Gene Details | GeDiPNet - Complete Gene Info, Disease Associations & Pathways

Gene Gene information from NCBI Gene database. Gene SNPs miRNA Transcription factors Gene ontology Other IDs Protein Pathways Associated diseases
Entrez ID	5498
Gene name	Protoporphyrinogen oxidase
Gene symbol	PPOX
Synonyms (NCBI Gene)	PPOV290MVPVPCO
Chromosome	1
Chromosome location	1q23.3
Summary	This gene encodes the penultimate enzyme of heme biosynthesis, which catalyzes the 6-electron oxidation of protoporphyrinogen IX to form protoporphyrin IX. Mutations in this gene cause variegate porphyria, an autosomal dominant disorder of heme metabolism

Show/Hide all (17)

SNP ID	Visualize variation	Clinical significance	Consequence
rs12735723	C>G,T	Pathogenic, benign, uncertain-significance	Coding sequence variant, intron variant, missense variant, non coding transcript variant
rs28936676	A>C	Pathogenic	Coding sequence variant, intron variant, missense variant, non coding transcript variant
rs28936677	T>C	Pathogenic	Genic upstream transcript variant, coding sequence variant, 5 prime UTR variant, missense variant, upstream transcript variant, non coding transcript variant
rs41270025	G>A,T	Pathogenic	Coding sequence variant, intron variant, missense variant, non coding transcript variant
rs121918323	G>C	Pathogenic	Missense variant, coding sequence variant, 5 prime UTR variant, intron variant, non coding transcript variant
rs121918324	C>T	Pathogenic	Missense variant, coding sequence variant, 5 prime UTR variant, upstream transcript variant, genic upstream transcript variant, non coding transcript variant
rs121918325	C>T	Pathogenic	Non coding transcript variant, missense variant, intron variant, coding sequence variant
rs121918326	A>C	Pathogenic	Missense variant, coding sequence variant, 5 prime UTR variant, upstream transcript variant, genic upstream transcript variant, non coding transcript variant
rs762280759	C>A,T	Pathogenic	Synonymous variant, coding sequence variant, stop gained, non coding transcript variant, genic upstream transcript variant, upstream transcript variant, 5 prime UTR variant
rs786204784	C>-	Pathogenic	Coding sequence variant, genic upstream transcript variant, 5 prime UTR variant, stop gained, upstream transcript variant, non coding transcript variant
rs956668146	C>T	Pathogenic	Coding sequence variant, stop gained, non coding transcript variant, intron variant
rs1558033572	TA>-	Likely-pathogenic	Splice acceptor variant, intron variant
rs1571325144	T>C	Pathogenic	Coding sequence variant, genic upstream transcript variant, missense variant, 5 prime UTR variant, upstream transcript variant, initiator codon variant, non coding transcript variant
rs1571352321	C>T	Pathogenic	Coding sequence variant, intron variant, missense variant, 5 prime UTR variant, synonymous variant, non coding transcript variant
rs1571357779	AT>-	Pathogenic	Frameshift variant, coding sequence variant, non coding transcript variant, intron variant
rs1571369150	->G	Pathogenic	Frameshift variant, coding sequence variant, non coding transcript variant, intron variant
rs1571406458	AG>-	Pathogenic	Frameshift variant, coding sequence variant, non coding transcript variant, intron variant

Show/Hide all (8)

miRTarBase ID	miRNA	Experiments	Reference
MIRT028501	hsa-miR-30a-5p	Proteomics	18668040
MIRT2457056	hsa-miR-2110	CLIP-seq
MIRT2457057	hsa-miR-3150a-3p	CLIP-seq
MIRT2457058	hsa-miR-4259	CLIP-seq
MIRT2457059	hsa-miR-433	CLIP-seq
MIRT2457060	hsa-miR-4693-3p	CLIP-seq
MIRT2457061	hsa-miR-4712-3p	CLIP-seq
MIRT2457062	hsa-miR-571	CLIP-seq

Show/Hide all (1)

Transcription factor	Regulation	Reference
GATA1	Unknown	18191920

Show/Hide all (29)

