ARSA N350S - GET-Evidence

Curation:
Currentness:

ARSA N350S

(ARSA Asn350Ser)


Short summary

This common variant (HapMap 24.1% allele frequency) causes a loss of a glycosylation site (affecting the size of the protein when studied with gel electrophoresis) but does not affect enzyme activity or stability.

Variant evidence
Computational 2

Amino acid change is not disruptive, polyphen 2 predict benign effect

Functional 2

Functional study supports no effect on enzyme stability or catalytic properties

See Gieselmann V et al. 1989 (2574462).

Case/Control 5

High frequency of the allele in the population supports no significant pathogenic effect.

Familial
 
Clinical importance
Severity -
Treatability -
Penetrance -
 

Impact

Low clinical importance, benign

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

Inheritance pattern

unknown

Summary of published research, and additional commentary

 

Allele frequency

  • C @ chr22:51064416: 18.3% (1954/10666) in EVS
  • C @ chr22:49411281: 25.0% (32/128) in GET-Evidence
  • Frequency shown in summary reports: 18.3% (1954/10666)

Publications
 

Gieselmann V, Polten A, Kreysing J, von Figura K. Arylsulfatase A pseudodeficiency: loss of a polyadenylylation signal and N-glycosylation site. Proc Natl Acad Sci U S A. 1989 Dec;86(23):9436-40. PubMed PMID: 2574462; PubMed Central PMCID: PMC298511.

These authors state, in the abstract, that this variant “leads to the loss of a utilized N-glycosylation site. This loss explains the smaller size of ASA in ASA pseudodeficiency fibroblasts. The introduction of Ser-350 into normal ASA cDNA does not affect the rate of synthesis, the stability, or the catalytic properties of ASA in stably transfected baby hamster kidney cells.”

Genomes
 

hu011C57 - CGI sample GS01669-DNA_B05 from PGP sample 86486261
het C @ chr22:51064416

 

hu034DB1 - CGI sample GS00253-DNA_A02_200_37
het C @ chr22:51064416

 

hu2D6140 - CGI sample GS01173-DNA_F06 from PGP sample 64191565
het C @ chr22:51064416

 

hu38168C - CGI sample GS01173-DNA_H06 from PGP sample 91708424
het C @ chr22:51064416

 

 

hu3CAB43 - CGI sample GS01175-DNA_D03 from PGP sample 27486199
het C @ chr22:51064416

 

hu4339C0 - CGI sample GS01175-DNA_H01 from PGP sample 94797469
het C @ chr22:51064416

 

hu43860C - CGI sample GS00253-DNA_A01_200_37
het C @ chr22:51064416

 

hu44DCFF - CGI sample GS01669-DNA_C07 from PGP sample 74521372
het C @ chr22:51064416

 

hu604D39 - CGI sample GS00253-DNA_B02_200_37
het C @ chr22:51064416

 

hu92C40A - CGI sample GS01175-DNA_G03 from PGP sample 92527586
het C @ chr22:51064416

 

huA0E089 - CGI sample GS01175-DNA_B04 from PGP sample 88590671
het C @ chr22:51064416

 

 

huAE6220 - CGI sample GS00253-DNA_H01_200_37
het C @ chr22:51064416

 

GS12004 - var-GS12004-1100-36-ASM
het C @ chr22:49411282

 

GS18502 - var-GS18502-1100-36-ASM
het C @ chr22:49411282

 

GS18504 - var-GS18504-1100-36-ASM
het C @ chr22:49411282

 

GS18508 - var-GS18508-1100-36-ASM
hom C @ chr22:49411282

 

GS18537 - var-GS18537-1100-36-ASM
het C @ chr22:49411282

 

GS18947 - var-GS18947-1100-36-ASM
het C @ chr22:49411282

 

GS19017 - var-GS19017-1100-36-ASM
het C @ chr22:49411282

 

GS19020 - var-GS19020-1100-36-ASM
hom C @ chr22:49411282

 

GS19025 - var-GS19025-1100-36-ASM
het C @ chr22:49411282

 

GS19026 - var-GS19026-1100-36-ASM
het C @ chr22:49411282

 

GS19239 - var-GS19239-1100-36-ASM
het C @ chr22:49411282

 

GS19240 - var-GS19240-1100-36-ASM
het C @ chr22:49411282

 

GS19648 - var-GS19648-1100-36-ASM
het C @ chr22:49411282

 

GS19700 - var-GS19700-1100-36-ASM
het C @ chr22:49411282

 

GS19701 - var-GS19701-1100-36-ASM
het C @ chr22:49411282

 

GS19703 - var-GS19703-1100-36-ASM
het C @ chr22:49411282

 

GS19704 - var-GS19704-1100-36-ASM
hom C @ chr22:49411282

 

GS19735 - var-GS19735-1100-36-ASM
het C @ chr22:49411282

 

GS19834 - var-GS19834-1100-36-ASM
het C @ chr22:49411282

 

GS21767 - var-GS21767-1100-36-ASM
het C @ chr22:49411282

 

Other external references
 

    dbSNP
  • rs2071421
    www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi
    PolyPhen-2
  • Score: 0.012 (benign)
    Web search results (26 hits -- see all)
  • European Journal of Human Genetics - An unusual arylsulfatase ...
    The European Journal of Human Genetics is the official Journal of the European Society of Human Genetics, publishing high-quality, original research papers, short ...
    www.nature.com/ejhg/journal/v12/n2/full/5201100a.html
  • Arylsulfatase A Deficiency
    conjunction with N350S mutation) is associated with ARSA enzyme activity ... Homozygosity for the N350S mutation alone results in 50% or more of the ...
    ncbi.nlm.nih.gov/bookshelf/picrender.fcgi?...&blobtype=pdf
  • An arylsulphatase A (ARSA) frameshift mutation (289insG) in ...
    The ARSA gene consists of eight. exons encoding the 507 amino acid enzyme (Stein et al, ... mutation is likely to totally disrupt ARSA activity and can ...
    www.libpubmedia.co.uk/MedJ-Issues/Issue-1/Perkins.pdf
  • Identification of 12 novel mutations and two new ...
    Arylsulfatase A (ARSA) deficiency is the main cause of metachromatic ... in the absence of the N350S mutation, and this infrequent haplotype reinforced ...
    www.ncbi.nlm.nih.gov/pubmed/10477432
  • Leucodistrofie/METACHROMATIC LEUKODYSTROPHY
    deficiency of ARSA activity is most marked in the late infantile form ... for the N350S mutation alone, and 1 was homozygous for the N350S mutation. ...
    web.peacelink.it/appeal/gianmarco/vi.html
  • The new programme for science funding
    destroying an ARSA glycosylation site (N350S, leading to lower ... The determination of the frequency of. the ARSA-PD associated alterations in ...
    www.ibmc.up.pt/newsletter/IBMCNews_Apr04.pdf
  • Kinetics and activity of arylsulfatase A in leukocytes ...
    The N350S and 1524+95 A>G mutations were determined according to the previously ... In the presence of the N350S mutation, the 275 bp fragment A (allele 2) is ...
    public.carnet.hr/acphee/9506.pdf
  • Type III 95%
    Gene name SWISS-PROT ID Variant site Phosphorylation site SWISS-PROT ... gruop(s) Added kinase family(s) Removed kinase gruop(s) Removed kinase family(s) ...
    www.nih.go.kr/phosphovariant/html/group_whole/TypeIII_95.txt

Other in silico analyses
 

  • NBLOSUM100 score = 0
  • GET-Evidence autoscore = 4

Edit history
 

Gene search

"GENE" or "GENE A123C":

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