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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q9HCF6: Variant p.Val1015Met

Transient receptor potential cation channel subfamily M member 3
Gene: TRPM3
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Variant information Variant position: help 1015 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: help LP/P [Disclaimer] The variants are classified into three categories: LP/P, LB/B and US.
  • LP/P: likely pathogenic or pathogenic.
  • LB/B: likely benign or benign.
  • US: uncertain significance
Residue change: help From Valine (V) to Methionine (M) at position 1015 (V1015M, p.Val1015Met). Indicates the amino acid change of the variant. The one-letter and three-letter codes for amino acids used in UniProtKB/Swiss-Prot are those adopted by the commission on Biochemical Nomenclature of the IUPAC-IUB.
Physico-chemical properties: help Similar physico-chemical property. Both residues are medium size and hydrophobic. The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help 1 The score within a Blosum matrix for the corresponding wild-type to variant amino acid change. The log-odds score measures the logarithm for the ratio of the likelihood of two amino acids appearing by chance. The Blosum62 substitution matrix is used. This substitution matrix contains scores for all possible exchanges of one amino acid with another:
  • Lowest score: -4 (low probability of substitution).
  • Highest score: 11 (high probability of substitution).
More information can be found on the following page
Variant description: help In NEDFSS; gain-of-function variant resulting in increased calcium ion transmembrane transport; basal channel activity is increased and the channel is more sensitive to stimulation by heat or the neurosteroid pregnenolone sulfate; the mutant channel can be down-regulated by the TRPM3 antagonist and anti-epileptic drug primidone. Any additional useful information about the variant.


Sequence information Variant position: help 1015 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 1732 The length of the canonical sequence.
Location on the sequence: help RVIYCVNIIYWYIRLLDIFG V NKYLGPYVMMIGKMMIDMMY The residue change on the sequence. Unless the variant is located at the beginning or at the end of the protein sequence, both residues upstream (20) and downstream (20) of the variant will be shown.
Residue conservation: help The multiple alignment of the region surrounding the variant against various orthologous sequences. 
Human                         RVIYCVNIIYWYIRLLDIFGVNKYLGPYVMMIGKMMIDMMY

Mouse                         RVIYCVNIIYWYIRLLDIFGVNKYLGPYVMMIGKMMIDMMY
Sequence annotation in neighborhood: help The regions or sites of interest surrounding the variant. In general the features listed are posttranslational modifications, binding sites, enzyme active sites, local secondary structure or other characteristics reported in the cited references. The "Sequence annotation in neighborhood" lines have a fixed format:
  • Type: the type of sequence feature.
  • Positions: endpoints of the sequence feature.
  • Description: contains additional information about the feature.
TypePositionsDescription
Chain 1 – 1732 Transient receptor potential cation channel subfamily M member 3
Topological domain 1014 – 1028 Cytoplasmic
Binding site 1017 – 1017
Binding site 1018 – 1018
Alternative sequence 409 – 1732 Missing. In isoform 12.



Literature citations
De novo substitutions of TRPM3 cause intellectual disability and epilepsy.
Dyment D.A.; Terhal P.A.; Rustad C.F.; Tveten K.; Griffith C.; Jayakar P.; Shinawi M.; Ellingwood S.; Smith R.; van Gassen K.; McWalter K.; Innes A.M.; Lines M.A.;
Eur. J. Hum. Genet. 27:1611-1618(2019)
Cited for: VARIANTS NEDFSS MET-1015 AND GLN-1115; INVOLVEMENT IN NEDFSS; Gain of channel function and modified gating properties in TRPM3 mutants causing intellectual disability and epilepsy.
Van Hoeymissen E.; Held K.; Nogueira Freitas A.C.; Janssens A.; Voets T.; Vriens J.;
Elife 9:0-0(2020)
Cited for: CHARACTERIZATION OF VARIANTS NEDFSS MET-1015 AND GLN-1115; Disease-associated mutations in the human TRPM3 render the channel overactive via two distinct mechanisms.
Zhao S.; Yudin Y.; Rohacs T.;
Elife 9:0-0(2020)
Cited for: FUNCTION; TRANSPORTER ACTIVITY; ACTIVITY REGULATION; CHARACTERIZATION OF VARIANTS NEDFSS MET-1015 AND GLN-1115; Confirmation and Expansion of the Phenotype Associated with the Recurrent p.Val837Met Variant in TRPM3.
de Sainte Agathe J.M.; Van-Gils J.; Lasseaux E.; Arveiler B.; Lacombe D.; Pfirrmann C.; Raclet V.; Gaston L.; Plaisant C.; Aupy J.; Trimouille A.;
Eur. J. Med. Genet. 63:103942-103942(2020)
Cited for: VARIANT NEDFSS MET-1015; Description of a novel patient with the TRPM3 recurrent p.Val837Met variant.
Gauthier L.W.; Chatron N.; Cabet S.; Labalme A.; Carneiro M.; Poirot I.; Delvert C.; Gleizal A.; Lesca G.; Putoux A.;
Eur. J. Med. Genet. 64:104320-104320(2021)
Cited for: VARIANT NEDFSS MET-1015; Phenotypic spectrum of the recurrent TRPM3 p.(Val837Met) substitution in seven individuals with global developmental delay and hypotonia.
Lines M.A.; Goldenberg P.; Wong A.; Srivastava S.; Bayat A.; Hove H.; Karstensen H.G.; Anyane-Yeboa K.; Liao J.; Jiang N.; May A.; Guzman E.; Morleo M.; D'Arrigo S.; Ciaccio C.; Pantaleoni C.; Castello R.; McKee S.; Ong J.; Zibdeh-Lough H.; Tran-Mau-Them F.; Gerasimenko A.; Heron D.; Keren B.; Margot H.; de Sainte Agathe J.M.; Burglen L.; Voets T.; Vriens J.; Innes A.M.; Dyment D.A.;
Am. J. Med. Genet. A 188:1667-1675(2022)
Cited for: VARIANT NEDFSS MET-1015;
Disclaimer: Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. They are not in any way intended to be used as a substitute for professional medical advice, diagnostic, treatment or care.