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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q8N6I4: Variant p.Arg39Trp

Lysosomal enzyme trafficking factor
Gene: LYSET
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Variant information Variant position: help 39 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 Arginine (R) to Tryptophan (W) at position 39 (R39W, p.Arg39Trp). 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 Change from large size and basic (R) to large size and aromatic (W) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help -3 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 DMAN; lower protein expression. Fails to rescue the lysosomal trafficking defect in LYSET-deficient cells. Severe reduction of interaction with GNPTAB. Any additional useful information about the variant.


Sequence information Variant position: help 39 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 163 The length of the canonical sequence.
Location on the sequence: help GTGRFSGPLHRAWRMMNFRQ R MGWIGVGLYLLASAAAFYYV 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                         GTGRFSGPLHRAWRMMNFRQRMGWIGVGLYLLASAAAFYYV

Mouse                         GTGRFSGPLHRAWRMMNFRQRMGWIGVGLYLLASAAAFYYV

Rat                           GTARFSGPLHRAWRMMNFRQRMGWIGVGLYLLASAAAFYYV

Pig                           GTGRFSGPLHRAWRMMNFRQRMGWIGVGLYLLASAAAFYYV

Bovine                        GTGRFSGPLHRAWRMMNFRQRMGWIGVGLYLLASAAAFYYV

Chicken                       --------------MMNFRQRMGWIGVGLYLLASAAAFYYV

Xenopus tropicalis            AMCSILSA-GRAWRMMNFRQRMGWIGVSLYLFVSAAAFYYV

Zebrafish                     --------------MMNFRQRMGWIGVGLYLLASVAAVYYI
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 – 163 Lysosomal enzyme trafficking factor



Literature citations
Biallelic TMEM251 variants in patients with severe skeletal dysplasia and extreme short stature.
Ain N.U.; Muhammad N.; Dianatpour M.; Baroncelli M.; Iqbal M.; Fard M.A.F.; Bukhari I.; Ahmed S.; Hajipour M.; Tabatabaie Z.; Foroutan H.; Nilsson O.; Faghihi M.A.; Makitie O.; Naz S.;
Hum. Mutat. 42:89-101(2021)
Cited for: SUBCELLULAR LOCATION; INVOLVEMENT IN DMAN; VARIANTS DMAN TRP-39 AND 66-TYR--THR-163 DEL; Lysosomal enzyme trafficking factor LYSET enables nutritional usage of extracellular proteins.
Pechincha C.; Groessl S.; Kalis R.; de Almeida M.; Zanotti A.; Wittmann M.; Schneider M.; de Campos R.P.; Rieser S.; Brandstetter M.; Schleiffer A.; Mueller-Decker K.; Helm D.; Jabs S.; Haselbach D.; Lemberg M.K.; Zuber J.; Palm W.;
Science 2022:eabn5637-eabn5637(2022)
Cited for: FUNCTION; INTERACTION WITH GNPTAB; CHARACTERIZATION OF VARIANTS DMAN TRP-39 AND 66-TYR--THR-163 DEL; The human disease gene LYSET is essential for lysosomal enzyme transport and viral infection.
Richards C.M.; Jabs S.; Qiao W.; Varanese L.D.; Schweizer M.; Mosen P.R.; Riley N.M.; Kluessendorf M.; Zengel J.R.; Flynn R.A.; Rustagi A.; Widen J.C.; Peters C.E.; Ooi Y.S.; Xie X.; Shi P.Y.; Bartenschlager R.; Puschnik A.S.; Bogyo M.; Bertozzi C.R.; Blish C.A.; Winter D.; Nagamine C.M.; Braulke T.; Carette J.E.;
Science 2022:eabn5648-eabn5648(2022)
Cited for: FUNCTION; SUBCELLULAR LOCATION; INTERACTION WITH GNPTAB; CHARACTERIZATION OF VARIANT DMAN TRP-39; MUTAGENESIS OF THR-86; ILE-136 AND LYS-150; FUNCTION (MICROBIAL INFECTION);
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.