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词条 PHF8
释义

  1. Function

  2. Regulation during differentation

  3. Clinical significance

  4. References

  5. External links

{{Infobox_gene}}PHD finger protein 8 is a protein that in humans is encoded by the PHF8 gene.[1]

Function

PHF8 belongs to the family of ferrous iron and alpha-ketoglutarate-dependent hydroxylases superfamily.,[2] and is active as a histone lysine demethylase with selectivity for the di-and monomethyl states.[3]

Regulation during differentation

PHF8 was found to be expressional increased during endothelial differentation and siginifcantly decreased during cardial differentation of murine embryonic stem cells.[4]

Clinical significance

Mutations in PHF8 cause Siderius type X-linked mental retardation (XLMR) ({{OMIM6|300263}}).[5][6][7]

In addition to moderate intellectual disability, features of the Siderius-Hamel syndrome include facial dysmorphism, cleft lip and/or cleft palate, and in some cases microcephaly.[8][9][10] A chromosomal microdeletion on Xp11.22 encompassing all of the PHF8 and FAM120C genes and a part of the WNK3 gene was reported in two brothers with autism spectrum disorder in addition to Siderius-type XLMR and cleft lip and palate.[11]

This catalytic activity is disrupted by clinically known mutations to PHF8, which were found to cluster in its catalytic JmjC domain. The F279S mutation of PHF8, found in 2 Finnish brothers with mild intellectual disability, facial dysmorphism and cleft lip/palate,[10] was found to additionally prevent nuclear localisation of PHF8 overexpressed in human cells.[3]

The catalytic activity of PHF8 depends on molecular oxygen,[3] a fact considered important with respect to reports on increased incidence of cleft lip/palate in mice that have been exposed to hypoxia during pregnancy.[12] In humans, fetal cleft lip and other congenital abnormalities have also been linked to maternal hypoxia, as caused by e.g. maternal smoking,[13] maternal alcohol abuse or maternal hypertension treatment.[14]

