MBD2

Summary

MBD2 (methyl-CpG binding domain protein 2, HGNC:6917) is a protein-coding gene on chromosome 18q21.2, encoding Methyl-CpG-binding domain protein 2 (Q9UBB5). Binds CpG islands in promoters where the DNA is methylated at position 5 of cytosine within CpG dinucleotides.

DNA methylation is the major modification of eukaryotic genomes and plays an essential role in mammalian development. Human proteins MECP2, MBD1, MBD2, MBD3, and MBD4 comprise a family of nuclear proteins related by the presence in each of a methyl-CpG binding domain (MBD). Each of these proteins, with the exception of MBD3, is capable of binding specifically to methylated DNA. MECP2, MBD1 and MBD2 can also repress transcription from methylated gene promoters. The protein encoded by this gene may function as a mediator of the biological consequences of the methylation signal. It is also reported that the this protein functions as a demethylase to activate transcription, as DNA methylation causes gene silencing. Two transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 8932 — RefSeq curated summary.

At a glance

• GWAS associations: 9
• Clinical variants (ClinVar): 51 total
• Druggable target: yes
• Transcription factor: yes — 94 downstream targets (CollecTRI)
• MANE Select transcript: NM_003927

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6917
Approved symbol	MBD2
Name	methyl-CpG binding domain protein 2
Location	18q21.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000134046
Ensembl biotype	protein_coding
OMIM	603547
Entrez	8932

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 7 protein_coding, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000256429, ENST00000398398, ENST00000578272, ENST00000579025, ENST00000583046, ENST00000958222, ENST00000958223, ENST00000958224, ENST00000958225

RefSeq mRNA: 2 — MANE Select: NM_003927 NM_003927, NM_015832

CCDS: CCDS11953, CCDS45871

Canonical transcript exons

ENST00000256429 — 7 exons

Exon	Start	End
ENSE00000950074	54188874	54189011
ENSE00001107092	54151606	54155311
ENSE00001199206	54204998	54205157
ENSE00001265644	54224018	54224669
ENSE00003579438	54166076	54166166
ENSE00003614142	54164523	54164700
ENSE00003621765	54159765	54159903

Expression profiles

Bgee: expression breadth ubiquitous, 299 present calls, max score 98.68.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 47.3097 / max 759.8381, expressed in 1823 samples.

FANTOM5 promoters (12 alternative TSS)

Promoter ID	TPM avg	Samples expressed
171995	27.3442	1817
171992	8.9656	1749
171993	4.6545	1633
171991	1.8031	785
171994	1.4054	916
171986	0.7589	418
171996	0.6463	339
208560	0.4693	194
171987	0.4130	184
171984	0.3993	173

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
gingival epithelium	UBERON:0001949	98.68	gold quality
gingiva	UBERON:0001828	98.55	gold quality
tonsil	UBERON:0002372	98.19	gold quality
oral cavity	UBERON:0000167	98.10	gold quality
colonic epithelium	UBERON:0000397	98.10	gold quality
bone marrow cell	CL:0002092	97.98	gold quality
parotid gland	UBERON:0001831	97.93	gold quality
monocyte	CL:0000576	97.48	gold quality
leukocyte	CL:0000738	97.48	gold quality
esophagus mucosa	UBERON:0002469	97.48	gold quality
sural nerve	UBERON:0015488	97.48	gold quality
tongue squamous epithelium	UBERON:0006919	97.46	gold quality
mononuclear cell	CL:0000842	97.45	gold quality
calcaneal tendon	UBERON:0003701	97.42	gold quality
lower esophagus mucosa	UBERON:0035834	97.38	gold quality
right lobe of thyroid gland	UBERON:0001119	97.30	gold quality
subcutaneous adipose tissue	UBERON:0002190	97.24	gold quality
adipose tissue	UBERON:0001013	97.22	gold quality
left lobe of thyroid gland	UBERON:0001120	97.18	gold quality
connective tissue	UBERON:0002384	97.17	gold quality
tendon of biceps brachii	UBERON:0008188	97.14	gold quality
right lung	UBERON:0002167	97.10	gold quality
pharyngeal mucosa	UBERON:0000355	97.09	gold quality
thyroid gland	UBERON:0002046	97.08	gold quality
penis	UBERON:0000989	97.07	gold quality
tendon	UBERON:0000043	97.04	gold quality
granulocyte	CL:0000094	97.02	gold quality
epithelium of nasopharynx	UBERON:0001951	97.01	gold quality
nasopharynx	UBERON:0001728	96.99	gold quality
skin of leg	UBERON:0001511	96.94	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	9.58

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

94 targets.

