysplasia, Kozlowski type and metatropic dysplasia.
PMID 20577006 2010 Novel and recurrent TRPV4 mutations and their association with distinct phenotypes within the TRPV4 dysplasia family.
PMID 20577006 2010 In MD, a recurrent P799L mutation was identified in nine subjects, as well as 10 novel mutations including F471del, the first deletion mutation of TRPV4.
rs1555205335 in
TRPV4 gene and
Multiple congenital anomalies
PMID 28898540 2017 Compound heterozygous TRPV4 mutations in two siblings with a complex phenotype including severe intellectual disability and neuropathy.
PMID 26249260 2015 A mutation in TRPV4 results in altered chondrocyte calcium signaling in severe metatropic dysplasia.
PMID 4056805 1985 A dominantly inherited lower motor neuron disorder presenting at birth with associated arthrogryposis.
PMID 956253 1976 Parastremmatic dwarfism.
PMID 27330106 2016 Gain-of-function mutation in TRPV4 identified in patients with osteonecrosis of the femoral head.
PMID 24677493 2014 Autosomal dominant brachyolmia in a large Swedish family: phenotypic spectrum and natural course.
PMID 25900305 2015 Phenotypic variability of TRPV4 related neuropathies.
PMID 22791502 2012 TRPV4-associated skeletal dysplasias.
PMID 22851605 2012 Comprehensive analysis of the TRPV4 gene in a large series of inherited neuropathies and controls.
PMID 20037586 2010 Mutations in TRPV4 cause Charcot-Marie-Tooth disease type 2C.
PMID 20037587 2010 Scapuloperoneal spinal muscular atrophy and CMT2C are allelic disorders caused by alterations in TRPV4.
PMID 19232556 2009 Mutations in the gene encoding the calcium-permeable ion channel TRPV4 produce spondylometaphyseal dysplasia, Kozlowski type and metatropic dysplasia.
PMID 1520078 1992 A large New England kindred with autosomal dominant neurogenic scapuloperoneal amyotrophy with unique features.
PMID 21115951 2010 CMT2C with vocal cord paresis associated with short stature and mutations in the TRPV4 gene.
PMID 14755468 2004 Spondyloepimetaphyseal dysplasia of Maroteaux (pseudo-Morquio type II syndrome): report of a new patient and review of the literature.
PMID 20037588 2010 Alterations in the ankyrin domain of TRPV4 cause congenital distal SMA, scapuloperoneal SMA and HMSN2C.
PMID 21288981 2011 TRPV4 mutations and cytotoxic hypercalcemia in axonal Charcot-Marie-Tooth neuropathies.
PMID 11891693 2002 Familial digital arthropathy-brachydactyly.
PMID 18587396 2008 Gain-of-function mutations in TRPV4 cause autosomal dominant brachyolmia.
PMID 20577006 2010 Novel and recurrent TRPV4 mutations and their association with distinct phenotypes within the TRPV4 dysplasia family.
PMID 21964574 2011 Mutations in TRPV4 cause an inherited arthropathy of hands and feet.
PMID 20503319 2010 Spondylo-epiphyseal dysplasia, Maroteaux type (pseudo-Morquio syndrome type 2), and parastremmatic dysplasia are caused by TRPV4 mutations.
PMID 20425821 2010 Dominant TRPV4 mutations in nonlethal and lethal metatropic dysplasia.
PMID 20460441 2010 Dominant mutations in the cation channel gene transient receptor potential vanilloid 4 cause an unusual spectrum of neuropathies.
rs387906905 in
TRPV4 gene and
Muscle Weakness Lower Limb
PMID 21288981 2011 TRPV4 mutations and cytotoxic hypercalcemia in axonal Charcot-Marie-Tooth neuropathies.
rs387906905 in
TRPV4 gene and
Muscle hypotonia
PMID 21288981 2011 TRPV4 mutations and cytotoxic hypercalcemia in axonal Charcot-Marie-Tooth neuropathies.
rs77975504 in
TRPV4 gene and
Parastremmatic dwarfism
PMID 20503319 2010 Spondylo-epiphyseal dysplasia, Maroteaux type (pseudo-Morquio syndrome type 2), and parastremmatic dysplasia are caused by TRPV4 mutations.
rs387906905 in
TRPV4 gene and
Reflex, Abnormal
PMID 21288981 2011 TRPV4 mutations and cytotoxic hypercalcemia in axonal Charcot-Marie-Tooth neuropathies.
rs267607144 in
TRPV4 gene and
SPINAL MUSCULAR ATROPHY, DISTAL, CONGENITAL NONPROGRESSIVE (disorder)
PMID 22526352 2012 TRPV4 mutations in children with congenital distal spinal muscular atrophy.
PMID 20037588 2010 Alterations in the ankyrin domain of TRPV4 cause congenital distal SMA, scapuloperoneal SMA and HMSN2C.
PMID 22702953 2012 Structural and biochemical consequences of disease-causing mutations in the ankyrin repeat domain of the human TRPV4 channel.
rs267607145 in
TRPV4 gene and
Scapuloperoneal Form of Spinal Muscular Atrophy
PMID 20037587 2010 Scapuloperoneal spinal muscular atrophy and CMT2C are allelic disorders caused by alterations in TRPV4.
PMID 22702953 2012 Structural and biochemical consequences of disease-causing mutations in the ankyrin repeat domain of the human TRPV4 channel.
rs267607144 in
TRPV4 gene and
Scoliosis, unspecified
PMID 24789864 2014 Phenotypic spectrum and incidence of TRPV4 mutations in patients with inherited axonal neuropathy.
PMID 20037588 2010 Alterations in the ankyrin domain of TRPV4 cause congenital distal SMA, scapuloperoneal SMA and HMSN2C.
PMID 22702953 2012 Structural and biochemical consequences of disease-causing mutations in the ankyrin repeat domain of the human TRPV4 channel.
PMID 20037586 2010 Mutations in TRPV4 cause Charcot-Marie-Tooth disease type 2C.
rs121912634 in
TRPV4 gene and
Spondylometaphyseal dysplasia, Kozlowski type
PMID 19232556 2009 Mutations in the gene encoding the calcium-permeable ion channel TRPV4 produce spondylometaphyseal dysplasia, Kozlowski type and metatropic dysplasia.
PMID 22702953 2012 Structural and biochemical consequences of disease-causing mutations in the ankyrin repeat domain of the human TRPV4 channel.
PMID 20577006 2010 Novel and recurrent TRPV4 mutations and their association with distinct phenotypes within the TRPV4 dysplasia family.
PMID 19232556 2009 Mutation analysis in six out of six patients with SMDK demonstrated heterozygosity for missense mutations in TRPV4, and one mutation, predicting a R594H substitution, was recurrent in four patients.
PMID 20577006 2010 In SMDK, a recurrent R594H mutation was identified in 12 subjects and seven novel mutations.
rs267607144 in
TRPV4 gene and
Vocal Cord Paralysis
PMID 22702953 2012 Structural and biochemical consequences of disease-causing mutations in the ankyrin repeat domain of the human TRPV4 channel.
PMID 20037588 2010 Alterations in the ankyrin domain of TRPV4 cause congenital distal SMA, scapuloperoneal SMA and HMSN2C.
PMID 24789864 2014 Phenotypic spectrum and incidence of TRPV4 mutations in patients with inherited axonal neuropathy.
PMID 20037586 2010 Mutations in TRPV4 cause Charcot-Marie-Tooth disease type 2C.