|Lysine (K)-specific demethylase 1A|
|Symbols||; AOF2; BHC110; KDM1; LSD1|
|External IDs||IUPHAR: GeneCards:|
Lysine-specific histone demethylase 1A (KDM1A) also known as lysine (K)-specific demethylase 1A (LSD1) is a protein in humans that is encoded by the KDM1A gene. LSD1 is a flavin-dependent monoamine oxidase, which can demethylate mono- and di-methylated lysines, specifically histone 3, lysines 4 and 9 (H3K4 and H3K9). This enzyme can have roles critical in embryogenesis and tissue-specific differentiation, as well as oocyte growth. KDM1A was the first demethylase to be discovered and thus it has been studied most extensively.
This gene encodes a nuclear protein containing a SWIRM domain, a FAD-binding motif, and an amine oxidase domain. This protein is a component of several histone deacetylase complexes, though it silences genes by functioning as a histone demethylase.
LSD1 (lysine-specific demethylase 1), also known as KDM1, is the first of several protein lysine demethylases discovered. Through a FAD-dependent oxidative reaction, LSD1 speficially removes histone H3K4me2 to H3K4me1 or H3K4me0. When forming a complex with androgen receptor (and possibly other nuclear hormone receptors), LSD1 changes its substrates to H3K9me2. It's now known LSD1 complex mediates a coordinated histone modification switch through enzymatic activities as well as histone modification readers in the complex.
KDM1A has many different binding partners, which may be necessary for its demethylation activity.
Deletion of the gene for KDM1A can have effects on the growth and differentiation of embryonic stem cells and can lead to embryonic lethality in knockout mice, who do not produce the KDM1A gene product KDM1A is also thought to play a role in cancer, as poorer outcomes can be correlated with higher expression of this gene. Therefore, the inhibition of KDM1A may be a possible treatment for cancer.
De novo mutations to KDM1A have been reported in two patients, both with severe developmental delays believed to be attributable in part to the mutations. Both mutations were missense substitutions. One of the affected families has created a public website in order to identify further cases. 
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- "Milo's Journey".
- lysine specific demethylase 1, human at the US National Library of Medicine Medical Subject Headings (MeSH)
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