PHF8
Encyclopedia
PHD finger protein 8 is a protein
that in humans is encoded by the PHF8 gene
.
lysine demethylase with selectivity for the di-and monomethyl states.
(XLMR) .
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
. 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 mental retardation
, 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.
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
that in humans is encoded by the PHF8 gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
.
Function
PHF8 belongs to the family of ferrous iron and 2-oxoglutarate dependent oxygenases, and is active as a histoneHistone
In biology, histones are highly alkaline proteins found in eukaryotic cell nuclei that package and order the DNA into structural units called nucleosomes. They are the chief protein components of chromatin, acting as spools around which DNA winds, and play a role in gene regulation...
lysine demethylase with selectivity for the di-and monomethyl states.
Clinical significance
Mutations in PHF8 cause Siderius type X-linked mental retardationX-Linked mental retardation
X-linked mental retardation refers to forms of mental retardation which are specifically associated with X-linked recessive inheritance....
(XLMR) .
In addition to moderate mental retardation
Mental retardation
Mental retardation is a generalized disorder appearing before adulthood, characterized by significantly impaired cognitive functioning and deficits in two or more adaptive behaviors...
, features of the Siderius-Hamel syndrome include facial dysmorphism, cleft lip and/or cleft palate, and in some cases microcephaly
Microcephaly
Microcephaly is a neurodevelopmental disorder in which the circumference of the head is more than two standard deviations smaller than average for the person's age and sex. Microcephaly may be congenital or it may develop in the first few years of life...
. 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 mental retardation
Mental retardation
Mental retardation is a generalized disorder appearing before adulthood, characterized by significantly impaired cognitive functioning and deficits in two or more adaptive behaviors...
, 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
Oxygen is the element with atomic number 8 and represented by the symbol O. Its name derives from the Greek roots ὀξύς and -γενής , because at the time of naming, it was mistakenly thought that all acids required oxygen in their composition...
, a fact considered important with respect to reports on increased incidence of cleft lip/palate in mice that have been exposed to hypoxia
Hypoxia (medical)
Hypoxia, or hypoxiation, is a pathological condition in which the body as a whole or a region of the body is deprived of adequate oxygen supply. Variations in arterial oxygen concentrations can be part of the normal physiology, for example, during strenuous physical exercise...
during pregnancy
Pregnancy
Pregnancy refers to the fertilization and development of one or more offspring, known as a fetus or embryo, in a woman's uterus. In a pregnancy, there can be multiple gestations, as in the case of twins or triplets...
. 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
Alcohol abuse
Alcohol abuse, as described in the DSM-IV, is a psychiatric diagnosis describing the recurring use of alcoholic beverages despite negative consequences. Alcohol abuse eventually progresses to alcoholism, a condition in which an individual becomes dependent on alcoholic beverages in order to avoid...
or maternal hypertension
Hypertension
Hypertension or high blood pressure is a cardiac chronic medical condition in which the systemic arterial blood pressure is elevated. What that means is that the heart is having to work harder than it should to pump the blood around the body. Blood pressure involves two measurements, systolic and...
treatment.