Reviewed May 2012
What is the official name of the UCHL1 gene?
The official name of this gene is “ubiquitin C-terminal hydrolase L1.”
UCHL1 is the gene's official symbol. The UCHL1 gene is also known by other names, listed below.
What is the normal function of the UCHL1 gene?
The UCHL1 gene provides instructions for making an enzyme called ubiquitin carboxyl-terminal esterase L1. This enzyme is found in nerve cells throughout the brain. Ubiquitin carboxyl-terminal esterase L1 is probably involved in the cell machinery that breaks down (degrades) unneeded proteins. In cells, damaged or excess proteins are tagged with molecules called ubiquitin. Ubiquitin serves as a signal to move these unneeded proteins into specialized structures known as proteasomes, where the proteins are degraded. The ubiquitin-proteasome system acts as the cell's quality control system by disposing of damaged, misshapen, and excess proteins.
Although the exact function of ubiquitin carboxyl-terminal esterase L1 is not fully understood, it appears to have two types of enzyme activity. One of these, called hydrolase activity, removes and recycles ubiquitin molecules from degraded proteins. This recycling step is important to sustain the degradation process. The other enzyme function, known as ligase activity, links together ubiquitin molecules for use in tagging proteins for disposal.
Does the UCHL1 gene share characteristics with other genes?
The UCHL1 gene belongs to a family of genes called PARK (Parkinson disease).
A gene family is a group of genes that share important characteristics. Classifying individual genes into families helps researchers describe how genes are related to each other. For more information, see What are gene families? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genefamilies) in the Handbook.
How are changes in the UCHL1 gene related to health conditions?
- Parkinson disease - associated with the UCHL1 gene
A relatively common variation (polymorphism) in the UCHL1 gene may reduce the risk of developing Parkinson disease, a condition characterized by progressive problems with movement and balance. The variation leads to a change in one of the building blocks (amino acids) used to make ubiquitin carboxyl-terminal esterase L1. Instead of serine at position 18 in the enzyme's chain of amino acids, people with the polymorphism have the amino acid tyrosine (written as Ser18Tyr or S18Y). This change is most common in Chinese and Japanese populations and occurs less frequently in European populations. The polymorphism reduces the ligase activity of ubiquitin carboxyl-terminal esterase L1 but has little effect on the hydrolase activity. Some studies suggest that having the S18Y polymorphism may help protect against Parkinson disease, particularly in young adults. However, other studies have not shown this effect. It remains unclear how this amino acid variation might reduce the risk of developing Parkinson disease.
A different change in the UCHL1 gene may increase the risk of Parkinson disease. This mutation has been reported in two siblings with the disease. The mutation replaces the amino acid isoleucine with the amino acid methionine at position 93 in ubiquitin carboxyl-terminal esterase L1 (written as Ile93Met or I93M). The mutation leads to decreased hydrolase activity, which may disrupt the ubiquitin-proteasome system. Instead of being degraded, unneeded proteins could accumulate to toxic levels that impair or kill nerve cells in the brain. The loss of these cells weakens communication between the brain and muscles, and ultimately the brain becomes unable to control muscle movement. It is unclear whether this UCHL1 gene mutation is a true risk factor for Parkinson disease, because it has been identified in only one family.
Where is the UCHL1 gene located?
Cytogenetic Location: 4p14
Molecular Location on chromosome 4: base pairs 41,256,881 to 41,268,429
(Homo sapiens Annotation Release 107, GRCh38.p2) (NCBI (http://www.ncbi.nlm.nih.gov/gene/7345))
The UCHL1 gene is located on the short (p) arm of chromosome 4 at position 14.
More precisely, the UCHL1 gene is located from base pair 41,256,881 to base pair 41,268,429 on chromosome 4.
See How do geneticists indicate the location of a gene? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genelocation) in the Handbook.
Where can I find additional information about UCHL1?
You and your healthcare professional may find the following resources about UCHL1 helpful.
Educational resources - Information pages
- Annual Reviews Collection: Overview of the Ubiquitin-Proteasome Degradation System (http://www.ncbi.nlm.nih.gov/books/NBK2229/)
- Biochemistry (fifth edition, 2002): Protein Turnover is Tightly Regulated (http://www.ncbi.nlm.nih.gov/books/NBK22397/)
- The Cell: A Molecular Approach (second edition, 2000): The Ubiquitin-Proteasome Pathway (http://www.ncbi.nlm.nih.gov/books/NBK9957/)
- Gene Reviews - Clinical summary (http://www.ncbi.nlm.nih.gov/books/NBK1223)
Genetic Testing Registry - Repository of genetic test information
- GTR: Genetic tests for UCHL1 (http://www.ncbi.nlm.nih.gov/gtr/tests/?term=7345%5Bgeneid%5D)
You may also be interested in these resources, which are designed for genetics professionals and researchers.