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References

1. ^{{cite web | title = Entrez Gene: PHF8 PHD finger protein 8| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=23133| accessdate = }}
2. ^{{cite journal | vauthors = Loenarz C, Schofield CJ | title = Expanding chemical biology of 2-oxoglutarate oxygenases | journal = Nature Chemical Biology | volume = 4 | issue = 3 | pages = 152–6 | date = Mar 2008 | pmid = 18277970 | doi = 10.1038/nchembio0308-152 }}
3. ^1 2 {{cite journal | vauthors = Loenarz C, Ge W, Coleman ML, Rose NR, Cooper CD, Klose RJ, Ratcliffe PJ, Schofield CJ | title = PHF8, a gene associated with cleft lip/palate and mental retardation, encodes for an Nepsilon-dimethyl lysine demethylase | journal = Human Molecular Genetics | volume = 19 | issue = 2 | pages = 217–22 | date = Jan 2010 | pmid = 19843542 | doi = 10.1093/hmg/ddp480 | pmc = 4673897 }}
4. ^{{Cite journal|last=Boeckel|first=Jes-Niels|last2=Derlet|first2=Anja|last3=Glaser|first3=Simone F.|last4=Luczak|first4=Annika|last5=Lucas|first5=Tina|last6=Heumüller|first6=Andreas W.|last7=Krüger|first7=Marcus|last8=Zehendner|first8=Christoph M.|last9=Kaluza|first9=David|date=July 2016|title=JMJD8 Regulates Angiogenic Sprouting and Cellular Metabolism by Interacting With Pyruvate Kinase M2 in Endothelial Cells|journal=Arteriosclerosis, Thrombosis, and Vascular Biology|volume=36|issue=7|pages=1425–1433|doi=10.1161/ATVBAHA.116.307695|issn=1524-4636|pmid=27199445}}
5. ^{{cite journal | vauthors = Siderius LE, Hamel BC, van Bokhoven H, de Jager F, van den Helm B, Kremer H, Heineman-de Boer JA, Ropers HH, Mariman EC | title = X-linked mental retardation associated with cleft lip/palate maps to Xp11.3-q21.3 | journal = American Journal of Medical Genetics | volume = 85 | issue = 3 | pages = 216–20 | date = Jul 1999 | pmid = 10398231 | doi = 10.1002/(SICI)1096-8628(19990730)85:3<216::AID-AJMG6>3.0.CO;2-X }}
6. ^{{cite web|url=https://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=300263|title=OMIM: Siderius X-linked mental retardation syndrome|accessdate=2009-10-21}}
7. ^{{cite web|url=https://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=300560|title=OMIM: PHD finger protein 8; PHF8|accessdate=2009-10-21}}
8. ^{{cite journal | vauthors = Abidi F, Miano M, Murray J, Schwartz C | title = A novel mutation in the PHF8 gene is associated with X-linked mental retardation with cleft lip/cleft palate | journal = Clinical Genetics | volume = 72 | issue = 1 | pages = 19–22 | date = Jul 2007 | pmid = 17594395 | pmc = 2570350 | doi = 10.1111/j.1399-0004.2007.00817.x }}
9. ^{{cite journal | vauthors = Laumonnier F, Holbert S, Ronce N, Faravelli F, Lenzner S, Schwartz CE, Lespinasse J, Van Esch H, Lacombe D, Goizet C, Phan-Dinh Tuy F, van Bokhoven H, Fryns JP, Chelly J, Ropers HH, Moraine C, Hamel BC, Briault S | title = Mutations in PHF8 are associated with X linked mental retardation and cleft lip/cleft palate | journal = Journal of Medical Genetics | volume = 42 | issue = 10 | pages = 780–6 | date = Oct 2005 | pmid = 16199551 | pmc = 1735927 | doi = 10.1136/jmg.2004.029439 }}
10. ^1 {{cite journal | vauthors = Koivisto AM, Ala-Mello S, Lemmelä S, Komu HA, Rautio J, Järvelä I | title = Screening of mutations in the PHF8 gene and identification of a novel mutation in a Finnish family with XLMR and cleft lip/cleft palate | journal = Clinical Genetics | volume = 72 | issue = 2 | pages = 145–9 | date = Aug 2007 | pmid = 17661819 | doi = 10.1111/j.1399-0004.2007.00836.x }}
11. ^{{cite journal | vauthors = Qiao Y, Liu X, Harvard C, Hildebrand MJ, Rajcan-Separovic E, Holden JJ, Lewis ME | title = Autism-associated familial microdeletion of Xp11.22 | journal = Clinical Genetics | volume = 74 | issue = 2 | pages = 134–44 | date = Aug 2008 | pmid = 18498374 | doi = 10.1111/j.1399-0004.2008.01028.x }}
12. ^{{cite journal | vauthors = Millicovsky G, Johnston MC | title = Hyperoxia and hypoxia in pregnancy: simple experimental manipulation alters the incidence of cleft lip and palate in CL/Fr mice | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 78 | issue = 9 | pages = 5722–3 | date = Sep 1981 | pmid = 6946511 | pmc = 348841 | doi = 10.1073/pnas.78.9.5722 }}
13. ^{{cite journal | vauthors = Shi M, Wehby GL, Murray JC | title = Review on genetic variants and maternal smoking in the etiology of oral clefts and other birth defects | journal = Birth Defects Research. Part C, Embryo Today | volume = 84 | issue = 1 | pages = 16–29 | date = Mar 2008 | pmid = 18383123 | pmc = 2570345 | doi = 10.1002/bdrc.20117 }}
14. ^{{cite journal | vauthors = Hurst JA, Houlston RS, Roberts A, Gould SJ, Tingey WG | title = Transverse limb deficiency, facial clefting and hypoxic renal damage: an association with treatment of maternal hypertension? | journal = Clinical Dysmorphology | volume = 4 | issue = 4 | pages = 359–63 | date = Oct 1995 | pmid = 8574428 | doi = 10.1097/00019605-199510000-00013 }}

External links

  • {{MeshName|PHF8+protein,+human}}
{{NLM content}}{{Transcription factors|g3}}{{Dioxygenases}}{{Enzymes}}{{Portal bar|Molecular and Cellular Biology|border=no}}

4 : Transcription factors|Genes on human chromosome X|Human 2OG oxygenases|EC 1.14.11
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