Details of Disease

General Information of Disease (ID: DISH4BY0)

• Disease Name: Erythropoietic protoporphyria
• Synonyms: protoporphyria; EPP (erythropoietic protoporphyria porphyria)
• Disease Class: 5C58: Inborn porphyrin/heme metabolism error
• Definition: A rare congenital metabolic disorder characterized by an inborn error of porphyrin-heme biosynthesis. Signs and symptoms include painful cutaneous photosensitivity leading to blistering and scarring of the exposed skin areas, erythrodontia, red discoloration of urine, hemolytic anemia, and splenomegaly.
• Disease Hierarchy:
  DISMI8EV: Hepatic porphyria
  DISEPFG2: Inherited porphyria
  DISH4BY0: Erythropoietic protoporphyria
• ICD Code: ICD-11: ICD-11: 5C58.12
• Disease Identifiers:
  MONDO ID: MONDO_0001676
  MESH ID: D046351
  UMLS CUI: C0162568
  MedGen ID: 56455
  SNOMED CT ID: 51022005

Drug-Interaction Atlas (DIA) of This Disease

This Disease is Treated as An Indication in 1 Approved Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
Afamelanotide	DMVWHTG	Approved	Small molecular drug	[1]

This Disease is Treated as An Indication in 1 Clinical Trial Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
Dersimelagon	DMMO0SU	Phase 3	Small molecule	[2]

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 5 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
ABCG2	TTIMJ02	Strong	Biomarker	[3]
ALAS1	TTG1FXO	Strong	Altered Expression	[4]
PPOX	TTNFMS9	Strong	Genetic Variation	[5]
AREG	TT76B3W	Definitive	Biomarker	[6]
EREG	TTYSB89	Definitive	Biomarker	[6]

This Disease Is Related to 1 DTP Molecule(s)

Gene Name	DTP ID	Evidence Level	Mode of Inheritance	REF
SLC25A37	DTLBGTZ	Strong	Altered Expression	[7]

This Disease Is Related to 1 DME Molecule(s)

Gene Name	DME ID	Evidence Level	Mode of Inheritance	REF
ALAS2	DE437BY	Strong	Genetic Variation	[4]

This Disease Is Related to 3 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
SUCLA2	OTMZD4PW	Limited	Genetic Variation	[8]
CLPX	OTIT4JL0	Strong	Biomarker	[9]
BTC	OTW4B2O0	Definitive	Biomarker	[6]

References

• [1] Afamelanotide FDA Label
• [2] ClinicalTrials.gov (NCT04402489) A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate Efficacy, Safety, and Tolerability of MT-7117 in Adults and Adolescents With Erythropoietic Protoporphyria or X-Linked Protoporphyria. U.S.National Institutes of Health.
• [3] The essential role of the transporter ABCG2 in the pathophysiology of erythropoietic protoporphyria.Sci Adv. 2019 Sep 18;5(9):eaaw6127. doi: 10.1126/sciadv.aaw6127. eCollection 2019 Sep.
• [4] Regulation and tissue-specific expression of -aminolevulinic acid synthases in non-syndromic sideroblastic anemias and porphyrias.Mol Genet Metab. 2019 Nov;128(3):190-197. doi: 10.1016/j.ymgme.2019.01.015. Epub 2019 Jan 23.
• [5] Molecular characterization of porphyrias in Italy: a diagnostic flow-chart.Cell Mol Biol (Noisy-le-grand). 2002 Dec;48(8):867-76.
• [6] Epidermal growth factor receptor ligands in murine models for erythropoietic protoporphyria: potential novel players in the progression of liver injury.Cell Mol Biol (Noisy-le-grand). 2009 Feb 16;55(1):29-37.
• [7] Strong correlation of ferrochelatase enzymatic activity with Mitoferrin-1 mRNA in lymphoblasts of patients with protoporphyria.Mol Genet Metab. 2019 Nov;128(3):391-395. doi: 10.1016/j.ymgme.2018.10.005. Epub 2018 Oct 22.
• [8] X-linked sideroblastic anemia due to carboxyl-terminal ALAS2 mutations that cause loss of binding to the -subunit of succinyl-CoA synthetase (SUCLA2).J Biol Chem. 2012 Aug 17;287(34):28943-55. doi: 10.1074/jbc.M111.306423. Epub 2012 Jun 27.
• [9] Mutation in human CLPX elevates levels of -aminolevulinate synthase and protoporphyrin IX to promote erythropoietic protoporphyria. Proc Natl Acad Sci U S A. 2017 Sep 19;114(38):E8045-E8052. doi: 10.1073/pnas.1700632114. Epub 2017 Sep 5.