Researchers have identified a rare disease in humans caused by mutations in the gene. (wikipedia.org)
Heterozygous mutations in KCNMA1 were first illustrated in a large family with generalized epilepsy and paroxysmal nonkinesigenic dyskinesia. (balkanmedicaljournal.org)
Recent research has established homozygous KCNMA1 mutations accountable for the phenotype of cerebellar atrophy, developmental delay, and seizures. (balkanmedicaljournal.org)
This study is of broad interest to neuroscientists interested in membrane excitability and translational biologists and physicians eager for robust animal models for disorders involving mutations in the KCNMA gene, such as paroxysmal nonkinesigenic dyskinesia PNKD3. (sciety.org)
This work establishes that BK channel mutations linked to human neurological disease can, on their own, cause similar pathology in mice, and it also begins to provide neurological bases for the associated behavioral deficits. (sciety.org)
However, the relevance of KCNMA1 mutations and the basis for clinical heterogeneity in PNKD3 has not been established. (sciety.org)
Mutations in this gene cause the early-onset epileptic disorders, malignant migrating partial seizures of infancy and autosomal dominant nocturnal frontal lobe epilepsy. (antikoerper-online.de)
21 allelic mutations have been discovered in the APP gene. (findzebra.com)
Encodes6
The KCNMA1 gene encodes the α-subunit of the large conductance, voltage, and calcium-sensitive potassium channel (BK channels) that plays a critical role in neuronal excitability. (balkanmedicaljournal.org)
In our project, we used CRISPR/Cas9 technology in human glioblastoma U-87 MG cells to generate knockout cell lines lacking the α-subunit of the BKCa channel encoded by the KCNMA1 gene, which also encodes cardiac mitoBKCa. (bvsalud.org)
This gene encodes a transcription factor that contains a cyclin D-binding domain, three central Myb-like repeats, and two flanking acidic transactivation domains at the N- and C-termini. (utsouthwestern.edu)
This gene encodes a sodium-activated potassium channel subunit which is thought to function in ion conductance and developmental signaling pathways. (antikoerper-online.de)
These guarantee onset of early-onset familial Alzheimer disease and all occur in the region of the APP gene that encodes the Aβ domain. (findzebra.com)
It delivers the gene that encodes the SARS-CoV-2 spike protein, to our cells. (epiphanyasd.com)
Heterozygous1
Recently, genetic screening identified heterozygous KCNMA1 variants in a subset of patients with debilitating paroxysmal non-kinesigenic dyskinesia, presenting with or without epilepsy (PNKD3). (sciety.org)
Neuronal5
KCNMA1 forms the pore of BK K + channels, which regulate neuronal and muscle excitability. (sciety.org)
Consistent with other studies, genes identified by disrupted protein interactions are expressed early in development and in excitatory and inhibitory neuronal lineages. (springer.com)
Using inferred gene co-expression for three neuronal cell types-excitatory, inhibitory, and neural progenitor-we implicate several hundred genes in risk (FDR \(\le \hspace{0.17em}\) 0.05), ~ 60% novel, with characteristics of genuine ASD genes. (springer.com)
Across cell types, these genes affect neuronal morphogenesis and neuronal communication, while neural progenitor cells show strong enrichment for development of the limbic system. (springer.com)
Human APP mRNA was detected in neurons and neuronal processes, but not in vessel walls. (findzebra.com)
KCa1.16
Calcium-activated potassium channel subunit alpha-1 also known as large conductance calcium-activated potassium channel, subfamily M, alpha member 1 (KCa1.1), or BK channel alpha subunit, is a voltage gated potassium channel encoded by the KCNMA1 gene and characterized by their large conductance of potassium ions (K+) through cell membranes. (wikipedia.org)
Inhibition of the pathogenic phenotypes of both FLS and T EM cells can be accomplished by selectively blocking the predominant potassium channels that they upregulate during RA: KCa1.1 (BK, Slo1, MaxiK, KCNMA1 ) upregulated by FLS and Kv1.3 ( KCNA3 ) upregulated by activated T EM cells. (biomedcentral.com)
