KDM1B

Summary

KDM1B (lysine demethylase 1B, HGNC:21577) is a protein-coding gene on chromosome 6p22.3, encoding Lysine-specific histone demethylase 2 (Q8NB78). Histone demethylase that demethylates ‘Lys-4’ of histone H3, a specific tag for epigenetic transcriptional activation, thereby acting as a corepressor.

Flavin-dependent histone demethylases, such as KDM1B, regulate histone lysine methylation, an epigenetic mark that regulates gene expression and chromatin function (Karytinos et al., 2009 [PubMed 19407342]).

Source: NCBI Gene 221656 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 87 total
• Druggable target: yes — 2 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001364614

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21577
Approved symbol	KDM1B
Name	lysine demethylase 1B
Location	6p22.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ34109, FLJ33898, dJ298J15.2, bA204B7.3, FLJ43328, LSD2
Ensembl gene	ENSG00000165097
Ensembl biotype	protein_coding
OMIM	613081
Entrez	221656

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 8 protein_coding, 1 retained_intron

ENST00000297792, ENST00000449850, ENST00000546309, ENST00000642162, ENST00000650836, ENST00000897548, ENST00000897549, ENST00000897550, ENST00000897551

RefSeq mRNA: 2 — MANE Select: NM_001364614 NM_001364614, NM_153042

CCDS: CCDS34343, CCDS93866

Canonical transcript exons

ENST00000650836 — 22 exons

Exon	Start	End
ENSE00000928743	18197587	18197661
ENSE00000928744	18200439	18200576
ENSE00000928746	18212488	18212604
ENSE00000928747	18213656	18213781
ENSE00000928749	18217733	18217885
ENSE00000973379	18197057	18197233
ENSE00001007362	18207398	18207529
ENSE00001090315	18208132	18208206
ENSE00001302836	18185772	18185810
ENSE00001478501	18171363	18171479
ENSE00001478502	18166267	18166378
ENSE00001478503	18162835	18162924
ENSE00001478504	18161327	18161454
ENSE00001478505	18159883	18159982
ENSE00001478506	18155883	18155926
ENSE00001504202	18187792	18188002
ENSE00001504205	18205537	18205664
ENSE00001504206	18201486	18201657
ENSE00001504207	18191197	18191381
ENSE00003517432	18215007	18215129
ENSE00003843472	18155422	18155571
ENSE00003848861	18221909	18223854

Expression profiles

Bgee: expression breadth ubiquitous, 248 present calls, max score 98.48.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 12.6040 / max 446.2443, expressed in 1786 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
66169	9.5226	1758
66170	2.3296	1033
66168	0.7519	368

Top tissues by expression

260 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	98.48	gold quality
oocyte	CL:0000023	98.03	gold quality
monocyte	CL:0000576	93.33	gold quality
leukocyte	CL:0000738	92.99	gold quality
cortical plate	UBERON:0005343	89.26	gold quality
upper arm skin	UBERON:0004263	88.97	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.08	gold quality
bronchial epithelial cell	CL:0002328	86.83	gold quality
islet of Langerhans	UBERON:0000006	86.46	gold quality
ileal mucosa	UBERON:0000331	86.39	gold quality
bronchus	UBERON:0002185	85.77	gold quality
bone marrow	UBERON:0002371	85.75	gold quality
ganglionic eminence	UBERON:0004023	85.29	gold quality
embryo	UBERON:0000922	85.28	gold quality
right lobe of thyroid gland	UBERON:0001119	84.82	gold quality
bone marrow cell	CL:0002092	84.77	gold quality
thyroid gland	UBERON:0002046	84.47	gold quality
left lobe of thyroid gland	UBERON:0001120	84.40	gold quality
granulocyte	CL:0000094	83.88	gold quality
rectum	UBERON:0001052	83.87	gold quality
gastrocnemius	UBERON:0001388	83.68	gold quality
muscle of leg	UBERON:0001383	83.34	gold quality
tibialis anterior	UBERON:0001385	82.63	gold quality
right uterine tube	UBERON:0001302	82.39	gold quality
vermiform appendix	UBERON:0001154	82.38	gold quality
blood	UBERON:0000178	82.25	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	81.65	gold quality
skeletal muscle organ	UBERON:0014892	81.37	gold quality
oviduct epithelium	UBERON:0004804	81.28	gold quality
hindlimb stylopod muscle	UBERON:0004252	81.13	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.59
E-MTAB-7303	no	389.31

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): FOXC1, KAT6B, TCF12

miRNA regulators (miRDB)

129 targeting KDM1B, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502
HSA-MIR-548BB-5P	99.94	71.27	3509
HSA-MIR-548C-5P	99.94	71.24	3488
HSA-MIR-548D-5P	99.94	71.23	3502
HSA-MIR-548H-5P	99.94	71.24	3488
HSA-MIR-548I	99.94	71.25	3481
HSA-MIR-548J-5P	99.94	71.14	3489

Literature-anchored findings (GeneRIF, showing 18)