Target	Regulation
ACOT13
ADGRB1	Unknown
ALOX15
ALOX5	Unknown
APP
AURKB
BCL2
BCOR
BMI1
BRCA1
CD24
CD70
CD74
CDH1
CDKN1A
CDKN1B
CDKN2A
CDKN2B
CEBPA
CHD4	Unknown
CP
DAPK1	Unknown
DMPK
DPEP1
EP300
EP400
EREG
FAAH
FGFR1
FOXP3

Upstream regulators (CollecTRI, top): BMAL1, CLOCK, DNMT1, HINFP, KDM5C, MBD2, SNAI1

miRNA regulators (miRDB)

231 targeting MBD2, 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-656-3P	100.00	72.15	2788
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-6759-5P	99.99	66.54	785
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-373-5P	99.98	75.36	4753

Literature-anchored findings (GeneRIF, showing 40)

• Methyl-CpG binding domain protein 2 represses transcription from hypermethylated pi-class glutathione S-transferase gene promoters in hepatocellular carcinoma cells (PMID:11960994)
• MBD2 protein activates CpG sites within the promoter region of reporter genes (PMID:12177048)
• interaction with two highly related p66 proteins (PMID:12183469)
• interacts with latency-associated nuclear antigen of Kaposi’s Sarcoma-associated herpesvirus (KSHV)to tether KSHV to cell chromosomes (PMID:12388720)
• MBDin relieves MBD2 repression potential and reactivates transcription from methylated promoters (PMID:12588985)
• Results show that methyl-CpG binding domain protein 1 (MBD1) is expressed in tumor cells, but methyl-CpG binding domain protein 2 (MBD2) and methyl CpG binding protein 2 (MeCP2) are not. (PMID:12646234)
• MBD2a and RNA helicase A cooperatively enhanced CREB-dependent gene expression. (PMID:12665568)
• MBD2 has a role in the methylation-mediated inhibition of ribosomal RNA gene expression (PMID:14610093)
• Antisenses oligoDNA suppresses tumor growth in nude mice, a potential anticaner therapy approach. (PMID:14688029)
• MBD2 gene expression may be significant factor in tumorigenesis. (PMID:15112265)
• role of MBD3L1 as a methylation-dependent transcriptional repressor that may interchange with MBD3 as an MBD2-interacting component of the NuRD complex (PMID:15456747)
• MBD3L2 interacts with MBD3 and components of the NuRD complex and can oppose MBD2-MeCP1-mediated methylation silencing (PMID:15701600)
• MBD2 is associated with the methylated region of a CpG island containing the bidirectional promoter of the Breast cancer predisposition gene 1, BRCA1, and the Near BRCA1 2 (NBR2) gene. (PMID:16052033)
• Genetic variations in rhis methylation related genes may potentially serve as a biomarker in risk estimates for breast cancer. (PMID:16168120)
• MBD2 assembles into mutually exclusive distinct Mi-2/NuRD-like complex, called MBD2/NuRD. (PMID:16428440)
• A previously unrecognized intracellular factor required for the efficient generation of protective memory CD8 T cells. (PMID:16951344)
• Sex-specific time windows for concomitant upregulation of MBD2 are associated with prenatal remethylation of the human male and female germ line. (PMID:16998846)
• Results suggest that modulation of MBD2 during gut development establishes a region-specific gene expression pattern that is essential for establishing correct segmental character. (PMID:17353267)
• MBD2 and MBD4 transcript overexpression and inverse correlations with DNA methylation indices indicate that both enzymes may really have a direct and active role on the genome-wide DNA hypomethylation observed in CD4+ T cells from SLE patients. (PMID:17360956)
• These data show, for the first time, the involvement of methyl-CpG binding domain proteins in the regulation of the MAGE-A genes. (PMID:17634428)
• We found clinically relevant levels of Hcy (0-500 microM) induced elevation of SAH, declination of SAM and SAM/SAH ratio and reduced expression of SAHH and MBD2, but increased activity of DNMT3a and DNMT3b affecting DNA methylation (PMID:17688412)
• MBD2 may play an important role in modulating NSCLC patient survival and thus be useful for identifying NSCLC patients who would benefit most from aggressive therapy. (PMID:18414412)
• These findings implicate MBD2 in transcriptional repression of the methylated p14(ARF) tumor suppressor gene and suggest that repression by MBD2 selectively affects a subset of methylated promoters. (PMID:18931530)
• results indicate MBD2 is specifically & directly involved in transcriptional repression of hTERT in HeLa cells & breast, liver & neuroblastoma cancer cell lines; MBD2 seems to be a general repressor of hTERT in hTERT-methylated telomerase-positive cells (PMID:18952593)
• The ratio of MBD-2/DNMT-1 might be valuable in explanation of hypomethylation and evaluation of clinical activity of systemic luopus erythematosus. (PMID:19019634)
• MBD2 and ERalpha drive opposite effects on pS2 expression, which are associated with specific steady state levels of histone H3 acetylation and methylation marks (PMID:20300195)
• The anti-TNFalpha biological agents do not seem to affect DNA methylation and mRNA expressions of DNMT1 and MBD2 in RA (PMID:20937307)
• This study demonstrated that patients with SLE had a significantly lower level of DNA methylation than the controls, and that expression of both DNMT1 and MBD2 mRNA was significantly increased in the SLE patients compared with controls. (PMID:21078759)
• In hilar cholangiocarcinoma, down-expression of miR-373 leads to increase of MBD2, which in turn suppresses the methylation-mediated gene such as RASSF1A. (PMID:21086164)
• miR-373 is a methylation-mediated gene and the implication of MBD2 in methylation-mediated suppression of miR-373 plays an important role in tumourigenesis and development in hilar cholangiocarcinoma. (PMID:21165562)
• human epsilon-globin gene is subject to multilayered silencing mediated in part by MBD2 (PMID:21296012)
• Expression level of MBD2 is significantly lower in endometriotic lesions compared with disease-free controls. (PMID:21316665)
• decreased expression in patients with primary immune thrombocytopenia (PMID:21377502)
• These results show a role for MBD2 in cancer progression and provide support for the prospect of targeting MBD2 therapeutically in aggressive breast cancers. (PMID:21693597)
• MBD2 overexpression during gliomagenesis may drive tumor growth by suppressing the antiangiogenic activity of a key tumor BAI1. (PMID:21724586)
• The association between MBD2 binding and transcriptional repression weakened as the distance between binding site and TSS increased, suggesting that MBD2 represses transcriptional initiation (PMID:22048253)
• A two-stage association study identifies methyl-CpG-binding domain protein 2 gene polymorphisms as candidates for breast cancer susceptibility. (PMID:22258532)
• MiR-373 behaves as a direct transcriptional target and negative regulator of MBD2 activity through a feedback loop of CpG island methylation in hilar cholangiocarcinoma (PMID:22876037)
• repressive functions of MBD2-containing NuRD complexes are dependent on cooperative interactions between the major domains of CHD4 with histones and DNA and on binding of methylated DNA by MBD2 (PMID:23071088)
• Abnormal expression levels of DNA (cytosine-5-)-methyltransferase 1 and MBD2 mRNA may be important causes of the global hypomethylation observed in CD4+T cells in systemic lupus erythematosus. (PMID:23127209)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
mus_musculus	Mbd2	ENSMUSG00000024513
rattus_norvegicus	Mbd2	ENSRNOG00000011853
drosophila_melanogaster	MBD-like	FBGN0027950