- PubMed - Recent literature (http://www.ncbi.nlm.nih.gov/pubmed?term=%28%28UCHL1%5BTIAB%5D%29%20OR%20%28UCHL-1%5BTIAB%5D%29%29%20AND%20%28%28Genes%5BMH%5D%29%20OR%20%28Genetic%20Phenomena%5BMH%5D%29%29%20AND%20english%5Bla%5D%20AND%20human%5Bmh%5D%20AND%20%22last%203600%20days%22%5Bdp%5D)
- OMIM - Genetic disorder catalog (http://omim.org/entry/191342)
Research Resources - Tools for researchers
- Atlas of Genetics and Cytogenetics in Oncology and Haematology (http://atlasgeneticsoncology.org/Genes/GC_UCHL1.html)
- HGNC Gene Family: Parkinson disease associated genes (http://www.genenames.org/cgi-bin/genefamilies/set/672)
- HGNC Gene Family: Ubiquitin C-terminal hydrolases (http://www.genenames.org/cgi-bin/genefamilies/set/998)
- HGNC Gene Symbol Report (http://www.genenames.org/cgi-bin/gene_symbol_report?q=data/hgnc_data.php&hgnc_id=12513)
- NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/7345)
- PDGene (http://www.pdgene.org/view?gene=UCHL1)
What other names do people use for the UCHL1 gene or gene products?
- neuron cytoplastic protein 9.5
- ubiquitin carboxyl-terminal esterase L1 (ubiquitin thiolesterase)
- ubiquitin thiolesterase
See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.
What glossary definitions help with understanding UCHL1?
amino acid ;
You may find definitions for these and many other terms in the Genetics Home Reference
- Facheris M, Strain KJ, Lesnick TG, de Andrade M, Bower JH, Ahlskog JE, Cunningham JM, Lincoln S, Farrer MJ, Rocca WA, Maraganore DM. UCHL1 is associated with Parkinson's disease: a case-unaffected sibling and case-unrelated control study. Neurosci Lett. 2005 Jun 10-17;381(1-2):131-4. Epub 2005 Feb 25. (http://www.ncbi.nlm.nih.gov/pubmed/15882803?dopt=Abstract)
- Healy DG, Abou-Sleiman PM, Casas JP, Ahmadi KR, Lynch T, Gandhi S, Muqit MM, Foltynie T, Barker R, Bhatia KP, Quinn NP, Lees AJ, Gibson JM, Holton JL, Revesz T, Goldstein DB, Wood NW. UCHL-1 is not a Parkinson's disease susceptibility gene. Ann Neurol. 2006 Apr;59(4):627-33. (http://www.ncbi.nlm.nih.gov/pubmed/16450370?dopt=Abstract)
- Hutter CM, Samii A, Factor SA, Nutt JG, Higgins DS, Bird TD, Griffith A, Roberts JW, Leis BC, Montimurro JS, Kay DM, Edwards KL, Payami H, Zabetian CP. Lack of evidence for an association between UCHL1 S18Y and Parkinson's disease. Eur J Neurol. 2008 Feb;15(2):134-9. Epub 2007 Dec 18. (http://www.ncbi.nlm.nih.gov/pubmed/18093156?dopt=Abstract)
- Liu Y, Fallon L, Lashuel HA, Liu Z, Lansbury PT Jr. The UCH-L1 gene encodes two opposing enzymatic activities that affect alpha-synuclein degradation and Parkinson's disease susceptibility. Cell. 2002 Oct 18;111(2):209-18. (http://www.ncbi.nlm.nih.gov/pubmed/12408865?dopt=Abstract)
- Maraganore DM, Lesnick TG, Elbaz A, Chartier-Harlin MC, Gasser T, Krüger R, Hattori N, Mellick GD, Quattrone A, Satoh J, Toda T, Wang J, Ioannidis JP, de Andrade M, Rocca WA; UCHL1 Global Genetics Consortium. UCHL1 is a Parkinson's disease susceptibility gene. Ann Neurol. 2004 Apr;55(4):512-21. Erratum in: Ann Neurol. 2004 Jun;55(6):899. Toda, Taksushi [corrected to Toda, Tatsushi]. (http://www.ncbi.nlm.nih.gov/pubmed/15048890?dopt=Abstract)
- NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/7345)
- Ragland M, Hutter C, Zabetian C, Edwards K. Association between the ubiquitin carboxyl-terminal esterase L1 gene (UCHL1) S18Y variant and Parkinson's Disease: a HuGE review and meta-analysis. Am J Epidemiol. 2009 Dec 1;170(11):1344-57. doi: 10.1093/aje/kwp288. Epub 2009 Oct 28. Review. (http://www.ncbi.nlm.nih.gov/pubmed/19864305?dopt=Abstract)
- Tan EK, Puong KY, Fook-Chong S, Chua E, Shen H, Yuen Y, Pavanni R, Wong MC, Puvan K, Zhao Y. Case-control study of UCHL1 S18Y variant in Parkinson's disease. Mov Disord. 2006 Oct;21(10):1765-8. (http://www.ncbi.nlm.nih.gov/pubmed/16941465?dopt=Abstract)
- Wintermeyer P, Krüger R, Kuhn W, Müller T, Woitalla D, Berg D, Becker G, Leroy E, Polymeropoulos M, Berger K, Przuntek H, Schöls L, Epplen JT, Riess O. Mutation analysis and association studies of the UCHL1 gene in German Parkinson's disease patients. Neuroreport. 2000 Jul 14;11(10):2079-82. (http://www.ncbi.nlm.nih.gov/pubmed/10923647?dopt=Abstract)
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
See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.