• Human LSD2/KDM1b/AOF1 regulates gene transcription by modulating intragenic H3K4me2 methylation. (PMID:20670891)
• The zinc finger-SWIRM-oxidase domains is required for KDM1B demethylase activity and the binding of FAD. (PMID:23266887)
• These results demonstrate an important role for LSD2 in regulation of DNA methylation and gene silencing in breast cancer. (PMID:24924415)
• regulation of tissue factor pathway inhibitor-2 (TFPI-2) expression by lysine-specific demethylase 1 and 2 (PMID:25036127)
• Using transcriptome and chromatin immunoprecipitation-sequencing analyses, the study revealed that LSD2 represses the genes involved in lipid influx and metabolism through demethylation of histone H3K4. (PMID:25624347)
• Histone demethylase LSD2 acts as an E3 ubiquitin ligase and inhibits cancer cell growth through promoting proteasomal degradation of OGT. (PMID:25773598)
• This review focuses on published small-molecule inhibitors targeted at the two flavin adenine dinucleotide-dependent lysine demethylases, lysine-specific demethylases 1 and 2, and how the inhibitors interact with the tertiary structures of the enzymes. (PMID:28277979)
• These results suggest that LSD2 achieves a promoting effect on small cell lung cancer by indirectly regulating TFPI2 expression through the mediation of DNMT3B expression or through the regulation of the demethylation of H3K4me1 in the promoter region of the TFPI2 gene. (PMID:29845195)
• our findings provided new insights into the critical and multifaceted roles of KDM1B in the regulation of cell proliferation and apoptosis, and offered a potentially novel target in preventing the progression of pancreatic cancer. (PMID:30846414)
• While LSD1/CoREST forms a nucleosome docking platform at silenced gene promoters, LSD2/NPAC is a multifunctional enzyme complex with flexible linkers, tailored for rapid chromatin modification, in conjunction with the advance of the RNA polymerase on actively transcribed genes. (PMID:30970244)
• Reduction in H3K4me patterns due to aberrant expression of methyltransferases and demethylases in renal cell carcinoma: prognostic and therapeutic implications. (PMID:31160694)
• The expression of LSD2 was associated with higher TNM stage and metastasis of the tumor and thus, might serve as a useful marker for Clear cell renal cell carcinoma (ccRCC) progression. (PMID:32097694)
• In vitro evidence of NLRP3 inflammasome regulation by histone demethylase LSD2 in renal cancer: a pilot study. (PMID:32754863)
• [Expression and Clinical Significance of MiR-215 and KDM1B in Patients with Diffuse Large B Cell Lymphoma]. (PMID:33067956)
• Histone demethylase AMX-1 is necessary for proper sensitivity to interstrand crosslink DNA damage. (PMID:34329293)
• The Role of LSD1 and LSD2 in Cancers of the Gastrointestinal System: An Update. (PMID:35327654)
• Lysine demethylase 1B (Kdm1b) enhances somatic reprogramming through inducing pluripotent gene expression and promoting cell proliferation. (PMID:36075448)
• CircKDM1B promotes hepatocellular carcinoma progression through regulating miR-1322/PRC1 axis. (PMID:37227723)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
mus_musculus	Kdm1b	ENSMUSG00000038080
rattus_norvegicus	Kdm1b	ENSRNOG00000016519
drosophila_melanogaster	CG10561	FBGN0002036
drosophila_melanogaster	CG8032	FBGN0037606
caenorhabditis_elegans	spr-5	WBGENE00005010
caenorhabditis_elegans		WBGENE00011615

Paralogs (7): KDM1A (ENSG00000004487), MAOB (ENSG00000069535), SMOX (ENSG00000088826), IL4I1 (ENSG00000104951), PPOX (ENSG00000143224), PAOX (ENSG00000148832), MAOA (ENSG00000189221)

Protein

Protein identifiers

Lysine-specific histone demethylase 2 — Q8NB78 (reviewed: Q8NB78)

Alternative names: Flavin-containing amine oxidase domain-containing protein 1, Lysine-specific histone demethylase 1B

All UniProt accessions (3): Q8NB78, H0Y6H0, Q08EI0

UniProt curated annotations — full annotation on UniProt →

Function. Histone demethylase that demethylates ‘Lys-4’ of histone H3, a specific tag for epigenetic transcriptional activation, thereby acting as a corepressor. Required for de novo DNA methylation of a subset of imprinted genes during oogenesis. Acts by oxidizing the substrate by FAD to generate the corresponding imine that is subsequently hydrolyzed. Demethylates both mono- and di-methylated ‘Lys-4’ of histone H3. Has no effect on tri-methylated ‘Lys-4’, mono-, di- or tri-methylated ‘Lys-9’, mono-, di- or tri-methylated ‘Lys-27’, mono-, di- or tri-methylated ‘Lys-36’ of histone H3, or on mono-, di- or tri-methylated ‘Lys-20’ of histone H4. Alone, it is unable to demethylate H3K4me on nucleosomes and requires the presence of GLYR1 to achieve such activity, they form a multifunctional enzyme complex that modifies transcribed chromatin and facilitates Pol II transcription through nucleosomes.

Subunit / interactions. Interacts with its cofactor GLYR1 at nucleosomes; this interaction stimulates H3K4me1 and H3K4me2 demethylation. In contrast to KDM1A, does not form a complex with RCOR1/CoREST. Possible accessory component of the polycomb repressive deubiquitinase (PR-DUB) complex, at least composed of BAP1, one of ASXL1, ASXL2 or (probably) ASXL3 and one of MBD5 or MBD6. The PR-DUB core associates with a number of accessory proteins, including FOXK1, FOXK2, KDM1B, HCFC1 and OGT; KDM1B specifically associates with ASXL2 PR-DUB complexes.