Paralogs (8): MBD3 (ENSG00000071655), MBD1 (ENSG00000141644), MBD3L1 (ENSG00000170948), MBD3L3 (ENSG00000182315), MBD3L2B (ENSG00000196589), MBD3L4 (ENSG00000205718), MBD3L2 (ENSG00000230522), MBD3L5 (ENSG00000237247)

Protein

Protein identifiers

Methyl-CpG-binding domain protein 2 — Q9UBB5 (reviewed: Q9UBB5)

Alternative names: Demethylase, Methyl-CpG-binding protein MBD2

All UniProt accessions (3): Q9UBB5, J3KSA7, X6RBL6

UniProt curated annotations — full annotation on UniProt →

Function. Binds CpG islands in promoters where the DNA is methylated at position 5 of cytosine within CpG dinucleotides. Binds hemimethylated DNA as well. Recruits histone deacetylases and DNA methyltransferases to chromatin. Acts as a component of the histone deacetylase NuRD complex which participates in the remodeling of chromatin. Acts as a transcriptional repressor and plays a role in gene silencing. Functions as a scaffold protein, targeting GATAD2A and GATAD2B to chromatin to promote repression. May enhance the activation of some unmethylated cAMP-responsive promoters.

Subunit / interactions. Heterodimer with MBD3 (via N-terminus). Component of the MeCP1 complex that contains HDAC1 and HDAC2. Component of the nucleosome remodeling and deacetylase (NuRD) repressor complex, composed of core proteins MTA1, MTA2, MTA3, RBBP4, RBBP7, HDAC1, HDAC2, MBD2, MBD3, and peripherally associated proteins CDK2AP1, CDK2AP2, GATAD2A, GATAD2B, CHD3, CHD4 and CHD5. The exact stoichiometry of the NuRD complex is unknown, and some subunits such as MBD2 and MBD3, GATAD2A and GATAD2B, and CHD3, CHD4 and CHD5 define mutually exclusive NuRD complexes. Interacts with CDK2AP1. Interacts with DHX9. Interacts with DNMT1. Interacts with GATAD2A/p66-alpha. Interacts with GATAD2B/p66-beta. Interacts with GPN1. Interacts with MIZF. Interacts with PRMT5. Interacts with SIN3A. Interacts with SPHK2.

Subcellular location. Nucleus. Chromosome.

Tissue specificity. Highly expressed in brain, heart, kidney, stomach, testis and placenta.

Miscellaneous. Incomplete sequence.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9UBB5-1	1, MBD2a, MBD2b	yes
Q9UBB5-3	3

RefSeq proteins (2): NP_003918, NP_056647 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001739	Methyl_CpG_DNA-bd	Domain
IPR016177	DNA-bd_dom_sf	Homologous_superfamily
IPR025884	MeCpG-bd_2/3_C_dom	Domain
IPR032343	MBD2/MBD3_p55-bd	Domain

Pfam: PF01429, PF14048, PF16564

UniProt features (21 total): strand 3, turn 3, helix 3, region of interest 3, compositionally biased region 3, splice variant 2, modified residue 2, chain 1, domain 1

Structure

Experimental structures (PDB)

14 structures.

