TRPV4

transient receptor potential cation channel subfamily V member 4, the group of Ankyrin repeat domain containing|Transient receptor potential cation channels

Basic information

Region (hg38): 12:109783086-109833406

Links

ENSG00000111199 ∙ NCBI:59341 ∙ OMIM:605427 ∙ HGNC:18083 ∙ Uniprot:Q9HBA0 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• spondylometaphyseal dysplasia, Kozlowski type (Definitive), mode of inheritance: AD
• metatropic dysplasia (Definitive), mode of inheritance: AD
• autosomal dominant brachyolmia (Strong), mode of inheritance: AD
• metatropic dysplasia (Supportive), mode of inheritance: AD
• neuronopathy, distal hereditary motor, autosomal dominant 8 (Supportive), mode of inheritance: AD
• parastremmatic dwarfism (Supportive), mode of inheritance: AD
• familial digital arthropathy-brachydactyly (Supportive), mode of inheritance: AD
• familial avascular necrosis of femoral head (Supportive), mode of inheritance: AD
• autosomal dominant brachyolmia (Supportive), mode of inheritance: AD
• spondylometaphyseal dysplasia, Kozlowski type (Supportive), mode of inheritance: AD
• Charcot-Marie-Tooth disease axonal type 2C (Supportive), mode of inheritance: AD
• scapuloperoneal spinal muscular atrophy, autosomal dominant (Supportive), mode of inheritance: AD
• scapuloperoneal spinal muscular atrophy, autosomal dominant (Moderate), mode of inheritance: AD
• TRPV4-related bone disorder (Definitive), mode of inheritance: AD
• Charcot-Marie-Tooth disease axonal type 2C (Strong), mode of inheritance: AD
• autosomal dominant brachyolmia (Strong), mode of inheritance: AD
• TRPV4-related bone disorder (Definitive), mode of inheritance: AD
• neuromuscular disease (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Avascular necrosis of femoral head, primary 2	AD	Musculoskeletal	In Avascular necrosis of femoral head, primary, identifying carriers before the onset of clinical symptoms can allow interventions in order to delay disease progression	Craniofacial; Musculoskeletal; Neurologic	4992387; 4056805; 1520078; 8179305; 9781046; 10463355; 12884428; 14755468; 15668982; 17879966; 18348257; 18587396; 19232556; 20037588; 20425821; 21115951; 20577006; 20037587; 20037586; 20503319; 21336783; 21288981; 21964829; 21964574; 22065612; 22206013; 22419508; 22526352; 22617546; 22675077; 22791502; 22851605; 27330106

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TRPV4 gene.

• Charcot-Marie-Tooth disease axonal type 2C (800 variants)
• not provided (334 variants)
• Inborn genetic diseases (206 variants)
• Charcot-Marie-Tooth disease (118 variants)
• Metatropic dysplasia (117 variants)
• Neuronopathy, distal hereditary motor, autosomal dominant 8 (111 variants)
• Spondylometaphyseal dysplasia, Kozlowski type (109 variants)
• Scapuloperoneal spinal muscular atrophy (109 variants)
• Brachyrachia (short spine dysplasia) (106 variants)
• not specified (97 variants)
• Connective tissue disorder (26 variants)
• Skeletal dysplasia (23 variants)
• 11 conditions (11 variants)
• Neuromuscular disease;Skeletal dysplasia (9 variants)
• TRPV4-related condition (8 variants)
• Neuromuscular disease (6 variants)
• Neuronopathy, distal hereditary motor, autosomal dominant (4 variants)
• Tip-toe gait (4 variants)
• Parastremmatic dwarfism (3 variants)
• Distal spinal muscular atrophy (3 variants)
• Spondyloepimetaphyseal dysplasia, Maroteaux type (3 variants)
• See cases (2 variants)
• TRPV4-Associated Disorders (2 variants)
• TRPV4-related bone disorder (2 variants)
• - (2 variants)
• Auditory neuropathy (1 variants)
• Sodium serum level quantitative trait locus 1 (1 variants)
• Spondylometaphyseal dysplasia (1 variants)
• TRPV4-related disorders (1 variants)
• Scapuloperoneal spinal muscular atrophy;Neuronopathy, distal hereditary motor, autosomal dominant 8;Charcot-Marie-Tooth disease axonal type 2C;TRPV4-related bone disorder (1 variants)
• TRPV4-associated skeletal dysplasias (1 variants)
• Neuronopathy, distal hereditary motor, autosomal dominant 8;Charcot-Marie-Tooth disease axonal type 2C (1 variants)
• Hereditary motor neuron disease (1 variants)
• Charcot-Marie-Tooth disease, type I (1 variants)
• Charcot-Marie-Tooth disease axonal type 2X;Charcot-Marie-Tooth disease axonal type 2C;Amyotrophic lateral sclerosis type 5 (1 variants)
• Skeletal dysplasia and progressive central nervous system degeneration, lethal (1 variants)
• Clubfoot;Lower limb amyotrophy;EMG abnormality (1 variants)
• Scapuloperoneal spinal muscular atrophy;Charcot-Marie-Tooth disease axonal type 2C;Neuronopathy, distal hereditary motor, autosomal dominant 8 (1 variants)
• Charcot-Marie-Tooth disease type 4 (1 variants)
• Mild short stature (1 variants)
• Charcot-Marie-Tooth disease type 2 (1 variants)
• Brachyolmia (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TRPV4 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		1	7	197	5	210
missense	19	28	387	20	2	456
nonsense			14			14
start loss						0
frameshift			18			18
inframe indel		2	5			7
splice donor/acceptor (+/-2bp)			12	1		13
splice region		1	12	26	1	40
non coding			20	106	45	171
Total	19	31	463	324	52

