PPOX

protoporphyrinogen oxidase

Basic information

Region (hg38): 1:161166055-161178013

Previous symbols: [ "VP" ]

Links

ENSG00000143224 ∙ NCBI:5498 ∙ OMIM:600923 ∙ HGNC:9280 ∙ Uniprot:P50336 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• variegate porphyria (Strong), mode of inheritance: AD
• variegate porphyria (Strong), mode of inheritance: AR
• variegate porphyria (Strong), mode of inheritance: AD
• variegate porphyria (Supportive), mode of inheritance: AD
• variegate porphyria (Definitive), mode of inheritance: Semidominant

Clinical Genomic Database

Source: CGD

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 ClinVar and linked to the PPOX gene.

• not provided (142 variants)
• Variegate porphyria (45 variants)
• Inborn genetic diseases (17 variants)
• Variegate porphyria, childhood-onset (3 variants)
• not specified (2 variants)
• See cases (2 variants)
• Porphyrinuria;Abdominal colic;Abnormal blistering of the skin (1 variants)
• Abnormality of metabolism/homeostasis (1 variants)
• Acute intermittent porphyria (1 variants)
• Abnormal urinary color;Constipation;Migraine;Abnormal blistering of the skin (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.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			5	21	1	27
missense	3	4	75	3	1	86
nonsense	8	2				10
start loss	1					1
frameshift	9	4				13
inframe indel			2			2
splice donor/acceptor (+/-2bp)	3	2				5
splice region		2	5	2		9
non coding			9	7	7	23
Total	24	12	91	31	9

Highest pathogenic variant AF is 0.000112

Variants in PPOX

This is a list of pathogenic ClinVar variants found in the PPOX region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
1-161166430-G-C		Variegate porphyria	Uncertain significance (Jan 12, 2018)
1-161166434-C-A		Variegate porphyria	Benign (Nov 12, 2018)
1-161166435-G-T		Variegate porphyria	Conflicting classifications of pathogenicity (Oct 01, 2022)
1-161166470-C-A		Variegate porphyria	Uncertain significance (Jan 12, 2018)
1-161166501-T-C		Variegate porphyria	Uncertain significance (Jan 13, 2018)
1-161166507-A-G		Variegate porphyria	Uncertain significance (Jun 14, 2016)
1-161166530-G-T		Variegate porphyria	Likely benign (Jan 13, 2018)
1-161166532-G-T		Variegate porphyria	Uncertain significance (Jan 13, 2018)
1-161166553-C-G		Variegate porphyria	Benign/Likely benign (Jun 19, 2021)
1-161166672-G-A			Likely pathogenic (Oct 04, 2023)
1-161166846-G-T		Variegate porphyria	Uncertain significance (Jan 12, 2018)
1-161166847-C-T		Variegate porphyria	Uncertain significance (Jan 13, 2018)
1-161166849-T-C			Pathogenic (Mar 24, 2023)
1-161166855-G-A			Uncertain significance (Dec 03, 2021)
1-161166870-T-C			Uncertain significance (Jan 01, 2021)
1-161166876-G-A			Likely pathogenic (Mar 23, 2023)
1-161166878-G-A			Uncertain significance (May 24, 2019)
1-161166878-G-T			Uncertain significance (May 03, 2019)
1-161166882-T-C		Variegate porphyria • Variegate porphyria, childhood-onset	Pathogenic (Apr 01, 2001)
1-161166885-G-A			Uncertain significance (Mar 25, 2021)
1-161166906-A-C		Variegate porphyria	Pathogenic (Jul 01, 1996)
1-161166914-C-T			Uncertain significance (Feb 10, 2023)
1-161166916-G-T		Variegate porphyria	Uncertain significance (Jan 13, 2018)
1-161166917-G-A			Uncertain significance (Aug 27, 2021)
1-161166918-C-T		Inborn genetic diseases	Conflicting classifications of pathogenicity (Jan 04, 2024)

GnomAD

Source: gnomAD

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: dbNSFP

• 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