PDB	Method	Resolution (Å)
7MWM	X-RAY DIFFRACTION	1.6
7RAY	X-RAY DIFFRACTION	1.78
6C1T	X-RAY DIFFRACTION	1.84
6C1A	X-RAY DIFFRACTION	2.05
6CNP	X-RAY DIFFRACTION	2.1
6CNQ	X-RAY DIFFRACTION	2.15
6C1U	X-RAY DIFFRACTION	2.3
6C1V	X-RAY DIFFRACTION	2.3
7MWK	X-RAY DIFFRACTION	2.45
6C2F	X-RAY DIFFRACTION	2.65
7AO8	ELECTRON MICROSCOPY	4.5
7AO9	ELECTRON MICROSCOPY	6.1
7AOA	ELECTRON MICROSCOPY	19.4
2L2L	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UBB5-F1	68.37	0.18

Functional residue map

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

Post-translational modifications (2): 181, 407

Function

Pathways and Gene Ontology

Reactome pathways

9 pathways

ID	Pathway
R-HSA-427413	NoRC negatively regulates rRNA expression
R-HSA-73728	RNA Polymerase I Promoter Opening
R-HSA-9937850	NuRD complex assembly
R-HSA-9940951	Interaction of NuRD complexes with transcription factors
R-HSA-212165	Epigenetic regulation of gene expression
R-HSA-5250941	Negative epigenetic regulation of rRNA expression
R-HSA-73854	RNA Polymerase I Promoter Clearance
R-HSA-73864	RNA Polymerase I Transcription
R-HSA-74160	Gene expression (Transcription)

MSigDB gene sets: 322 (showing top): PID_HDAC_CLASSI_PATHWAY, SHEPARD_BMYB_MORPHOLINO_UP, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_MUSCLE_TISSUE_DEVELOPMENT, GOBP_BEHAVIOR, GOBP_RESPONSE_TO_ESTRADIOL, GNF2_BNIP2, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GENTILE_RESPONSE_CLUSTER_D3, GOBP_REGULATION_OF_WNT_SIGNALING_PATHWAY, KAUFFMANN_DNA_REPAIR_GENES, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_NEGATIVE_REGULATION_OF_GENE_EXPRESSION_EPIGENETIC, GOBP_DNA_METHYLATION_DEPENDENT_CONSTITUTIVE_HETEROCHROMATIN_FORMATION

GO Biological Process (19): negative regulation of transcription by RNA polymerase II (GO:0000122), ventricular cardiac muscle tissue development (GO:0003229), chromatin remodeling (GO:0006338), DNA methylation-dependent constitutive heterochromatin formation (GO:0006346), response to mechanical stimulus (GO:0009612), Wnt signaling pathway (GO:0016055), positive regulation of Wnt signaling pathway (GO:0030177), response to nutrient levels (GO:0031667), response to estradiol (GO:0032355), regulation of cell population proliferation (GO:0042127), maternal behavior (GO:0042711), negative regulation of DNA-templated transcription (GO:0045892), positive regulation of DNA-templated transcription (GO:0045893), embryonic organ development (GO:0048568), protein-containing complex assembly (GO:0065003), response to bisphenol A (GO:1903925), cellular response to serotonin (GO:1904015), regulation of transcription by RNA polymerase II (GO:0006357), epigenetic regulation of gene expression (GO:0040029)

GO Molecular Function (12): chromatin binding (GO:0003682), satellite DNA binding (GO:0003696), mRNA binding (GO:0003729), methyl-CpG binding (GO:0008327), protein domain specific binding (GO:0019904), siRNA binding (GO:0035197), identical protein binding (GO:0042802), molecular adaptor activity (GO:0060090), C2H2 zinc finger domain binding (GO:0070742), DNA binding (GO:0003677), protein binding (GO:0005515), nucleosomal DNA binding (GO:0031492)

GO Cellular Component (10): chromatin (GO:0000785), heterochromatin (GO:0000792), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytosol (GO:0005829), NuRD complex (GO:0016581), protein-containing complex (GO:0032991), histone deacetylase complex (GO:0000118), chromosome (GO:0005694), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-7 pathways:

