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
• GTEx eGene: eQTL in 13 tissues, sQTL in 1 (q < 0.05)
• Constraint (gnomAD): pLI 0.95 (loss-of-function intolerant), LOEUF 0.54 (moderately constrained)
• Transcription factor: yes — 94 downstream targets (CollecTRI)
• MANE Select transcript: NM_003927
• Notable: 51 clinical variants but no curated precision-oncology (CIViC) evidence yet

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: 14 — 7 protein_coding, 6 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

MANE Select: ENST00000256429

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2, TSL 2: 1, TSL 3: 1, TSL 5: 1

ENST00000256429, ENST00000398398, ENST00000578272, ENST00000579025, ENST00000583046, ENST00000958222, ENST00000958223, ENST00000958224, ENST00000958225, ENST00001037516, ENST00001037517, ENST00001037518, ENST00001037520, ENST00001122960

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.

Highest expression (Bgee): gingival epithelium, gingiva, tonsil, oral cavity, colonic epithelium.

Genetic regulation across tissues (GTEx eQTL / sQTL)

MBD2 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 13 tissues and its splicing (sQTL) in 1 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

14 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Cells EBV-transformed lymphocytes	eqtl	9.3e-09	-0.27	18:54271156:C:CAAAG
Colon Transverse	eqtl	2.2e-08	+0.17	18:54225897:C:T
Thyroid	eqtl	5.7e-08	+0.18	18:54267396:G:A
Skin Sun Exposed Lower leg	eqtl	1.3e-05	-0.17	18:54257678:G:C
Cells Cultured fibroblasts	eqtl	5.5e-05	+0.13	18:54312343:G:C
Vagina	sqtl	6.3e-04	-3.51	18:53415089:T:C
Muscle Skeletal	eqtl	1.8e-03	-0.12	18:54244140:A:C
Skin Not Sun Exposed Suprapubic	eqtl	2.0e-03	+0.10	18:54057590:C:A
Heart Atrial Appendage	eqtl	5.2e-03	+0.13	18:54220886:G:A
Stomach	eqtl	7.3e-03	+0.13	18:54225897:C:T
Adipose Visceral Omentum	eqtl	1.1e-02	+0.22	18:54237006:T:A
Brain Frontal Cortex BA9	eqtl	1.7e-02	-0.19	18:54316312:C:A
Esophagus Mucosa	eqtl	2.3e-02	-0.19	18:54452255:T:C
Esophagus Muscularis	eqtl	3.6e-02	-0.11	18:54842602:C:T

