Details of Disease

General Information of Disease (ID: DISQ9H19)

• Disease Name: Xeroderma pigmentosum
• Synonyms: xeroderma pigmentosa; Kaposi dermatosis; xeroderma of Kaposi; angioma pigmentosum atrophicum; melanosis lenticularis progressiva; atrophoderma pigmentosum; pigmented epitheliomatosis; xeroderma pigmentosum syndrome; Kaposi disease; XP
• Definition: Xeroderma pigmentosum (XP) is a rare genodermatosis characterized by extreme sensitivity to ultraviolet (UV)-induced changes in the skin and eyes, and multiple skin cancers. It is subdivided into 8 complementation groups, according to the affected gene: classical XP (XPA to XPG) and XP variant (XPV).
• Disease Hierarchy:
  DISN7YWO: DNA repair disease
  DISYJQB2: Hereditary photodermatosis
  DISQ9H19: Xeroderma pigmentosum
• Disease Identifiers:
  MONDO ID: MONDO_0019600
  MESH ID: D014983
  UMLS CUI: C0043346
  MedGen ID: 21943
  Orphanet ID: 910
  SNOMED CT ID: 44600005

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 35 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
XPA	OTO2MEFR	Supportive	Autosomal recessive	[1]
XPC	OTB09PXO	Supportive	Autosomal recessive	[1]
AAGAB	OTRGGM2Z	Limited	Genetic Variation	[9]
CRLF3	OTT9TMXN	Limited	Genetic Variation	[10]
DDB1	OTTR2L3Z	Limited	Genetic Variation	[11]
IFI44	OTOKSZVA	Limited	Genetic Variation	[9]
IRF9	OTK4MYQJ	Limited	Genetic Variation	[10]
LRRC59	OT6BQJ5E	Limited	Genetic Variation	[9]
PTF1A	OT7SWA57	Limited	Genetic Variation	[10]
RAD23A	OTBPAWHX	Limited	Altered Expression	[12]
DDB2	OTO8HVVB	Supportive	Autosomal recessive	[1]
ERCC2	OT1C8HQ4	Supportive	Autosomal recessive	[1]
ERCC3	OTVAW3P1	Supportive	Autosomal recessive	[1]
ERCC4	OTFIOPG1	Supportive	Autosomal recessive	[1]
ERCC5	OTQAKFJM	Supportive	Autosomal recessive	[1]
RAD54L	OTEGMAKG	moderate	Genetic Variation	[13]
BTN2A2	OTUOAJZA	Strong	Genetic Variation	[14]
CCNH	OTKDU3SR	Strong	Genetic Variation	[9]
CETN2	OTJTTGS0	Strong	Biomarker	[15]
DDX11	OT1WR3MD	Strong	Genetic Variation	[2]
ENDOV	OTX2GXXX	Strong	Biomarker	[16]
EXO1	OTI87RS5	Strong	Biomarker	[5]
HERC2	OTNQYKOB	Strong	Genetic Variation	[17]
HFM1	OTHV3EFE	Strong	Genetic Variation	[18]
KAT7	OTUN98IC	Strong	Biomarker	[19]
LCE2B	OTA53PGQ	Strong	Genetic Variation	[20]
LIG4	OT40DNXU	Strong	Biomarker	[21]
MEPE	OTXJRUW0	Strong	Biomarker	[22]
POLH	OTN07WXU	Strong	Genetic Variation	[4]
POLQ	OTBHK0E6	Strong	Genetic Variation	[23]
RAD23B	OT0PGOG3	Strong	Altered Expression	[12]
RECQL	OTPCH3JH	Strong	Biomarker	[24]
SLX4	OTF6236I	Strong	Genetic Variation	[25]
SYCP1	OTWFV4KA	Strong	Genetic Variation	[26]
TALDO1	OTDKV2S2	Strong	Altered Expression	[27]

This Disease Is Related to 7 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
BRIP1	TTZV7LJ	Limited	Biomarker	[2]
XPA	TTGT87E	Supportive	Autosomal recessive	[1]
XPA	TTGT87E	moderate	Altered Expression	[3]
CATSPER1	TT5CISB	Strong	Genetic Variation	[4]
GOT1	TTU507L	Strong	Biomarker	[5]
TDG	TTEXRQD	Strong	Altered Expression	[6]
CSNK2A1	TTER6YH	Definitive	Biomarker	[7]

This Disease Is Related to 1 DME Molecule(s)

Gene Name	DME ID	Evidence Level	Mode of Inheritance	REF
HPRT1	DEVXTP5	Strong	Genetic Variation	[8]