Category	Pathways
Gene expression (Transcription)	2
Negative epigenetic regulation of rRNA expression	1
RNA Polymerase I Promoter Clearance	1
CHD3, CHD4, CHD5 subfamily	1
NuRD complex assembly	1
Epigenetic regulation of gene expression	1
RNA Polymerase I Transcription	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
regulation of DNA-templated transcription	3
binding	3
transcription by RNA polymerase II	2
response to oxygen-containing compound	2
DNA-templated transcription	2
protein binding	2
regulation of transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
cardiac muscle tissue development	1
chromatin organization	1
constitutive heterochromatin formation	1
response to external stimulus	1
response to abiotic stimulus	1
cell surface receptor signaling pathway	1
positive regulation of signal transduction	1
Wnt signaling pathway	1
regulation of Wnt signaling pathway	1
response to stimulus	1
response to lipid	1
cell population proliferation	1
regulation of cellular process	1
parental behavior	1
negative regulation of RNA biosynthetic process	1
positive regulation of RNA biosynthetic process	1
embryo development	1
animal organ development	1
cellular component assembly	1
protein-containing complex organization	1
cellular response to monoamine stimulus	1
cellular response to oxygen-containing compound	1
response to serotonin	1
chromatin remodeling	1
regulation of gene expression	1
sequence-specific double-stranded DNA binding	1
RNA binding	1
nucleotide binding	1
sequence-specific DNA binding	1
regulatory RNA binding	1
molecular_function	1

Protein interactions and networks

STRING

804 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MBD2	DNMT1	P26358	927
MBD2	DNMT3A	Q9Y6K1	915
MBD2	HDAC1	Q13547	811
MBD2	MTA1	Q13330	796
MBD2	GATAD2A	Q86YP4	791
MBD2	MBD4	O95243	779
MBD2	GATAD2B	Q8WXI9	734
MBD2	GPN1	Q9HCN4	674
MBD2	HDAC2	Q92769	661
MBD2	CHD3	Q12873	637
MBD2	RBBP7	Q16576	628
MBD2	CHD4	Q14839	625
MBD2	KDM1A	O60341	620
MBD2	RCOR1	Q9UKL0	613
MBD2	RBBP4	P31149	602

IntAct

127 interactions, top by confidence:

A	B	Type	Score
HDAC1	KDM1A	psi-mi:“MI:0914”(association)	0.910
HDAC2	KDM1A	psi-mi:“MI:0914”(association)	0.890
MBD2	GATAD2A	psi-mi:“MI:0407”(direct interaction)	0.880
GATAD2A	MBD2	psi-mi:“MI:0915”(physical association)	0.880
MBD2	GATAD2A	psi-mi:“MI:0915”(physical association)	0.880
HDAC1	CDK2AP1	psi-mi:“MI:0914”(association)	0.840
RBBP7	CDK2AP1	psi-mi:“MI:0914”(association)	0.840
CHD3	CDK2AP1	psi-mi:“MI:0914”(association)	0.790
GATAD2B	CDK2AP1	psi-mi:“MI:0914”(association)	0.790
RBBP4	CDK2AP1	psi-mi:“MI:0914”(association)	0.790
HDAC1	TNRC18	psi-mi:“MI:0914”(association)	0.790
HMG20A	KDM1A	psi-mi:“MI:0914”(association)	0.730
CHD4	CDK2AP1	psi-mi:“MI:0914”(association)	0.730
GATAD2A	CDK2AP1	psi-mi:“MI:0914”(association)	0.730
CDK2AP1	MTA2	psi-mi:“MI:0914”(association)	0.730
HDAC1	ZNF609	psi-mi:“MI:0914”(association)	0.730
RBBP7	HAT1	psi-mi:“MI:0914”(association)	0.730

BioGRID (304): MBD2 (Affinity Capture-MS), MBD2 (Affinity Capture-MS), MBD2 (Affinity Capture-MS), MBD2 (Affinity Capture-MS), MBD2 (Affinity Capture-MS), HDAC2 (Co-fractionation), MBD2 (Co-fractionation), MBD2 (Co-fractionation), MBD2 (Co-fractionation), MTA1 (Co-fractionation), MTA2 (Co-fractionation), DHX9 (Reconstituted Complex), DHX9 (Affinity Capture-Western), MBD2 (Reconstituted Complex), MBD2 (Affinity Capture-Western)

ESM2 similar proteins: A4D2P6, A5PJV8, A6NFD8, D4AE48, O00268, O00287, O35274, O35779, O43566, P04198, P12755, P55199, Q08DA0, Q0D2I5, Q2KJ58, Q504T8, Q5XKK7, Q60698, Q61976, Q6NZ67, Q6P582, Q6R891, Q6T4P5, Q7Z6J2, Q80YR4, Q86UD0, Q86UK7, Q8BXL9, Q8CEG5, Q8R4T5, Q8TF61, Q8VCG9, Q969F2, Q969G9, Q96HZ4, Q96SB3, Q99PV5, Q9BQ61, Q9BUN5, Q9BZE9

Diamond homologs: A0A1B0GVZ6, A6NDZ8, A6NE82, A6NJ08, O95983, Q8NHZ7, Q8WWY6, Q9D9H3, Q9UBB5, Q9Z2D8, Q9Z2E1, O95243, P51608, Q00566, Q0IGK1, Q95LG8, Q9YDP0, Q9Z2D6, Q9Z2D7, Q9UIS9, Q9Z2E2, Q9VGA4, Q5XEN5, Q8LA53, Q9FZP6, Q9LYB9, Q9UIF8, Q9LTJ1, Q9SNC0, Q4PSK1, O08550, Q27746, Q5EA28, Q9CWW7, Q9P0U4, Q9UMN6, Q7LX22, A0A1L8GSA2, A0JP82