We interrogated the predicted targets of these differentially expressed microRNA families in MPM cell lines, and identified KCa1.1, a calcium-activated potassium channel subunit alpha 1 encoded by the KCNMA1 gene, as a target of miR-17-5p. (bairdinstitute.org.au)
Transfection of MPM cells with a miR-17-5p mimic or KCNMA1-specific siRNAs reduced mRNA expression of KCa1.1 and inhibited MPM cell migration. (bairdinstitute.org.au)
These functional data implicating KCa1.1 in MPM cell migration support our integrative approach using MPM gene expression datasets to identify novel and potentially druggable targets. (bairdinstitute.org.au)
KCNMA1/KCa1.1 (1184-1200) Blocking Peptide (#BLP-PC107) is the original antigen used for immunization during Anti-KCNMA1 (KCa1.1) (1184-1200) Antibody (#APC-107) generation. (scientist.com)
Homozygous3
Here, we report the case of a patient with a novel homozygous truncating mutation in KCNMA1 (p.Arg458Ter) presenting with both the loss- and gain-of-function phenotype with paroxysmal dyskinesia, epilepsy, intellectual delay, and corticospinal-cerebellar tract atrophy. (balkanmedicaljournal.org)
A recent study established a correlation of the homozygous KCNMA1 mutation with cerebellar ataxia, developmental delay, and seizures. (balkanmedicaljournal.org)
Homozygous Kcnma1 D434G/D434G mice showed similar immobility, but in contrast, homozygous Kcnma1 H444Q/H444Q mice displayed hyperkinetic behavior. (sciety.org)
Mutation4
Genetic Heterogeneity of Alternating Hemiplegia of ChildhoodSee also AHC2 ( OMIM ), caused by mutation in the ATP1A3 gene ( OMIM ). (mendelian.co)
This condition is caused by a spontaneous mutation in the IRF2BPL gene. (spotify.com)
2005) identified a mutation in the APP gene (104760.0019). (findzebra.com)
This subtype is due to a mutation in the APP gene (21q21.2), encoding the beta-amyloid precursor protein. (findzebra.com)
Channelopathy1
KCNMA1-linked channelopathy can cause neurological conditions like seizures and movement disorders. (wikipedia.org)
Conductance1
Available X-ray structures include: 3U6N - Open structure of the BK channel gating ring 3MT5 - Crystal structure of the human BK gating apparatus 3NAF - Structure of the intracellular gating ring from the human high-conductance Ca2+ gated K+ channel (BK Channel) BK channels are pharmacological targets for the treatment of stroke. (wikipedia.org)
Dyskinesia1
In a novel behavioral test for paroxysmal dyskinesia, the more severely affected Kcnma1 N999S/WT mice became immobile after stress, consistent with stress-induced immobility episodes observed in PNKD3-affected individuals. (sciety.org)
Autism8
Whole-exome sequencing studies have been useful for identifying genes that, when mutated, affect risk for autism spectrum disorder (ASD). (springer.com)
The problem is that most autism and all Down syndrome is polygenic, there can be hundreds of miss-expressed genes. (epiphanyasd.com)
But the researchers in Italy show us that even polygenic autism and Down syndrome can benefit from therapy targeting a single gene. (epiphanyasd.com)
The question is will it ever going be available to humans with Down Syndrome, Autism or even Parkinson's disease? (epiphanyasd.com)
It is true that asthma and eczema (atopic dermatitis) are common in people with autism, but variations in the broader SLC6 family of genes are known to affect people with ADHD, Fragile X, Tourette's and broad autism. (epiphanyasd.com)
MRNA3
MicroRNAs (miRNAs), single-stranded RNA molecules with 19~25 nucleotides in length, are recognized as key modulators governing multiple gene expression via binding to the 3' untranslated region (3'-UTR) of target mRNA at the posttranscriptional level [ 7 ]. (oncotarget.com)
Utilizing mRNA-microRNA correlations based on differential gene expression using Gene Set Enrichment Analysis (GSEA), we systematically combined publicly available gene expression datasets with our own MPM data in order to identify candidate targets for MPM therapy. (bairdinstitute.org.au)
