BTB domain containing 9 is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...

that in humans is encoded by the BTBD9

gene In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...

. BTBD9 is in a subgroup of BTB(POZ) proteins, which contribute to the forming of limbs and determination of cell fate in developing

Drosophila melanogaster ''Drosophila melanogaster'' is a species of fly (the taxonomic order Diptera) in the family Drosophilidae. The species is often referred to as the fruit fly or lesser fruit fly, or less commonly the " vinegar fly" or "pomace fly". Starting with ...

. BTB(POZ) proteins also play a role in cellular functions such as: cytoskeleton regulation,

transcription regulation In molecular biology and genetics, transcriptional regulation is the means by which a cell regulates the conversion of DNA to RNA (transcription), thereby orchestrating gene activity. A single gene can be regulated in a range of ways, from alt ...

, the gating and assembly of ion channels, and ubiquitination of proteins. BTBD9 is highly expressed throughout the brain and shows variable levels of expression in most other body tissues. The gene is located on the short arm of chromosome 6 and the domain contains eight exons and seven introns. The chromosome 6 locational domain that codes for BTB(POZ) proteins is understood to contain genes encoding protein-protein interactions. BTBD9 is a protein located in cellular cytosol and also expressed within Human embryonic kidney cell lineages. There is also evidence suggesting that BTBD9 is highly expressed within the human nervous system from comparison analysis to Drosophila and human cell studies.

Animal models

There are extensive

homologs A couple of homologous chromosomes, or homologs, are a set of one maternal and one paternal chromosome that pair up with each other inside a cell during fertilization. Homologs have the same genes in the same loci where they provide points alon ...

to BTBD9 which allow for the use of animal models in deciphering its functions and interactions. The BTBD9 homolog Btbd9 is extensively expressed in the central nervous system of adult mice including the

thalamus The thalamus (from Greek θάλαμος, "chamber") is a large mass of gray matter located in the dorsal part of the diencephalon (a division of the forebrain). Nerve fibers project out of the thalamus to the cerebral cortex in all directions, ...

, sub-thalamic nuclei,

cerebral cortex The cerebral cortex, also known as the cerebral mantle, is the outer layer of neural tissue of the cerebrum of the brain in humans and other mammals. The cerebral cortex mostly consists of the six-layered neocortex, with just 10% consistin ...

, cerebellum,

hippocampus The hippocampus (via Latin from Greek , ' seahorse') is a major component of the brain of humans and other vertebrates. Humans and other mammals have two hippocampi, one in each side of the brain. The hippocampus is part of the limbic system, ...

, and

caudate nucleus The caudate nucleus is one of the structures that make up the corpus striatum, which is a component of the basal ganglia in the human brain. While the caudate nucleus has long been associated with motor processes due to its role in Parkinson's d ...

. The

Drosophila ''Drosophila'' () is a genus of flies, belonging to the family Drosophilidae, whose members are often called "small fruit flies" or (less frequently) pomace flies, vinegar flies, or wine flies, a reference to the characteristic of many speci ...

homolog dBTBD9, was shown to regulate dopamine levels in the Drosophila brain and iron regulation in human cell-lines.

Synaptic plasticity

A recent study using Btbd9 knockout mice argued that BTBD9 is involved in

synaptic plasticity In neuroscience, synaptic plasticity is the ability of synapses to strengthen or weaken over time, in response to increases or decreases in their activity. Since memories are postulated to be represented by vastly interconnected neural circuits ...

, learning and memory, and protein alterations associated with vesicle recycling and endocytosis.

Clinical relevance

There is some evidence that BTBD9 may be associated with

Restless legs syndrome Restless legs syndrome (RLS), also known as Willis-Ekbom disease (WED), is generally a long-term disorder that causes a strong urge to move one's legs. There is often an unpleasant feeling in the legs that improves somewhat by moving them. This ...

. However, there is not a known mutation of the BTBD9 gene that is responsible for the onset of the RLS. Mutations to BTBD9 are positively correlated with characteristic symptoms of Restless leg syndrome such as decreased dopamine levels, increased movement, and disrupted sleep patterns. The overrepresentation of single nucleotide polymorphisms expressed in BTBD9 may be associated with Restless legs syndrome and nighttime leg movements. Single nucleotide polymorphisms in BTBD9 that have been linked to Restless leg syndrome are also correlated with Tourette’s Syndrome that doesn’t present with Obsessive Compulsive Disorder. One scientific review regarding Restless Legs Syndrome expressed that Restless Legs Syndrome is a complex syndrome that has many risk factor indicators including the presence of the BTBD9 gene. Drosophila CG18126 gene loss was found to be correlated to sleep lost behavior within fruit fly experiments. The BTBD9 gene through the use of iron regulatory protein-2 in human cell line is found to be associated with the regulation of iron levels in human cells. One scientific review discussed how the iron level association found in human cell lines was also present in animal phenotypes. These model organisms could have normal iron levels present throughout the body even when the dopamine neural pathways had below normal iron levels within the brain due to the BTBD9 presence. One study was able to look at a single nucleotide polymorphism in BTBD9. This mutation can be contributed to these various health issues. The BTBD9 gene has also been linked to blood anemia in a study. The study linked a genetic marker in the BTBD9 gene with anemia in blood donors. It was found that higher ferritin levels could be connected to a variant in the allele (G) in the BTBD9 gene. The study was only conducted with Australian blood donors. The high ferritin levels indicated a contribution to the variant allel (G) while decreased ferritin levels indicate the BTBD9 gene is being over expressed.

References

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