GO ID	Ontology	Definition	Evidence	Reference
GO:0004729	Function	Oxygen-dependent protoporphyrinogen oxidase activity	IBA
GO:0004729	Function	Oxygen-dependent protoporphyrinogen oxidase activity	IDA	7713909, 21048046
GO:0004729	Function	Oxygen-dependent protoporphyrinogen oxidase activity	IEA
GO:0005739	Component	Mitochondrion	HTP	34800366
GO:0005739	Component	Mitochondrion	IEA
GO:0005743	Component	Mitochondrial inner membrane	IBA
GO:0005743	Component	Mitochondrial inner membrane	IEA
GO:0005743	Component	Mitochondrial inner membrane	ISS
GO:0005758	Component	Mitochondrial intermembrane space	IEA
GO:0005758	Component	Mitochondrial intermembrane space	IEA
GO:0005758	Component	Mitochondrial intermembrane space	TAS
GO:0006779	Process	Porphyrin-containing compound biosynthetic process	IDA	7713909
GO:0006779	Process	Porphyrin-containing compound biosynthetic process	IEA
GO:0006782	Process	Protoporphyrinogen IX biosynthetic process	IEA
GO:0006783	Process	Heme biosynthetic process	IBA
GO:0006783	Process	Heme biosynthetic process	IDA	7713909
GO:0006783	Process	Heme biosynthetic process	IEA
GO:0006783	Process	Heme biosynthetic process	IEA
GO:0006784	Process	Heme A biosynthetic process	IEA
GO:0006785	Process	Heme B biosynthetic process	IDA	7713909
GO:0006785	Process	Heme B biosynthetic process	IEA
GO:0009410	Process	Response to xenobiotic stimulus	IEA
GO:0016020	Component	Membrane	IEA
GO:0016491	Function	Oxidoreductase activity	IEA
GO:0031966	Component	Mitochondrial membrane	IEA
GO:0031966	Component	Mitochondrial membrane	IMP	7713909
GO:0046501	Process	Protoporphyrinogen IX metabolic process	IEA
GO:0048034	Process	Heme O biosynthetic process	IEA
GO:0050660	Function	Flavin adenine dinucleotide binding	TAS	7713909

MIM	HGNC	e!Ensembl
600923	9280	ENSG00000143224

P50336

Protein name

Protoporphyrinogen oxidase (PPO) (EC 1.3.3.4)

Protein function

Catalyzes the 6-electron oxidation of protoporphyrinogen-IX to form protoporphyrin-IX.

PDB

3NKS , 4IVM , 4IVO

Family and domains

Pfam

Accession	ID	Position in sequence	Description	Type
PF01593	Amino_oxidase	12 → 471	Flavin containing amine oxidoreductase	Domain

Tissue specificity

TISSUE SPECIFICITY: Expressed in heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas. {ECO:0000269|PubMed:8771201}.

Sequence

MGRTVVVLGGGISGLAASYHLSRAPCPPKVVLVESSERLGGWIRSVRGPNGAIFELGPRG
IRPAGALGARTLLLVSELGLDSEVLPVRGDHPAAQNRFLYVGGALHALPTGLRGLLRPSP
PFSKPLFWAGLRELTKPRGKEPDETVHSFAQRRLGPEVASLAMDSLCRGVFAGNSRELSI
RSCFPSLFQAEQTHRSILLGLLLGAGRTPQPDSALIRQALAERWSQWSLRGGLEMLPQAL
ETHLTSRGVSVLRGQPVCGLSLQAEGRWKVSLRDSSLEADHVISAIPASVLSELLPAEAA
PLARALSAITAVSVAVVNLQYQGAHLPVQGFGHLVPSSEDPGVLGIVYDSVAFPEQDGSP
PGLRVTVMLGGSWLQTLEASGCVLSQELFQQRAQEAAATQLGLKEMPSHCLVHLHKNCIP
QYTLGHWQKLESARQFLTAHRLPLTLAGASYEGVAVNDCIESGRQAAVSVLGTEPNS

Sequence length

477

Interactions

View interactions

	KEGG		Reactome
	Porphyrin metabolism Metabolic pathways Biosynthesis of cofactors		Heme biosynthesis

