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URL of this page: https://medlineplus.gov/genetics/gene/jph3/

JPH3 gene

junctophilin 3

Normal Function

The JPH3 gene provides instructions for making a protein called junctophilin-3, which is found primarily in the brain.  Research shows that junctophilin-3 plays a role in the formation of a structure called the junctional membrane complex. This complex acts as a link between the inside of the cell and the outside of the cell. Specifically, it connects certain channels on the surface of a cell compartment called the endoplasmic reticulum with other channels at the cell surface. The junctional membrane complex appears to be involved in transmitting signals after these channels release of charged calcium atoms (calcium ions). As part of the junctional membrane complex, junctophilin-3 is probably involved in signaling within and between nerve cells (neurons) in the brain.

One region of the JPH3 gene contains a particular DNA segment known as a CAG/CTG trinucleotide repeat. This segment is made up of a series of three DNA building blocks (nucleotides) that appear multiple times in a row. Normally, the CAG/CTG segment is repeated 6 to 28 times within the gene.



Health Conditions Related to Genetic Changes

Huntington's disease-like

A particular type of variant (also called a mutation) in the JPH3 gene has been found to cause a condition called Huntington's disease-like 2 (HDL2). The signs and symptoms of HDL2 resemble those of a more common condition called Huntington's disease. These signs and symptoms include uncontrolled movements, emotional problems, and a loss of thinking ability.

The variant associated with HDL2 increases the size of the CAG/CTG trinucleotide repeat in the JPH3 gene. People with this condition have 40 or more CAG/CTG repeats. People with 29 to about 39 CAG/CTG repeats may or may not develop the signs and symptoms of HDL2 or other related health problems.

Researchers are working to determine the effects of the longer CAG/CTG segment. They believe that the altered JPH3 gene produces an altered version of messenger RNA (mRNA), which is a molecular blueprint of the gene that is normally used for protein production. The altered mRNA cannot produce a functional junctophilin-3 protein. Additionally, the abnormal mRNA forms clumps inside neurons that interfere with the normal functions of these cells. The lack of normal junctophilin-3 protein combined with the dysfunction and eventual death of neurons in certain areas of the brain cause the signs and symptoms of HDL2.

More About This Health Condition

Other Names for This Gene

  • JP-3
  • JP3
  • JPH3_HUMAN
  • junctophilin type 3
  • junctophilin-3

Additional Information & Resources

Tests Listed in the Genetic Testing Registry

Scientific Articles on PubMed

Catalog of Genes and Diseases from OMIM

Gene and Variant Databases

References

  • Anderson DG, Krause A, Margolis RL. Huntington Disease-Like 2. 2004 Jan 30 [updated 2019 Jun 27]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2025. Available from http://www.ncbi.nlm.nih.gov/books/NBK1529/ Citation on PubMed
  • Bourinaris T, Athanasiou A, Efthymiou S, Wiethoff S, Salpietro V, Houlden H. Allelic and phenotypic heterogeneity in Junctophillin-3 related neurodevelopmental and movement disorders. Eur J Hum Genet. 2021 Jun;29(6):1027-1031. doi: 10.1038/s41431-021-00866-1. Epub 2021 Apr 6. Citation on PubMed
  • Greenstein PE, Vonsattel JG, Margolis RL, Joseph JT. Huntington's disease like-2 neuropathology. Mov Disord. 2007 Jul 30;22(10):1416-1423. doi: 10.1002/mds.21417. Citation on PubMed
  • Krause A, Mitchell C, Essop F, Tager S, Temlett J, Stevanin G, Ross C, Rudnicki D, Margolis R. Junctophilin 3 (JPH3) expansion mutations causing Huntington disease like 2 (HDL2) are common in South African patients with African ancestry and a Huntington disease phenotype. Am J Med Genet B Neuropsychiatr Genet. 2015 Oct;168(7):573-85. doi: 10.1002/ajmg.b.32332. Epub 2015 Jun 16. Citation on PubMed
  • Margolis RL, O'Hearn E, Rosenblatt A, Willour V, Holmes SE, Franz ML, Callahan C, Hwang HS, Troncoso JC, Ross CA. A disorder similar to Huntington's disease is associated with a novel CAG repeat expansion. Ann Neurol. 2001 Dec;50(6):373-80. doi: 10.1002/ana.1312. Citation on PubMed
  • Nishi M, Mizushima A, Nakagawara Ki, Takeshima H. Characterization of human junctophilin subtype genes. Biochem Biophys Res Commun. 2000 Jul 14;273(3):920-7. doi: 10.1006/bbrc.2000.3011. Citation on PubMed
  • Rudnicki DD, Pletnikova O, Vonsattel JP, Ross CA, Margolis RL. A comparison of huntington disease and huntington disease-like 2 neuropathology. J Neuropathol Exp Neurol. 2008 Apr;67(4):366-74. doi: 10.1097/NEN.0b013e31816b4aee. Citation on PubMed
  • Takeshima H, Komazaki S, Nishi M, Iino M, Kangawa K. Junctophilins: a novel family of junctional membrane complex proteins. Mol Cell. 2000 Jul;6(1):11-22. doi: 10.1016/s1097-2765(00)00003-4. Citation on PubMed
  • Walker RH, Jankovic J, O'Hearn E, Margolis RL. Phenotypic features of Huntington's disease-like 2. Mov Disord. 2003 Dec;18(12):1527-30. doi: 10.1002/mds.10587. 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.