Subcellular location. Nucleus. Chromosome.

Activity regulation. Histone H3K4me1 and H3K4me2 demethylase activity is inhibited by DNA, this inhibition is released in complex with GLYR1.

Cofactor. Binds 3 Zn(2+) ions per subunit.

Similarity. Belongs to the flavin monoamine oxidase family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q8NB78-1	1	yes
Q8NB78-2	2
Q8NB78-4	4

RefSeq proteins (2): NP_001351543, NP_694587 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002937	Amino_oxidase	Domain
IPR007526	SWIRM	Domain
IPR009057	Homeodomain-like_sf	Homologous_superfamily
IPR011124	Znf_CW	Domain
IPR036188	FAD/NAD-bd_sf	Homologous_superfamily
IPR036388	WH-like_DNA-bd_sf	Homologous_superfamily
IPR050281	Flavin_monoamine_oxidase	Family

Pfam: PF01593, PF04433, PF07496

Catalyzed reactions (Rhea), 2 shown:

• N(6),N(6)-dimethyl-L-lysyl(4)-[histone H3] + 2 A + 2 H2O = L-lysyl(4)-[histone H3] + 2 formaldehyde + 2 AH2 (RHEA:60244)
• N(6)-methyl-L-lysyl(4)-[histone H3] + A + H2O = L-lysyl(4)-[histone H3] + formaldehyde + AH2 (RHEA:60256)

UniProt features (152 total): helix 37, strand 36, mutagenesis site 33, binding site 16, turn 10, region of interest 7, modified residue 4, splice variant 3, sequence conflict 2, chain 1, domain 1, compositionally biased region 1, zinc finger region 1

Structure

Experimental structures (PDB)

15 structures.

PDB	Method	Resolution (Å)
4HSU	X-RAY DIFFRACTION	1.99
4GUT	X-RAY DIFFRACTION	2
7XE2	X-RAY DIFFRACTION	2.05
7XE1	X-RAY DIFFRACTION	2.07
4FWE	X-RAY DIFFRACTION	2.13
4GUS	X-RAY DIFFRACTION	2.23
4GUU	X-RAY DIFFRACTION	2.3
4GUR	X-RAY DIFFRACTION	2.51
4FWF	X-RAY DIFFRACTION	2.7
7XE3	X-RAY DIFFRACTION	2.82
4FWJ	X-RAY DIFFRACTION	2.9
4GU1	X-RAY DIFFRACTION	2.94
4GU0	X-RAY DIFFRACTION	3.1
6R1U	ELECTRON MICROSCOPY	4.36
6R25	ELECTRON MICROSCOPY	4.61

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NB78-F1	91.65	0.88

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (16): 53; 58; 65; 73; 84; 90; 92; 95; 142; 147; 169; 185 …

Post-translational modifications (4): 13, 17, 26, 247

Mutagenesis-validated functional residues (33):

Position	Phenotype
48–49	normal demethylase activity.
51–52	reduced demethylase activity.
53	loss of demethylase activity.
82	loss of demethylase activity.
84	loss of demethylase activity. defective in the binding of fad.
90	loss of demethylase activity. defective in the binding of fad.
101	reduced demethylase activity.
103	no effect on dna or nucleosome binding.
104	no effect on dna or nucleosome binding.
109	no effect on dna or nucleosome binding.
114–115	reduced demethylase activity.
114	no effect on dna or nucleosome binding.
115	no effect on dna or nucleosome binding.
122	no effect on dna or nucleosome binding.
139	loss of demethylase activity.
150	loss of demethylase activity. defective in the binding of fad.
151	loss of demethylase activity.
185	loss of demethylase activity.
273–278	strongly reduced demethylase activity. loss of enzymatic activity; when associated with 285-a–a-287.
285–287	strongly reduced demethylase activity. loss of enzymatic activity; when associated with 273-g–s-278.
302	no effect on dna or nucleosome binding.
318–319	loss of demethylase activity.
340–341	loss of demethylase activity. defective in the binding of fad.
361–362	loss of demethylase activity. defective in the binding of fad.
443–444	loss of demethylase activity. defective in the binding of fad.

Function

Pathways and Gene Ontology

Reactome pathways

11 pathways

ID	Pathway
R-HSA-3214842	HDMs demethylate histones
R-HSA-5689603	UCH proteinases
R-HSA-9029569	NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflux
R-HSA-162582	Signal Transduction
R-HSA-3247509	Chromatin modifying enzymes
R-HSA-392499	Metabolism of proteins
R-HSA-4839726	Chromatin organization
R-HSA-5688426	Deubiquitination
R-HSA-597592	Post-translational protein modification
R-HSA-9006931	Signaling by Nuclear Receptors
R-HSA-9024446	NR1H2 and NR1H3-mediated signaling

