KDM1A

Chr 1p36.12

lysine demethylase 1A

Aliases:: KIAA0601, BHC110, LSD1
MANE:: ENST00000400181.9

OMIM: 609132 ↗NCBI: 23028 ↗Ensembl ↗

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Predicted protein structure

AlphaFold predicted structure

KDM1A · O60341

v62025-08-01

Predicted Aligned Error matrix for KDM1A — diagonal shows residue index, colour shows pairwise prediction confidence (lower is better) — Predicted Aligned Error

Mean pLDDT

84.2/ 100

Confident

852 residues

Confidence breakdown

Very high(≥ 90)76%
Confident(70–90)2%
Low(50–70)1%
Very low(< 50)20%

Open interactive 3D viewer

AlphaFold (Jumper et al., 2021) · CC BY 4.0

Clinical relevance (Genomics England PanelApp)

Diagnostic Grade (Green)

DDG2P
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Intellectual disability
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Clefting
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Fetal anomalies
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Haematological malignancies cancer susceptibility
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital adrenal hypoplasia
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Disease associations (Open Targets)

palatal anomalies-widely spaced teeth-facial dysmorphism-developmental delay syndrome
0.74
neurodegenerative disease
0.55
ACTH-independent macronodular adrenal hyperplasia 3
0.47
Global developmental delay
0.40
Cushing syndrome due to macronodular adrenal hyperplasia
0.38
essential thrombocythemia
0.36
Intellectual disability
0.30
Neurodevelopmental delay
0.27
plasma cell myeloma
0.20
AL amyloidosis
0.20

Score is the Open Targets composite evidence score (0-1). Higher = stronger gene-disease association.

Protein function (UniProt)

Lysine-specific histone demethylase 1A

Histone demethylase that can demethylate both 'Lys-4' (H3K4me) and 'Lys-9' (H3K9me) of histone H3, thereby acting as a coactivator or a corepressor, depending on the context (PubMed:15620353, PubMed:15811342, PubMed:16079794, PubMed:16079795, PubMed:16140033, PubMed:16223729, PubMed:27292636). Acts by oxidizing the substrate by FAD to generate the corresponding imine that is subsequently hydrolyzed (PubMed:15620353, PubMed:15811342, PubMed:16079794, PubMed:21300290, PubMed:26214369). Acts as a corepressor by mediating demethylation of H3K4me, a specific tag for epigenetic transcriptional activation. Demethylates both mono- (H3K4me1) and di-methylated (H3K4me2) (PubMed:15620353, PubMed:20389281, PubMed:21300290, PubMed:23721412). May play a role in the repression of neuronal genes. Alone, it is unable to demethylate H3K4me on nucleosomes and requires the presence of RCOR1/CoREST to achieve such activity (PubMed:16079794, PubMed:16140033, PubMed:16885027, PubMed:21300290, PubMed:23721412). Also acts as a coactivator of androgen receptor (AR)-dependent transcription, by being recruited to AR target genes and mediating demethylation of H3K9me, a specific tag for epigenetic transcriptional repression. The presence of PRKCB in AR-containing complexes, which mediates phosphorylation of 'Thr-6' of histone H3 (H3T6ph), a specific tag that prevents demethylation H3K4me, prevents H3K4me demethylase activity of KDM1A (PubMed:16079795). Demethylates di-methylated 'Lys-370' of p53/TP53 which prevents interaction of p53/TP53 with TP53BP1 and represses p53/TP53-mediated transcriptional activation. Demethylates and stabilizes the DNA methylase DNMT1 (PubMed:29691401). Demethylates methylated 'Lys-42' and methylated 'Lys-117' of SOX2 (PubMed:29358331). Required for gastrulation during embryogenesis. Component of a RCOR/GFI/KDM1A/HDAC complex that suppresses, via histone deacetylase (HDAC) recruitment, a number of genes implicated in multilineage blood cell development (PubMed:16079794, PubMed:16140033). Facilitates epithelial-to-mesenchymal transition by acting as an effector of SNAI1-mediated transcription repression of epithelial markers E-cadherin/CDH1, CDN7 and KRT8 (PubMed:20562920, PubMed:27292636). Required for the maintenance of the silenced state of the SNAI1 target genes E-cadherin/CDH1 and CDN7 (PubMed:20389281). Required for the repression of GIPR expression (PubMed:34655521, PubMed:34906447)