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NM_021625.5(TRPV4):c.991A>T (p.Ile331Phe) AND Metatropic dysplasia

Germline classification:
Pathogenic (1 submission)
Last evaluated:
May 1, 2010
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV000005286.13

Allele description [Variation Report for NM_021625.5(TRPV4):c.991A>T (p.Ile331Phe)]

NM_021625.5(TRPV4):c.991A>T (p.Ile331Phe)

Gene:
TRPV4:transient receptor potential cation channel subfamily V member 4 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
12q24.11
Genomic location:
Preferred name:
NM_021625.5(TRPV4):c.991A>T (p.Ile331Phe)
HGVS:
  • NC_000012.12:g.109798775T>A
  • NG_017090.1:g.39633A>T
  • NM_001177428.1:c.850A>T
  • NM_001177431.1:c.889A>T
  • NM_001177433.1:c.850A>T
  • NM_021625.5:c.991A>TMANE SELECT
  • NM_147204.2:c.991A>T
  • NP_001170899.1:p.Ile284Phe
  • NP_001170902.1:p.Ile297Phe
  • NP_001170904.1:p.Ile284Phe
  • NP_067638.3:p.Ile331Phe
  • NP_671737.1:p.Ile331Phe
  • LRG_372t1:c.991A>T
  • LRG_372:g.39633A>T
  • LRG_372p1:p.Ile331Phe
  • NC_000012.11:g.110236580T>A
  • NM_021625.4:c.991A>T
  • Q9HBA0:p.Ile331Phe
Protein change:
I284F; ILE331PHE
Links:
UniProtKB: Q9HBA0#VAR_062331; OMIM: 605427.0006; dbSNP: rs121912636
NCBI 1000 Genomes Browser:
rs121912636
Molecular consequence:
  • NM_001177428.1:c.850A>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001177431.1:c.889A>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001177433.1:c.850A>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_021625.5:c.991A>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_147204.2:c.991A>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Metatropic dysplasia (MTD)
Synonyms:
Metatropic dwarfism; Metatropic dysplasia, nonlethal dominant
Identifiers:
MONDO: MONDO:0007986; MedGen: C0265281; Orphanet: 2635; OMIM: 156530

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000025464OMIM
no assertion criteria provided
Pathogenic
(May 1, 2010) 		germlineliterature only

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only

Citations

PubMed

Mutations in the gene encoding the calcium-permeable ion channel TRPV4 produce spondylometaphyseal dysplasia, Kozlowski type and metatropic dysplasia.

Krakow D, Vriens J, Camacho N, Luong P, Deixler H, Funari TL, Bacino CA, Irons MB, Holm IA, Sadler L, Okenfuss EB, Janssens A, Voets T, Rimoin DL, Lachman RS, Nilius B, Cohn DH.

Am J Hum Genet. 2009 Mar;84(3):307-15. doi: 10.1016/j.ajhg.2009.01.021. Epub 2009 Feb 19.

PubMed [citation]
PMID:
19232556
PMCID:
PMC2667978

Dominant TRPV4 mutations in nonlethal and lethal metatropic dysplasia.

Camacho N, Krakow D, Johnykutty S, Katzman PJ, Pepkowitz S, Vriens J, Nilius B, Boyce BF, Cohn DH.

Am J Med Genet A. 2010 May;152A(5):1169-77. doi: 10.1002/ajmg.a.33392.

PubMed [citation]
PMID:
20425821
PMCID:
PMC4169191

Details of each submission

From OMIM, SCV000025464.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (2)

Description

In a patient with metatropic dysplasia (MTD; 156530), Krakow et al. (2009) identified heterozygosity for a c.1080A-T transversion in exon 6 of the TRPV4 gene, resulting in an ile331-to-phe (I331F) substitution in the ankyrin-5 domain. The mutation occurs in a highly conserved residue and was not identified in the unaffected parents or in at least 214 control chromosomes.

Variant Function

By in vitro functional expression studies in HEK cells, Camacho et al. (2010) showed that the I331F-mutant protein had larger basal currents with constitutive open channels compared to wildtype. Treatment with agonists resulted in even larger calcium currents and increased intracellular calcium levels.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot providednot providednot providednot providednot provided

Last Updated: Oct 13, 2024