UniProtKB/Swiss-Prot Q5S007: Variant p.Ile2020Thr

Leucine-rich repeat serine/threonine-protein kinase 2
Gene: LRRK2
Chromosomal location: 12q12
Variant information

Variant position:  2020
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 Isoleucine (I) to Threonine (T) at position 2020 (I2020T, p.Ile2020Thr).
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 hydrophobic (I) to medium size and polar (T)
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 PARK8; significant increase in autophosphorylation of about 40% in comparison to wild-type protein in vitro; 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.



Sequence information

Variant position:  2020
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  2527
The length of the canonical sequence.

Location on the sequence:   VLLFTLYPNAAIIAKIADYG  I AQYCCRMGIKTSEGTPGFRA
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                         VLLFTLYPNAAIIAKIADYGIAQYCCRMGIKTSEGTPGFRA

Mouse                         VLLFTLYPNAAIIAKIADYGIAQYCCRMGIKTSEGTPGFRA

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 – 2527 Leucine-rich repeat serine/threonine-protein kinase 2
Domain 1879 – 2138 Protein kinase


Literature citations

Mutations in LRRK2 cause autosomal-dominant parkinsonism with pleomorphic pathology.
Zimprich A.; Biskup S.; Leitner P.; Lichtner P.; Farrer M.; Lincoln S.J.; Kachergus J.M.; Hulihan M.M.; Uitti R.J.; Calne D.B.; Stoessl A.J.; Pfeiffer R.F.; Patenge N.; Carballo Carbajal I.; Vieregge P.; Asmus F.; Mueller-Myhsok B.; Dickson D.W.; Meitinger T.; Strom T.M.; Wszolek Z.K.; Gasser T.;
Neuron 44:601-607(2004)
Cited for: NUCLEOTIDE SEQUENCE [MRNA]; TISSUE SPECIFICITY; VARIANTS PARK8 VAL-1122; CYS-1441; CYS-1699 AND THR-2020;

The Parkinson disease causing LRRK2 mutation I2020T is associated with increased kinase activity.
Gloeckner C.J.; Kinkl N.; Schumacher A.; Braun R.J.; O'Neill E.; Meitinger T.; Kolch W.; Prokisch H.; Ueffing M.;
Hum. Mol. Genet. 15:223-232(2006)
Cited for: SUBCELLULAR LOCATION; CHARACTERIZATION OF VARIANT PARK8 THR-2020;

The familial Parkinsonism gene LRRK2 regulates neurite process morphology.
MacLeod D.; Dowman J.; Hammond R.; Leete T.; Inoue K.; Abeliovich A.;
Neuron 52:587-593(2006)
Cited for: FUNCTION; CHARACTERIZATION OF VARIANTS PARK8 GLY-1441; CYS-1699; SER-2019 AND THR-2020; VARIANT MET-1906;

An LRRK2 mutation as a cause for the parkinsonism in the original PARK8 family.
Funayama M.; Hasegawa K.; Ohta E.; Kawashima N.; Komiyama M.; Kowa H.; Tsuji S.; Obata F.;
Ann. Neurol. 57:918-921(2005)
Cited for: VARIANT PARK8 THR-2020;

Type and frequency of mutations in the LRRK2 gene in familial and sporadic Parkinson's disease.
Berg D.; Schweitzer K.; Leitner P.; Zimprich A.; Lichtner P.; Belcredi P.; Bruessel T.; Schulte C.; Maass S.; Naegele T.;
Brain 128:3000-3011(2005)
Cited for: VARIANTS PARK8 MET-793; ARG-930; CYS-1096 THR-1228; SER-2019 AND THR-2020; VARIANT LYS-551;

Lrrk2 pathogenic substitutions in Parkinson's disease.
Mata I.F.; Kachergus J.M.; Taylor J.P.; Lincoln S.; Aasly J.; Lynch T.; Hulihan M.M.; Cobb S.A.; Wu R.-M.; Lu C.-S.; Lahoz C.; Wszolek Z.K.; Farrer M.J.;
Neurogenetics 6:171-177(2005)
Cited for: VARIANTS PARK8 CYS-1441; GLY-1441; HIS-1441; GLN-1514; SER-1542; GLU-1598; CYS-1699; THR-1869; THR-2012; SER-2019; THR-2020 AND ARG-2385; VARIANTS PRO-119; LYS-551; VAL-723; MET-793; VAL-1122; ALA-1262; HIS-1398; PRO-1628; THR-1646; THR-1647; ASP-2081; LEU-2119; ILE-2261 AND THR-2397;

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.