Our cells then transcribe this gene into messenger RNA, or mRNA, which in turn prompts our cellular machine to make the spike protein in the main body of the cell. (epiphanyasd.com)
Datasets to identify1
In this study, we used 7 publicly available microarray datasets to identify gene signatures related to recurrence in optimally debulked SOC patients, and validated their expressions in an independent clinic cohort of 127 patients using immunohistochemistry (IHC). (oncotarget.com)
Variants4
Here we evaluate the relative severity of three KCNMA1 patient variants in BK channels, neurons, and mice. (sciety.org)
Despite their commonness in humans, determining which missense variants affect phenotypes and how remains a challenge. (springer.com)
We investigate the functional relevance of de novo missense variants, specifically whether they are likely to disrupt protein interactions, and nominate novel genes in risk for ASD through integrated genomic, transcriptomic, and proteomic analyses. (springer.com)
Multiple transcript variants encoding different isoforms have been found for this gene. (utsouthwestern.edu)
Seizure2
BK currents and action potential firing were increased, and seizure thresholds decreased, in Kcnma1 N999S/WT and Kcnma1 D434G/WT transgenic mice but not Kcnma1 H444Q/WT mice. (sciety.org)
H444Q and validate Kcnma1 N999S/WT mice as a model for PNKD3 with increased seizure propensity. (sciety.org)
Expression8
Protein expression of BK-ß1, phosphorylation of adenosine 5'-monophosphate-activated protein kinase (AMPK), and protein kinase B (PKB or Akt) were down-regulated, while F-box protein 32 (FBXO32) expression increased in the DM+V group and in high glucose (HG) cultured human coronary smooth muscle cells. (bvsalud.org)
For genes encoding the disrupted interactions, we evaluate their expression patterns across developing brains and within specific cell types, using both bulk and inferred cell-type-specific brain transcriptomes. (springer.com)
Finally, we integrate protein interactions and cell-type-specific co-expression networks together with published association data to implicate novel genes in ASD risk in a cell-type-specific manner. (springer.com)
Their gene expression during brain development and within cell types highlights how they relate to ASD. (springer.com)
Using the newly released and larger ASC dataset, we confirm these observations and take them in several new directions: (1) By defining a set of genes encoding these disrupted protein interactors in ASD subjects and another for their siblings, we evaluate their expression patterns in developing brain from fetal to early postnatal development and within general cell types of brain tissue. (springer.com)
Direct comparison of the cell types were made to primary tissues using gene expression atlases and fetal human brain single-cell gene expression data, and this established that the cell types resembled early human brain cell types, including preplate cells. (uth.edu)
In addition, gene expression analysis shows that E-cadherin loss results in the induction of multiple transcription factors, at least one of which, Twist, is necessary for E-cadherin loss-induced metastasis. (gsea-msigdb.org)
Polymorphisms in transporter genes may influence expression and activity of transporters and contribute to behavior, traits, and disease. (epiphanyasd.com)
Recurrence2
For some genes, recurrence across ASD subjects is far more than expected by chance and is evidence for association with ASD. (springer.com)
We identified a two-gene signature including KCNN4 and S100A14 which was related to recurrence in optimally debulked SOC patients. (oncotarget.com)
Caused transien1
An episode of the Diagnosis TV show, based on a column in the New York Times, was about a young girl with a KCNMA1 disorder that caused transient episodes of muscle weakness. (wikipedia.org)
Protein2
