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UniProtKB/Swiss-Prot Q9GZU1: Variant p.Val446Leu

Mucolipin-1
Gene: MCOLN1
Variant information

Variant position:  446
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  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:  From Valine (V) to Leucine (L) at position 446 (V446L, p.Val446Leu).
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:  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:  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:  In ML4; does not affect channel activity; affects channel inhibition by low pH; impairs Fe(2+) permeability.
Any additional useful information about the variant.

Other resources:  
Links to websites of interest for the variant.



Sequence information

Variant position:  446
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  580
The length of the canonical sequence.

Location on the sequence:   MRFCCCVAVIYLGYCFCGWI  V LGPYHVKFRSLSMVSECLFS
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: 
The multiple alignment of the region surrounding the variant against various orthologous sequences.

Human                         MRFCCCVAVIYLGYCFCGWIVLGPYHVKFRSLSMVSECLFS

Mouse                         MRFCCCVAVIYLGYCFCGWIVLGPYHVKFRSLSMVSECLFS

Sequence annotation in neighborhood:  
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 – 580 Mucolipin-1
Transmembrane 428 – 448 Helical; Name=5
Mutagenesis 432 – 432 V -> P. Mediates localization to the plasma membrane and strong inwardly rectifying current.
Helix 417 – 447


Literature citations

Mucolipidosis type IV is caused by mutations in a gene encoding a novel transient receptor potential channel.
Sun M.; Goldin E.; Stahl S.; Falardeau J.L.; Kennedy J.C.; Acierno J.S. Jr.; Bove C.; Kaneski C.R.; Nagle J.; Bromley M.C.; Colman M.; Schiffmann R.; Slaugenhaupt S.A.;
Hum. Mol. Genet. 9:2471-2478(2000)
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA]; TISSUE SPECIFICITY; VARIANTS ML4 TYR-362; PHE-408 DEL AND LEU-446;

Molecular pathophysiology of mucolipidosis type IV: pH dysregulation of the mucolipin-1 cation channel.
Raychowdhury M.K.; Gonzalez-Perrett S.; Montalbetti N.; Timpanaro G.A.; Chasan B.; Goldmann W.H.; Stahl S.; Cooney A.; Goldin E.; Cantiello H.F.;
Hum. Mol. Genet. 13:617-627(2004)
Cited for: FUNCTIONAL CHARACTERIZATION; SUBUNIT; CHARACTERIZATION OF VARIANTS ML4 TYR-362; PHE-408 DEL AND LEU-446;

The type IV mucolipidosis-associated protein TRPML1 is an endolysosomal iron release channel.
Dong X.P.; Cheng X.; Mills E.; Delling M.; Wang F.; Kurz T.; Xu H.;
Nature 455:992-996(2008)
Cited for: FUNCTION; MUTAGENESIS OF VAL-432; CHARACTERIZATION OF VARIANTS ML4 PRO-232; TYR-362; CYS-403 AND LEU-446;

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.