Highest pathogenic variant AF is 0.0000131

Variants in TRPV4

This is a list of pathogenic ClinVar variants found in the TRPV4 region.

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

Position	Type	Phenotype	Significance	ClinVar
12-109783121-G-A		Brachyrachia (short spine dysplasia) • Spondylometaphyseal dysplasia, Kozlowski type • Neuronopathy, distal hereditary motor, autosomal dominant 8 • Metatropic dysplasia • Charcot-Marie-Tooth disease axonal type 2C • Scapuloperoneal spinal muscular atrophy	Uncertain significance (Jan 12, 2018)
12-109783135-A-G		Brachyrachia (short spine dysplasia) • Scapuloperoneal spinal muscular atrophy • Neuronopathy, distal hereditary motor, autosomal dominant 8 • Charcot-Marie-Tooth disease axonal type 2C • Spondylometaphyseal dysplasia, Kozlowski type • Metatropic dysplasia	Benign (Jan 13, 2018)
12-109783198-C-T		Spondylometaphyseal dysplasia, Kozlowski type • Neuronopathy, distal hereditary motor, autosomal dominant 8 • Scapuloperoneal spinal muscular atrophy • Charcot-Marie-Tooth disease axonal type 2C • Brachyrachia (short spine dysplasia) • Metatropic dysplasia	Benign/Likely benign (Jun 01, 2023)
12-109783200-C-T		Metatropic dysplasia • Spondylometaphyseal dysplasia, Kozlowski type • Charcot-Marie-Tooth disease axonal type 2C • Brachyrachia (short spine dysplasia) • Neuronopathy, distal hereditary motor, autosomal dominant 8 • Scapuloperoneal spinal muscular atrophy	Uncertain significance (Jan 12, 2018)
12-109783210-T-C		Charcot-Marie-Tooth disease axonal type 2C • Spondylometaphyseal dysplasia, Kozlowski type • Brachyrachia (short spine dysplasia) • Neuronopathy, distal hereditary motor, autosomal dominant 8 • Metatropic dysplasia • Scapuloperoneal spinal muscular atrophy	Uncertain significance (Apr 27, 2017)
12-109783216-C-T		Charcot-Marie-Tooth disease axonal type 2C • Metatropic dysplasia • Neuronopathy, distal hereditary motor, autosomal dominant 8 • Spondylometaphyseal dysplasia, Kozlowski type • Scapuloperoneal spinal muscular atrophy • Brachyrachia (short spine dysplasia)	Uncertain significance (Jan 13, 2018)
12-109783243-C-G		Scapuloperoneal spinal muscular atrophy • Spondylometaphyseal dysplasia, Kozlowski type • Metatropic dysplasia • Neuronopathy, distal hereditary motor, autosomal dominant 8 • Brachyrachia (short spine dysplasia) • Charcot-Marie-Tooth disease axonal type 2C	Benign (Jan 13, 2018)
12-109783256-G-A		Spondylometaphyseal dysplasia, Kozlowski type • Scapuloperoneal spinal muscular atrophy • Brachyrachia (short spine dysplasia) • Charcot-Marie-Tooth disease axonal type 2C • Neuronopathy, distal hereditary motor, autosomal dominant 8 • Metatropic dysplasia	Benign (Jan 13, 2018)
12-109783318-C-T		Spondylometaphyseal dysplasia, Kozlowski type • Metatropic dysplasia • Neuronopathy, distal hereditary motor, autosomal dominant 8 • Brachyrachia (short spine dysplasia) • Scapuloperoneal spinal muscular atrophy • Charcot-Marie-Tooth disease axonal type 2C	Uncertain significance (Jan 13, 2018)
12-109783391-C-T		Charcot-Marie-Tooth disease axonal type 2C • Spondylometaphyseal dysplasia, Kozlowski type • Metatropic dysplasia • Neuronopathy, distal hereditary motor, autosomal dominant 8 • Brachyrachia (short spine dysplasia) • Scapuloperoneal spinal muscular atrophy	Benign (Jan 13, 2018)
