Expasy logo

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P49754: Variant p.Ser285Pro

Vacuolar protein sorting-associated protein 41 homolog
Gene: VPS41
Feedback?
Variant information Variant position: help 285 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 Serine (S) to Proline (P) at position 285 (S285P, p.Ser285Pro). 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 small size and polar (S) to medium size and hydrophobic (P) 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 SCAR29; decreased protein abundance; cannot form a functional HOPS complex; causes a kinetic defect in the endosome-lysosome fusion process. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 285 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 854 The length of the canonical sequence.
Location on the sequence: help FETEFYISGLAPLCDQLVVL S YVKEISEKTEREYCARPRLD 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                         FETEFYISGLAPL-CD-----QLVVLSYVKEISE--------KTEREYCAR----------PRLD

Mouse                         FETEFYISGLAPL-CD-----QLVVLSYVKEVSE-------

Zebrafish                     FETEFFISGLAPL-AD-----QLVTLYYVKENSD-------

Caenorhabditis elegans        FHVSMFICGISYIPESGIDNMELFLVGLQLE----------

Drosophila                    FQTTFYVCGLAPLSAK-----QLVVLGF-------------

Baker's yeast                 FTVSMLITGLASFKDD-----QLLCLGFDIDIEEEATIDED

Fission yeast                 LEIDSIVSGVLML-GF-----NILTLAYIANVED-------
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 – 854 Vacuolar protein sorting-associated protein 41 homolog
Region 1 – 540 Interaction with ARL8B



Literature citations
Bi-allelic variants in HOPS complex subunit VPS41 cause cerebellar ataxia and abnormal membrane trafficking.
Sanderson L.E.; Lanko K.; Alsagob M.; Almass R.; Al-Ahmadi N.; Najafi M.; Al-Muhaizea M.A.; Alzaidan H.; AlDhalaan H.; Perenthaler E.; van der Linde H.C.; Nikoncuk A.; Kuehn N.A.; Antony D.; Owaidah T.M.; Raskin S.; Vieira L.G.D.R.; Mombach R.; Ahangari N.; Silveira T.R.D.; Ameziane N.; Rolfs A.; Alharbi A.; Sabbagh R.M.; AlAhmadi K.; Alawam B.; Ghebeh H.; AlHargan A.; Albader A.A.; Binhumaid F.S.; Goljan E.; Monies D.; Mustafa O.M.; Aldosary M.; AlBakheet A.; Alyounes B.; Almutairi F.; Al-Odaib A.; Aksoy D.B.; Basak A.N.; Palvadeau R.; Trabzuni D.; Rosenfeld J.A.; Karimiani E.G.; Meyer B.F.; Karakas B.; Al-Mohanna F.; Arold S.T.; Colak D.; Maroofian R.; Houlden H.; Bertoli-Avella A.M.; Schmidts M.; Barakat T.S.; van Ham T.J.; Kaya N.;
Brain 144:769-780(2021)
Cited for: INVOLVEMENT IN SCAR29; VARIANTS SCAR29 GLY-13; PRO-285; PRO-633 AND PHE-791; CHARACTERIZATION OF VARIANTS SCAR29 GLY-13; PRO-285; PRO-633 AND PHE-791; TISSUE SPECIFICITY;
Neurodegenerative VPS41 variants inhibit HOPS function and mTORC1-dependent TFEB/TFE3 regulation.
van der Welle R.E.N.; Jobling R.; Burns C.; Sanza P.; van der Beek J.A.; Fasano A.; Chen L.; Zwartkruis F.J.; Zwakenberg S.; Griffin E.F.; Ten Brink C.; Veenendaal T.; Liv N.; van Ravenswaaij-Arts C.M.A.; Lemmink H.H.; Pfundt R.; Blaser S.; Sepulveda C.; Lozano A.M.; Yoon G.; Santiago-Sim T.; Asensio C.S.; Caldwell G.A.; Caldwell K.A.; Chitayat D.; Klumperman J.;
EMBO Mol. Med. 13:e13258-e13258(2021)
Cited for: VARIANTS SCAR29 662-ARG--LYS-854 DEL AND PRO-285; CHARACTERIZATION OF VARIANTS SCAR29 662-ARG--LYS-854 DEL AND PRO-285; FUNCTION; SUBUNIT; SUBCELLULAR LOCATION;
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.