MSigDB gene sets: 123 (showing top): GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_PAIRED_DONORS_WITH_INCORPORATION_OR_REDUCTION_OF_MOLECULAR_OXYGEN, CAGGTCC_MIR492, GOBP_DNA_TEMPLATED_TRANSCRIPTION_INITIATION, GOBP_GENOMIC_IMPRINTING, GOBP_CELLULAR_PROCESS_INVOLVED_IN_REPRODUCTION_IN_MULTICELLULAR_ORGANISM, GOBP_TRANSCRIPTION_INITIATION_AT_RNA_POLYMERASE_II_PROMOTER, GOBP_DEVELOPMENTAL_PROCESS_INVOLVED_IN_REPRODUCTION, SENESE_HDAC1_TARGETS_UP, GOBP_CHROMATIN_REMODELING, GOBP_EPIGENETIC_REGULATION_OF_GENE_EXPRESSION, GOCC_PROTEIN_DNA_COMPLEX, GOMF_HISTONE_BINDING, GOMF_DEMETHYLASE_ACTIVITY, GEORGES_TARGETS_OF_MIR192_AND_MIR215, GOMF_FAD_BINDING

GO Biological Process (5): epigenetic programing of female pronucleus (GO:0044726), transcription initiation-coupled chromatin remodeling (GO:0045815), genomic imprinting (GO:0071514), chromatin organization (GO:0006325), epigenetic regulation of gene expression (GO:0040029)

GO Molecular Function (10): zinc ion binding (GO:0008270), oxidoreductase activity (GO:0016491), histone demethylase activity (GO:0032452), histone binding (GO:0042393), FAD binding (GO:0071949), FAD-dependent H3K4me/H3K4me3 demethylase activity (GO:0140682), protein binding (GO:0005515), histone H3K4 demethylase activity (GO:0032453), metal ion binding (GO:0046872), flavin adenine dinucleotide binding (GO:0050660)

GO Cellular Component (5): chromatin (GO:0000785), nucleosome (GO:0000786), nucleus (GO:0005634), nucleoplasm (GO:0005654), chromosome (GO:0005694)

Reactome top-level categories

Rollup of top-8 pathways:

Category	Pathways
Chromatin modifying enzymes	1
Deubiquitination	1
NR1H2 and NR1H3-mediated signaling	1
Chromatin organization	1
Post-translational protein modification	1
Metabolism of proteins	1
Signal Transduction	1
Signaling by Nuclear Receptors	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
epigenetic programming in the zygotic pronuclei	1
transcription initiation at RNA polymerase II promoter	1
positive regulation of gene expression, epigenetic	1
germ cell development	1
epigenetic programming of gene expression	1
cellular component organization	1
chromatin remodeling	1
regulation of gene expression	1
transition metal ion binding	1
catalytic activity	1
protein demethylase activity	1
histone modifying activity	1
protein binding	1
flavin adenine dinucleotide binding	1
oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen	1
histone H3K4 demethylase activity	1
binding	1
histone H3 demethylase activity	1
cation binding	1
nucleotide binding	1
anion binding	1
chromosome	1
chromatin	1
protein-DNA complex	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

44 interactions, top by confidence:

A	B	Type	Score
BAP1	OGT	psi-mi:“MI:0914”(association)	0.730
SPATA17	KDM1B	psi-mi:“MI:0915”(physical association)	0.590
HAVCR2	TCAF2	psi-mi:“MI:0914”(association)	0.530
ABLIM2	AFDN	psi-mi:“MI:0914”(association)	0.530
GLYR1	MAGEB2	psi-mi:“MI:0914”(association)	0.530
H3C1	SMCHD1	psi-mi:“MI:2364”(proximity)	0.410
NSD3	LSM3	psi-mi:“MI:0914”(association)	0.350
KDM1B	ASXL2	psi-mi:“MI:0914”(association)	0.350
Bap1	HCFC1	psi-mi:“MI:0914”(association)	0.350
HSCB	RBP5	psi-mi:“MI:0914”(association)	0.350
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350
TAFA3	FUOM	psi-mi:“MI:0914”(association)	0.350
NDUFA10	DCX	psi-mi:“MI:0914”(association)	0.350
GLYR1	FNTB	psi-mi:“MI:0914”(association)	0.350
ASXL2	FOXK1	psi-mi:“MI:0914”(association)	0.350
SH2D2A	KDM1B	psi-mi:“MI:0914”(association)	0.350
BAP1	IPO5	psi-mi:“MI:0914”(association)	0.350
CBX1	EXOC5	psi-mi:“MI:0914”(association)	0.350
H2BC21	SMCHD1	psi-mi:“MI:0914”(association)	0.350
S100A6	VWA8	psi-mi:“MI:0914”(association)	0.350
PTGES3	SBNO1	psi-mi:“MI:0914”(association)	0.350
NDUFA10	AURKA	psi-mi:“MI:0914”(association)	0.350
ANKRD9	TIMM8A	psi-mi:“MI:0914”(association)	0.350
C8B	PAPSS2	psi-mi:“MI:0914”(association)	0.350
GLYR1	LCP1	psi-mi:“MI:0914”(association)	0.350

BioGRID (97): KDM1B (Affinity Capture-MS), KDM1B (Affinity Capture-MS), KDM1B (Affinity Capture-MS), KDM1B (Affinity Capture-MS), KDM1B (Affinity Capture-MS), KDM1B (Proximity Label-MS), KDM1B (Proximity Label-MS), DYNC1I2 (Affinity Capture-MS), BAP1 (Affinity Capture-MS), COX5A (Affinity Capture-MS), CASC3 (Affinity Capture-MS), CPSF3 (Affinity Capture-MS), WHSC1L1 (Affinity Capture-MS), HEATR3 (Affinity Capture-MS), CEP192 (Affinity Capture-MS)

