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PHD finger protein 8
Symbols PHF8; ZNF422; DKFZp686E0868; KIAA1111; MRXSSD
External IDs OMIM300560 MGI2444341 HomoloGene49405 GeneCards: PHF8 Gene
Species Human Mouse
Entrez 23133 320595
Ensembl ENSG00000172943 ENSMUSG00000041229
UniProt Q9UPP1 Q3UXF1
RefSeq (mRNA) NM_015107 NM_177201
RefSeq (protein) NP_055922 NP_796175
Location (UCSC) Chr X:
53.96 - 54.08 Mb
Chr X:
146.86 - 146.97 Mb
PubMed search [1] [2]

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



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

Clinical significance

Mutations in PHF8 cause Siderius type X-linked mental retardation (XLMR) (OMIM 300263).[4][5][6] In addition to moderate mental retardation, features of the Siderius-Hamel syndrome include facial dysmorphism, cleft lip and/or cleft palate, and in some cases microcephaly.[7][8][9] 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.[10]

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 mental retardation, facial dysmorphism and cleft lip/palate,[9] 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.[11] In humans, fetal cleft lip and other congenital abnormalities have also been linked to maternal hypoxia, as caused by e.g. maternal smoking,[12] maternal alcohol abuse or maternal hypertension treatment.[13]


  1. ^ "Entrez Gene: PHF8 PHD finger protein 8".  
  2. ^ Loenarz, C.; Schofield, C. J. (2008). "Expanding chemical biology of 2-oxoglutarate oxygenases". Nat. Chem. Biol. 4 (3): 152-156. doi:10.1038/nchembio0308-152. PMID 18277970.  
  3. ^ a b c Loenarz, C.; Ge W., Coleman M. L., Rose N. R., Cooper C. D. O., Klose R. J., Ratcliffe P. J., Schofield, C. J. (2009). "PHF8, a gene associated with cleft lip/palate and mental retardation, encodes for an N{varepsilon}-dimethyl lysine demethylase". Hum. Mol. Genet.. doi:10.1093/hmg/ddp480. PMID 19843542.  
  4. ^ Siderius LE, Hamel BC, van Bokhoven H, et al. (2000). "X-linked mental retardation associated with cleft lip/palate maps to Xp11.3-q21.3.". Am. J. Med. Genet. 85 (3): 216–220. doi:10.1002/(SICI)1096-8628(19990730)85:3<216::AID-AJMG6>3.0.CO;2-X. PMID 10398231.  
  5. ^ "OMIM: Siderius X-linked mental retardation syndrome". Retrieved 2009-10-21.  
  6. ^ "OMIM: PHD finger protein 8; PHF8". Retrieved 2009-10-21.  
  7. ^ Abidi, F. E.; Miano, M. G.; Murray, J. C.; Schwartz, C. E. (2007). "A novel mutation in the PHF8 gene is associated with X-linked mental retardation with cleft lip/cleft palate". Clin. Genet. 72 (1): 19-22. doi:10.1111/j.1399-0004.2007.00817.x. PMID 17594395.  
  8. ^ Laumonnier F, Holbert S, Ronce N, et al. (2006). "Mutations in PHF8 are associated with X linked mental retardation and cleft lip/cleft palate.". J. Med. Genet. 42 (10): 780–786. doi:10.1136/jmg.2004.029439. PMID 16199551.  
  9. ^ a b Koivisto AM, Ala-Mello S, Lemmelä S, et al. (2007). "Screening of mutations in the PHF8 gene and identification of a novel mutation in a Finnish family with XLMR and cleft lip/cleft palate.". Clin. Genet. 72 (2): 145–149. doi:10.1111/j.1399-0004.2007.00836.x. PMID 17661819.  
  10. ^ Qiao, Y; Liu, X.; Harvard, C.; Hildebrand, M. J.; Rajcan-Separovic, E.; Holden, J. J. A.; Lewis, M. E. S. (2008). "Autism-associated familial microdeletion of Xp11.22". Clin. Genet. 74 (2): 134-144. doi:10.1111/j.1399-0004.2008.01028.x. PMID 18498374.  
  11. ^ Millicovsky, G.; Johnston, M.C. (1981). "Hyperoxia and hypoxia in pregnancy: simple experimental manipulation alters the incidence of cleft lip and palate in CL/Fr mice". Proc. Natl. Acad. Sci. U. S. A. 78 (9): 5722-5723. PMID 6946511.  
  12. ^ Shi, M.; Wehby, G.L. and Murray, J.C. (2008). "Review on genetic variants and maternal smoking in the etiology of oral clefts and other birth defects". Birth Defects Res., Part C 84 (1): 16-29. doi:10.1002/bdrc.20117. PMID 18383123.  
  13. ^ Hurst, J. A.; Houlston, R.S., Roberts, A., Gould, S.J. and Tingey, W.G. (1995). "Transverse limb deficiency, facial clefting and hypoxic renal damage: an association with treatment of maternal hypertension?". Clin. Dysmorphol. 4: 359-363. PMID 8574428.  

Further reading

External links

This article incorporates text from the United States National Library of Medicine, which is in the public domain.



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