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Mutations in PHF8 cause Siderius type X-linked mental retardation (XLMR) (OMIM 300263). 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. 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.
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, was found to additionally prevent nuclear localisation of PHF8 overexpressed in human cells.
The catalytic activity of PHF8 depends on molecular oxygen, 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. In humans, fetal cleft lip and other congenital abnormalities have also been linked to maternal hypoxia, as caused by e.g. maternal smoking, maternal alcohol abuse or maternal hypertension treatment.
- "Diseases that are genetically associated with PHF8 view/edit references on wikidata".
- "Drugs that physically interact with Histone lysine demethylase PHF8 view/edit references on wikidata".
- "Human PubMed Reference:".
- "Mouse PubMed Reference:".
- "Entrez Gene: PHF8 PHD finger protein 8".
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- "OMIM: Siderius X-linked mental retardation syndrome". Retrieved 2009-10-21.
- "OMIM: PHD finger protein 8; PHF8". Retrieved 2009-10-21.
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