FANTOM5 promoters

showing 10 of 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

showing 100 of 299 tissues 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
mouth mucosa	UBERON:0003729	96.90	gold quality
seminal vesicle	UBERON:0000998	96.89	gold quality
palpebral conjunctiva	UBERON:0001812	96.84	gold quality
zone of skin	UBERON:0000014	96.80	gold quality
trabecular bone tissue	UBERON:0002483	96.79	gold quality
minor salivary gland	UBERON:0001830	96.71	gold quality
mammalian vulva	UBERON:0000997	96.68	gold quality
upper arm skin	UBERON:0004263	96.66	gold quality
saliva-secreting gland	UBERON:0001044	96.64	gold quality
vermiform appendix	UBERON:0001154	96.63	gold quality
skin of abdomen	UBERON:0001416	96.62	gold quality
body of pancreas	UBERON:0001150	96.61	gold quality
lymph node	UBERON:0000029	96.60	gold quality
upper leg skin	UBERON:0004262	96.60	gold quality
adipose tissue of abdominal region	UBERON:0007808	96.60	gold quality
omental fat pad	UBERON:0010414	96.52	gold quality
left coronary artery	UBERON:0001626	96.51	gold quality
peritoneum	UBERON:0002358	96.49	gold quality
nerve	UBERON:0001021	96.45	gold quality
tibial nerve	UBERON:0001323	96.45	gold quality
vagina	UBERON:0000996	96.44	gold quality
skin of hip	UBERON:0001554	96.44	gold quality
popliteal artery	UBERON:0002250	96.43	gold quality
squamous epithelium	UBERON:0006914	96.43	gold quality
tibial artery	UBERON:0007610	96.43	gold quality
right coronary artery	UBERON:0001625	96.34	gold quality
cervix squamous epithelium	UBERON:0006922	96.34	gold quality
blood	UBERON:0000178	96.32	gold quality
esophagus	UBERON:0001043	96.29	gold quality
nasal cavity mucosa	UBERON:0001826	96.23	gold quality
colonic mucosa	UBERON:0000317	96.22	gold quality
aorta	UBERON:0000947	96.21	gold quality
coronary artery	UBERON:0001621	96.19	gold quality
mucosa of sigmoid colon	UBERON:0004993	96.11	gold quality
descending thoracic aorta	UBERON:0002345	96.08	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	96.08	gold quality
caecum	UBERON:0001153	96.03	gold quality
amniotic fluid	UBERON:0000173	95.99	gold quality
ascending aorta	UBERON:0001496	95.97	gold quality
thoracic aorta	UBERON:0001515	95.96	gold quality
buccal mucosa cell	CL:0002336	95.92	gold quality
bone marrow	UBERON:0002371	95.80	gold quality
upper lobe of left lung	UBERON:0008952	95.76	gold quality
spleen	UBERON:0002106	95.75	gold quality
mucosa of transverse colon	UBERON:0004991	95.75	gold quality
metanephros cortex	UBERON:0010533	95.75	gold quality
urinary bladder	UBERON:0001255	95.68	gold quality
pancreas	UBERON:0001264	95.61	gold quality
upper lobe of lung	UBERON:0008948	95.56	gold quality
small intestine Peyer’s patch	UBERON:0003454	95.53	gold quality
esophagus squamous epithelium	UBERON:0006920	95.51	gold quality
placenta	UBERON:0001987	95.49	gold quality
germinal epithelium of ovary	UBERON:0001304	95.47	gold quality
epithelium of esophagus	UBERON:0001976	95.44	gold quality
superficial temporal artery	UBERON:0001614	95.42	gold quality
synovial joint	UBERON:0002217	95.42	gold quality
mucosa of paranasal sinus	UBERON:0005030	95.30	gold quality
stromal cell of endometrium	CL:0002255	95.28	gold quality
renal glomerulus	UBERON:0000074	95.24	gold quality
small intestine	UBERON:0002108	95.24	gold quality
colon	UBERON:0001155	95.22	gold quality
ectocervix	UBERON:0012249	95.22	gold quality
bronchial epithelial cell	CL:0002328	95.21	gold quality
large intestine	UBERON:0000059	95.20	gold quality
jejunal mucosa	UBERON:0000399	95.17	gold quality
intestine	UBERON:0000160	95.15	gold quality
transverse colon	UBERON:0001157	95.08	gold quality
metanephric glomerulus	UBERON:0004736	95.08	gold quality
uterine cervix	UBERON:0000002	95.04	gold quality
parietal pleura	UBERON:0002400	95.03	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

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Caudate putamen	tissue	46.3
Tonsil	tissue	33.0	high
Frontal cortex	tissue	30.1
Lymph node	tissue	30.0	medium
Thyroid gland	tissue	29.0	medium
Adipose tissue	tissue	25.2	low
Skin 1	tissue	24.0	high
Spinal cord	tissue	22.2
Esophagus	tissue	21.2	high
Vagina	tissue	20.0	high
Spleen	tissue	19.9	low
Urinary bladder	tissue	19.6	high
Bone marrow	tissue	19.2	low
Corpus callosum	tissue	19.0
Putamen	tissue	18.8
Testis	tissue	18.7	medium
Thalamus	tissue	18.7
Thymus	tissue	18.7
Midbrain	tissue	18.4
Salivary gland	tissue	18.3	medium
Medulla oblongata	tissue	18.3
Superior colliculi	tissue	18.3
Appendix	tissue	18.1	medium
Pons	tissue	17.7
Placenta	tissue	17.7	medium
Substantia nigra	tissue	17.6
Cerebral cortex	tissue	16.2	medium
Colon	tissue	16.2	medium
Somatosensory cortex	tissue	16.2
Liver	tissue	15.8	low
Tongue	tissue	15.7
Parathyroid gland	tissue	15.5	low
Lung	tissue	15.5	low
Kidney	tissue	15.5	medium
Rectum	tissue	15.4	high
Ventral forebrain	tissue	15.4
Occipital cortex	tissue	15.3
Hypothalamus	tissue	15.2
Epididymis	tissue	15.0	medium
Basal ganglia	tissue	15.0	low
Septum	tissue	14.9
Breast	tissue	14.6	medium
Postcentral gyrus	tissue	14.4
Skeletal muscle	tissue	14.3	medium
Periaqueductal gray	tissue	14.3
Seminal vesicle	tissue	14.2	medium
Motor cortex	tissue	13.9
Nucleus accumbens	tissue	13.7
Temporal cortex	tissue	13.5
Pancreas	tissue	13.4	medium
Stomach 1	tissue	13.2	low
Retina	tissue	13.2
Hippocampal formation	tissue	13.2
Entorhinal cortex	tissue	13.0
Olfactory bulb	tissue	12.9
Prefrontal cortex	tissue	12.8
Small intestine	tissue	12.7	medium
Cerebellum	tissue	12.6	high
Retrosplenial and cingulate cortex	tissue	12.4
Cervix	tissue	12.2	high

