UniProtKB/Swiss-Prot Q96QK1: Variant p.Asp620Asn

Vacuolar protein sorting-associated protein 35
Gene: VPS35
Chromosomal location: 16q13-q21
Variant information

Variant position:  620
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Disease [Disclaimer]
The variants are classified into three categories: Disease, Polymorphism and Unclassified.
  • Disease: Variants have been found in patients and disease-association is reported in literature. However, this classification is not a definitive assessment of variant pathogenicity.
  • Polymorphism: No disease-association has been reported.
  • Unclassified: Variants have been found in patients but disease-association remains unclear.

Residue change:  From Aspartate (D) to Asparagine (N) at position 620 (D620N, p.Asp620Asn).
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:  Change from medium size and acidic (D) to medium size and polar (N)
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 PARK17; shows reduce retrograde transport of selective cargo between lysosomes and the Golgi apparatus; shows a progressive reduction in neurite length and branching.
Any additional useful information about the variant.

Sequence information

Variant position:  620
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  796
The length of the canonical sequence.

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.







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.

Chain 1 – 796 Vacuolar protein sorting-associated protein 35

Literature citations

RAB7L1 interacts with LRRK2 to modify intraneuronal protein sorting and Parkinson's disease risk.
MacLeod D.A.; Rhinn H.; Kuwahara T.; Zolin A.; Di Paolo G.; McCabe B.D.; MacCabe B.D.; Marder K.S.; Honig L.S.; Clark L.N.; Small S.A.; Abeliovich A.;
Neuron 77:425-439(2013)

VPS35 mutations in Parkinson disease.
Vilarino-Guell C.; Wider C.; Ross O.A.; Dachsel J.C.; Kachergus J.M.; Lincoln S.J.; Soto-Ortolaza A.I.; Cobb S.A.; Wilhoite G.J.; Bacon J.A.; Behrouz B.; Melrose H.L.; Hentati E.; Puschmann A.; Evans D.M.; Conibear E.; Wasserman W.W.; Aasly J.O.; Burkhard P.R.; Djaldetti R.; Ghika J.; Hentati F.; Krygowska-Wajs A.; Lynch T.; Melamed E.; Rajput A.; Rajput A.H.; Solida A.; Wu R.M.; Uitti R.J.; Wszolek Z.K.; Vingerhoets F.; Farrer M.J.;
Am. J. Hum. Genet. 89:162-167(2011)
Cited for: VARIANT PARK17 ASN-620; VARIANTS SER-316 AND VAL-737;

A mutation in VPS35, encoding a subunit of the retromer complex, causes late-onset Parkinson disease.
Zimprich A.; Benet-Pages A.; Struhal W.; Graf E.; Eck S.H.; Offman M.N.; Haubenberger D.; Spielberger S.; Schulte E.C.; Lichtner P.; Rossle S.C.; Klopp N.; Wolf E.; Seppi K.; Pirker W.; Reinthaler E.; Harutyunyan A.; Kralovics R.; Peters A.; Zimprich F.; Brucke T.; Poewe W.; Auff E.; Trenkwalder C.; Rost B.; Ransmayr G.; Winkelmann J.; Meitinger T.; Strom T.M.;
Am. J. Hum. Genet. 89:168-175(2011)
Cited for: VARIANT PARK17 ASN-620; VARIANTS SER-51; ILE-57; ARG-82; MET-241; TRP-524 AND MET-774;

Identification of VPS35 mutations replicated in French families with Parkinson disease.
Lesage S.; Condroyer C.; Klebe S.; Honore A.; Tison F.; Brefel-Courbon C.; Durr A.; Brice A.;
Neurology 78:1449-1450(2012)
Cited for: VARIANT PARK17 ASN-620;

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.