12-109783394-T-C		Brachyrachia (short spine dysplasia) • Spondylometaphyseal dysplasia, Kozlowski type • Metatropic dysplasia • Neuronopathy, distal hereditary motor, autosomal dominant 8 • Scapuloperoneal spinal muscular atrophy • Charcot-Marie-Tooth disease axonal type 2C	Uncertain significance (Apr 27, 2017)
12-109783409-C-T		Brachyrachia (short spine dysplasia) • Scapuloperoneal spinal muscular atrophy • Spondylometaphyseal dysplasia, Kozlowski type • Charcot-Marie-Tooth disease axonal type 2C • Metatropic dysplasia • Neuronopathy, distal hereditary motor, autosomal dominant 8	Uncertain significance (Jan 13, 2018)
12-109783431-G-A		Spondylometaphyseal dysplasia, Kozlowski type • Brachyrachia (short spine dysplasia) • Metatropic dysplasia • Charcot-Marie-Tooth disease axonal type 2C • Scapuloperoneal spinal muscular atrophy • Neuronopathy, distal hereditary motor, autosomal dominant 8	Benign (Jan 13, 2018)
12-109783476-G-A		Scapuloperoneal spinal muscular atrophy • Neuronopathy, distal hereditary motor, autosomal dominant 8 • Metatropic dysplasia • Spondylometaphyseal dysplasia, Kozlowski type • Brachyrachia (short spine dysplasia) • Charcot-Marie-Tooth disease axonal type 2C	Uncertain significance (Jan 13, 2018)
12-109783522-G-A		Scapuloperoneal spinal muscular atrophy • Brachyrachia (short spine dysplasia) • Spondylometaphyseal dysplasia, Kozlowski type • Charcot-Marie-Tooth disease axonal type 2C • Metatropic dysplasia • Neuronopathy, distal hereditary motor, autosomal dominant 8	Uncertain significance (Jan 12, 2018)
12-109783538-G-C		Charcot-Marie-Tooth disease axonal type 2C • Spondylometaphyseal dysplasia, Kozlowski type • Neuronopathy, distal hereditary motor, autosomal dominant 8 • Scapuloperoneal spinal muscular atrophy • Brachyrachia (short spine dysplasia) • Metatropic dysplasia	Uncertain significance (Jan 13, 2018)
12-109783570-C-T		Metatropic dysplasia • Brachyrachia (short spine dysplasia) • Scapuloperoneal spinal muscular atrophy • Spondylometaphyseal dysplasia, Kozlowski type • Neuronopathy, distal hereditary motor, autosomal dominant 8 • Charcot-Marie-Tooth disease axonal type 2C	Uncertain significance (Jan 12, 2018)
12-109783613-T-G		TRPV4-related disorder	Likely benign (Jan 08, 2020)
12-109783619-C-T		Metatropic dysplasia • Charcot-Marie-Tooth disease axonal type 2C • Scapuloperoneal spinal muscular atrophy • Neuronopathy, distal hereditary motor, autosomal dominant 8 • Spondylometaphyseal dysplasia, Kozlowski type • Brachyrachia (short spine dysplasia)	Uncertain significance (Mar 02, 2018)
12-109783620-C-T		not specified	Likely benign (Nov 29, 2016)
12-109783622-T-C		Charcot-Marie-Tooth disease	Uncertain significance (-)
12-109783627-C-T		Charcot-Marie-Tooth disease • Charcot-Marie-Tooth disease axonal type 2C	Likely benign (Jun 19, 2023)
12-109783628-G-A		Charcot-Marie-Tooth disease axonal type 2C • Inborn genetic diseases	Conflicting classifications of pathogenicity (Jan 12, 2024)
12-109783632-C-A		Charcot-Marie-Tooth disease axonal type 2C	Uncertain significance (Dec 15, 2021)
12-109783632-C-T		Charcot-Marie-Tooth disease axonal type 2C • Spondylometaphyseal dysplasia, Kozlowski type • Brachyrachia (short spine dysplasia) • Scapuloperoneal spinal muscular atrophy • Neuronopathy, distal hereditary motor, autosomal dominant 8 • Metatropic dysplasia • Connective tissue disorder • Inborn genetic diseases	Conflicting classifications of pathogenicity (Jan 04, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TRPV4	protein_coding	protein_coding	ENST00000418703	15	50323

