PHF8

PHD finger protein 8 is a is_associated_with::protein that in humans is encoded by the PHF8 is_associated_with::gene.

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

Clinical significance
Mutations in PHF8 cause Siderius type X-linked mental retardation (XLMR). In addition to moderate is_associated_with::intellectual disability, features of the Siderius-Hamel syndrome include facial dysmorphism, is_associated_with::cleft lip and/or cleft palate, and in some cases is_associated_with::microcephaly. A chromosomal is_associated_with::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 is_associated_with::autism spectrum disorder in addition to Siderius-type XLMR and is_associated_with::cleft lip and palate.

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 is_associated_with::intellectual disability, facial is_associated_with::dysmorphism and is_associated_with::cleft lip/palate, was found to additionally prevent is_associated_with::nuclear localisation of PHF8 overexpressed in human cells.

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