UniProtKB/Swiss-Prot Q96QK1: Variant p.Asp620Asn

Vacuolar protein sorting-associated protein 35
Gene: VPS35
Feedback?

Variant information Variant position:

620 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 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; decreases interaction with WASHC2C, FKBP15 and the WASH complex; impairs recruitment of the WASH complex to endosomes; shows reduced 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.
Other resources:

Links to websites of interest for the variant.

Variant rs188286943 [ dbSNP | Ensembl ]

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.
Location on the sequence:

ETVAYEFMSQAFSLYEDEIS D SKAQLAAITLIIGTFERMKC 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                         ETVAYEFMSQAFSLYEDEISDSKAQLAAITLIIGTFERMK-C

Mouse                         ETVAYEFMSQAFSLYEDEISDSKAQLAAITLIIGTFERMK-

Bovine                        ETVAYEFMSQAFSLYEDEISDSKAQLAAITLIIGTFERMK-

Slime mold                    --RVKELAIKALLIFQEDIADFKAQVMALQLLISTLNSLS-

Baker's yeast                 --ISYDFFSQAFTIFEESLSDSKTQLQALIYIAQSLQKTRS

Fission yeast                 --FAYEFFTQAFSIYEESVLDSELQYQQLLMIIGKLQKTR-

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.

Type	Positions	Description
Chain	1 – 796	Vacuolar protein sorting-associated protein 35
Region	438 – 796	Interaction with SLC11A2
Region	500 – 693	Interaction with IGF2R cytoplasmic domain

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)
Cited for: FUNCTION IN RETROGRADE TRANSPORT; INTERACTION WITH LRRK2; CHARACTERIZATION OF VARIANT PARK17 ASN-620; Retromer binding to FAM21 and the WASH complex is perturbed by the Parkinson disease-linked VPS35(D620N) mutation.
McGough I.J.; Steinberg F.; Jia D.; Barbuti P.A.; McMillan K.J.; Heesom K.J.; Whone A.L.; Caldwell M.A.; Billadeau D.D.; Rosen M.K.; Cullen P.J.;
Curr. Biol. 24:1670-1676(2014)
Cited for: FUNCTION; INTERACTION WITH WASHC2C; CHARACTERIZATION OF VARIANT PARK17 ASN-620; Mutation in VPS35 associated with Parkinson's disease impairs WASH complex association and inhibits autophagy.
Zavodszky E.; Seaman M.N.; Moreau K.; Jimenez-Sanchez M.; Breusegem S.Y.; Harbour M.E.; Rubinsztein D.C.;
Nat. Commun. 5:3828-3828(2014)
Cited for: FUNCTION; CHARACTERIZATION OF VARIANT PARK17 ASN-620; 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.