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Ventral spinal cord (22.2), Dorsal spinal cord (19.4), White matter (19.0), Blood vessel (18.3), Cerebellar cortex (17.2).

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

showing 30 of 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)

Targeting MBD2 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 231 miRNAs:

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

Functional genomics

gnomAD constraint: pLI 0.947, LOEUF 0.539, missense Z 0.289 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000256429 splits into 2 regions with different missense tolerance; 0 are missense-constrained. Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
18:54,159,780–54,224,071	189 / 296.6	0.64	no
18:54,224,072–54,224,559	269 / 236.0	1.14	no

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

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	mbd2	ENSDARG00000075952
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)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1333813) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 19 distinct phenotype terms.

Mouse phenotype (MP)	Records
enlarged spleen	1
enlarged lymph nodes	1
abnormal retina morphology	1
abnormal pup retrieval	1
abnormal maternal nurturing	1
hyperglycemia	1
abnormal homeostasis	1
salivary gland inflammation	1
decreased litter size	1
abnormal effector T cell morphology	1
abnormal CD8-positive, alpha-beta cytotoxic T cell morphology	1
abnormal retina outer nuclear layer morphology	1
insulitis	1
abnormal pancreatic islet morphology	1
increased T cell proliferation	1
abnormal CD4-positive, alpha-beta T cell physiology	1
increased T-helper 1 cell number	1
increased T-helper 2 cell number	1
increased cornea thickness	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Macaca fascicularis	Q95LG8	100.0%	Diamond
Arabidopsis thaliana	Q9LYB9	67.5%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
MIR4528	ncRNA	100616232
LINC01919	ncRNA	102724651
DCC	protein-coding	1630
SNORA37	snoRNA	677819
LINC01917	ncRNA	101928167
STARD6	protein-coding	147323
C18orf54	protein-coding	162681
POLI	protein-coding	11201

Protein

Protein identifiers

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

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

All UniProt accessions (3): J3KSA7, Q9UBB5, 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 by resolution:

PDB	Title	Method	Resolution (Å)
7MWM	Crystal structure of MBD2 with DNA	X-RAY DIFFRACTION	1.6
7RAY	Crystal structure of MBD2 with DNA	X-RAY DIFFRACTION	1.78
6C1T	MBD2 in complex with a partially methylated DNA	X-RAY DIFFRACTION	1.84
6C1A	MBD2 in complex with methylated DNA	X-RAY DIFFRACTION	2.05
6CNP	Crystal structure of MBD2 complex with methylated CpG island	X-RAY DIFFRACTION	2.1
6CNQ	MBD2 in complex with methylated DNA	X-RAY DIFFRACTION	2.15
6C1U	MBD2 in complex with a deoxy-oligonucleotide	X-RAY DIFFRACTION	2.3
6C1V	MBD2 in complex with double-stranded DNA	X-RAY DIFFRACTION	2.3
7MWK	Crystal structure of MBD2 with DNA	X-RAY DIFFRACTION	2.45
6C2F	MBD2 in complex with methylated DNA	X-RAY DIFFRACTION	2.65
7AO8	Structure of the MTA1/HDAC1/MBD2 NURD deacetylase complex	ELECTRON MICROSCOPY	4.5
7AO9	Structure of the core MTA1/HDAC1/MBD2 NURD deacetylase complex	ELECTRON MICROSCOPY	6.1
7AOA	Structure of the extended MTA1/HDAC1/MBD2/RBBP4 NURD deacetylase complex	ELECTRON MICROSCOPY	19.4
2L2L	Solution structure of the coiled-coil complex between MBD2 and p66alpha	SOLUTION NMR