ESM2 similar proteins: A0A024RBG1, A2VE79, A3KMI0, A7E320, B0R160, B6CHA3, F4JLK2, F6UA42, O22951, O45830, O59761, O95989, P0C027, P0C028, P32271, Q08C92, Q09790, Q566C7, Q58CW0, Q5RAF0, Q5RDX4, Q5U243, Q6NPD7, Q6P5D3, Q7TMI3, Q7TPK1, Q7YTB0, Q8BJM7, Q8CIG3, Q8L7W2, Q8NB78, Q8NFP7, Q8R2U6, Q8VDF2, Q8VHT6, Q91WU5, Q96G61, Q96PU4, Q96T88, Q99321

Diamond homologs: A0A024BTN9, A0A0A1GKA2, A0A2U8QPE6, A1C8C5, A2XDA1, A6MFL0, A8QL51, A8QL52, A8QL58, B0VXW0, B5AR80, B5U6Y8, C0HJE7, C3VEP9, F8S0Z5, G8XQX1, G9F1Y9, J7H670, K9N7B7, O07855, O08615, O09046, O24164, O34363, O60341, O93364, P0C2D1, P0C2D2, P0C2D4, P0C2D5, P0C2D7, P0CC17, P0CJ40, P0DI84, P0DI87, P0DI88, P0DI89, P0DI91, P0DPS2, P0DQH9

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 53 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
UCH proteinases	7	21.2×	8e-06
Estrogen-dependent gene expression	6	11.1×	2e-03
HATs acetylate histones	5	9.7×	9e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

87 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	63
Likely benign	1
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

3499 predictions. Top by Δscore:

Variant	Effect	Δscore
6:18156010:G:GT	donor_gain	1.0000
6:18156063:TCCTG:T	donor_gain	1.0000
6:18159877:TTGCA:T	acceptor_loss	1.0000
6:18159878:TGCAG:T	acceptor_loss	1.0000
6:18159879:GCAG:G	acceptor_loss	1.0000
6:18159880:CAGA:C	acceptor_loss	1.0000
6:18159881:A:AG	acceptor_gain	1.0000
6:18159881:A:C	acceptor_loss	1.0000
6:18159882:G:GA	acceptor_gain	1.0000
6:18159882:G:T	acceptor_loss	1.0000
6:18159882:GA:G	acceptor_gain	1.0000
6:18159882:GAT:G	acceptor_gain	1.0000
6:18159882:GATT:G	acceptor_gain	1.0000
6:18159882:GATTA:G	acceptor_gain	1.0000
6:18161383:G:GT	donor_gain	1.0000
6:18161392:G:GT	donor_gain	1.0000
6:18161393:A:T	donor_gain	1.0000
6:18161408:GGCT:G	donor_gain	1.0000
6:18161409:GCTG:G	donor_gain	1.0000
6:18162824:A:AG	acceptor_gain	1.0000
6:18162825:C:G	acceptor_gain	1.0000
6:18162827:A:AG	acceptor_gain	1.0000
6:18162828:T:G	acceptor_gain	1.0000
6:18162829:TTTCA:T	acceptor_loss	1.0000
6:18162830:TTCA:T	acceptor_loss	1.0000
6:18162831:TCAG:T	acceptor_loss	1.0000
6:18162832:CAGA:C	acceptor_loss	1.0000
6:18162833:A:AG	acceptor_gain	1.0000
6:18162833:A:AT	acceptor_loss	1.0000
6:18162833:AGAT:A	acceptor_gain	1.0000

AlphaMissense

5433 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:18161396:T:A	C53S	1.000
6:18161396:T:C	C53R	1.000
6:18161397:G:C	C53S	1.000
6:18161411:T:C	C58R	1.000
6:18161432:T:C	C65R	1.000
6:18161434:C:G	C65W	1.000
6:18162836:T:C	C73R	1.000
6:18162861:G:C	R81P	1.000
6:18162863:T:A	W82R	1.000
6:18162863:T:C	W82R	1.000
6:18162865:G:C	W82C	1.000
6:18162865:G:T	W82C	1.000
6:18162869:C:G	H84D	1.000
6:18162893:T:C	C92R	1.000
6:18162894:G:A	C92Y	1.000
6:18162894:G:T	C92F	1.000
6:18162895:T:G	C92W	1.000
6:18162902:T:C	C95R	1.000
6:18162904:C:G	C95W	1.000
6:18162921:G:C	R101T	1.000
6:18162922:A:C	R101S	1.000
6:18162922:A:T	R101S	1.000
6:18166298:T:A	W113R	1.000
6:18166298:T:C	W113R	1.000
6:18166300:G:C	W113C	1.000
6:18166300:G:T	W113C	1.000
6:18166310:T:A	W117R	1.000
6:18166310:T:C	W117R	1.000
6:18171393:T:A	W150R	1.000
6:18171393:T:C	W150R	1.000

dbSNP variants (sampled 300 via entrez): RS1000017171 (6:18168710 T>A), RS1000036179 (6:18224186 T>C), RS1000048980 (6:18219850 G>A), RS1000069492 (6:18168498 A>G), RS1000100555 (6:18163386 C>G,T), RS1000202115 (6:18189790 G>C), RS1000218120 (6:18196200 G>A), RS1000218763 (6:18186586 T>C), RS1000266889 (6:18183895 T>C), RS1000292618 (6:18178430 G>A), RS1000303922 (6:18163570 C>T), RS1000345132 (6:18157451 C>G,T), RS1000363827 (6:18164029 G>A), RS1000467244 (6:18202435 CTTTTGTA>C), RS1000479805 (6:18163829 A>G)

