UniProtKB/Swiss-Prot P10636: Variant p.Asn596Lys

Microtubule-associated protein tau
Gene: MAPT
Chromosomal location: 17q21.1
Variant information

Variant position:  596
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 Asparagine (N) to Lysine (K) at position 596 (N596K, p.Asn596Lys).
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 polar (N) to large size and basic (K)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  0
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:  Frontotemporal dementia (FTD) [MIM:600274]: A form of dementia characterized by pathologic finding of frontotemporal lobar degeneration, presenile dementia with behavioral changes, deterioration of cognitive capacities and loss of memory. In some cases, parkinsonian symptoms are prominent. Neuropathological changes include frontotemporal atrophy often associated with atrophy of the basal ganglia, substantia nigra, amygdala. In most cases, protein tau deposits are found in glial cells and/or neurons. 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 FTD; with parkinsonism.
Any additional useful information about the variant.



Sequence information

Variant position:  596
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  758
The length of the canonical sequence.

Location on the sequence:   KIGSTENLKHQPGGGKVQII  N KKLDLSNVQSKCGSKDNIKH
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                         KIGSTENLKHQPGGGKVQIINKKLDLSNVQSKCGSKDNIKH

Gorilla                       KIGSTENLKHQPGGGKVQIINKKLDLSNVQSKCGSKDNIKH

Rhesus macaque                KIGSTENLKHQPGGGKVQIINKKLDLSNVQSKCGSKDNIKH

Chimpanzee                    KIGSTENLKHQPGGGKVQIINKKLDLSNVQSKCGSKDNIKH

Mouse                         KIGSTENLKHQPGGGKVQIINKKLDLSNVQSKCGSKDNIKH

Rat                           KIGSTENLKHQPGGGKVQIINKKLDLSNVQSKCGSKDNIKH

Bovine                        KIGSTENLKHQPGGGKVQIINKKLDLSNVQSKCGSKDNIKH

Goat                          KIGSTENLKHQPGGGKVQIINKKLDLSNVQSKCGSKDNIKH

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 2 – 758 Microtubule-associated protein tau
Repeat 592 – 622 Tau/MAP 2
Site 584 – 584 Not glycated
Site 591 – 591 Not glycated
Site 607 – 607 Not glycated
Site 611 – 611 Not glycated
Site 615 – 615 Not glycated
Modified residue 579 – 579 Phosphoserine; by MARK1, BRSK1, BRSK2 and PHK
Modified residue 596 – 596 Deamidated asparagine; in tau and PHF-tau; partial
Modified residue 602 – 602 Phosphoserine; by PHK
Modified residue 606 – 606 Phosphoserine; by PHK
Modified residue 610 – 610 Phosphoserine; by MARK1; in PHF-tau
Glycosylation 576 – 576 N-linked (Glc) (glycation); in PHF-tau; in vitro
Glycosylation 597 – 597 N-linked (Glc) (glycation); in PHF-tau; in vitro
Glycosylation 598 – 598 N-linked (Glc) (glycation); in PHF-tau; in vitro
Alternative sequence 592 – 622 Missing. In isoform Tau-A, isoform Tau-B, isoform Tau-C and isoform Fetal-tau.
Mutagenesis 579 – 579 S -> A. 8% decrease in microtubule-binding after in vitro phosphorylation of mutant protein.


Literature citations

Pathogenic implications of mutations in the tau gene in pallido-ponto-nigral degeneration and related neurodegenerative disorders linked to chromosome 17.
Clark L.N.; Poorkaj P.; Wszolek Z.; Geschwind D.H.; Nasreddine Z.S.; Miller B.; Li D.; Payami H.; Awert F.; Markopoulou K.; Andreadis A.; D'Souza I.; Lee V.M.-Y.; Reed L.; Trojanowski J.Q.; Zhukareva V.; Bird T.; Schellenberg G.; Wilhelmsen K.C.;
Proc. Natl. Acad. Sci. U.S.A. 95:13103-13107(1998)
Cited for: VARIANTS FTD LYS-596 AND LEU-618;

A mutation at codon 279 (N279K) in exon 10 of the Tau gene causes a tauopathy with dementia and supranuclear palsy.
Delisle M.-B.; Murrell J.R.; Richardson R.; Trofatter J.A.; Rascol O.; Soulages X.; Mohr M.; Calvas P.; Ghetti B.;
Acta Neuropathol. 98:62-77(1999)
Cited for: VARIANT PPND LYS-596;

A mutation in the microtubule-associated protein tau in pallido-nigro-luysian degeneration.
Yasuda M.; Kawamata T.; Komure O.; Kuno S.; D'Souza I.; Poorkaj P.; Kawai J.; Tanimukai S.; Yamamoto Y.; Hasegawa H.; Sasahara M.; Hazama F.; Schellenberg G.D.; Tanaka C.;
Neurology 53:864-868(1999)
Cited for: VARIANT FTD LYS-596;

Two brothers with frontotemporal dementia and parkinsonism with an N279K mutation of the tau gene.
Arima K.; Kowalska A.; Hasegawa M.; Mukoyama M.; Watanabe R.; Kawai M.; Takahashi K.; Iwatsubo T.; Tabira T.; Sunohara N.;
Neurology 54:1787-1795(2000)
Cited for: VARIANT FTD LYS-596;

Clinical and genetic studies of families with the tau N279K mutation (FTDP-17).
Tsuboi Y.; Baker M.; Hutton M.L.; Uitti R.J.; Rascol O.; Delisle M.-B.; Soulages X.; Murrell J.R.; Ghetti B.; Yasuda M.; Komure O.; Kuno S.; Arima K.; Sunohara N.; Kobayashi T.; Mizuno Y.; Wszolek Z.K.;
Neurology 59:1791-1793(2002)
Cited for: VARIANT FTD LYS-596;

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.