Mutations

MAPT R370W

Overview

Pathogenicity: Frontotemporal Dementia : Benign
Clinical Phenotype: None
Reference Assembly: GRCh37/hg19
Position: Chr17:44061278 C>T
dbSNP ID: rs17651549
Coding/Non-Coding: Coding
DNA Change: Substitution
Expected RNA Consequence: Substitution
Expected Protein Consequence: Missense
Codon Change: CGG to TGG
Reference Isoform: Tau Isoform PNS Tau (758 aa)
Genomic Region: Exon 4a

Findings

This variant in exon 4a of MAPT is thought to be benign. Originally described according to nucleotide position in exon 4a (735), this variant was associated with a haplotype more common in controls than Alzheimer's disease patients (Lilius et al., 1999). Exon 4a is excluded from most tau isoforms, but is present in a large isoform known as PNS-tau which is expressed primarily in the peripheral nervous system (Goedert et al., 1992; Georgieff et al., 1993). The position of this variant (370) is numbered according to amino acid position in PNS-tau rather than isoform 441 (TauF).

Neuropathology

Not applicable.

Biological Effect

Unknown.

Last Updated: 27 Oct 2013

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References

Paper Citations

  1. Lilius L, Froelich Fabre S, Basun H, Forsell C, Axelman K, Mattila K, Andreadis A, Viitanen M, Winblad B, Fratiglioni L, Lannfelt L. Tau gene polymorphisms and apolipoprotein E epsilon4 may interact to increase risk for Alzheimer's disease. Neurosci Lett. 1999 Dec 17;277(1):29-32. PubMed.
  2. Goedert M, Spillantini MG, Crowther RA. Cloning of a big tau microtubule-associated protein characteristic of the peripheral nervous system. Proc Natl Acad Sci U S A. 1992 Mar 1;89(5):1983-7. PubMed.
  3. Georgieff IS, Liem RK, Couchie D, Mavilia C, Nunez J, Shelanski ML. Expression of high molecular weight tau in the central and peripheral nervous systems. J Cell Sci. 1993 Jul;105 ( Pt 3):729-37. PubMed.

External Citations

  1. PNS-tau

Further Reading

Papers

  1. Sobrido MJ, Abu-Khalil A, Weintraub S, Johnson N, Quinn B, Cummings JL, Mesulam MM, Geschwind DH. Possible association of the tau H1/H1 genotype with primary progressive aphasia. Neurology. 2003 Mar 11;60(5):862-4. PubMed.
  2. Stanford PM, Brooks WS, Teber ET, Hallupp M, McLean C, Halliday GM, Martins RN, Kwok JB, Schofield PR. Frequency of tau mutations in familial and sporadic frontotemporal dementia and other tauopathies. J Neurol. 2004 Sep;251(9):1098-104. PubMed.
  3. Rademakers R, Cruts M, van Broeckhoven C. The role of tau (MAPT) in frontotemporal dementia and related tauopathies. Hum Mutat. 2004 Oct;24(4):277-95. PubMed.
  4. 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.

Learn More

  1. Alzheimer Disease & Frontotemporal Dementia Mutation Database

Protein Diagram

Primary Papers

  1. Lilius L, Froelich Fabre S, Basun H, Forsell C, Axelman K, Mattila K, Andreadis A, Viitanen M, Winblad B, Fratiglioni L, Lannfelt L. Tau gene polymorphisms and apolipoprotein E epsilon4 may interact to increase risk for Alzheimer's disease. Neurosci Lett. 1999 Dec 17;277(1):29-32. PubMed.

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