References

• [1] Xeroderma Pigmentosum. 2003 Jun 20 [updated 2022 Mar 24]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews(?) [Internet]. Seattle (WA): University of Washington, Seattle; 1993C2024.
• [2] Specialization among iron-sulfur cluster helicases to resolve G-quadruplex DNA structures that threaten genomic stability.J Biol Chem. 2013 Sep 27;288(39):28217-29. doi: 10.1074/jbc.M113.496463. Epub 2013 Aug 9.
• [3] Endothelin-1 and -melanocortin have redundant effects on global genome repair in UV-irradiated human melanocytes despite distinct signaling pathways.Pigment Cell Melanoma Res. 2020 Mar;33(2):293-304. doi: 10.1111/pcmr.12823. Epub 2019 Oct 4.
• [4] Exome-based search for recurrent disease-causing alleles in Russian population.Eur J Med Genet. 2019 Jul;62(7):103656. doi: 10.1016/j.ejmg.2019.04.013. Epub 2019 Apr 24.
• [5] XPG-related nucleases are hierarchically recruited for double-stranded rDNA break resection.J Biol Chem. 2019 May 10;294(19):7632-7643. doi: 10.1074/jbc.RA118.005415. Epub 2019 Mar 18.
• [6] Xeroderma pigmentosum group C protein interacts physically and functionally with thymine DNA glycosylase.EMBO J. 2003 Jan 2;22(1):164-73. doi: 10.1093/emboj/cdg016.
• [7] Expression of the cDNA for the beta subunit of human casein kinase II confers partial UV resistance on xeroderma pigmentosum cells.Mutat Res. 1990 Jul;236(1):85-97. doi: 10.1016/0921-8777(90)90036-5.
• [8] Elevated levels of somatic mutation in a manifesting BRCA1 mutation carrier.Pathol Oncol Res. 2007;13(4):276-83. doi: 10.1007/BF02940305. Epub 2007 Dec 25.
• [9] The intricate network between the p34 and p44 subunits is central to the activity of the transcription/DNA repair factor TFIIH.Nucleic Acids Res. 2017 Oct 13;45(18):10872-10883. doi: 10.1093/nar/gkx743.
• [10] Xeroderma pigmentosum p48 gene enhances global genomic repair and suppresses UV-induced mutagenesis.Mol Cell. 2000 Apr;5(4):737-44. doi: 10.1016/s1097-2765(00)80252-x.
• [11] Dynamics of DDB2-DDB1 complex under different naturally-occurring mutants in Xeroderma Pigmentosum disease.Biochim Biophys Acta Gen Subj. 2018 Dec;1862(12):2579-2589. doi: 10.1016/j.bbagen.2018.08.007. Epub 2018 Aug 6.
• [12] C9ORF72 poly(GA) aggregates sequester and impair HR23 and nucleocytoplasmic transport proteins.Nat Neurosci. 2016 May;19(5):668-677. doi: 10.1038/nn.4272. Epub 2016 Mar 21.
• [13] hRAD54 gene and 1p high-resolution deletion-mapping analyses in oligodendrogliomas.Cancer Genet Cytogenet. 2000 Jan 15;116(2):142-7. doi: 10.1016/s0165-4608(99)00122-3.
• [14] DNA repair helicase: a component of BTF2 (TFIIH) basic transcription factor.Science. 1993 Apr 2;260(5104):58-63. doi: 10.1126/science.8465201.
• [15] Xeroderma pigmentosum group C protein possesses a high affinity binding site to human centrin 2 and calmodulin.J Biol Chem. 2003 Oct 10;278(41):40252-61. doi: 10.1074/jbc.M302546200. Epub 2003 Jul 30.
• [16] Cell-free repair of UV-damaged simian virus 40 chromosomes in human cell extracts. II. Defective DNA repair synthesis by xeroderma pigmentosum cell extracts.J Biol Chem. 1993 Apr 25;268(12):9105-9.
• [17] Whole genome sequencing and 6-year follow-up of a mother and daughter with frontometaphyseal dysplasia associated with keratitis, xerosis, poikiloderma, and acro-osteolysis: A case report.Medicine (Baltimore). 2018 Jul;97(28):e11283. doi: 10.1097/MD.0000000000011283.
• [18] Differential developmental expression of the rep B and rep D xeroderma pigmentosum related DNA helicase genes from Dictyostelium discoideum.Nucleic Acids Res. 1997 Jun 15;25(12):2365-74. doi: 10.1093/nar/25.12.2365.
• [19] Phosphorylated HBO1 at UV irradiated sites is essential for nucleotide excision repair.Nat Commun. 2017 Jul 18;8:16102. doi: 10.1038/ncomms16102.
• [20] Clinical and molecular epidemiological study of xeroderma pigmentosum in China: A case series of 19 patients. J Dermatol. 2017 Jan;44(1):71-75. doi: 10.1111/1346-8138.13576. Epub 2016 Sep 8.
• [21] Accelerated telomere shortening and telomere abnormalities in radiosensitive cell lines.Radiat Res. 2005 Jul;164(1):53-62. doi: 10.1667/rr3376.
• [22] Clinical symptoms and DNA repair characteristics of xeroderma pigmentosum patients from Germany.Cancer Res. 1991 Jul 1;51(13):3456-70.
• [23] Differential Roles of Rad18 and Chk2 in Genome Maintenance and Skin Carcinogenesis Following UV Exposure.J Invest Dermatol. 2018 Dec;138(12):2550-2557. doi: 10.1016/j.jid.2018.05.015. Epub 2018 May 31.
• [24] Alteration of a DNA-dependent ATPase activity in xeroderma pigmentosum complementation group C cells.J Biol Chem. 1992 Feb 25;267(6):3585-8.
• [25] Physical interaction between SLX4 (FANCP) and XPF (FANCQ) proteins and biological consequences of interaction-defective missense mutations.DNA Repair (Amst). 2015 Nov;35:48-54. doi: 10.1016/j.dnarep.2015.09.022. Epub 2015 Sep 30.
• [26] Reactivity of germ cell maturation stage-specific markers in spermatocytic seminoma: diagnostic and etiological implications.Lab Invest. 2001 Jul;81(7):919-28. doi: 10.1038/labinvest.3780302.
• [27] Relationship between posttranslational modification of transaldolase and catalase deficiency in UV-sensitive repair-deficient xeroderma pigmentosum fibroblasts and SV40-transformed human cells.Free Radic Biol Med. 2001 Jun 15;30(12):1365-73. doi: 10.1016/s0891-5849(01)00532-9.