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.24e-16	0.196	125476	0	272	125748	0.00108

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.92	418	544	0.768	0.0000388	5674
Missense in Polyphen		135	200.35	0.67382		2201
Synonymous	0.0253	240	241	0.998	0.0000181	1801
Loss of Function	1.28	29	37.4	0.775	0.00000213	406

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00174	0.00174
Ashkenazi Jewish	0.0000993	0.0000992
East Asian	0.0000544	0.0000544
Finnish	0.00402	0.00403
European (Non-Finnish)	0.000980	0.000976
Middle Eastern	0.0000544	0.0000544
South Asian	0.000490	0.000490
Other	0.000653	0.000652

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Non-selective calcium permeant cation channel involved in osmotic sensitivity and mechanosensitivity. Activation by exposure to hypotonicity within the physiological range exhibits an outward rectification (PubMed:18826956, PubMed:18695040). Also activated by heat, low pH, citrate and phorbol esters (PubMed:16293632, PubMed:18826956, PubMed:18695040, PubMed:25256292, PubMed:20037586, PubMed:21964574). Increase of intracellular Ca(2+) potentiates currents. Channel activity seems to be regulated by a calmodulin-dependent mechanism with a negative feedback mechanism (PubMed:12724311, PubMed:18826956). Promotes cell-cell junction formation in skin keratinocytes and plays an important role in the formation and/or maintenance of functional intercellular barriers (By similarity). Acts as a regulator of intracellular Ca(2+) in synoviocytes (PubMed:19759329). 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 (PubMed:19759329). Together with PKD2, forms mechano- and thermosensitive channels in cilium (PubMed:18695040). Negatively regulates expression of PPARGC1A, UCP1, oxidative metabolism and respiration in adipocytes (By similarity). Regulates expression of chemokines and cytokines related to proinflammatory pathway in adipocytes (By similarity). Together with AQP5, controls regulatory volume decrease in salivary epithelial cells (By similarity). Required for normal development and maintenance of bone and cartilage (PubMed:26249260). {ECO:0000250|UniProtKB:Q9EPK8, ECO:0000269|PubMed:11025659, ECO:0000269|PubMed:12724311, ECO:0000269|PubMed:16293632, ECO:0000269|PubMed:18587396, ECO:0000269|PubMed:18695040, ECO:0000269|PubMed:18826956, ECO:0000269|PubMed:19759329, ECO:0000269|PubMed:20037586, ECO:0000269|PubMed:21964574, ECO:0000269|PubMed:25256292, ECO:0000269|PubMed:26249260}.; FUNCTION: Isoform 2: Lacks channel activity, due to impaired oligomerization and intracellular retention. {ECO:0000269|PubMed:16293632}.; FUNCTION: Isoform 6: Lacks channel activity, due to impaired oligomerization and intracellular retention. {ECO:0000269|PubMed:16293632}.
• Disease: DISEASE: Brachyolmia 3 (BCYM3) [MIM:113500]: A form of brachyolmia, a clinically and genetically heterogeneous skeletal dysplasia primarily affecting the spine and characterized by a short trunk, short stature, and platyspondyly. BCYM3 is an autosomal dominant form with severe scoliosis with or without kyphosis, and flattened irregular cervical vertebrae. {ECO:0000269|PubMed:18587396}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Spondylometaphyseal dysplasia Kozlowski type (SMDK) [MIM:184252]: A form of spondylometaphyseal dysplasia, a group of short stature disorders distinguished by abnormalities in the vertebrae and the metaphyses of the tubular bones. It is characterized by postnatal dwarfism, significant scoliosis and mild metaphyseal abnormalities in the pelvis. The vertebrae exhibit platyspondyly and overfaced pedicles. {ECO:0000269|PubMed:19232556, ECO:0000269|PubMed:20577006, ECO:0000269|PubMed:22702953}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Metatropic dysplasia (MTD) [MIM:156530]: 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. {ECO:0000269|PubMed:19232556, ECO:0000269|PubMed:20425821, ECO:0000269|PubMed:20577006, ECO:0000269|PubMed:22702953, ECO:0000269|PubMed:26249260, ECO:0000269|Ref.6}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Neuronopathy, distal hereditary motor, 8 (HMN8) [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. {ECO:0000269|PubMed:20037588, ECO:0000269|PubMed:22526352, ECO:0000269|PubMed:22702953}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Charcot-Marie-Tooth disease 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 degeneration in the absence of obvious myelin alterations, normal or slightly reduced nerve conduction velocities, and progressive distal muscle weakness and atrophy. {ECO:0000269|PubMed:20037586, ECO:0000269|PubMed:20037587, ECO:0000269|PubMed:20037588, ECO:0000269|PubMed:21115951, ECO:0000269|PubMed:21288981, ECO:0000269|PubMed:22702953, ECO:0000269|PubMed:25256292}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Scapuloperoneal spinal muscular atrophy (SPSMA) [MIM:181405]: 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. {ECO:0000269|PubMed:20037587, ECO:0000269|PubMed:22702953}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Spondyloepiphyseal dysplasia Maroteaux type (SEDM) [MIM:184095]: 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. {ECO:0000269|PubMed:20503319, ECO:0000269|PubMed:22702953}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Parastremmatic dwarfism (PSTD) [MIM:168400]: 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. {ECO:0000269|PubMed:20503319}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: 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. {ECO:0000269|PubMed:21964574}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Avascular necrosis of the femoral head, primary 2 (ANFH2) [MIM:617383]: A disease characterized by mechanical failure of the subchondral bone, and degeneration of the hip joint. It usually leads to destruction of the hip joint in the third to fifth decade of life. The clinical manifestations, such as pain on exertion, a limping gait, and a discrepancy in leg length, cause considerable disability. {ECO:0000269|PubMed:27330106}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Inflammatory mediator regulation of TRP channels - Homo sapiens (human);Fluid shear stress and atherosclerosis - Homo sapiens (human);Cellular senescence - Homo sapiens (human);ion channels and their functional role in vascular endothelium;Stimuli-sensing channels;Ion channel transport;Transport of small molecules;TRP channels (Consensus)