Show/Hide Causal Diseases (13)

Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession
Causal Diseases associated with Pathogenic or Likely Pathogenic variants in ClinVar
Abdominal colic	Likely pathogenic	rs1057518798	RCV000415419
Abnormal blistering of the skin	Likely pathogenic; Pathogenic	rs1057518798, rs148292941	RCV000415419 RCV000626658
Abnormal urinary color	Pathogenic	rs148292941	RCV000626658
Abnormality of metabolism/homeostasis	Likely pathogenic	rs2101886463	RCV001814441
Cardiomyopathy	Likely pathogenic; Pathogenic	rs2525306943	RCV006255220
Cervical cancer	Likely pathogenic	rs999497211	RCV005930670
Constipation	Pathogenic	rs148292941	RCV000626658
Hepatocellular carcinoma	Pathogenic	rs2101862742	RCV005868483
Migraine	Pathogenic	rs148292941	RCV000626658
Porphyrinuria	Likely pathogenic	rs1057518798	RCV000415419
See cases	Likely pathogenic; Pathogenic	rs41270025, rs2525251745	RCV002251893 RCV003334422
Variegate porphyria	Pathogenic; Likely pathogenic	rs2525204882, rs786204784, rs121918323, rs121918325, rs121918326, rs121918324, rs41270025, rs1571357779, rs2101902523, rs28936677, rs1659156571, rs1558033572, rs1571369150, rs1571418365	RCV002281665 RCV000169672 RCV000009230 RCV000009231 RCV000009232 RCV000009233 RCV000009234 RCV000009236 RCV000009237 RCV003324494 RCV003993553 RCV000761331 RCV002271591 RCV001253784
Variegate porphyria, childhood-onset	Likely pathogenic; Pathogenic	rs121918325, rs121918324, rs28936676, rs2101876868, rs28936677, rs2525249140, rs900431442, rs767419411, rs2525294446	RCV003324488 RCV003324489 RCV003324490 RCV003324491 RCV003324495 RCV003324652 RCV003324654 RCV003324655 RCV003324656

Show/Hide Unknown Diseases (5)

Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession
Unknown Diseases with uncertain, conflicting, or no pathogenic evidence in ClinVar
Acute intermittent porphyria	Uncertain significance	rs1553238545	RCV001844183
Acute myeloid leukemia	Likely benign	rs140861330	RCV005903267
PPOX-related disorder	Likely benign; Conflicting classifications of pathogenicity; Uncertain significance	rs150603927, rs12735723, rs2525192004	RCV003953767 RCV003924820 RCV003896266
Sarcoma	Uncertain significance; Likely benign	rs1661012592, rs140861330	RCV005932527 RCV005903268
Uterine corpus endometrial carcinoma	Likely benign	rs140861330	RCV005903269

Show/Hide Text Mining Associations (18)

Disease Name	Relationship Type	References
Associations from Text MiningDisease associations identified through Pubtator
Abdominal Pain	Associate	29516370
Adenocarcinoma	Associate	29425880
Carcinoma Hepatocellular	Associate	20814629
Coproporphyria Hereditary	Associate	21734717, 31073229
Genetic Diseases Inborn	Associate	23324528
Glomerulonephritis IGA	Associate	11286631
Nephrogenic Syndrome of Inappropriate Antidiuresis	Associate	29516370
Pediatric acute onset neuropsychiatric syndrome	Associate	23324528
Porphyria Acute Intermittent	Stimulate	27788171
Porphyria Acute Intermittent	Associate	31073229
Porphyria Chester type	Associate	11800145
Porphyria Variegate	Associate	10486317, 11286631, 17298217, 18570668, 20331452, 20814629, 21734717, 23324528, 23467411, 27746433, 28653968, 29516370, 31073229, 34968794, 36224252
Porphyria Variegate	Inhibit	11800145, 27788171
Porphyrias	Associate	21734717
Sarcoma	Associate	38316340
Skin Diseases	Associate	29130490, 29516370
Stomach Neoplasms	Associate	29425880
Urethral Neoplasms	Associate	24486590

PPOX (protoporphyrinogen oxidase)