PHD finger protein 8 is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

that in humans is encoded by the ''PHF8''

gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

Function

PHF8 belongs to the family of ferrous iron and

alpha-ketoglutarate-dependent hydroxylases Alpha-ketoglutarate-dependent hydroxylases are a major class of non-heme iron proteins that catalyse a wide range of reactions. These reactions include hydroxylation reactions, demethylations, ring expansions, ring closures, and desaturations. Func ...

superfamily., and is active as a histone lysine demethylase with selectivity for the di-and monomethyl states. PHF8 induces an EMT (epithelial to mesenchymal transition)-like process by upregulating key EMT transcription factors SNAI1 and ZEB1.

Regulation during differentiation

PHF8 was found to be expressional increased during endothelial differentiation and significantly decreased during cardial differentiation of murine embryonic stem cells.

Clinical significance

Mutations in PHF8 cause Siderius type

X-linked intellectual disability X-linked intellectual disability refers to medical disorders associated with X-linked recessive inheritance that result in intellectual disability. As with most X-linked disorders, males are more heavily affected than females. Females with one a ...

(XLMR) (). In addition to moderate

intellectual disability Intellectual disability (ID), also known as general learning disability (in the United Kingdom), and formerly mental retardation (in the United States), Rosa's Law, Pub. L. 111-256124 Stat. 2643(2010).Archive is a generalized neurodevelopmental ...

, features of the Siderius-Hamel syndrome include facial dysmorphism,

cleft lip A cleft lip contains an opening in the upper lip that may extend into the nose. The opening may be on one side, both sides, or in the middle. A cleft palate occurs when the palate (the roof of the mouth) contains an opening into the nasal cavi ...

and/or cleft palate, and in some cases

microcephaly Microcephaly (from Neo-Latin ''microcephalia'', from Ancient Greek μικρός ''mikrós'' "small" and κεφαλή ''kephalé'' "head") is a medical condition involving a smaller-than-normal head. Microcephaly may be present at birth or it m ...

. A chromosomal

microdeletion In genetics, a deletion (also called gene deletion, deficiency, or Deletion anomaly, deletion mutation) (sign: delta (letter), Δ) is a mutation (a genetic aberration) in which a part of a chromosome or a sequence of DNA is left out during DNA rep ...

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 Autism, also known as autism spectrum disorder (ASD), is a neurodevelopmental disorder characterized by differences or difficulties in social communication and interaction, a preference for predictability and routine, sensory processing di ...

in addition to Siderius-type XLMR and

cleft lip and palate A cleft lip contains an opening in the upper lip that may extend into the nose. The opening may be on one side, both sides, or in the middle. A cleft palate occurs when the palate (the roof of the mouth) contains an opening into the nose. The ...

. 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

, 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 Oxygen is a chemical element; it has chemical symbol, symbol O and atomic number 8. It is a member of the chalcogen group (periodic table), group in the periodic table, a highly reactivity (chemistry), reactive nonmetal (chemistry), non ...

, 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 Pregnancy is the time during which one or more offspring gestation, gestates inside a woman's uterus. A multiple birth, multiple pregnancy involves more than one offspring, such as with twins. Conception (biology), Conception usually occurs ...

. In humans,

fetal A fetus or foetus (; : fetuses, foetuses, rarely feti or foeti) is the unborn offspring of a viviparous animal that develops from an embryo. Following the embryonic stage, the fetal stage of development takes place. Prenatal development is a ...

cleft lip and other

congenital abnormalities A birth defect is an abnormal condition that is present at birth, regardless of its cause. Birth defects may result in disabilities that may be physical, intellectual, or developmental. The disabilities can range from mild to severe. Birth de ...

have also been linked to maternal hypoxia, as caused by e.g. maternal smoking, heavy maternal alcohol use, or maternal

hypertension Hypertension, also known as high blood pressure, is a Chronic condition, long-term Disease, medical condition in which the blood pressure in the artery, arteries is persistently elevated. High blood pressure usually does not cause symptoms i ...

treatment.

References

External links

* {{Portal bar, Biology, border=no Transcription factors Genes on human chromosome X Human 2OG oxygenases EC 1.14.11