GAA E689K - GET-Evidence

Curation:
Currentness:

GAA E689K

(GAA Glu689Lys)


Short summary

This is also known as the GAA*4 allozyme is frequent in the Asian population and appears to have somewhat reduced enzyme activity. Kroos et al. rule out pathogenic effect.

Variant evidence
Computational 1

Not a disruptive amino acid change.

Functional 1

Enzyme retains 50-100% activity.

Case/Control 3

Kroos et al. support no pathogenic effect despite reduced enzyme activity. Frequent population in asian population.

See Kroos MA et al. 2008 (18301443).

Familial
 
Clinical importance
Severity -
Treatability -
Penetrance -
 

Impact

Low clinical importance, Likely benign

(The "low clinical importance, likely" qualifier is assigned automatically based on the above evidence and importance scores.)

Inheritance pattern

other

Summary of published research, and additional commentary

 

Allele frequency

  • A @ chr17:78087041: 3.0% (324/10734) in EVS
  • A @ chr17:75701635: 5.3% (6/114) in GET-Evidence
  • Frequency shown in summary reports: 3.0% (324/10734)

Publications
 

Kroos MA, Mullaart RA, Van Vliet L, Pomponio RJ, Amartino H, Kolodny EH, Pastores GM, Wevers RA, Van der Ploeg AT, Halley DJ, Reuser AJ. p.[G576S; E689K]: pathogenic combination or polymorphism in Pompe disease? Eur J Hum Genet. 2008 Aug;16(8):875-9. Epub 2008 Feb 27. PubMed PMID: 18301443.

These authors investigate whether the combination of G576S and E689K plays a role in Pompe disease and conclude that homozygosity for both does not cause the disease because ~4% of the Asian population has this. They report reduced enzyme activity (54%) and summarize other studies as 72–125% activity. The cases they discuss have alpha-glucosidase deficiency but no evident symptoms—screening the Asian population based on this is likely to result in a high rate of false positives.

Genomes
 

hu2D6140 - CGI sample GS01173-DNA_F06 from PGP sample 64191565
het A @ chr17:78087041

 

hu38168C - CGI sample GS01173-DNA_H06 from PGP sample 91708424
het A @ chr17:78087041

 

hu44DCFF - CGI sample GS01669-DNA_C07 from PGP sample 74521372
het A @ chr17:78087041

 

 

hu92FD55 - CGI sample GS01669-DNA_A04 from PGP sample 08188426
het A @ chr17:78087041

 

huCA017E - CGI sample GS01175-DNA_B01 from PGP sample 86206034
het A @ chr17:78087041

 

GS10851 - var-GS10851-1100-36-ASM
het A @ chr17:75701636

 

GS18537 - var-GS18537-1100-36-ASM
het A @ chr17:75701636

 

GS18942 - var-GS18942-1100-36-ASM
het A @ chr17:75701636

 

GS18956 - var-GS18956-1100-36-ASM
het A @ chr17:75701636

 

GS19026 - var-GS19026-1100-36-ASM
het A @ chr17:75701636

 

Other external references
 

    dbSNP
  • rs1800309
    www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi

Other in silico analyses
 

  • NBLOSUM100 score = 0
  • GET-Evidence autoscore = 5

Edit history
 

Gene search

"GENE" or "GENE A123C":

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