Disease associations

OMIM: gene MIM:613081 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST006061_8	Atrial fibrillation	3.000000e-25
GCST006061_9	Atrial fibrillation	4.000000e-22
GCST006414_141	Atrial fibrillation	2.000000e-19

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1938208 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

2 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,716 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1232461	MOLIBRESIB	2	1,538
CHEMBL3781751	IADADEMSTAT	2	178

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — 1.14.11.- Histone demethylases

ChEMBL bioactivities

34 potent at pChembl≥5 of 75 total, top 34 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.92	IC50	120	nM	MOLIBRESIB
6.22	IC50	600	nM	CHEMBL5206450
6.12	IC50	760	nM	CHEMBL5191047
6.10	IC50	800	nM	CHEMBL5205837
6.00	IC50	1010	nM	CHEMBL5181753
5.99	IC50	1020	nM	CHEMBL5196564
5.84	IC50	1430	nM	CHEMBL4170687
5.83	IC50	1480	nM	CHEMBL5177857
5.80	IC50	1600	nM	CHEMBL4857247
5.65	IC50	2260	nM	CHEMBL5194745
5.59	IC50	2550	nM	CHEMBL5184995
5.49	IC50	3260	nM	CHEMBL5170567
5.40	IC50	4000	nM	CHEMBL5172252
5.40	IC50	3950	nM	CHEMBL5174650
5.40	IC50	4000	nM	CHEMBL5204790
5.38	IC50	4120	nM	CHEMBL5191876
5.37	IC50	4300	nM	CHEMBL3781560
5.37	IC50	4300	nM	CHEMBL3780774
5.35	IC50	4510	nM	CHEMBL4176756
5.35	IC50	4510	nM	CHEMBL5201504
5.30	IC50	5000	nM	CHEMBL5170011
5.27	IC50	5420	nM	CHEMBL5208082
5.24	IC50	5700	nM	CHEMBL3780542
5.19	IC50	6470	nM	CHEMBL5175125
5.17	IC50	6770	nM	CHEMBL4170367
5.17	IC50	6800	nM	CHEMBL4872682
5.16	Ki	7000	nM	CHEMBL5201156
5.16	Ki	7000	nM	CHEMBL5193019
5.12	IC50	7510	nM	CHEMBL4299307
5.12	IC50	7510	nM	CHEMBL5197243
5.08	Ki	8400	nM	CHEMBL5206551
5.05	IC50	8890	nM	CHEMBL5171190
5.04	IC50	9130	nM	CHEMBL5191605
5.01	IC50	9800	nM	CHEMBL5183291

