Health Topics
Official websites use .gov
A
.gov website belongs to an official government
organization in the United States.
Secure .gov websites use HTTPS
A
lock (
) or https:// means you’ve safely connected to
the .gov website. Share sensitive information only on official,
secure websites.
Normal Function
The PHF21A gene provides instructions for making a protein that helps regulate gene activity. The PHF21A protein does this by interacting with proteins that modify histones, which are structural proteins that bind to DNA and package it into chromosomes. Particular regions of the PHF21A protein can recognize certain histone patterns and help regulate whether certain genes are turned on (active) or turned off (inactive).
The PHF21A protein appears to be particularly important in regulating genes that are involved in the development of the brain and face.
Health Conditions Related to Genetic Changes
Potocki-Shaffer syndrome
Certain genetic changes that affect the PHF21A gene are associated with a condition called Potocki-Shaffer syndrome. This condition affects the development of the bones, brain, and other tissues. Characteristic bone abnormalities include enlarged openings (foramina) in the two bones that form the top and sides of the skull (enlarged parietal foramina) and multiple noncancerous bone tumors (osteochondromas). Other signs and symptoms seen in people with Potocki-Shaffer syndrome include intellectual disabilities, developmental delays, and distinctive facial features.
Potocki-Shaffer syndrome is caused by a deletion of genetic material from the short (p) arm of chromosome 11. In people with this condition, the loss of the PHF21A gene within this region is thought to play a major role in the development of intellectual disabilities and distinctive facial features. The deletion likely reduces the number of PHF21A proteins, which then disrupts the regulation of gene activity during the development of the brain and face.
The loss of additional genes in the deleted region likely contributes to the other features of Potocki-Shaffer syndrome. For example, the loss of the ALX4 gene causes enlarged parietal foramina in people with this condition, and the deletion of the EXT2 gene causes osteochondromas.
More About This Health ConditionOther disorders
Changes in the PHF21A gene cause a condition called PHF21A neurodevelopmental disorder. Genetic changes that cause disease are called pathogenic variants. People with PHF21A neurodevelopmental disorder often have faster than normal growth after birth, an unusually large head size (macrocephaly), intellectual disabilities, behavioral problems, low muscle tone, and seizures. Because of these signs and symptoms, this condition is sometimes known as intellectual developmental disorder with behavioral abnormalities and craniofacial dysmorphism with or without seizures (IDDBCS). The pathogenic variants that cause this condition occur in the PHF21A gene and lead to disruptions in the normal function of the PHF21A protein. It is likely that a decrease in normal PHF21A protein activity impairs the activity of certain genes, particularly those involved in the development of the brain and face.
Other Names for This Gene
- BHC80
- BM-006
- KIAA1696
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
References
- Kim HG, Kim HT, Leach NT, Lan F, Ullmann R, Silahtaroglu A, Kurth I, Nowka A, Seong IS, Shen Y, Talkowski ME, Ruderfer D, Lee JH, Glotzbach C, Ha K, Kjaergaard S, Levin AV, Romeike BF, Kleefstra T, Bartsch O, Elsea SH, Jabs EW, MacDonald ME, Harris DJ, Quade BJ, Ropers HH, Shaffer LG, Kutsche K, Layman LC, Tommerup N, Kalscheuer VM, Shi Y, Morton CC, Kim CH, Gusella JF. Translocations disrupting PHF21A in the Potocki-Shaffer-syndrome region are associated with intellectual disability and craniofacial anomalies. Am J Hum Genet. 2012 Jul 13;91(1):56-72. doi: 10.1016/j.ajhg.2012.05.005. Epub 2012 Jul 5. Citation on PubMed or Free article on PubMed Central
- Labonne JD, Vogt J, Reali L, Kong IK, Layman LC, Kim HG. A microdeletion encompassing PHF21A in an individual with global developmental delay and craniofacial anomalies. Am J Med Genet A. 2015 Dec;167A(12):3011-8. doi: 10.1002/ajmg.a.37344. Epub 2015 Sep 3. Citation on PubMed
- Lan F, Collins RE, De Cegli R, Alpatov R, Horton JR, Shi X, Gozani O, Cheng X, Shi Y. Recognition of unmethylated histone H3 lysine 4 links BHC80 to LSD1-mediated gene repression. Nature. 2007 Aug 9;448(7154):718-22. doi: 10.1038/nature06034. Citation on PubMed or Free article on PubMed Central
- Montgomery ND, Turcott CM, Tepperberg JH, McDonald MT, Aylsworth AS. A 137-kb deletion within the Potocki-Shaffer syndrome interval on chromosome 11p11.2 associated with developmental delay and hypotonia. Am J Med Genet A. 2013 Jan;161A(1):198-202. doi: 10.1002/ajmg.a.35671. Epub 2012 Dec 13. Citation on PubMed
- Poole RL, Bijlsma EK, Houge G, Jones G, Mikstiene V, Preiksaitiene E, Thompson L, Tatton-Brown K. The PHF21A neurodevelopmental disorder: an evaluation of clinical data from 13 patients. Clin Dysmorphol. 2023 Apr 1;32(2):49-54. doi: 10.1097/MCD.0000000000000455. Epub 2023 Feb 21. Citation on PubMed
The information on this site should not be used as a substitute for professional medical care or advice. Contact a health care provider if you have questions about your health.