PPOX
protoporphyrinogen oxidase
Basic information
Region (hg38): 1:161166056-161178013
Previous symbols: [ "VP" ]
Links
Phenotypes
GenCC
Source:
- variegate porphyria (Strong), mode of inheritance: AD
- variegate porphyria (Strong), mode of inheritance: AR
- variegate porphyria (Supportive), mode of inheritance: AD
- variegate porphyria (Strong), mode of inheritance: AD
- variegate porphyria (Definitive), mode of inheritance: Semidominant
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Variegate porphyria; Variegate porphyria, childhood-onset | AD/AR | Dermatologic; Pharmacogenomic | Acute attacks may be precipitated by porphyrinogenic agents, which, along with other exacerbating factors, should be avoided; Skin protection is warranted | Biochemical; Dermatologic; Musculoskeletal; Neurologic; Renal | 6143163; 4059081; 3723537; 3319294; 2222353; 2020301; 8852667; 8673113; 8817334; 9738863; 9811936; 10401000; 11286631; 12357337; 19460837; 19656457; 19845869; 21734717; 21910705 |
| Homozygosity/compound heterozygosity results in a distinct and much more severe phenotype |
ClinVar
This is a list of variants' phenotypes submitted to
- not_provided (185 variants)
- Variegate_porphyria (46 variants)
- Inborn_genetic_diseases (43 variants)
- Variegate_porphyria,_childhood-onset (13 variants)
- PPOX-related_disorder (3 variants)
- See_cases (2 variants)
- not_specified (2 variants)
- Abnormal_blistering_of_the_skin (2 variants)
- Migraine (1 variants)
- Abnormal_urinary_color (1 variants)
- Acute_intermittent_porphyria (1 variants)
- Abnormality_of_metabolism/homeostasis (1 variants)
- Porphyrinuria (1 variants)
- Abdominal_colic (1 variants)
- Constipation (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the PPOX gene is commonly pathogenic or not. These statistics are base on transcript: NM_001122764.3. Only rare variants are included in the table.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 32 | 37 | ||||
| missense | 11 | 123 | 147 | |||
| nonsense | 10 | 14 | ||||
| start loss | 1 | 1 | ||||
| frameshift | 13 | 19 | ||||
| splice donor/acceptor (+/-2bp) | 8 | |||||
| Total | 38 | 22 | 126 | 39 | 1 |
Highest pathogenic variant AF is 0.000118529
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| PPOX | protein_coding | protein_coding | ENST00000367999 | 12 | 11604 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.0283 | 0.971 | 125730 | 0 | 18 | 125748 | 0.0000716 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 0.975 | 216 | 260 | 0.830 | 0.0000155 | 3005 |
| Missense in Polyphen | 60 | 96.147 | 0.62404 | 1153 | ||
| Synonymous | -0.431 | 108 | 102 | 1.05 | 0.00000542 | 1065 |
| Loss of Function | 3.09 | 7 | 23.0 | 0.305 | 0.00000103 | 274 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000615 | 0.0000615 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.0000544 | 0.0000544 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.000123 | 0.000123 |
| Middle Eastern | 0.0000544 | 0.0000544 |
| South Asian | 0.0000327 | 0.0000327 |
| Other | 0.000163 | 0.000163 |
dbNSFP
Source:
- Function
- FUNCTION: Catalyzes the 6-electron oxidation of protoporphyrinogen-IX to form protoporphyrin-IX. {ECO:0000269|PubMed:21048046, ECO:0000269|PubMed:23467411, ECO:0000269|PubMed:7713909}.;
- Pathway
- Porphyrin and chlorophyll metabolism - Homo sapiens (human);Hereditary Coproporphyria (HCP);Porphyria Variegata (PV);Congenital Erythropoietic Porphyria (CEP) or Gunther Disease;Acute Intermittent Porphyria;Porphyrin Metabolism;Heme Biosynthesis;Heme biosynthesis;Metabolism of porphyrins;Metabolism;Porphyrin metabolism;Porphyrin metabolism;heme biosynthesis from uroporphyrinogen-III I;heme biosynthesis
(Consensus)
Recessive Scores
- pRec
- 0.297
Intolerance Scores
- loftool
- 0.0727
- rvis_EVS
- -0.25
- rvis_percentile_EVS
- 35.99
Haploinsufficiency Scores
- pHI
- 0.190
- hipred
- Y
- hipred_score
- 0.613
- ghis
- 0.567
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.999
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Ppox
- Phenotype
- renal/urinary system phenotype; digestive/alimentary phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); homeostasis/metabolism phenotype;
Zebrafish Information Network
- Gene name
- ppox
- Affected structure
- nucleate erythrocyte
- Phenotype tag
- abnormal
- Phenotype quality
- decreased amount
Gene ontology
- Biological process
- porphyrin-containing compound biosynthetic process;protoporphyrinogen IX biosynthetic process;heme biosynthetic process;response to drug;oxidation-reduction process
- Cellular component
- mitochondrion;mitochondrial intermembrane space;intrinsic component of mitochondrial inner membrane;integral component of mitochondrial inner membrane;mitochondrial membrane
- Molecular function
- oxygen-dependent protoporphyrinogen oxidase activity;oxidoreductase activity;flavin adenine dinucleotide binding