Mutations

MAPT T504T

Other Names: 5‛-splice-site (Thr2Thr)

Overview

Pathogenicity: Frontotemporal Dementia : Benign
Clinical Phenotype: None
Position: (GRCh38/hg38):Chr17:45993928 T>C
Position: (GRCh37/hg19):Chr17:44071294 T>C
dbSNP ID: rs62063845
Coding/Non-Coding: Coding
DNA Change: Substitution
Expected RNA Consequence: Substitution
Expected Protein Consequence: Silent
Codon Change: ACT to ACC
Reference Isoform: Tau Isoform PNS Tau (758 aa)
Genomic Region: Exon 8

Findings

This variant resides in exon 8, which is excluded from the six major tau isoforms expressed in the human brain, including Tau-F, the isoform most commonly used as a reference. Exon 8 is included in longer tau isoforms PNS-Tau and Tau-G. The numbering of this variant (504) is thus according to amino acid position in these longer isoforms. This variant is also referred to in the literature as 5‛-splice-site (Thr2Thr).

The site of this polymorphism has been implicated in risk of progressive supranuclear palsy (Higgins et al., 1999; Higgins et al., 2000). It is one of a series of polymorphic sites within the 17q21 region that together constitute an extended haplotype (for review, see Pittman et al., 2006) .

Neuropathology

Unknown.

Biological Effect

Unknown.

Last Updated: 31 Dec 2012

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References

Paper Citations

  1. Higgins JJ, Adler RL, Loveless JM. Mutational analysis of the tau gene in progressive supranuclear palsy. Neurology. 1999 Oct 22;53(7):1421-4. PubMed.
  2. Higgins JJ, Golbe LI, De Biase A, Jankovic J, Factor SA, Adler RL. An extended 5'-tau susceptibility haplotype in progressive supranuclear palsy. Neurology. 2000 Nov 14;55(9):1364-7. PubMed.
  3. Pittman AM, Fung HC, de Silva R. Untangling the tau gene association with neurodegenerative disorders. Hum Mol Genet. 2006 Oct 15;15 Spec No 2:R188-95. PubMed.

Further Reading

Papers

  1. Ingelson M, Fabre SF, Lilius L, Andersen C, Viitanen M, Almkvist O, Wahlund LO, Lannfelt L. Increased risk for frontotemporal dementia through interaction between tau polymorphisms and apolipoprotein E epsilon4. Neuroreport. 2001 Apr 17;12(5):905-9. PubMed.
  2. Kowalska A, Asada T, Arima K, Kumakiri C, Kozubski W, Takahashi K, Tabira T. Genetic analysis in patients with familial and sporadic frontotemporal dementia: two tau mutations in only familial cases and no association with apolipoprotein epsilon4. Dement Geriatr Cogn Disord. 2001;12(6):387-92. PubMed.

Learn More

  1. Alzheimer Disease & Frontotemporal Dementia Mutation Database

Protein Diagram

Primary Papers

  1. Higgins JJ, Adler RL, Loveless JM. Mutational analysis of the tau gene in progressive supranuclear palsy. Neurology. 1999 Oct 22;53(7):1421-4. PubMed.

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