UniProtKB/Swiss-Prot P10636: Variant p.Arg723Trp

Microtubule-associated protein tau
Gene: MAPT
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Variant information Variant position:

723 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant:

LB/B 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 Arginine (R) to Tryptophan (W) at position 723 (R723W, p.Arg723Trp). 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 large size and aromatic (W) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score:

-3 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 FTD/Alzheimer disease; accelerates aggregation of tau into filaments; reduces tau phosphorylation in cells compared to both the wild-type and other mutant forms. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs63750424 [ dbSNP | Ensembl ]

Sequence information Variant position:

723 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:

TDHGAEIVYKSPVVSGDTSP R HLSNVSSTGSIDMVDSPQLA 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                         TDHGAEIVYKSPVVSGDTSPRHLSNVSSTGSIDMVDSPQLA

Gorilla                       TDHGAEIVYKSPVVSGDTSPRHLSNVSSTGSIDMVDSPQLA

Rhesus macaque                TDHGAEIVYKSPVVSGDTSPRHLSNVSSTGSIDMVDSPQLA

Chimpanzee                    TDHGAEIVYKSPVVSGDTSPRHLSNVSSTGSIDMVDSPQLA

Mouse                         TDHGAEIVYKSPVVSGDTSPRHLSNVSSTGSIDMVDSPQLA

Rat                           TDHGAEIVYKSPVVSGDTSPRHLSNVSSTGSIDMVDSPQLA

Bovine                        TDHGAEIVYKSPVVSGDTSPRHLSNVSSTGSIDMVDSPQLA

Goat                          TDHGAEIVYKSPVVSGDTSPRHLSNVSSTGSIDMVDSPQLA

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	2 – 758	Microtubule-associated protein tau
Region	715 – 734	Disordered
Compositional bias	719 – 734	Polar residues
Site	712 – 712	Not glycated
Modified residue	711 – 711	Phosphotyrosine
Modified residue	713 – 713	Phosphoserine; by CK1 and PDPK1
Modified residue	717 – 717	Phosphoserine; alternate
Modified residue	720 – 720	Phosphothreonine
Modified residue	721 – 721	Phosphoserine; by CK1 and PDPK1
Modified residue	726 – 726	Phosphoserine
Modified residue	733 – 733	Phosphoserine; by CaMK2 and TTBK1
Modified residue	739 – 739	Phosphoserine; by PDPK1 and TTBK1
Glycosylation	717 – 717	O-linked (GlcNAc) serine; alternate
Mutagenesis	713 – 713	S -> E. No association with plasma membrane.
Mutagenesis	721 – 721	S -> E. No association with plasma membrane.
Mutagenesis	726 – 726	S -> E. No association with plasma membrane.
Mutagenesis	730 – 730	S -> E. No association with plasma membrane.
Mutagenesis	739 – 739	S -> E. No association with plasma membrane.
Beta strand	723 – 732

Literature citations
Association of missense and 5'-splice-site mutations in tau with the inherited dementia FTDP-17.
Hutton M.; Lendon C.L.; Rizzu P.; Baker M.; Froelich S.; Houlden H.; Pickering-Brown S.; Chakraverty S.; Isaacs A.; Grover A.; Hackett J.; Adamson J.; Lincoln S.; Dickson D.; Davies P.; Petersen R.C.; Stevens M.; de Graaff E.; Wauters E.; van Baren J.; Hillebrand M.; Joosse M.; Kwon J.M.; Nowotny P.; Che L.K.; Norton J.; Morris J.C.; Reed L.A.; Trojanowski J.; Basun H.; Lannfelt L.; Neystat M.; Fahn S.; Dark F.; Tannenberg T.; Dodd P.R.; Hayward N.; Kwok J.B.J.; Schofield P.R.; Andreadis A.; Snowden J.; Craufurd D.; Neary D.; Owen F.; Oostra B.A.; Hardy J.; Goate A.; van Swieten J.; Mann D.; Lynch T.; Heutink P.;
Nature 393:702-705(1998)
Cited for: VARIANTS FTD VAL-589; LEU-618 AND TRP-723; High prevalence of mutations in the microtubule-associated protein tau in a population study of frontotemporal dementia in the Netherlands.
Rizzu P.; Van Swieten J.C.; Joosse M.; Hasegawa M.; Stevens M.; Tibben A.; Niermeijer M.F.; Hillebrand M.; Ravid R.; Oostra B.A.; Goedert M.; van Duijn C.M.; Heutink P.;
Am. J. Hum. Genet. 64:414-421(1999)
Cited for: VARIANTS FTD VAL-589; LYS-597 DEL; LEU-618 AND TRP-723; Accelerated filament formation from tau protein with specific FTDP-17 missense mutations.
Nacharaju P.; Lewis J.; Easson C.; Yen S.; Hackett J.; Hutton M.; Yen S.H.;
FEBS Lett. 447:195-199(1999)
Cited for: VARIANTS FTD LEU-618; MET-654 AND TRP-723; Effects of FTDP-17 mutations on the in vitro phosphorylation of tau by glycogen synthase kinase 3beta identified by mass spectrometry demonstrate certain mutations exert long-range conformational changes.
Connell J.W.; Gibb G.M.; Betts J.C.; Blackstock W.P.; Gallo J.-M.; Lovestone S.; Hutton M.; Anderton B.H.;
FEBS Lett. 493:40-44(2001)
Cited for: CHARACTERIZATION OF VARIANT FTD TRP-723; Early-onset, rapidly progressive familial tauopathy with R406W mutation.
Saito Y.; Geyer A.; Sasaki R.; Kuzuhara S.; Nanba E.; Miyasaka T.; Suzuki K.; Murayama S.;
Neurology 58:811-813(2002)
Cited for: VARIANT FTD TRP-723; Tau (MAPT) mutation arg406trp presenting clinically with Alzheimer disease does not share a common founder in western Europe.
Rademakers R.; Dermaut B.; Peeters K.; Cruts M.; Heutink P.; Goate A.; Van Broeckhoven C.;
Hum. Mutat. 22:409-411(2003)
Cited for: VARIANT FTD/ALZHEIMER DISEASE TRP-723; INVOLVEMENT IN ALZHEIMER DISEASE; Homozygous MAPT R406W mutation causing FTDP phenotype: A unique instance of a unique mutation.
Behnam M.; Ghorbani F.; Shin J.H.; Kim D.S.; Jang H.; Nouri N.; Sedghi M.; Salehi M.; Ansari B.; Basiri K.;
Gene 570:150-152(2015)
Cited for: VARIANT FTD/ALZHEIMER DISEASE TRP-723;

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.