PHF8 belongs to the family of ferrous iron andalpha-ketoglutarate-dependent hydroxylases superfamily.,[6] and is active as ahistone lysine demethylase with selectivity for the di-and monomethyl states.[7] PHF8 induces an EMT (epithelial to mesenchymal transition)-like process by upregulating key EMT transcription factors SNAI1 and ZEB1.
PHF8 was found to be expressional increased during endothelial differentiation and significantly decreased during cardial differentiation of murine embryonic stem cells.[8]
This catalytic activity is disrupted by clinically known mutations toPHF8, which were found to cluster in its catalytic JmjC domain. The F279S mutation of PHF8, found in 2 Finnish brothers with mildintellectual disability, facialdysmorphism andcleft lip/palate,[14] was found to additionally preventnuclear localisation of PHF8 overexpressed in human cells.[7]
^Loenarz C, Schofield CJ (Mar 2008). "Expanding chemical biology of 2-oxoglutarate oxygenases".Nature Chemical Biology.4 (3):152–6.doi:10.1038/nchembio0308-152.PMID18277970.
^abKoivisto AM, Ala-Mello S, Lemmelä S, Komu HA, Rautio J, Järvelä I (Aug 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".Clinical Genetics.72 (2):145–9.doi:10.1111/j.1399-0004.2007.00836.x.PMID17661819.S2CID23326755.
^Hurst JA, Houlston RS, Roberts A, Gould SJ, Tingey WG (Oct 1995). "Transverse limb deficiency, facial clefting and hypoxic renal damage: an association with treatment of maternal hypertension?".Clinical Dysmorphology.4 (4):359–63.doi:10.1097/00019605-199510000-00013.PMID8574428.S2CID6330050.
