Home  |  Contact

UniProtKB/Swiss-Prot O43426: Variant p.Arg219Gln

Synaptojanin-1
Gene: SYNJ1
Variant information

Variant position:  219
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 implicated in disease according to literature reports.
  • Polymorphism: Variants not reported to be implicated in disease.
  • Unclassified: Variants with uncertain implication in disease according to literature reports. Evidence against or in favor of a pathogenic role is limited and/or conflicting.

Residue change:  From Arginine (R) to Glutamine (Q) at position 219 (R219Q, p.Arg219Gln).
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 large size and basic (R) to medium size and polar (Q)
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

Involvement in disease:  Parkinson disease 20, early-onset (PARK20) [MIM:615530]: An early-onset form of Parkinson disease, a complex neurodegenerative disorder characterized by bradykinesia, resting tremor, muscular rigidity and postural instability, as well as by a clinically significant response to treatment with levodopa. The pathology involves the loss of dopaminergic neurons in the substantia nigra and the presence of Lewy bodies (intraneuronal accumulations of aggregated proteins), in surviving neurons in various areas of the brain. PARK20 is characterized by young adult-onset of parkinsonism. Additional features may include seizures, cognitive decline, abnormal eye movements, and dystonia. {ECO:0000269|PubMed:23804563, ECO:0000269|PubMed:23804577, ECO:0000269|PubMed:27496670}. Note=The disease is caused by mutations affecting the gene represented in this entry.
The name and a short description of the disease associated with the variant. For more information about the disease, the user can refer to OMIM, following the link provided after the disease acronym.

Variant description:  In PARK20; impairs the phosphatase activity of the enzyme toward phosphatidylinositol-3-phosphate and phosphatidylinositol-4-phosphate.
Any additional useful information about the variant.



Sequence information

Variant position:  219
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  1573
The length of the canonical sequence.

Location on the sequence:   AKACLISRLSCERAGTRFNV  R GTNDDGHVANFVETEQVVYL
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                         AKACLISRLSCERAGTRFNVRGTNDDGHVANFVETEQVVYL

Mouse                         AKACLISRLSCERAGTRFNVRGTNDDGHVANFVETEQVIYL

Rat                           AKACLISRLSCERAGTRFNVRGTNDDGHVANFVETEQVIYL

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 – 1573 Synaptojanin-1
Domain 119 – 442 SAC


Literature citations

The Sac1 domain of SYNJ1 identified mutated in a family with early-onset progressive Parkinsonism with generalized seizures.
Krebs C.E.; Karkheiran S.; Powell J.C.; Cao M.; Makarov V.; Darvish H.; Di Paolo G.; Walker R.H.; Shahidi G.A.; Buxbaum J.D.; De Camilli P.; Yue Z.; Paisan-Ruiz C.;
Hum. Mutat. 34:1200-1207(2013)
Cited for: VARIANT PARK20 GLN-219; CHARACTERIZATION OF VARIANT PARK20 GLN-219;

Mutation in the SYNJ1 gene associated with autosomal recessive, early-onset Parkinsonism.
Quadri M.; Fang M.; Picillo M.; Olgiati S.; Breedveld G.J.; Graafland J.; Wu B.; Xu F.; Erro R.; Amboni M.; Pappata S.; Quarantelli M.; Annesi G.; Quattrone A.; Chien H.F.; Barbosa E.R.; Oostra B.A.; Barone P.; Wang J.; Bonifati V.;
Hum. Mutat. 34:1208-1215(2013)
Cited for: VARIANTS PARK20 GLN-219 AND ARG-1383;

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.