Details of Disease

General Information of Disease (ID: DIS8WUQG)

Disease Name	Pseudoxanthoma elasticum
Synonyms	PXE; pseudoxanthoma elasticum
Disease Class	EC40: Pseudoxanthoma elasticum
Definition	An inherited disorder that causes calcium and other minerals to accumulate in the elastic fibers of the skin, eyes, and blood vessels, and less frequently in other areas such as the digestive tract.
Disease Hierarchy	DISTXWNT: Integumentary system disorder DIS8WUQG: Pseudoxanthoma elasticum
ICD Code	ICD-11 ICD-11: EC40
Disease Identifiers	MONDO ID MONDO_0024308 MESH ID D011561 UMLS CUI C0033847 OMIM ID 264800 MedGen ID 18733 SNOMED CT ID 252246005

Drug-Interaction Atlas (DIA) of This Disease

Drug-Interaction Atlas (DIA)

This Disease is Treated as An Indication in 2 Clinical Trial Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
DS-1211	DMY3T0L	Phase 2	Small molecule	[1]
INZ-701	DMNC1AS	Phase 1/2	Enzyme replacement	[2]
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Molecular Interaction Atlas (MIA) of This Disease

Molecular Interaction Atlas (MIA)

This Disease Is Related to 7 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
ABCG2	TTIMJ02	Limited	Genetic Variation	[3]
S100A12	TTQ4ESF	Limited	Biomarker	[4]
VKORC1	TTEUC8H	Limited	Biomarker	[5]
ABCC2	TTFLHJV	Strong	Genetic Variation	[6]
AHSG	TTKF4WV	Strong	Biomarker	[7]
ENPP1	TTZTIWS	Strong	Biomarker	[8]
NT5E	TTK0O6Y	Strong	Genetic Variation	[9]
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⏷ Show the Full List of 7 DTT(s)

This Disease Is Related to 3 DTP Molecule(s)

Gene Name	DTP ID	Evidence Level	Mode of Inheritance	REF
ABCA12	DT7LDG0	Strong	Biomarker	[10]
ABCA3	DT2T6VQ	Strong	Genetic Variation	[11]
ABCB6	DTF9Y2V	Strong	Genetic Variation	[12]
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This Disease Is Related to 5 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
ELN	OTFSO7PG	Limited	Biomarker	[13]
ANKH	OTCN25R5	moderate	Altered Expression	[14]
MGP	OTZWU3FU	Strong	Biomarker	[15]
NPIPA1	OTAUFC2I	Strong	Genetic Variation	[16]
NPIPA5	OTGIKZ9V	Strong	Genetic Variation	[16]
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References

1	ClinicalTrials.gov (NCT05569252) A Phase 2, 12-Week, Randomized, Double-Blind, Placebo-Controlled Study of DS-1211b in Individuals With PseudoXanthoma Elasticum. U.S.National Institutes of Health.
2	ClinicalTrials.gov (NCT05030831) A Phase 1/2, Open-Label, Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of INZ-701 Followed by an Open-Label Long-Term Extension Period in Adults With ABCC6 Deficiency Manifesting as Pseudoxanthoma Elasticum (PXE). U.S.National Institutes of Health.
3	Stabilization of Nucleotide Binding Domain Dimers Rescues ABCC6 Mutants Associated with Pseudoxanthoma Elasticum.J Biol Chem. 2017 Feb 3;292(5):1559-1572. doi: 10.1074/jbc.M116.759811. Epub 2016 Dec 19.
4	Whole exome sequencing identified three ABCC6 variants in two Pakistani families with pseudoxanthoma elasticum phenotype.Mol Biol Rep. 2019 Feb;46(1):1363-1368. doi: 10.1007/s11033-018-04581-x. Epub 2019 Feb 25.
5	Efficiency of exome sequencing for the molecular diagnosis of pseudoxanthoma elasticum.J Invest Dermatol. 2015 Apr;135(4):992-998. doi: 10.1038/jid.2014.421. Epub 2014 Sep 29.
6	Multidrug resistance proteins (MRPs/ABCCs) in cancer chemotherapy and genetic diseases.FEBS J. 2011 Sep;278(18):3226-45. doi: 10.1111/j.1742-4658.2011.08235.x. Epub 2011 Aug 1.
7	An unusual severe vascular case of pseudoxanthoma elasticum presenting as generalized arterial calcification of infancy.Am J Med Genet A. 2010 Jan;152A(1):118-23. doi: 10.1002/ajmg.a.33162.
8	Inhibition of Tissue-Nonspecific Alkaline Phosphatase Attenuates Ectopic Mineralization in the Abcc6(-/-) Mouse Model of PXE but Not in the Enpp1 Mutant Mouse Models of GACI.J Invest Dermatol. 2019 Feb;139(2):360-368. doi: 10.1016/j.jid.2018.07.030. Epub 2018 Aug 18.
9	Severe early-onset manifestations of pseudoxanthoma elasticum resulting from the cumulative effects of several deleterious mutations in ENPP1, ABCC6 and HBB: transient improvement in ectopic calcification with sodium thiosulfate.Br J Dermatol. 2020 Aug;183(2):367-372. doi: 10.1111/bjd.18632. Epub 2019 Dec 22.
10	The gene family of ABC transporters--novel mutations, new phenotypes.Trends Mol Med. 2005 Aug;11(8):341-3. doi: 10.1016/j.molmed.2005.06.004.
11	Gene expression profiling of ABC transporters in dermal fibroblasts of pseudoxanthoma elasticum patients identifies new candidates involved in PXE pathogenesis.Lab Invest. 2008 Dec;88(12):1303-15. doi: 10.1038/labinvest.2008.96. Epub 2008 Oct 20.
12	Structural analysis reveals pathomechanisms associated with pseudoxanthoma elasticum-causing mutations in the ABCC6 transporter. J Biol Chem. 2018 Oct 12;293(41):15855-15866.
13	Microscopy with ultraviolet surface excitation (MUSE): A novel approach to real-time inexpensive slide-free dermatopathology.J Cutan Pathol. 2018 Jul;45(7):498-503. doi: 10.1111/cup.13255. Epub 2018 May 8.
14	Cellular signaling in pseudoxanthoma elasticum: an update.Cell Signal. 2019 Mar;55:119-129. doi: 10.1016/j.cellsig.2018.12.009. Epub 2019 Jan 4.
15	Matrix gla protein and alkaline phosphatase are differently modulated in human dermal fibroblasts from PXE patients and controls.J Invest Dermatol. 2013 Apr;133(4):946-54. doi: 10.1038/jid.2012.460. Epub 2012 Dec 6.
16	Identification of novel polymorphisms in the pM5 and MRP1 (ABCC1) genes at locus 16p13.1 and exclusion of both genes as responsible for pseudoxanthoma elasticum.Hum Mutat. 2001;17(1):74-5. doi: 10.1002/1098-1004(2001)17:1<74::AID-HUMU14>3.0.CO;2-F.