Mutations

MAPT Y441H

Other Names: H441Y, H47Y, His47Tyr

Overview

Pathogenicity: Frontotemporal Dementia : Benign
Clinical Phenotype: None
Position: (GRCh38/hg38):Chr17:45990016 C>T
Position: (GRCh37/hg19):Chr17:44067382 C>T
dbSNP ID: rs2258689
Coding/Non-Coding: Coding
DNA Change: Substitution
Expected RNA Consequence: Substitution
Expected Protein Consequence: Missense
Codon Change: CAC to TAC
Reference Isoform: Tau Isoform PNS Tau (758 aa)
Genomic Region: Exon 6

Findings

This variant has been reported in healthy controls and is thought to be benign (Poorkaj et al., 1998). The polymorphism resides in exon 6, which is excluded from the major tau isoforms expressed in the human brain, but is included in PNS-tau (P10636-1) and Tau-G (P10636-9), which are 758 and 776 amino acids long, respectively. Therefore, the position of this variant is in reference to these isoforms, rather than to isoform Tau-F (P10636-8). In the literature this variant has also been referred to as H47Y or His47Tyr (e.g., Poorkaj et al., 1998). Both alleles are fairly common, and both have been reported as the ancestral allele in the published record.

Neuropathology

Not applicable.

Biological Effect

Unknown.

Last Updated: 31 Dec 2012

Comments

No Available Comments

Make a Comment

To make a comment you must login or register.

References

Paper Citations

  1. Poorkaj P, Bird TD, Wijsman E, Nemens E, Garruto RM, Anderson L, Andreadis A, Wiederholt WC, Raskind M, Schellenberg GD. Tau is a candidate gene for chromosome 17 frontotemporal dementia. Ann Neurol. 1998 Jun;43(6):815-25. PubMed.

External Citations

  1. P10636-1
  2. P10636-9
  3. P10636-8

Further Reading

Papers

  1. 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.
  2. Crawford F, Freeman M, Town T, Fallin D, Gold M, Duara R, Mullan M. No genetic association between polymorphisms in the Tau gene and Alzheimer's disease in clinic or population based samples. Neurosci Lett. 1999 May 14;266(3):193-6. PubMed.
  3. 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.

Protein Diagram

Primary Papers

  1. Poorkaj P, Bird TD, Wijsman E, Nemens E, Garruto RM, Anderson L, Andreadis A, Wiederholt WC, Raskind M, Schellenberg GD. Tau is a candidate gene for chromosome 17 frontotemporal dementia. Ann Neurol. 1998 Jun;43(6):815-25. PubMed.

Alzpedia

Disclaimer: Alzforum does not provide medical advice. The Content is for informational, educational, research and reference purposes only and is not intended to substitute for professional medical advice, diagnosis or treatment. Always seek advice from a qualified physician or health care professional about any medical concern, and do not disregard professional medical advice because of anything you may read on Alzforum.