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
MBD2	“down-regulates quantity by repression”	ALOX5	“transcriptional regulation”
DNMT1	“down-regulates quantity by repression”	MBD2	“transcriptional regulation”
MBD2	“form complex”	“MBD2/NuRD complex”	binding
MBD2	“down-regulates quantity by repression”	CHD4	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 95 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
Regulation of TP53 Activity through Acetylation	10	73.7×	3e-15
Transcriptional regulation of brown and beige adipocyte differentiation by EBF2	11	67.5×	5e-16
Regulation of PTEN gene transcription	16	46.0×	1e-20
RNA Polymerase I Transcription Initiation	11	39.7×	1e-13
Differentiation of naive CD4+ T cells to T helper 2 cells (Th2 cells)	14	33.1×	5e-16
NuRD complex assembly	13	29.6×	2e-14
Interaction of NuRD complexes with transcription factors	14	28.6×	3e-15
ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression	11	27.0×	7e-12

GO biological processes:

GO term	Partners	Fold	FDR
regulation of stem cell differentiation	11	104.0×	4e-18
positive regulation of stem cell population maintenance	5	21.2×	2e-04
chromatin remodeling	18	16.2×	5e-15
chromatin organization	9	11.0×	1e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	35
Likely benign	0
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1421 predictions. Top by Δscore:

Variant	Effect	Δscore
18:54159761:TTAC:T	donor_loss	1.0000
18:54159763:A:T	donor_loss	1.0000
18:54159764:C:CA	donor_loss	1.0000
18:54159900:TTTC:T	acceptor_gain	1.0000
18:54159901:TTC:T	acceptor_gain	1.0000
18:54159902:TC:T	acceptor_gain	1.0000
18:54159903:CC:C	acceptor_gain	1.0000
18:54159904:C:CC	acceptor_gain	1.0000
18:54159904:C:T	acceptor_gain	1.0000
18:54159905:T:C	acceptor_gain	1.0000
18:54159905:T:TC	acceptor_gain	1.0000
18:54159906:T:C	acceptor_gain	1.0000
18:54159906:T:TC	acceptor_gain	1.0000
18:54159907:T:C	acceptor_gain	1.0000
18:54159907:T:TC	acceptor_gain	1.0000
18:54159908:T:C	acceptor_gain	1.0000
18:54159908:T:TC	acceptor_gain	1.0000
18:54164519:TTACC:T	donor_loss	1.0000
18:54164520:TACC:T	donor_loss	1.0000
18:54164522:C:CT	donor_loss	1.0000
18:54164696:AACTC:A	acceptor_gain	1.0000
18:54164698:CTC:C	acceptor_gain	1.0000
18:54164699:TC:T	acceptor_gain	1.0000
18:54164699:TCC:T	acceptor_loss	1.0000
18:54164700:CC:C	acceptor_gain	1.0000
18:54164700:CCTGC:C	acceptor_loss	1.0000
18:54164701:C:CC	acceptor_gain	1.0000
18:54164701:CTGC:C	acceptor_loss	1.0000
18:54164702:T:G	acceptor_loss	1.0000
18:54187712:A:AC	donor_gain	1.0000

AlphaMissense

2662 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
18:54159853:A:G	L387P	1.000
18:54159857:C:G	A386P	1.000
18:54159864:C:A	L383F	1.000
18:54159864:C:G	L383F	1.000
18:54159865:A:G	L383S	1.000
18:54159874:C:G	R380P	1.000
18:54159875:G:T	R380S	1.000
18:54159897:C:A	Q372H	1.000
18:54159897:C:G	Q372H	1.000
18:54159898:T:G	Q372P	1.000
18:54164526:A:T	I369N	1.000
18:54164541:A:T	V364D	1.000
18:54164555:G:C	C359W	1.000
18:54164557:A:G	C359R	1.000
18:54164562:G:C	P357R	1.000
18:54164562:G:T	P357H	1.000
18:54164563:G:A	P357S	1.000
18:54164577:A:G	L352P	1.000
18:54164583:A:T	V350D	1.000
18:54164619:C:A	G338V	1.000
18:54164619:C:T	G338E	1.000
18:54164620:C:A	G338W	1.000
18:54164620:C:G	G338R	1.000
18:54164620:C:T	G338R	1.000
18:54164625:A:T	I336N	1.000
18:54164644:G:C	H330D	1.000
18:54164646:A:G	L329S	1.000
18:54164650:C:G	A328P	1.000
18:54164655:G:T	A326D	1.000
18:54164656:C:G	A326P	1.000

dbSNP variants (sampled 300 via entrez): RS1000019161 (18:54156212 T>C,G), RS1000038126 (18:54163861 G>A), RS1000050436 (18:54218952 ACTC>A), RS1000063872 (18:54157017 A>C), RS1000105883 (18:54207571 A>G), RS1000144949 (18:54208023 T>C,G), RS1000160038 (18:54206730 C>A,T), RS1000177563 (18:54210849 A>G), RS1000233014 (18:54189644 C>G), RS1000264447 (18:54165499 C>T), RS1000272067 (18:54172950 T>G), RS1000354716 (18:54151647 C>T), RS1000386710 (18:54158835 C>A,T), RS1000401316 (18:54204792 T>G), RS1000439164 (18:54158550 C>G)

