PPOX P256R

(PPOX Pro256Arg)

This variant has 0.7% allele frequency in HapMap and occurs in a heme biosynthesis gene. Other variants in this gene are implicated in causing porphyria in a recessive manner, but this variant is considered a polymorphism and retains normal function in a eukaryotic expression system.

Variant evidence
Computational	1	Amino acid position not conserved. See Whatley SD et al. 1999 (10486317).

Functional	1	Normal function in eukaryotic expression system. See Kauppinen R et al. 2001 (11286631).

Case/Control	1	5% allele frequency in French population implies this is not significantly pathogenic. See Whatley SD et al. 1999 (10486317).

Familial	-


Clinical importance
Severity	-

Treatability	-

Penetrance	-

Low clinical importance, Uncertain benign

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

recessive

Allele frequency

G @ chr1:161138933: 0.7% (78/10756) in EVS
Frequency shown in summary reports: 0.7% (78/10756)

Publications

This authors note that this variant is present in ~10% of the French population (allele frequency of 5%) and that this residue is poorly conserved between species.

Reported a compound homozygote (together with I12T) in variegate porphyria. In eukarytotic cell lines this mutation shows normal activity, while I12T shows loss of enzyme function.

Genomes

Other external references

GeneTests

GeneTests records for the PPOX gene
Variegate Porphyria
www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/PPOX

OMIM

Variegate porphyria, homozygous
www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=600923

PolyPhen-2

Score: 0.381 (possibly damaging)

Web search results (10 hits -- see all)

Variegate Porphyria in Western Europe: Identiﬁcation of PPOX ...
Variegate Porphyria in Western Europe: Identiﬁcation of PPOX Gene ... P256R mutation has previously been reported to be one. of two mutant PPOX alleles in a ...
sciencedirect.com/science?_ob=MImg&...&ie=/sdarticle.pdf
Mutation Screening of the Entire Coding Region of the ...
... activity of protoporphyrinogen oxidase (PPOX), the penultimate enzyme in the ... with mutations in the gene encoding PPOX and is usually inherited as an ...
www.clinchem.org/cgi/content/full/47/6/1115
Homozygous variegate porphyria: 20 y follow-up and ...
Department of Medicine, Division of Diabetology, Dermatology and Clinical ... (I12T) and a 767C to G transversion in exon 7 (P256R) of the protoporphyrinogen ...
www.ncbi.nlm.nih.gov/pubmed/11286631
1115
PPOX by substitution of the nucleotide positioned in. IVS7–9 has been reported, which ... Variegate porphyria in Western Europe: identification of PPOX gene muta ...
www.clinchem.org/cgi/reprint/47/6/1115.pdf
Type III 97%
... SWISS-PROT ID Variant site Phosphorylation site SWISS-PROT variant ID ... Reference(s) for variant Reference(s) for phosphorylation site TPSD1 Q9BZJ3 P15R ...
nih.go.kr/phosphovariant/html/family_whole/TypeIII_97.txt
OMIM: 600923
The authors concluded that mild PPOX mutations occur in the general population ... P256R mutation resulted in less than half of normal PPOX activity in the ...
www.genome.jp/htbin/www_bget?omim+600923
Homozygous variegate porphyria: 20 y follow-up and ...
The long-term follow-up of a homozygous variegate porphyria patient revealed severe photosensitivity accompanied by mild sensory neuropathy and IgA nephropathy.
www.medscape.com/medline/abstract/11286631

Other in silico analyses

NBLOSUM100 score = 5
GET-Evidence autoscore = 4

Edit history

Jun 22 2011 Genome Importing Robot removed J. Craig Venter view
Jun 3 2010 Madeleine Ball edited article 10486317 summary view
Jun 3 2010 Madeleine Ball edited variant summary view
Jun 3 2010 Madeleine Ball edited article 10486317 summary view
Jun 3 2010 Madeleine Ball edited variant summary view
Jun 3 2010 Madeleine Ball added article 10486317 view
Jan 12 2010 Alexander Wait Zaranek edited article 11286631 summary view
Jan 12 2010 Alexander Wait Zaranek edited variant summary view
Jan 12 2010 Alexander Wait Zaranek added article 11286631 view
Jan 5 2010 OMIM Importing Robot edited variant summary view
Dec 27 2009 Genome Importing Robot added J. Craig Venter view
Dec 27 2009 Genome Importing Robot added variant view

PPOX P256R - GET-Evidence