PHF8

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What is the official name of the PHF8 gene?

The official name of this gene is “PHD finger protein 8.”

PHF8 is the gene's official symbol. The PHF8 gene is also known by other names, listed below.

Read more about gene names and symbols on the About page.

What is the normal function of the PHF8 gene?

The PHF8 gene provides instructions for making a protein that is found in the cell nucleus, particularly in brain cells before and just after birth. The PHF8 protein is part of a group known as zinc finger proteins, which contain one or more short regions called zinc finger domains. These regions include a specific pattern of protein building blocks (amino acids) and one or more charged atoms of zinc (zinc ions). The folded configuration of the zinc finger domain stabilizes the protein and allows it to attach (bind) to other molecules.

The PHF8 protein contains a specific zinc finger domain called a PHD domain, which binds to complexes called chromatin, the network of DNA and proteins (called histones) that packages DNA into chromosomes. Binding with the PHF8 protein is part of the process that changes the structure of chromatin (chromatin remodeling) to alter how tightly regions of DNA are packaged. Chromatin remodeling is one way gene activity (expression) is regulated; when DNA is tightly packed genes tend to be turned off, compared to when DNA is loosely packed and genes are usually turned on. While the PHF8 protein is bound to chromatin, another domain of the PHF8 protein, called Jumonji C (JmjC), removes molecules called methyl groups from histones. Removing these methyl groups (demethylation) causes the chromatin to become loosely packed and increases the expression of specific genes.

Does the PHF8 gene share characteristics with other genes?

The PHF8 gene belongs to a family of genes called chromatin-modifying enzymes (chromatin-modifying enzymes). It also belongs to a family of genes called PHF (PHD-type zinc fingers).

A gene family is a group of genes that share important characteristics. Classifying individual genes into families helps researchers describe how genes are related to each other. For more information, see What are gene families? in the Handbook.

How are changes in the PHF8 gene related to health conditions?

X-linked intellectual disability, Siderius type - caused by mutations in the PHF8 gene: At least four mutations in the PHF8 gene have been found to cause X-linked intellectual disability, Siderius type. This condition is characterized by mild to moderate intellectual disability, and it occurs only in males. Affected boys often have an opening in the lip (cleft lip) with an opening in the roof of the mouth (cleft palate). Most PHF8 gene mutations lead to an abnormally short protein that gets transported out of the cell's nucleus. Outside of the nucleus, the PHF8 protein cannot interact with chromatin to regulate gene expression. Other mutations impair the protein's ability to remove methyl groups from histones within chromatin, leading to a decrease in gene expression.
While the exact disease mechanism is unknown, it is likely that impaired protein function or a lack of PHF8 protein in the nucleus of brain cells before birth prevents chromatin remodeling, altering the normal expression of genes involved in intellectual function and formation of structures along the midline of the skull. This altered gene expression leads to intellectual disability and cleft lip and palate found in males with X-linked intellectual disability, Siderius type.

Where is the PHF8 gene located?

Cytogenetic Location: Xp11.22

Molecular Location on the X chromosome: base pairs 53,936,679 to 54,048,934

The PHF8 gene is located on the short (p) arm of the X chromosome at position 11.22.

More precisely, the PHF8 gene is located from base pair 53,936,679 to base pair 54,048,934 on the X chromosome.

See How do geneticists indicate the location of a gene? in the Handbook.

Where can I find additional information about PHF8?

You and your healthcare professional may find the following resources about PHF8 helpful.

Genetic Testing Registry - Repository of genetic test information (1 link)

You may also be interested in these resources, which are designed for genetics professionals and researchers.

PubMed - Recent literature
OMIM - Genetic disorder catalog
Research Resources - Tools for researchers (6 links)

What other names do people use for the PHF8 gene or gene products?

histone lysine demethylase PHF8
JHDM1F
jumonji C domain-containing histone demethylase 1F
KIAA1111
PHF8_HUMAN
ZNF422

See How are genetic conditions and genes named? in the Handbook.

Where can I find general information about genes?

The Handbook provides basic information about genetics in clear language.

These links provide additional genetics resources that may be useful.

What glossary definitions help with understanding PHF8?

acids ; cell ; cell nucleus ; chromatin ; chromatin remodeling ; cleft palate ; disability ; DNA ;domain ; gene ; gene expression ; histone ; ions ; lysine ; methyl ; nucleus ; palate ; protein ;zinc finger domain

You may find definitions for these and many other terms in the Genetics Home Reference Glossary.

References (7 links)

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? in the Handbook