KDM1A (Lysine Demethylase 1A)
A flavin-dependent histone demethylase regulating gene expression through H3K4me1/me2 and H3K9me1/me2 demethylation
Gene Information Card
| Symbol | KDM1A |
|---|---|
| Full Name | Lysine Demethylase 1A |
| Gene Type | Protein coding |
| Chromosomal Location | 1p36.12 |
| NCBI Gene ID | 23028 ncbi.nlm.nih.gov/gene/23028 |
| Ensembl ID | ENSG00000004487 |
| UniProt ID | O60341 |
| OMIM ID | 609132 |
| HGNC ID | 29079 |
| Aliases | LSD1, AOF2, BHC110, KIAA0601 |
Description
KDM1A (lysine demethylase 1A), also known as LSD1, encodes a flavin-dependent histone demethylase that specifically demethylates mono- and dimethylated lysine 4 of histone H3 (H3K4me1/me2) and, in complex with other factors, can also demethylate H3K9me1/me2. It plays a critical role in transcriptional regulation, chromatin remodeling, and cellular differentiation. KDM1A is involved in various biological processes including stem cell pluripotency, neurogenesis, and hematopoiesis. Dysregulation of KDM1A is associated with multiple cancers and neurodevelopmental disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Acute myeloid leukemia | KDM1A overexpression promotes leukemogenesis by repressing tumor suppressor genes via H3K4 demethylation | PMID: 22158538 |
| Breast cancer | KDM1A overexpression correlates with poor prognosis; promotes invasion and metastasis through EMT regulation | PMID: 22751019 |
| Prostate cancer | KDM1A interacts with androgen receptor to drive proliferation; inhibition reduces tumor growth | PMID: 20010870 |
| Neuroblastoma | KDM1A is highly expressed and associated with aggressive disease; targeting KDM1A reduces tumor growth | PMID: 23558952 |
| Intellectual disability | De novo KDM1A mutations cause a syndromic form of intellectual disability with developmental delay | PMID: 31006510 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Testis | 10.8 | Medium |
| Bone marrow | 9.2 | Medium |
| Lung | 7.1 | Low |
| Liver | 5.3 | Low |
| Kidney | 6.8 | Low |
| Heart | 4.5 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 14.2 | High expression |
| K562 | 11.5 | Medium expression |
| HeLa | 9.8 | Medium expression |
| MCF7 | 8.3 | Medium expression |
| HepG2 | 6.1 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1061G>A (p.Arg354His) | Missense | Rare | Reduced demethylase activity; associated with intellectual disability |
| c.1580C>T (p.Thr527Met) | Missense | Rare | Impaired interaction with CoREST; loss of function |
| c.1960G>A (p.Gly654Arg) | Missense | Rare | Decreased stability and activity |
| Amplification | Copy number gain | ~5% in AML | Overexpression; oncogenic |
Mutation functional classification
Loss of Function (LOF)
Missense mutations (e.g., Arg354His, Thr527Met) reduce or abolish demethylase activity, impairing H3K4 demethylation and leading to altered gene expression.
Gain of Function (GOF)
Gene amplification and overexpression in cancers enhance demethylase activity, promoting oncogenic transcriptional programs.
Dominant Negative (DN)
No well-characterized dominant-negative mutations reported; some missense variants may exert dominant-negative effects by disrupting complex formation.
View complete mutation data：
Gene Ontology (GO)
| • Histone H3-K4 demethylation (GO:0034720) | • Histone H3-K9 demethylation (GO:0033169) |
| • Chromatin remodeling (GO:0006338) | • Transcription corepressor activity (GO:0003714) |
| • Flavin adenine dinucleotide binding (GO:0050660) | • Oxidoreductase activity (GO:0016491) |
Pathways
• Chromatin modifying enzymes (Reactome R-HSA-3247509)
• Transcriptional regulation by the AP-2 family (Reactome R-HSA-8866907)
• HDACs deacetylate histones (Reactome R-HSA-3214815)
• Regulation of gene expression by epigenetic modification (KEGG hsa05202)
Protein Summary
KDM1A (LSD1) is a 852-amino acid flavin-dependent amine oxidase that demethylates mono- and dimethylated lysine residues on histone H3, primarily H3K4me1/me2 and H3K9me1/me2. It contains a SWIRM domain, a Tower domain, and an amine oxidase domain. KDM1A functions as part of multiprotein complexes including CoREST, NuRD, and CtBP, which target it to specific genomic loci. Its activity is essential for maintaining cellular identity, and its dysregulation contributes to cancer and neurodevelopmental disorders.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| KDM1A Knockout HEK293 Cell Line | EDJ-KQ13915 | Human | 23028 | Details Get a Quote |
| KDM1A Knockout A-549 Cell Line | EDJ-KQ18105 | Human | 23028 | Details Get a Quote |
| KDM1A Knockout HCT 116 Cell Line | EDJ-KQ26287 | Human | 23028 | Details Get a Quote |
| KDM1A Knockout HeLa Cell Line | EDJ-KQ42520 | Human | 23028 | Details Get a Quote |
| KDM1A Knockout HAP1 Cell Line | EDC08098 | Human | 23028 | Details Get a Quote |
