ABCA4 R943Q - GET-Evidence

Curation:
Currentness:

ABCA4 R943Q

(ABCA4 Arg943Gln)


Short summary

This is a polymorphism in a gene associated with Stargardt disease. Although it has a slight detectable effect in functional study, it is common in control groups and is not believed to have any significant pathogenic effect.

Variant evidence
Computational -1

Polyphen 2 predicts damaging effect

Functional -1

Slight functional effect

See Suárez T et al. 2002 (11919200).

Case/Control 1

High incidence in control group

See Allikmets R et al. 1997 (9295268).

Familial -
 
Clinical importance
Severity -
Treatability -
Penetrance -
 

Impact

Low clinical importance, Uncertain benign

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

Inheritance pattern

unknown

Summary of published research, and additional commentary

 

Allele frequency

  • T @ chr1:94512565: 3.2% (340/10758) in EVS
  • T @ chr1:94285152: 3.9% (5/128) in GET-Evidence
  • Frequency shown in summary reports: 3.2% (340/10758)

Publications
 

Allikmets R, Shroyer NF, Singh N, Seddon JM, Lewis RA, Bernstein PS, Peiffer A, Zabriskie NA, Li Y, Hutchinson A, Dean M, Lupski JR, Leppert M. Mutation of the Stargardt disease gene (ABCR) in age-related macular degeneration. Science. 1997 Sep 19;277(5333):1805-7. PubMed PMID: 9295268.

These authors investigated whether variants in this gene (associated with Stargardt disease (SD)) contribute to age-related macular degeneration (AMD). The authors found no increased incidence in AMD patients (6/127, 4.7%) or SD patients (4/47, 9.5%) compared to controls (13/80, 16.25%), supporting a nonpathogenic effect.

In fact, this is a significant difference in the other direction — a p=0.0067 for the AMD vs. control set, p = 0.0096 for the combined AMD + SD set. This may mean the control population was not ethnically matched well with the disease cases. Alternatively, the variant could have some protective effect for AMD — the authors do not make this hypothesis, however.

Suárez T, Biswas SB, Biswas EE. Biochemical defects in retina-specific human ATP binding cassette transporter nucleotide binding domain 1 mutants associated with macular degeneration. J Biol Chem. 2002 Jun 14;277(24):21759-67. Epub 2002 Mar 27. PubMed PMID: 11919200.

This group reports that the R943Q mutation has small (but detectable) reduction in nucleotidase activity and nucleotide binding affinity.

Genomes
 

hu04FD18 - CGI sample GS00253-DNA_F01_200_37
het T @ chr1:94512565

 

hu0D879F - CGI sample GS00253-DNA_G01_200_37
het T @ chr1:94512565

 

 

 

 

 

 

GS12004 - var-GS12004-1100-36-ASM
het T @ chr1:94285153

 

Other external references
 

    dbSNP
  • rs1801581
    www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi
    GeneTests
  • GeneTests records for the ABCA4 gene
    Age-related macular degeneration
    ABCA4-Related Retinitis Pigmentosa
    ABCA4-Related Stargardt Disease 1
    Age-Related Macular Degeneration 2
    Cone-Rod Dystrophy, Type 3
    Retinitis Pigmentosa, Autosomal Recessive
    Stargardt Disease, Autosomal Recessive
    www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/ABCA4
    PolyPhen-2
  • Score: 0.922 (probably damaging)

Other in silico analyses
 

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

Edit history
 

Gene search

"GENE" or "GENE A123C":

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