PRODH R431H - GET-Evidence

Note: This variant has not been sufficiently evaluated by a GET-Evidence editor.

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Curation:
Currentness:

PRODH R431H

(PRODH Arg431His)


Short summary

This variant is associated with type I hyperprolinemia and leads to a reduction of POX activity to 60% of wildtype.

Variant evidence
Computational 2

Gene associated with disease, conserved in mouse.

See Jacquet H et al. 2002 (12217952), Bender HU et al. 2005 (15662599).

Functional 1

Reduction of enzyme activity to 60% of wildtype

See Bender HU et al. 2005 (15662599).

Case/Control

OR data weak

See Jacquet H et al. 2002 (12217952).

Familial

No family evidence.

See unpublished research (below).

 
Clinical importance
Severity 1

Type I hyperprolemia is often asymptomatic.

Treatability
Penetrance -
 

Impact

Insufficiently evaluated pathogenic

(The "insufficiently evaluated" qualifier is assigned automatically based on the above evidence and importance scores.)

Inheritance pattern

recessive

Summary of published research, and additional commentary

 

Total cases/controls case+ case– control+ control– p-value odds ratio
Hyperprolinemia, Type I
9 54 12 56 0.6408 0.778

 

Allele frequency

  • T @ chr22:18905964: 8.0% (858/10752) in EVS
  • T @ chr22:17285963: 3.5% (4/114) in GET-Evidence
  • Frequency shown in summary reports: 8.0% (858/10752)

Publications
 

Jacquet H, Raux G, Thibaut F, Hecketsweiler B, Houy E, Demilly C, Haouzir S, Allio G, Fouldrin G, Drouin V, Bou J, Petit M, Campion D, Frébourg T. PRODH mutations and hyperprolinemia in a subset of schizophrenic patients. Hum Mol Genet. 2002 Sep 15;11(19):2243-9. PubMed PMID: 12217952.

In a screen of 63 individuals with hyperprolinemia, this variant was seen in 9/63 patients and 12/68 controls. It was seen homozygously in two from each group.

Cases/controls case+ case– control+ control– p-value odds ratio
Hyperprolinemia, Type I
9 54 12 56 0.6408 0.778

 

Bender HU, Almashanu S, Steel G, Hu CA, Lin WW, Willis A, Pulver A, Valle D. Functional consequences of PRODH missense mutations. Am J Hum Genet. 2005 Mar;76(3):409-20. Epub 2005 Jan 20. PubMed PMID: 15662599; PubMed Central PMCID: PMC1196393.

In transfected cell lines this variant was shown to decrease enzyme activity to 60% of wild type. It is conserved in mouse and C. elegans, but not in drosophila nor S. cervisiae.

Genomes
 

 

hu342A08 - CGI sample GS01175-DNA_B05 from PGP sample 83494370
hom T @ chr22:18905964

 

huAE4A11 - CGI sample GS01669-DNA_F02 from PGP sample 40767107
het T @ chr22:18905964

 

huAE6220

 

huB1FD55 - CGI sample GS01173-DNA_B07 from PGP sample 61499538
het T @ chr22:18905964

 

huBEDA0B - CGI sample GS00253-DNA_C01_200_37
het T @ chr22:18905964

 

GS20502 - var-GS20502-1100-36-ASM
het T @ chr22:17285964

 

Other external references
 

    dbSNP
  • rs2904552
    www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi
    Web search results (18 hits -- see all)
  • Functional Consequences of PRODH Missense Mutations
    PRODH maps to 22q11 in the region deleted in the velocardiofacial syndrome ... At least 16 PRODH missense mutations have been identified in studies ...
    www.ncbi.nlm.nih.gov/pmc/articles/PMC1196393
  • Functional consequences of PRODH missense mutations.
    At least 16 PRODH missense mutations have been identified in studies of type I hyperprolinemia (HPI) and ... six (Q19P, A167V, R185W, D426N, V427M, and R431H) in moderate (30 ...
    www.ncbi.nlm.nih.gov/pubmed/15662599
  • Trends in Plant Science - Proline: a multifunctional amino acid
    PRODH maps to 22q11 in the region deleted in the velocardiofacial syndrome ... six (Q19P, A167V, R185W, D426N, V427M, and R431H) in moderate (30 ...
    cell.com/trends/plant-science/abstract/S1360-1385(09)00298-2
  • INVOLVEMENT OF HYPERPROLINEMIA IN COGNITIVE AND PSYCHIATRIC ...
    entire PRODH gene and the neighbouring DGCR6 gene, or from a PRODH homozygous ... subjects with and without hyperprolinemia, with the exception of the R431H variation that ...
    hmg.oxfordjournals.org/cgi/reprint/ddl443v1.pdf
  • Involvement of hyperprolinemia in cognitive and psychiatric ...
    P406L + R431H/R431H. 006. 12. seizures. 403–862. R453C + V427M + T275N ... Mutations with severe effect on PRODH activity appear in bold, mutations with moderate ...
    hmg.oxfordjournals.org/cgi/content/full/16/1/83/DDL443TB1
  • EC 1.5.99.8 - proline dehydrogenase
    Information on EC 1.5.99.8 - proline dehydrogenase ... and hypoosmolarity-responsive expression of the ProDH gene encoding proline dehydrogenase in Arabidopsis. ...
    www.brenda-enzymes.info/php/result_flat.php4?ecno=1.5.99.8
  • Functional Consequences of PRODH Missense Mutations
    PRODH maps to 22q11 in the region deleted in the velocardiofacial syndrome ... At least 16 PRODH missense mutations have been identified in studies ...
    sciencedirect.com/science?_ob=MImg&...&ie=/sdarticle.pdf
  • PubMed: 15662599
    At least 16 PRODH missense mutations have been identified in studies of type I hyperprolinemia (HPI) and ... six (Q19P, A167V, R185W, D426N, V427M, and R431H) in moderate (30 ...
    www.genome.jp/dbget-bin/www_bget?pubmed+15662599
  • PRODH variants and risk for schizophrenia.
    BioInfoBank Library :: PRODH variants and risk for schizophrenia. Dietary supplementation with cholesterol and docosahexaenoic acid affects concentrations of amino ...
    lib.bioinfo.pl/pmid:18528746

Other in silico analyses
 

  • NBLOSUM100 score = 1
  • GET-Evidence autoscore = 3

Edit history
 

Gene search

"GENE" or "GENE A123C":

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