Predicted structure (AlphaFold)

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

Human Protein Atlas

Protein class: Predicted intracellular proteins, Cancer-related genes, Candidate cancer biomarkers

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nucleoplasm

Antibody reliability (HPA): IH approved · IF supported

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)

Type	Positions
Phosphoserine	181, 407

Function

Pathways and Gene Ontology

Reactome pathways

4 curated (TAS) of 9; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

9 pathways:

ID	Pathway	Evidence
R-HSA-9940951	Interaction of NuRD complexes with transcription factors	curated
R-HSA-427413	NoRC negatively regulates rRNA expression	curated
R-HSA-9937850	NuRD complex assembly	curated
R-HSA-73728	RNA Polymerase I Promoter Opening	curated
R-HSA-212165	Epigenetic regulation of gene expression	—
R-HSA-74160	Gene expression (Transcription)	—
R-HSA-5250941	Negative epigenetic regulation of rRNA expression	—
R-HSA-73854		—
R-HSA-73864	RNA Polymerase I 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 (16): 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), DNA-templated transcription (GO:0006351), response to mechanical stimulus (GO:0009612), response to nutrient levels (GO:0031667), response to estradiol (GO:0032355), 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), 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), 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), identical protein binding (GO:0042802)

GO Cellular Component (9): chromatin (GO:0000785), heterochromatin (GO:0000792), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), NuRD complex (GO:0016581), protein-containing complex (GO:0032991), histone deacetylase complex (GO:0000118), chromosome (GO:0005694)

Reactome top-level categories

6 top-level categories:

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

GO top-level categories

51 GO namespaces:

Category	Terms
regulation of DNA-templated transcription	3
binding	3
cellular anatomical structure	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
gene expression	1
RNA biosynthetic process	1
response to external stimulus	1
response to abiotic stimulus	1
response to stimulus	1
response to lipid	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 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 domain specific binding	1
nucleic acid binding	1
chromatin DNA binding	1
nucleosome binding	1
chromosome	1
chromatin	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
histone deacetylase complex	1
transcription regulator complex	1
CHD-type complex	1
cellular_component	1
nucleoplasm	1
nuclear protein-containing complex	1
catalytic complex	1
intracellular membraneless organelle	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 12 of 37 annotations. The rest are phylogenetic / computational / electronic (IEA).

12 experimentally-supported GO terms:

GO term	NS	Evidence
DNA methylation-dependent constitutive heterochromatin formation	BP	genetic interaction
chromatin remodeling	BP	direct assay
negative regulation of transcription by RNA polymerase II	BP	genetic interaction
NuRD complex	CC	direct assay
chromatin	CC	direct assay
nucleoplasm	CC	direct assay
nucleus	CC	direct assay
protein-containing complex	CC	high-throughput assay
C2H2 zinc finger domain binding	MF	physical interaction
methyl-CpG binding	MF	direct assay
molecular adaptor activity	MF	experiment
protein domain specific binding	MF	physical interaction

Protein interactions and networks

STRING

showing 16 of 742 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MBD2	MBD4	O95243	753
MBD2	DNMT1	P26358	701
MBD2	GPN1	Q9HCN4	700
MBD2	DNMT3A	Q9Y6K1	700
MBD2	MTA1	Q13330	676
MBD2	HDAC1	Q13547	618
MBD2	KDM1A	O60341	606
MBD2	XPA	P23025	510
MBD2	GATA3	P23771	492
MBD2	GATAD2A	Q86YP4	487
MBD2	TRDMT1	O14717	427
MBD2	MECP2	P51608	414
MBD2	HDAC2	Q92769	410
MBD2	RCOR1	Q9UKL0	394
MBD2	H3-4	Q16695	389
MBD2	H3-7	Q5TEC6	389