PubChem BioAssay actives

34 with measured affinity, of 159 total; 33 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2178519: Inhibition of AOF1 (unknown origin) incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	ic50	0.1200	uM
2-[1-(benzenesulfonyl)-2,3-dihydroindol-5-yl]-N-[(4-methylpiperidin-4-yl)methyl]cyclopropan-1-amine	1903137: Inhibition of recombinant human full length LSD2 using biotinylated H3K4Me2 peptide as substrate by TR-FRET assay	ic50	0.6000	uM
2-(1-naphthalen-2-ylsulfonyl-2,3-dihydroindol-5-yl)-N-(piperidin-4-ylmethyl)cyclopropan-1-amine	1903137: Inhibition of recombinant human full length LSD2 using biotinylated H3K4Me2 peptide as substrate by TR-FRET assay	ic50	0.7600	uM
2-[1-(4-phenylphenyl)sulfonyl-2,3-dihydroindol-5-yl]-N-(piperidin-4-ylmethyl)cyclopropan-1-amine	1903137: Inhibition of recombinant human full length LSD2 using biotinylated H3K4Me2 peptide as substrate by TR-FRET assay	ic50	0.8000	uM
2-[1-(3-chlorophenyl)sulfonyl-2,3-dihydroindol-5-yl]-N-(piperidin-4-ylmethyl)cyclopropan-1-amine	1903137: Inhibition of recombinant human full length LSD2 using biotinylated H3K4Me2 peptide as substrate by TR-FRET assay	ic50	1.0100	uM
N-(piperidin-4-ylmethyl)-2-[1-[3-(trifluoromethyl)phenyl]sulfonyl-2,3-dihydroindol-5-yl]cyclopropan-1-amine	1903137: Inhibition of recombinant human full length LSD2 using biotinylated H3K4Me2 peptide as substrate by TR-FRET assay	ic50	1.0200	uM
(1S,1aS,6aS)-N-(piperidin-4-ylmethyl)-1,1a,6,6a-tetrahydrocyclopropa[a]inden-1-amine;hydrochloride	1503465: Inhibition of human full length LSD2 using biotin-labeled H3K4me2 (1 to 24 residues) as substrate after 1 hr by TR-FRET assay	ic50	1.4300	uM
4-[[[2-[1-(benzenesulfonyl)-2,3-dihydroindol-5-yl]cyclopropyl]amino]methyl]cyclohexan-1-amine	1903137: Inhibition of recombinant human full length LSD2 using biotinylated H3K4Me2 peptide as substrate by TR-FRET assay	ic50	1.4800	uM
N-[(2-chloro-3,4-dimethoxyphenyl)methyl]spiro[1,2-dihydroindene-3,2’-cyclopropane]-1’-amine	1755620: Inhibition of human LSD2 using Bio-H3K4me2 (1 to 24 residues) as substrate incubated for 1 hr by TR-FRET assay	ic50	1.6000	uM
2-(1-cyclohexylsulfonyl-2,3-dihydroindol-5-yl)-N-(piperidin-4-ylmethyl)cyclopropan-1-amine	1903137: Inhibition of recombinant human full length LSD2 using biotinylated H3K4Me2 peptide as substrate by TR-FRET assay	ic50	2.2600	uM
1-[5-[2-(piperidin-4-ylmethylamino)cyclopropyl]-2,3-dihydroindol-1-yl]pentan-1-one	1903137: Inhibition of recombinant human full length LSD2 using biotinylated H3K4Me2 peptide as substrate by TR-FRET assay	ic50	2.5500	uM
N-[2-[1-(benzenesulfonyl)-2,3-dihydroindol-5-yl]cyclopropyl]-7-azaspiro[3.5]nonan-2-amine	1903137: Inhibition of recombinant human full length LSD2 using biotinylated H3K4Me2 peptide as substrate by TR-FRET assay	ic50	3.2600	uM
1-[5-[2-(piperidin-4-ylmethylamino)cyclopropyl]-2,3-dihydroindol-1-yl]butan-1-one	1903137: Inhibition of recombinant human full length LSD2 using biotinylated H3K4Me2 peptide as substrate by TR-FRET assay	ic50	3.9500	uM
2-[1-(3-methoxyphenyl)sulfonyl-2,3-dihydroindol-5-yl]-N-(piperidin-4-ylmethyl)cyclopropan-1-amine	1903137: Inhibition of recombinant human full length LSD2 using biotinylated H3K4Me2 peptide as substrate by TR-FRET assay	ic50	4.0000	uM
2-phenyl-1-[5-[2-(piperidin-4-ylmethylamino)cyclopropyl]-2,3-dihydroindol-1-yl]ethanone	1903137: Inhibition of recombinant human full length LSD2 using biotinylated H3K4Me2 peptide as substrate by TR-FRET assay	ic50	4.0000	uM
N-(piperidin-4-ylmethyl)-2-[1-(trifluoromethylsulfonyl)-2,3-dihydroindol-5-yl]cyclopropan-1-amine	1903137: Inhibition of recombinant human full length LSD2 using biotinylated H3K4Me2 peptide as substrate by TR-FRET assay	ic50	4.1200	uM
benzyl N-[5-[[4-[(1S,2R)-2-aminocyclopropyl]phenyl]carbamoyl]-2-piperidin-1-ylphenyl]carbamate;hydrochloride	1286215: Inhibition of KDM1B (unknown origin)	ic50	4.3000	uM
benzyl N-[5-[[4-[(1S,2R)-2-aminocyclopropyl]phenyl]carbamoyl]-2-(4-methylpiperazin-1-yl)phenyl]carbamate;dihydrochloride	1286215: Inhibition of KDM1B (unknown origin)	ic50	4.3000	uM
phenyl-[5-[2-(piperidin-4-ylmethylamino)cyclopropyl]-2,3-dihydroindol-1-yl]methanone	1903137: Inhibition of recombinant human full length LSD2 using biotinylated H3K4Me2 peptide as substrate by TR-FRET assay	ic50	4.5100	uM
4-N-[(1S,1aS,6aS)-1,1a,6,6a-tetrahydrocyclopropa[a]inden-1-yl]cyclohexane-1,4-diamine;hydrochloride	1503465: Inhibition of human full length LSD2 using biotin-labeled H3K4me2 (1 to 24 residues) as substrate after 1 hr by TR-FRET assay	ic50	4.5100	uM
2-[1-(benzenesulfonyl)-2,3-dihydroindol-5-yl]-N-(piperidin-4-ylmethyl)cyclopropan-1-amine	1903137: Inhibition of recombinant human full length LSD2 using biotinylated H3K4Me2 peptide as substrate by TR-FRET assay	ic50	5.0000	uM
2,2-dimethyl-1-[5-[2-(piperidin-4-ylmethylamino)cyclopropyl]-2,3-dihydroindol-1-yl]propan-1-one	1903137: Inhibition of recombinant human full length LSD2 using biotinylated H3K4Me2 peptide as substrate by TR-FRET assay	ic50	5.4200	uM
benzyl N-[5-[[4-[(1S,2R)-2-aminocyclopropyl]phenyl]carbamoyl]-2-morpholin-4-ylphenyl]carbamate;hydrochloride	1286215: Inhibition of KDM1B (unknown origin)	ic50	5.7000	uM
2-[1-(benzenesulfonyl)-2,3-dihydroindol-5-yl]-N-[(1-benzylpiperidin-4-yl)methyl]cyclopropan-1-amine	1903137: Inhibition of recombinant human full length LSD2 using biotinylated H3K4Me2 peptide as substrate by TR-FRET assay	ic50	6.4700	uM
N-[(5-bromo-2-methoxyphenyl)methyl]spiro[1,2-dihydroindene-3,2’-cyclopropane]-1’-amine	1755620: Inhibition of human LSD2 using Bio-H3K4me2 (1 to 24 residues) as substrate incubated for 1 hr by TR-FRET assay	ic50	6.8000	uM
cis-(1R,2R)-2-(4-bromo-3,5-difluorophenyl)cyclopropan-1-amine	1881252: Inhibition of LSD2 (unknown origin) (26 to 822 residues) expressed in baculovirus-infected Sf9 insect cells using K4-dimethylated H3 as substrate by peroxidase-coupled method	ki	7.0000	uM
cis-(1R,2R)-2-[2,5-difluoro-4-(3-methoxyphenyl)phenyl]cyclopropan-1-amine	1881252: Inhibition of LSD2 (unknown origin) (26 to 822 residues) expressed in baculovirus-infected Sf9 insect cells using K4-dimethylated H3 as substrate by peroxidase-coupled method	ki	7.0000	uM
N-(azetidin-3-ylmethyl)-2-[1-(benzenesulfonyl)-2,3-dihydroindol-5-yl]cyclopropan-1-amine	1903137: Inhibition of recombinant human full length LSD2 using biotinylated H3K4Me2 peptide as substrate by TR-FRET assay	ic50	7.5100	uM
(3S)-4-[(2S)-2-[[(2S)-4-amino-1-[[(2S)-1-[[(2R)-6-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2R)-2-amino-5-carbamimidamidopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]-1-[(2S)-2-[[(2R)-4-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-1,5-diamino-1,5-dioxopentan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-1,4-dioxobutan-2-yl]carbamoyl]pyrrolidin-1-yl]-1-oxohexan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-1,4-dioxobutan-2-yl]carbamoyl]pyrrolidin-1-yl]-3-[[(2S)-2-[[(2R)-1-[(2R)-6-amino-2-[[(2R)-5-carbamimidamido-2-[[(2R)-2-[[(2R)-2-[[(2R)-2-[[(2R)-2-[[(2S)-5-carbamimidamido-2-[[(2S)-pyrrolidine-2-carbonyl]amino]pentanoyl]amino]-3-hydroxypropanoyl]amino]-5-hydrazinylpentanoyl]amino]-4-methylpentanoyl]amino]-3-methylbutanoyl]amino]pentanoyl]amino]hexanoyl]pyrrolidine-2-carbonyl]amino]-3-hydroxypropanoyl]amino]-4-oxobutanoic acid	1282331: Inhibition of full length N-terminal His-tagged human LSD2 (1 to 822 residues) expressed in Escherichia coli BL21(DE3) cells using H3K4me2 peptide substrate by MALDI-TOF mass spectrometric analysis	ic50	7.5100	uM
cis-(1R,2R)-2-(4-bromo-2,5-difluorophenyl)cyclopropan-1-amine	1881252: Inhibition of LSD2 (unknown origin) (26 to 822 residues) expressed in baculovirus-infected Sf9 insect cells using K4-dimethylated H3 as substrate by peroxidase-coupled method	ki	8.4000	uM
4-N-[2-[1-(benzenesulfonyl)-2,3-dihydroindol-5-yl]cyclopropyl]cyclohexane-1,4-diamine	1903137: Inhibition of recombinant human full length LSD2 using biotinylated H3K4Me2 peptide as substrate by TR-FRET assay	ic50	8.8900	uM
2-[1-(benzenesulfonyl)-2,3-dihydroindol-5-yl]-N-(2-piperidin-4-ylethyl)cyclopropan-1-amine	1903137: Inhibition of recombinant human full length LSD2 using biotinylated H3K4Me2 peptide as substrate by TR-FRET assay	ic50	9.1300	uM
2-(1-ethylsulfonyl-2,3-dihydroindol-5-yl)-N-(piperidin-4-ylmethyl)cyclopropan-1-amine	1903137: Inhibition of recombinant human full length LSD2 using biotinylated H3K4Me2 peptide as substrate by TR-FRET assay	ic50	9.8000	uM