Recessive Scores

• pRec: 0.258

Intolerance Scores

• loftool: 0.0117
• rvis_EVS: -1.3
• rvis_percentile_EVS: 4.95

Haploinsufficiency Scores

• pHI: 0.133
• hipred: Y
• hipred_score: 0.637
• ghis: 0.590

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.718

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Trpv4
• Phenotype: hearing/vestibular/ear phenotype; 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); vision/eye phenotype; renal/urinary system phenotype; respiratory system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); muscle phenotype; homeostasis/metabolism phenotype; 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: trpv4
• Affected structure: atrioventricular valve
• Phenotype tag: abnormal
• Phenotype quality: shape

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;diet induced thermogenesis;calcium ion transport;cellular calcium ion homeostasis;cell volume homeostasis;actin filament organization;cell-cell junction assembly;positive regulation of cytosolic calcium ion concentration;osmosensory signaling pathway;response to mechanical stimulus;positive regulation of gene expression;positive regulation of macrophage chemotaxis;negative regulation of neuron projection development;vasopressin secretion;positive regulation of microtubule depolymerization;actin cytoskeleton reorganization;response to insulin;cellular response to heat;hyperosmotic salinity response;glucose homeostasis;positive regulation of vascular permeability;cortical microtubule organization;positive regulation of JNK cascade;microtubule polymerization;regulation of response to osmotic stress;positive regulation of inflammatory response;multicellular organismal water homeostasis;cartilage development involved in endochondral bone morphogenesis;positive regulation of ERK1 and ERK2 cascade;calcium ion import;calcium ion transmembrane transport;cellular response to osmotic stress;cellular hypotonic response;cellular hypotonic salinity response;positive regulation of monocyte chemotactic protein-1 production;positive regulation of macrophage inflammatory protein 1 alpha production;positive regulation of chemokine (C-C motif) ligand 5 production;energy homeostasis;blood vessel endothelial cell delamination;negative regulation of brown fat cell differentiation;signal transduction involved in regulation of aerobic respiration;positive regulation of chemokine (C-X-C motif) ligand 1 production;positive regulation of interleukin-6 secretion
• Cellular component: endoplasmic reticulum;cytoplasmic microtubule;plasma membrane;integral component of plasma membrane;adherens junction;focal adhesion;cilium;cell surface;integral component of membrane;apical plasma membrane;lamellipodium;filopodium;growth cone;cortical actin cytoskeleton;cytoplasmic vesicle;ruffle membrane
• Molecular function: actin binding;osmosensor activity;protein kinase C binding;ion channel activity;cation channel activity;calcium channel activity;protein binding;calmodulin binding;ATP binding;microtubule binding;lipid binding;stretch-activated, cation-selective, calcium channel activity;protein kinase binding;SH2 domain binding;identical protein binding;alpha-tubulin binding;metal ion binding;beta-tubulin binding;actin filament binding