Mutations

MAPT T504T

Overview

Pathogenicity: Frontotemporal Dementia : Not Pathogenic
Clinical Phenotype: None
Reference Assembly: GRCh37/hg19
Position: Chr17:44071294 T>C
dbSNP ID: rs62063845
Coding/Non-Coding: Coding
Mutation Type: Point, Silent
Codon Change: ACT to ACC
Reference Isoform: Tau Isoform Tau-G (776 aa)
Genomic Region: Exon 8

Findings

This variant resides in exon 8, which is excluded from the majority of tau isoforms. Exon 8 is included in transcripts for the longest tau isoform, which has 776 amino acids and is known as isoform 6  or Tau-G P10636-9. The numbering of this variant (504) is thus according to amino acid position in this isoform, rather than isoform 441. 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.

Comments

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References

Paper Citations

  1. . Mutational analysis of the tau gene in progressive supranuclear palsy. Neurology. 1999 Oct 22;53(7):1421-4. PubMed.
  2. . An extended 5'-tau susceptibility haplotype in progressive supranuclear palsy. Neurology. 2000 Nov 14;55(9):1364-7. PubMed.
  3. . Untangling the tau gene association with neurodegenerative disorders. Hum Mol Genet. 2006 Oct 15;15 Spec No 2:R188-95. PubMed.

External Citations

  1. isoform 6 
  2. Tau-G P10636-9

Further Reading

Papers

  1. . Increased risk for frontotemporal dementia through interaction between tau polymorphisms and apolipoprotein E epsilon4. Neuroreport. 2001 Apr 17;12(5):905-9. PubMed.
  2. . 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 Nov-Dec;12(6):387-92. PubMed.

Learn More

  1. Alzheimer Disease & Frontotemporal Dementia Mutation Database

Protein Diagram

Primary Papers

  1. . Mutational analysis of the tau gene in progressive supranuclear palsy. Neurology. 1999 Oct 22;53(7):1421-4. PubMed.

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