IntAct

Human interaction partners of MBD2 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

19 partners by confidence:

Partner	Interaction type	MIscore	Records
GATAD2A	direct interaction	0.880	6
PURB	physical association	0.560	3
SMN1	physical association	0.510	2
DNMT1	association	0.460	1
BEND7	physical association	0.370	1
C1QBP	physical association	0.370	1
LAMTOR3	physical association	0.370	1
PRMT1	physical association	0.370	1
RALYL	physical association	0.370	1
ASS1	association	0.350	1
BARHL2	association	0.350	1
CDC42EP3	association	0.350	1
LHX8	association	0.350	1
MTA2	association	0.350	1
OAT	association	0.350	1
SGK2	association	0.350	1
TESK2	association	0.350	1
HDAC1	physical association	0.000	1
RFX3	physical association	0.000	1

BioGRID (306 interactions; top human partners by supporting records): HDAC1 (Affinity Capture-Western; 22 records), GATAD2A (Co-fractionation; 13 records), MBD3 (Two-hybrid; 12 records), HDAC2 (Co-fractionation; 11 records), GATAD2B (Affinity Capture-MS; 10 records), MTA2 (Co-fractionation; 9 records), RBBP7 (Affinity Capture-MS; 8 records), RBBP4 (Affinity Capture-MS; 7 records), CHD3 (Affinity Capture-MS; 5 records), CHD4 (Affinity Capture-MS; 5 records), DHX9 (Reconstituted Complex; 5 records), CDK2AP1 (Affinity Capture-MS; 4 records), KDM1A (Negative Genetic; 4 records), MBD3L1 (Two-hybrid; 4 records), ZNF219 (Affinity Capture-MS; 4 records)

SIGNOR signaling

4 signaling 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”

Protein complexes (CORUM) (7)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

7 complexes by size:

Complex	Subunits	Members
★ LARC complex (LCR-associated remodeling complex)	19	SMARCC1, SMARCC2, SMARCD2, SMARCE1, ACTL6A, CHD4, MBD3, RBBP4, ACTB, MTA2, SMARCA4, HDAC1, HDAC2, HNRNPC, MBD2, ARID1A, DPF2, GATAD2B, SMARCB1
★ SNF2h-cohesin-NuRD complex	16	MBD2, MTA2, RBBP7, SMARCA5, MTA1, RBBP4, HDAC2, RAD21, SMC3, STAG1, STAG2, BAZ1A, HDAC1, MBD3, SMC1A, CHD3
★ HDAC1-associated protein complex	9	HDAC1, KDM1A, MBD2, MBD3, MTA2, RBBP4, RBBP7, RCOR1, CHD3
★ HDAC1-associated core complex cII	9	CHD3, HDAC1, MBD2, MTA2, RBBP4, RBBP7, RCOR1, GATAD2A, MBD3
★ MeCP1 complex	9	MTA2, RBBP4, RBBP7, MBD3, CHD4, GATAD2B, HDAC1, HDAC2, MBD2
★ SIX3-LSD1-NuRD(MTA3) complex	9	HDAC1, HDAC2, KDM1A, MBD2, RBBP7, MBD3, MTA3, RBBP4, SIX3
★ MeCP1 complex	8	RBBP7, CHD4, HDAC1, HDAC2, MBD2, MBD3, MTA2, RBBP4

Disease & clinical

Genetic variants

Variant evidence for MBD2: 51 ClinVar records (0 pathogenic / likely pathogenic); 9 GWAS associations.

