UPB1 gene
beta-ureidopropionase 1
The UPB1 gene provides instructions for making an enzyme called beta-ureidopropionase. This enzyme is involved in the breakdown of molecules called pyrimidines, which are building blocks of DNA and its chemical cousin RNA.
The beta-ureidopropionase enzyme is involved in the last step of the process that breaks down pyrimidines. This step converts N-carbamyl-beta-aminoisobutyric acid to beta-aminoisobutyric acid and also breaks down N-carbamyl-beta-alanine to beta-alanine, ammonia, and carbon dioxide. Both beta-aminoisobutyric acid and beta-alanine are thought to play roles in the nervous system. Beta-aminoisobutyric acid increases the production of a protein called leptin, which has been found to help protect brain cells from damage caused by toxins, inflammation, and other factors. Research suggests that beta-alanine is involved in sending signals between nerve cells (synaptic transmission) and in controlling the level of a chemical messenger (neurotransmitter) called dopamine.
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At least 16 UPB1 gene mutations have been identified in people with beta-ureidopropionase deficiency. This disorder causes excessive amounts of N-carbamyl-beta-aminoisobutyric acid and N-carbamyl-beta-alanine to be released in the urine. Affected individuals may also have a variety of neurological problems such as seizures and intellectual disability, ranging from mild to severe. Some people with beta-ureidopropionase deficiency have no neurological symptoms, and the disorder can only be diagnosed with laboratory testing.
The mutations that cause beta-ureidopropionase deficiency reduce or eliminate beta-ureidopropionase enzyme activity. Loss of this enzyme function reduces the production of beta-aminoisobutyric acid and beta-alanine, and leads to an excess of their precursor molecules, N-carbamyl-beta-aminoisobutyric acid and N-carbamyl-beta-alanine, which are released in the urine. Reduced production of beta-aminoisobutyric acid and beta-alanine may impair their functions in the nervous system, leading to neurological problems in some people with beta-ureidopropionase deficiency. The extent of the reduction in enzyme activity caused by a particular UPB1 gene mutation, along with other genetic and environmental factors, may determine whether people with beta-ureidopropionase deficiency develop neurological problems and the severity of these problems.
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Cytogenetic Location: 22q11.23, which is the long (q) arm of chromosome 22 at position 11.23
Molecular Location: base pairs 24,495,060 to 24,528,681 on chromosome 22 (Homo sapiens Updated Annotation Release 109.20191205, GRCh38.p13) (NCBI)
Related Information
- beta-alanine synthase
- beta-ureidopropionase
- BUP1
- n-carbamoyl-beta-alanine amidohydrolase
- ureidopropionase, beta
Related Information
- OMIM: BETA-UREIDOPROPIONASE
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- van Kuilenburg AB, Meinsma R, Beke E, Assmann B, Ribes A, Lorente I, Busch R, Mayatepek E, Abeling NG, van Cruchten A, Stroomer AE, van Lenthe H, Zoetekouw L, Kulik W, Hoffmann GF, Voit T, Wevers RA, Rutsch F, van Gennip AH. beta-Ureidopropionase deficiency: an inborn error of pyrimidine degradation associated with neurological abnormalities. Hum Mol Genet. 2004 Nov 15;13(22):2793-801. Epub 2004 Sep 22.