BTB domain containing 9 is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

that in humans is encoded by the BTBD9

gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

. 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 (an insect of the Order (biology), 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", "pomace fly" ...

. 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 Chromosome 6 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 6 spans nearly 171 million base pairs (the building material of DNA) and represents between 5.5 and 6% of the total DNA i ...

and the domain contains eight

exon An exon is any part of a gene that will form a part of the final mature RNA produced by that gene after introns have been removed by RNA splicing. The term ''exon'' refers to both the DNA sequence within a gene and to the corresponding sequence ...

s and seven

intron An intron is any nucleotide sequence within a gene that is not expressed or operative in the final RNA product. The word ''intron'' is derived from the term ''intragenic region'', i.e., a region inside a gene."The notion of the cistron .e., gen ...

s. 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 Homologous chromosomes or homologs are a set of one maternal and one paternal chromosome that pair up with each other inside a cell during meiosis. Homologs have the same genes in the same loci, where they provide points along each chromosome th ...

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 (: thalami; from Greek language, Greek Wikt:θάλαμος, θάλαμος, "chamber") is a large mass of gray matter on the lateral wall of the third ventricle forming the wikt:dorsal, dorsal part of the diencephalon (a division of ...

, 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. It is the largest site of Neuron, neural integration in the central nervous system, and plays ...

cerebellum The cerebellum (: cerebella or cerebellums; Latin for 'little brain') is a major feature of the hindbrain of all vertebrates. Although usually smaller than the cerebrum, in some animals such as the mormyrid fishes it may be as large as it or eve ...

hippocampus The hippocampus (: hippocampi; via Latin from Ancient Greek, Greek , 'seahorse'), also hippocampus proper, is a major component of the brain of humans and many other vertebrates. In the human brain the hippocampus, the dentate gyrus, and the ...

, and

caudate nucleus The caudate nucleus is one of the structures that make up the corpus striatum, which is part of the basal ganglia in the human brain. Although the caudate nucleus has long been associated with motor processes because of its relation to Parkinso ...

. The

Drosophila ''Drosophila'' (), from Ancient Greek δρόσος (''drósos''), meaning "dew", and φίλος (''phílos''), meaning "loving", is a genus of fly, belonging to the family Drosophilidae, whose members are often called "small fruit flies" or p ...

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 A knockout mouse, or knock-out mouse, is a genetically modified mouse (''Mus musculus'') in which researchers have inactivated, or " knocked out", an existing gene by replacing it or disrupting it with an artificial piece of DNA. They are importan ...

argued that BTBD9 is involved in

synaptic plasticity In neuroscience, synaptic plasticity is the ability of synapses to Chemical synapse#Synaptic strength, strengthen or weaken over time, in response to increases or decreases in their activity. Since memory, memories are postulated to be represent ...

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

endocytosis Endocytosis is a cellular process in which Chemical substance, substances are brought into the cell. The material to be internalized is surrounded by an area of cell membrane, which then buds off inside the cell to form a Vesicle (biology and chem ...

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 a neurological disorder, usually chronic, that causes an overwhelming urge to move one's legs. There is often an unpleasant feeling in the legs that improves temporaril ...

. 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 Obsession may refer to: Psychology * Celebrity worship syndrome, obsessive addictive disorder to a celebrity's personal and professional life * Obsession (psychology), a persistent attachment to an object or idea * Fixation (psychology), persi ...

. 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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