Disease associations

OMIM: gene MIM:603547 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST002127_30	Periodontitis (Mean PAL)	4.000000e-06
GCST002928_18	Nickel levels	3.000000e-06
GCST005527_35	Psoriasis	4.000000e-10
GCST006085_94	Prostate cancer	2.000000e-08
GCST010984_42	Allergic disease (asthma, hay fever and/or eczema) (multivariate analysis)	3.000000e-10
GCST010985_47	Allergic disease (asthma, hay fever and/or eczema) (age of onset)	2.000000e-10
GCST010989_282	Body size at age 10	4.000000e-08
GCST90002390_555	Mean corpuscular hemoglobin	1.000000e-16
GCST90002392_43	Mean corpuscular volume	8.000000e-16

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004847	age at onset
EFO:0009819	comparative body size at age 10, self-reported
EFO:0004527	mean corpuscular hemoglobin

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3707462 (SINGLE PROTEIN)

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

Binding affinities (BindingDB)

47 measured of 47 human assays (54 total across all organisms); most potent 47 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
4-(5-phenyl-2,3-dihydro-1,3,4-thiadiazol-2-yl)phenol	IC50	11 nM	US-9034574: Agents for reversing epigenetic silencing of genes
2-(4-chlorophenyl)-5-phenyl-2,3-dihydro-1,3,4-thiadiazole	IC50	210 nM	US-9034574: Agents for reversing epigenetic silencing of genes
[5-hydroxy-3-phenyl-5-(trifluoromethyl)-4H-pyrazol-1-yl]-phenylmethanethione	IC50	470 nM	US-9034574: Agents for reversing epigenetic silencing of genes
1-(5-phenyl-2,3-dihydro-1,3,4-thiadiazol-2-yl)naphthalen-2-ol	IC50	670 nM	US-9034574: Agents for reversing epigenetic silencing of genes
8-methoxy-2-(4-methylphenyl)-3-phenyl-chromeno[2,3-d]pyrimidine-4,5-dione	IC50	988 nM
3-[(4-pyridin-2-yl-1,3-thiazol-2-yl)amino]phenol	IC50	1550 nM	US-9034574: Agents for reversing epigenetic silencing of genes
TCMDC-124275	IC50	1550 nM	US-9034574: Agents for reversing epigenetic silencing of genes
4-[[(Z)-[1-(furan-2-ylmethyl)-2,4,6-trioxo-1,3-diazinan-5-ylidene]methyl]amino]benzamide	IC50	3450 nM
MLS003178551	IC50	4070 nM
3,4,5-trihydroxy-N’-((1E)-{4-methoxy-3-[(4-nitro-1H-pyrazol-1-yl)methyl]phenyl}methylene)benzohydrazide	IC50	4310 nM
4-[(2-cyano-1-oxoethyl)amino]benzoic acid [2-oxo-2-(3-oxo-4H-1,4-benzoxazin-6-yl)ethyl] ester	IC50	4390 nM
(2Z,3Z)-2-[4-(3,4-dimethoxyphenyl)-3H-1,3-thiazol-2-ylidene]-3-(3-nitro-4-oxidanylidene-cyclohexa-2,5-dien-1-ylidene)propanenitrile	IC50	4670 nM
N-[3-(1,3-benzothiazol-2-yl)-6-methyl-5,7-dihydro-4H-thieno[2,3-c]pyridin-2-yl]ethanamide;2,2,2-tris(fluoranyl)ethanoic acid	IC50	5860 nM
4-methyl-2-(4-nitrophenyl)imidazo[1,2-a]benzimidazole	IC50	6140 nM	US-9034574: Agents for reversing epigenetic silencing of genes
1-[2-(dimethylamino)ethylamino]-7-hydroxy-4-(hydroxymethyl)thioxanthen-9-one	IC50	6610 nM
MLS002920531	IC50	6690 nM
3-(diethylamino)-N-(9,10-dioxo-1-anthracenyl)propanamide;hydrochloride	IC50	6860 nM
MLS000688773	IC50	6920 nM
N-[(2-chlorophenyl)methyl]-2-methyl-3-[(3-oxidanylidene-4H-1,4-benzothiazin-6-yl)sulfonyl]propanamide	EC50	7530 nM
MLS001182542	IC50	8020 nM
cid_386511	IC50	8210 nM
MLS002920530	IC50	9240 nM
MLS002701807	IC50	9440 nM
MLS002607798	IC50	9590 nM
cid_12627139	IC50	10200 nM
SMR000271925	IC50	11500 nM
N-[3-(1,3-benzothiazol-2-yl)-5,6,7,8-tetrahydro-4H-thieno[2,3-c]azepin-2-yl]acetamide;2,2,2-trifluoroacetic acid	IC50	12600 nM
MLS001360883	IC50	13500 nM
SMR000263783	IC50	14600 nM
cid_386523	IC50	15400 nM
cid_1561354	IC50	17100 nM
SMR001566705	IC50	17400 nM
(4-oxidanylidenepyrimido[2,1-b][1,3]benzothiazol-2-yl)methyl 2-(6,7-dihydro-5H-cyclopenta[f][1]benzofuran-3-yl)ethanoate	IC50	17600 nM
cid_327045	IC50	20200 nM
MLS000054842	IC50	23500 nM
SMR001522665	IC50	24200 nM
MLS001199163	IC50	24300 nM
N-(6-amino-1-butyl-2,4-dioxopyrimidin-5-yl)-N-butyl-3-pyrrol-1-ylbenzamide	IC50	30500 nM
6,8-dimethyl-4-[3-(4-morpholinyl)propylamino]-3-quinolinecarboxylic acid ethyl ester	IC50	31800 nM
cid_54687404	IC50	35100 nM
4-chloro-8-methyl-N-[3-(1-pyrrolidinyl)propyl]-2-thieno[3,2-c]quinolinecarboxamide	IC50	37300 nM
US9034574, XVIII	IC50	38000 nM	US-9034574: Agents for reversing epigenetic silencing of genes
5-(1-butyl-1,2,3,4-tetrazol-5-yl)-1-(3-imidazol-1-ylpropyl)-5-methyl-pyrrolidin-2-one	IC50	43700 nM
MLS003124333	IC50	43800 nM
cid_664896	IC50	43900 nM
3-(2-chlorophenyl)-N-(2-furanylmethyl)-5-methyl-4-isoxazolecarboxamide	IC50	50000 nM
2-[6-(2-fluorobenzyl)-4-keto-5,7-dimethyl-pyrrolo[3,4-d]pyridazin-3-yl]-N-(2,3,5,6-tetrafluorophenyl)acetamide	IC50	50000 nM

