Huntington Disease-Like 2 (JPH3)
| Dred_ID | RD00044 |
| OMIM ID | 606438 |
| Disease name | Huntington Disease-Like 2 |
| Alternative names | HDL2 |
| Category | Genetic diseases, Neuronal diseases, Rare diseases |
| Phenotype | OMIM: Huntington disease-like 2 (HDL2) is characterized by onset in the fourth decade, involuntary movements and abnormalities of voluntary movements, psychiatric symptoms, weight loss, dementia, and relentless course with death about 20 years after disease onset. Brain magnetic resonance imaging scans and an autopsy revealed marked striatal atrophy and moderate cortical atrophy, with striatal neurodegeneration in a dorsal-to-ventral gradient and occasional intranuclear inclusions. |
| Miscellaneouse | OMIM: mean age of onset 35-40 years normal alleles contain 6 to 28 repeats pathogenic alleles contain greater than 41 repeats |
| Prevalence | Prevalence: <1/1000000 (Worldwide) [source: MalaCards] |
| Inheritance | Autosomal dominant |
| Anticipation | Yes |
| Evidence | Strong |
| Gene symbol | JPH3 |
| Alias symbols | JP3; HDL2; JP-3; TNRC22; CAGL237 |
| Gene name | junctophilin 3 |
| Gene map locus | 16q24.3; chr16:87,601,835-87,698,156(+) |
| Ensembl Gene ID | ENSG00000154118 |
| Gene expression and Gene Ontology | BioGPS |
| Protein expression | Human Protein Atlas |
| Gene sequence | Sequence |
| Variation | ClinVar, dbSNP | Gene conservation | Gene Conservation from UCSC Genome Browser |
| Gene Description | Junctional complexes between the plasma membrane and endoplasmic/sarcoplasmic reticulum are a common feature of all excitable cell types and mediate cross talk between cell surface and intracellular ion channels. The protein encoded by this gene is a component of junctional complexes and is composed of a C-terminal hydrophobic segment spanning the endoplasmic/sarcoplasmic reticulum membrane and a remaining cytoplasmic domain that shows specific affinity for the plasma membrane. CAG/CTG repeat expansion from normally 6-28 repeats to 40-59 repeats in the 3' UTR of this gene have been associated with Huntington disease-like 2 (HDL2). This gene is a member of the junctophilin gene family. Alternatively spliced transcript variants have been described for this gene. [provided by RefSeq, Jul 2016] |
| Repeat unit | CTG |
| Normal repeat copies | 6-28 |
| Pathogenic repeat copies | ≥42 |
| Gene | JPH3 |
| Repeat location | 3' UTR |
| Chromosome locus | chr16:87604288-87604332 (+) |
| Repeat conservation | Repeat Conservation from UCSC Genome Browser |
| Toxic cause | RNA |
| Possible toxicity | Rudnicki et al. (2007) detected RNA foci within frontal lobe neurons of 4 patients with HDL2 using riboprobes specific for expanded CUG tracts and with riboprobes specific for JPH3 intron 1, exon 2A, or exon 2B. The RNA foci resembled those detected in DM1 (160900) in terms of size, restriction to nuclei, and colocalization with MBNL1 (606516). Approximately 30% of neurons contained foci, and most neurons contained more than 1 focus. Similar foci were also observed in the striatum. There was also a significant decrease in general MBNL1 expression compared to controls. No foci were detected in control brains or HD frontal cortex used as control. Overexpression of JPH3 transcripts containing an expanded CUG repeat expansion were toxic to HEK293 and HT22 cells, suggesting that the RNA transcripts play an important role in the pathogenesis of HDL2 via a toxic RNA gain-of-function effect. [By OMIM] |
| Pathway annotation | Reactome, KEGG |
| PMID | 11694876 |
| Authors | Holmes SE, O'Hearn E, Rosenblatt A, Callahan C, Hwang HS, Ingersoll-Ashworth RG, Fleisher A, Stevanin G, Brice A, Potter NT, Ross CA, Margolis RL. |
| Title | A repeat expansion in the gene encoding junctophilin-3 is associated with Huntington disease-like 2 |
| Journal | Nat Genet. 29(4):377-8 |
| Year | 2001 |
| PMID | 17387722 |
| Authors | Rudnicki DD1, Holmes SE, Lin MW, Thornton CA, Ross CA, Margolis RL. |
| Title | Huntington’s disease-like 2 is associated with CUG repeat containing RNA foci |
| Journal | Ann Neurol. 61(3):272-82 |
| Year | 2007 |