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

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 38 predictions of 765):

Position(s)	Effect	Δscore	Sites
18:54159763–54159764	donor_loss	1.0000	6
18:54159904–54159908	acceptor_gain	1.0000	5
18:54159904–54159905	acceptor_loss	1.0000	4
18:54164521–54164522	donor_loss	1.0000	5
18:54164701–54164702	acceptor_loss	1.0000	5
18:54188872–54188873	donor_loss	1.0000	5
18:54189012–54189013	acceptor_loss	1.0000	4
18:54159765	donor_loss	0.9900	2
18:54164701	acceptor_loss	0.9900
18:54164705	acceptor_gain	0.9900

AlphaMissense

1,274 missense substitutions predicted likely pathogenic (of 2,662 scored), across 261 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
D176	8	1.000	1.000
D207	8	0.999	1.000
F252	8	0.999	1.000
F206	8	0.998	1.000
S189	8	0.995	1.000
S171	8	0.993	1.000
F187	8	0.992	1.000
D202	8	0.992	0.999
H330	8	0.992	1.000
D294	8	0.987	0.996
D368	8	0.987	0.998
F208	8	0.984	1.000
F282	8	0.984	0.999
D390	8	0.982	0.994
D238	8	0.977	0.995
F362	8	0.975	0.999
H262	8	0.964	0.994
S181	8	0.963	0.999
N347	8	0.955	0.998
D366	8	0.943	0.994

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

3 prognostic cancer types:

Cancer	Prognostic	p-value
Lung Adenocarcinoma (TCGA)	unfavorable	2.26e-06
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	1.6e-05
Kidney Renal Clear Cell Carcinoma (validation)	favorable	0.000608

Disease associations

OMIM: gene MIM:603547 | disease phenotypes:

GWAS associations

9 associations:

Study	Trait	p-value
GCST90002390_322	Mean corpuscular hemoglobin	1e-16
GCST90002392_297	Mean corpuscular volume	8e-16
GCST010985_50	Allergic disease (asthma, hay fever and/or eczema) (age of onset)	2e-10
GCST010984_42	Allergic disease (asthma, hay fever and/or eczema) (multivariate analysis)	3e-10
GCST005527_35	Psoriasis	4e-10
GCST006085_54	Prostate cancer	2e-8
GCST010989_282	Body size at age 10	4e-8
GCST002928_22	Nickel levels	3e-6
GCST002127_27	Periodontitis (Mean PAL)	4e-6

EFO canonical traits (from GWAS)

3 canonical traits:

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 (CPIC guideline: no)

Binding affinities (BindingDB)

50 measured of 50 human assays (54 total across all organisms); most potent 50 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
MLS003178551	IC50	1000 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
SMR001522665	IC50	3100 nM
4-[[(Z)-[1-(furan-2-ylmethyl)-2,4,6-trioxo-1,3-diazinan-5-ylidene]methyl]amino]benzamide	IC50	3450 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	3800 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
(E)-2-[4-(3,4-Dimethoxy-phenyl)-thiazol-2-yl]-3-(4-hydroxy-3-nitro-phenyl)-acrylonitrile	IC50	4670 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
cid_12627139	IC50	10200 nM
N,10-dimethyl-2-phenazin-10-iumamine;perchlorate	IC50	11500 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
MLS002607798	IC50	13000 nM
MLS001360883	IC50	13500 nM
SMR000263783	IC50	14600 nM
7-Methyl-6,7,7a,8-tetrahydro-5H-benzo[g][1,3]dioxolo[4’,5’:4,5]benzo[1,2,3-de]quinoline	IC50	15000 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
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
4-[(3-methoxy-5-nitro-4-oxidanyl-phenyl)-(3-methyl-5-oxidanylidene-1,2-dihydropyrazol-4-yl)methyl]-5-methyl-1,2-dihydropyrazol-3-one	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 binding, affects cotreatment, decreases reaction, decreases activity	3
trichostatin A	affects cotreatment, decreases reaction, increases expression, affects binding	2
hydroquinone	increases expression, affects reaction, decreases expression	2
methacrylaldehyde	affects cotreatment, increases expression, increases abundance	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 binding, affects cotreatment, increases reaction, increases activity, increases expression (+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	affects cotreatment, increases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases expression, increases abundance	1
bisphenol A	increases methylation	1
deoxynivalenol	decreases expression, increases expression	1
pyrimidin-2-one beta-ribofuranoside	decreases expression	1
sulforaphane	affects binding, decreases reaction, increases reaction, increases activity, increases expression	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)

Via MONDO — disease-level, not drug-specific.

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for MBD2 across ~30M SureChEMBL compounds — explore on Sugi Predict.