Disrupted protein interactions identify gene sets involved in risk for ASD. (springer.com)
The PARK10 gene USP24 is a negative regulator of autophagy and ULK1 protein stability. (umaryland.edu)
Interaction1
Genes encoding disrupted complementary interactors tend to be risk genes, and an interaction network built from these proteins is enriched for ASD proteins. (springer.com)
Neurons1
CREB activates transcription of genes which are important for axonal growth, survival, and synaptic plasticity in neurons.NCAM1 mediated intracellular signal transduction is represented in the figure below. (uni-freiburg.de)
Lineages1
In summary, we present an experimentally validated lineage tree that encompasses multiple brain regions, and our work sheds light on the molecular regulation of region-specific neural lineages during human brain development. (uth.edu)
Homeostasis1
Solute carrier 6 (SLC6) is a gene family of ion-coupled plasma membrane cotransporters, including transporters of neurotransmitters, amino acids, and osmolytes that mediate the movement of their substrates into cells to facilitate or regulate synaptic transmission, neurotransmitter recycling, metabolic function, and fluid homeostasis. (epiphanyasd.com)
Genetics1
By Center for Human Genetics, Inc (United States). (mendelian.co)
Proteins1
The SLC6 family is among the largest SLC families, containing 20 genes that encode a group of highly similar transporter proteins. (epiphanyasd.com)
Cells4
Using this method the main genes conferring estrogen independence in human breast cancer cells where identified. (cancertools.org)
The transcriptomes of 1846 single cells were profiled by SmartSeq2 at different timepoints throughout a 54-day differentiation protocol that converted H1 human embryonic stem cells to a variety of brain cell types. (uth.edu)
Here we report a system to generate early human brain forebrain and mid/hindbrain cell types from human embryonic stem cells (hESCs), and infer and experimentally confirm a lineage tree for the generation of these types based on single-cell RNA-Seq analysis. (uth.edu)
Genes changed in HMLE cells (mmortalized nontransformed mammary epithelium) after RNAi knockdown of both CDH1 and CTNNB1 [GeneID=999;1499], compared to the knockdown of CDH1 alone. (gsea-msigdb.org)
Clinical1
Notably, pharmacological inhibition of the chloride importer NKCC1 is able to rescue brain-related core deficits in animal models of these pathologies and some human clinical studies. (epiphanyasd.com)
Change2
This may be about to change given that the Biontech (AKA Pfizer vaccine), Moderna, Janssen (Johnson & Johnson) and Oxford AstraZeneca vaccines for Covid 19 are all based on gene therapy. (epiphanyasd.com)
Changing the methylation of this gene will change when it turns on/off. (epiphanyasd.com)
Mouse2
FUNCTION: [Summary is not available for the mouse gene. (utsouthwestern.edu)
Hier sind KCNT1 Antikörper für eine Vielzahl von Species wie anti-Human KCNT1, anti-Rat KCNT1, anti-Mouse KCNT1 zu finden. (antikoerper-online.de)
Many supplements and herbal medicines do show promise in the laboratory, when tests are conducted in vitro, but very often when tests are made in humans the results are much weaker, or just not present. (epiphanyasd.com)
Target1
This gene is hemizygously deleted in approximately 40% of human non-small-cell lung cancer and is a potential prognostic and gene-therapy target for non-small-cell lung cancer. (utsouthwestern.edu)
Out of 15 candidate breast cancer antigen resistance (BCAR) genes, seven (AKT1, AKT2, BCAR1, BCAR3, EGFR2, GRB7 and TRERF1/BCAR2) were shown to directly underline estrogen independence. (cancertools.org)
The Biontech people are really clever and were already trying to treat various kinds of cancer and other condition using gene therapy, before they developed their highly successful Covid vaccine. (epiphanyasd.com)
Studies1
in the test tube it has a wide range of potent benefits, but due to low absorption into humans (bioavailability) it does not show such conclusive results in human studies. (epiphanyasd.com)