ChEMBL bioactivities

7 potent at pChembl≥5 of 8 total, top 7 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.96	IC50	11	nM	CHEMBL3687963
6.68	IC50	210	nM	CHEMBL3687966
6.33	IC50	470	nM	CHEMBL3687965
6.17	IC50	670	nM	CHEMBL520851
5.81	IC50	1550	nM	CHEMBL489770
5.81	IC50	1550	nM	CHEMBL3687961
5.21	IC50	6140	nM	CHEMBL3687962

CTD chemical–gene interactions

52 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	4
Decitabine	affects cotreatment, decreases reaction, decreases activity, affects binding	3
trichostatin A	affects cotreatment, decreases reaction, increases expression, affects binding	2
hydroquinone	affects reaction, decreases expression, increases expression	2
methacrylaldehyde	increases abundance, affects cotreatment, increases expression	2
mercuric bromide	increases expression, affects cotreatment	2
Resveratrol	affects binding, affects cotreatment, decreases reaction, increases reaction	2
Acrolein	affects cotreatment, increases expression, increases abundance	2
Estradiol	affects cotreatment, increases reaction, increases activity, increases expression, decreases reaction (+1 more)	2
Ozone	increases abundance, affects cotreatment, increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Tetrachlorodibenzodioxin	affects cotreatment, increases reaction, decreases reaction, affects binding	2
Genistein	affects binding, increases reaction, decreases activity, increases activity, decreases reaction	2
bisphenol F	increases expression, affects cotreatment	1
triphenyl phosphate	affects expression	1
alpha-pinene	increases abundance, affects cotreatment, increases expression	1
bisphenol A	increases methylation	1
deoxynivalenol	decreases expression, increases expression	1
pyrimidin-2-one beta-ribofuranoside	decreases expression	1
sulforaphane	increases expression, affects binding, decreases reaction, increases reaction, increases activity	1
sodium arsenite	decreases expression	1
coumarin	increases phosphorylation	1
bicalutamide	increases expression	1
fumonisin B1	increases activity, increases expression	1
arsenic disulfide	increases expression	1
di-n-butylphosphoric acid	affects expression	1
entinostat	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3707490	Binding	Binding Assay: DNA binding assays using recombinant MBDs. To produce recombinant His6-tagged MBD polypeptides from human MBD2 (MBD2-MBD), MBD2-MBD cDNA was amplified from clone MGC-45084 (American Type Culture Collection), using PCR primers	Agents for reversing epigenetic silencing of genes

Cellosaurus cell lines

4 cell lines: 4 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_A8P5	MCF-7 TTE-MBD2	Cancer cell line	Female
CVCL_SX43	HAP1 MBD2 (-) 1	Cancer cell line	Male
CVCL_SX44	HAP1 MBD2 (-) 2	Cancer cell line	Male
CVCL_XQ31	HAP1 MBD2 (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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