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Genetics Home Reference: your guide to understanding genetic conditions     A service of the U.S. National Library of Medicine®

PHF gene family

Reviewed October 2013

What are the PHF genes?

Genes in the PHF family provide instructions for making proteins known as PHD-type zinc finger proteins. This family is a subset of a much larger group of zinc finger proteins, which are involved in many cellular functions.

Zinc finger proteins 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) in a folded configuration that stabilizes the protein and allows it to attach (bind) to other molecules. In PHD-type zinc finger proteins, the zinc finger domain (called a PHD domain) consists of an amino acid cluster of seven cysteines and one histidine that fold around two zinc ions.

Some PHD-type zinc finger proteins are involved in a process known as chromatin remodeling. Chromatin is the network of DNA and protein that packages DNA into chromosomes. The structure of chromatin can be changed (remodeled) to alter how tightly DNA is packaged. Chromatin remodeling is one way gene activity (expression) is regulated during development; when DNA is tightly packed, gene expression is lower than when DNA is loosely packed. The PHD domain appears to detect certain chromatin modifications and bind to them as well as to other proteins, thus participating in a complex network of molecular interactions that affect gene expression.

The PHD acronym comes from the term "plant homeodomain" because the structure was first discovered in a plant named Arabidopsis thaliana. There are now hundreds of mammalian proteins known to contain the PHD domain. In humans, mutations in genes in this family may be associated with many types of disorders, including defects in development before birth, immune problems, and cancers.

Which genes are included in the PHF gene family?

The HUGO Gene Nomenclature Committee (HGNC) provides an index of gene families ( and their member genes.

Genetics Home Reference summarizes the normal function and health implications of these members of the PHF gene family: AIRE, KAT6B, KMT2D, NSD1, PHF8, and WHSC1.

What conditions are related to genes in the PHF gene family?

Genetics Home Reference includes these conditions related to genes in the PHF gene family:

  • autoimmune polyglandular syndrome, type 1
  • genitopatellar syndrome
  • Kabuki syndrome
  • Ohdo syndrome, Say-Barber-Biesecker-Young-Simpson variant
  • Sotos syndrome
  • Weaver syndrome
  • Wolf-Hirschhorn syndrome
  • X-linked intellectual disability, Siderius type

What glossary definitions help with understanding the PHF gene family?

acids ; amino acid ; autoimmune ; chromatin ; chromatin remodeling ; DNA ; domain ; gene ; gene expression ; histidine ; homeodomain ; ions ; lysine ; methyltransferase ; protein ; receptor ; syndrome ; zinc finger domain

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


These sources were used to develop the Genetics Home Reference summary for the PHF gene family.

  • Sanchez R, Zhou MM. The PHD finger: a versatile epigenome reader. Trends Biochem Sci. 2011 Jul;36(7):364-72. doi: 10.1016/j.tibs.2011.03.005. Epub 2011 Apr 21. Review. (
  • Chi P, Allis CD, Wang GG. Covalent histone modifications--miswritten, misinterpreted and mis-erased in human cancers. Nat Rev Cancer. 2010 Jul;10(7):457-69. doi: 10.1038/nrc2876. Review. (
  • Bienz M. The PHD finger, a nuclear protein-interaction domain. Trends Biochem Sci. 2006 Jan;31(1):35-40. Epub 2005 Nov 16. Review. (
  • Matthews JM, Bhati M, Lehtomaki E, Mansfield RE, Cubeddu L, Mackay JP. It takes two to tango: the structure and function of LIM, RING, PHD and MYND domains. Curr Pharm Des. 2009;15(31):3681-96. Review. (
  • Matthews JM, Sunde M. Zinc fingers--folds for many occasions. IUBMB Life. 2002 Dec;54(6):351-5. Review. (


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.

Reviewed: October 2013
Published: February 1, 2016