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


Reviewed March 2014

What is the official name of the GPHN gene?

The official name of this gene is “gephyrin.”

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

What is the normal function of the GPHN gene?

The GPHN gene provides instructions for making a protein called gephyrin, which has two major functions in the body: the protein aids in the formation (biosynthesis) of a molecule called molybdenum cofactor, and it also plays a role in communication between nerve cells (neurons).

Gephyrin performs the final two steps in molybdenum cofactor biosynthesis. Molybdenum cofactor, which contains the element molybdenum, is essential to the function of several enzymes called sulfite oxidase, aldehyde oxidase, xanthine dehydrogenase, and mitochondrial amidoxime reducing component (mARC). These enzymes help break down (metabolize) different substances in the body, some of which are toxic if not metabolized.

Gephyrin also plays an important role in neurons. Communication between neurons depends on chemicals called neurotransmitters. To relay signals, a neuron releases neurotransmitters, which attach to receptor proteins on neighboring neurons. Gephyrin anchors certain receptor proteins to the correct location in neurons so that the receptors can receive the signals relayed by neurotransmitters.

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

molybdenum cofactor deficiency - caused by mutations in the GPHN gene

GPHN gene mutations cause a disorder called molybdenum cofactor deficiency. This disorder is characterized by seizures that begin early in life and brain dysfunction that worsens over time (encephalopathy); the condition is usually fatal by early childhood. At least two mutations in the GPHN gene have been found to cause a form of the disorder designated type C or complementation group C. This is the rarest form of the condition, affecting only a small number of individuals.

The GPHN gene mutations involved in molybdenum cofactor deficiency likely reduce or eliminate the function of gephyrin. The known mutations impair gephyrin's ability to perform one or both of the final two steps of molybdenum cofactor biosynthesis. Without the cofactor, the metabolic enzymes that rely on it cannot function.

The resulting loss of enzyme activity leads to buildup of certain chemicals, including sulfite, S-sulfocysteine, xanthine, and hypoxanthine, and low levels of another chemical called uric acid. (Testing for these chemicals can help in the diagnosis of this condition.) Sulfite, which is normally broken down by sulfite oxidase, is toxic, especially to the brain. Researchers suggest that damage caused by the abnormally high levels of sulfite (and possibly other chemicals) leads to encephalopathy, seizures, and the other features of molybdenum cofactor deficiency.

Where is the GPHN gene located?

Cytogenetic Location: 14q23.3

Molecular Location on chromosome 14: base pairs 66,507,407 to 67,181,808

(Homo sapiens Annotation Release 107, GRCh38.p2) (NCBI (

The GPHN gene is located on the long (q) arm of chromosome 14 at position 23.3.

The GPHN gene is located on the long (q) arm of chromosome 14 at position 23.3.

More precisely, the GPHN gene is located from base pair 66,507,407 to base pair 67,181,808 on chromosome 14.

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

Where can I find additional information about GPHN?

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

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

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

  • GEPH
  • gephyrin isoform 1
  • gephyrin isoform 2
  • GPH
  • HKPX1
  • KIAA1385

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

What glossary definitions help with understanding GPHN?

aldehyde ; cofactor ; deficiency ; dehydrogenase ; diagnosis ; encephalopathy ; enzyme ; gene ; hereditary ; molecule ; neuron ; neurotransmitters ; oxidase ; protein ; receptor ; toxic ; uric acid

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


  • Belaidi AA, Schwarz G. Metal insertion into the molybdenum cofactor: product-substrate channelling demonstrates the functional origin of domain fusion in gephyrin. Biochem J. 2013 Feb 15;450(1):149-57. doi: 10.1042/BJ20121078. Erratum in: Biochem J. 2013 Mar 15;450(3):639. (
  • Mendel RR. The molybdenum cofactor. J Biol Chem. 2013 May 10;288(19):13165-72. doi: 10.1074/jbc.R113.455311. Epub 2013 Mar 28. Review. (
  • NCBI Gene (
  • Reiss J, Gross-Hardt S, Christensen E, Schmidt P, Mendel RR, Schwarz G. A mutation in the gene for the neurotransmitter receptor-clustering protein gephyrin causes a novel form of molybdenum cofactor deficiency. Am J Hum Genet. 2001 Jan;68(1):208-13. Epub 2000 Nov 28. (
  • Reiss J, Lenz U, Aquaviva-Bourdain C, Joriot-Chekaf S, Mention-Mulliez K, Holder-Espinasse M. A GPHN point mutation leading to molybdenum cofactor deficiency. Clin Genet. 2011 Dec;80(6):598-9. doi: 10.1111/j.1399-0004.2011.01709.x. (
  • Saiyed T, Paarmann I, Schmitt B, Haeger S, Sola M, Schmalzing G, Weissenhorn W, Betz H. Molecular basis of gephyrin clustering at inhibitory synapses: role of G- and E-domain interactions. J Biol Chem. 2007 Feb 23;282(8):5625-32. Epub 2006 Dec 20. (


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: March 2014
Published: February 1, 2016