Platelet-activating factor acetylhydrolase IB subunit alpha is an enzyme that in humans is encoded by the PAFAH1B1 gene. [5] [6] [7] The protein is often referred to as Lis1 and plays an important role in regulating the motor protein Dynein. [8]
Platelet-activating factor acetylhydrolase IB subunit alpha is an enzyme that in humans is encoded by the PAFAH1B1 gene. [5] [6] [7] The protein is often referred to as Lis1 and plays an important role in regulating the motor protein Dynein. [8]
PAFAH1B1 was identified as encoding a gene that when mutated or lost caused the lissencephaly associated with Miller–Dieker syndrome. PAFAH1B1 encodes the non-catalytic alpha subunit of the intracellular Ib isoform of platelet-activating factor acetylhydrolase, a heterotrimeric enzyme that specifically catalyzes the removal of the acetyl group at the SN-2 position of platelet-activating factor (identified as 1-O-alkyl-2-acetyl-sn-glyceryl-3-phosphorylcholine). Two other isoforms of intracellular platelet-activating factor acetylhydrolase exist: one composed of multiple subunits, the other, a single subunit. In addition, a single-subunit isoform of this enzyme is found in serum. [7]
According to one study, PAFAH1B1 interacts with VLDLR receptor activated by reelin. [9]
The gene is located at chromosome 17p13.3 on the Watson (plus) strand. The gene is 91,953 bases in length and encodes a protein of 410 amino acids (predicted molecular weight 46.638 kilodaltons).
PAFAH1B1 has been shown to interact with DYNC1H1, [10] CLIP1, [11] NDEL1, [12] [13] NDE1, [14] PAFAH1B3, [15] PAFAH1B2, [15] NUDC, [16] TUBA1A [17] and Doublecortin. [18]
Lissencephaly is a set of rare brain disorders whereby the whole or parts of the surface of the brain appear smooth. It is caused by defective neuronal migration during the 12th to 24th weeks of gestation resulting in a lack of development of brain folds (gyri) and grooves (sulci). It is a form of cephalic disorder. Terms such as agyria and pachygyria are used to describe the appearance of the surface of the brain.
Miller–Dieker syndrome, Miller–Dieker lissencephaly syndrome (MDLS), and chromosome 17p13.3 deletion syndrome is a micro deletion syndrome characterized by congenital malformations. Congenital malformations are physical defects detectable in an infant at birth which can involve many different parts of the body including the brain, hearts, lungs, liver, bones, or intestinal tract. MDS is a contiguous gene syndrome – a disorder due to the deletion of multiple gene loci adjacent to one another. The disorder arises from the deletion of part of the small arm of chromosome 17p, leading to partial monosomy. There may be unbalanced translocations, or the presence of a ring chromosome 17.
Platelet-activating factor, also known as PAF, PAF-acether or AGEPC (acetyl-glyceryl-ether-phosphorylcholine), is a potent phospholipid activator and mediator of many leukocyte functions, platelet aggregation and degranulation, inflammation, and anaphylaxis. It is also involved in changes to vascular permeability, the oxidative burst, chemotaxis of leukocytes, as well as augmentation of arachidonic acid metabolism in phagocytes.
Pachygyria is a congenital malformation of the cerebral hemisphere. It results in unusually thick convolutions of the cerebral cortex. Typically, children have developmental delay and seizures, the onset and severity depending on the severity of the cortical malformation. Infantile spasms are common in affected children, as is intractable epilepsy.
Neuronal migration protein doublecortin, also known as doublin or lissencephalin-X is a protein that in humans is encoded by the DCX gene.
Tubulin alpha-1A chain is a protein that in humans is encoded by the TUBA1A gene.
Nuclear distribution protein nudE-like 1 is a protein that in humans is encoded by the NDEL1 gene.
Nuclear migration protein nudC is a protein that in humans is encoded by the NUDC gene.
Nuclear distribution protein nudE homolog 1 is a protein that in humans is encoded by the NDE1 gene.
Rab-interacting lysosomal protein is a protein that in humans is encoded by the RILP gene.
Rab effector Noc2 is a protein that in humans is encoded by the RPH3AL gene.
MNT is a Max-binding protein that is encoded by the MNT gene
Platelet-activating factor acetylhydrolase IB subunit beta is an enzyme that in humans is encoded by the PAFAH1B2 gene.
Platelet-activating factor acetylhydrolase IB subunit gamma is an enzyme that in humans is encoded by the PAFAH1B3 gene.
SKIP is an acronym for Skeletal muscle and kidney enriched inositol phosphatase, which is a human gene.
Double C2-like domain-containing protein beta is a protein that in humans is encoded by the DOC2B gene.
Lipoprotein-associated phospholipase A2 (Lp-PLA2) also known as platelet-activating factor acetylhydrolase (PAF-AH) is a phospholipase A2 enzyme that in humans is encoded by the PLA2G7 gene. Lp-PLA2 is a 45-kDa protein of 441 amino acids. It is one of several PAF acetylhydrolases.
Vacuolar protein sorting 53 homolog is a protein that in humans is encoded by the VPS53 gene.
Microlissencephaly (MLIS) is a rare congenital brain disorder that combines severe microcephaly with lissencephaly. Microlissencephaly is a heterogeneous disorder, i.e. it has many different causes and a variable clinical course. Microlissencephaly is a malformation of cortical development (MCD) that occurs due to failure of neuronal migration between the third and fifth month of gestation as well as stem cell population abnormalities. Numerous genes have been found to be associated with microlissencephaly, however, the pathophysiology is still not completely understood.
David Hamilton Ledbetter is a human geneticist best known for his contributions to the discovery of the genetic causes of Prader–Willi and Miller–Dieker syndromes. His research has focused on developing and applying technologies to understand neurodevelopmental conditions such as autism spectrum disorders. He has held leadership positions at the National Institutes of Health, the University of Chicago, Emory University, and is currently the Executive Vice President and Chief Scientific Officer of Geisinger Health System.
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