CTD chemical–gene interactions

24 total (human), top 24 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression	4
Cyclosporine	increases expression	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
trichostatin A	affects expression	1
methylparaben	increases expression	1
aflatoxin B2	increases methylation	1
(+)-JQ1 compound	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Acetaminophen	increases expression	1
Air Pollutants, Occupational	decreases expression	1
Calcitriol	increases expression	1
Coumestrol	decreases expression	1
Doxorubicin	decreases expression	1
Endosulfan	increases expression	1
Nickel	decreases expression	1
Plant Extracts	affects cotreatment, increases expression	1
Quercetin	decreases expression	1
Silicon Dioxide	increases expression	1
Urethane	increases expression	1
Sodium Selenite	decreases expression	1
Okadaic Acid	increases expression	1
Particulate Matter	decreases expression	1

ChEMBL screening assays

33 unique, capped per target: 33 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1942533	Binding	Inhibition of LSD2	Lysine demethylases inhibitors. — J Med Chem

Cellosaurus cell lines

6 cell lines: 6 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B1V4	Abcam HeLa KDM1B KO	Cancer cell line	Female
CVCL_B7XU	Abcam Raji KDM1B KO	Cancer cell line	Male
CVCL_B9YJ	Abcam THP-1 KDM1B KO	Cancer cell line	Male
CVCL_C7AB	Abcam PC-3 KDM1B KO	Cancer cell line	Male
CVCL_SU15	HAP1 KDM1B (-) 1	Cancer cell line	Male
CVCL_SU16	HAP1 KDM1B (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.