MBD3

Summary

MBD3 (methyl-CpG binding domain protein 3, HGNC:6918) is a protein-coding gene on chromosome 19p13.3, encoding Methyl-CpG-binding domain protein 3 (O95983). Acts as a component of the histone deacetylase NuRD complex which participates in the remodeling of chromatin.

DNA methylation is the major modification of eukaryotic genomes and plays an essential role in mammalian development. This gene belongs to a family of nuclear proteins which are characterized by the presence of a methyl-CpG binding domain (MBD). The encoded protein is a subunit of the NuRD, a multisubunit complex containing nucleosome remodeling and histone deacetylase activities. Unlike the other family members, the encoded protein is not capable of binding to methylated DNA. The protein mediates the association of metastasis-associated protein 2 with the core histone deacetylase complex. Alternative splicing results in multiple transcript variants of this gene.

Source: NCBI Gene 53615 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 7 total
• MANE Select transcript: NM_001281453

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6918
Approved symbol	MBD3
Name	methyl-CpG binding domain protein 3
Location	19p13.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000071655
Ensembl biotype	protein_coding
OMIM	603573
Entrez	53615

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 12 protein_coding, 2 nonsense_mediated_decay, 2 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000156825, ENST00000434436, ENST00000585903, ENST00000585967, ENST00000589064, ENST00000589901, ENST00000590550, ENST00000590830, ENST00000592012, ENST00000592361, ENST00000592965, ENST00000890872, ENST00000931264, ENST00000931265, ENST00000931266, ENST00000931267, ENST00000931268

RefSeq mRNA: 2 — MANE Select: NM_001281453 NM_001281453, NM_001281454

CCDS: CCDS12072, CCDS62481

Canonical transcript exons

ENST00000434436 — 7 exons

Exon	Start	End
ENSE00001709127	1592522	1592865
ENSE00002818414	1573596	1578158
ENSE00003482251	1581092	1581269
ENSE00003539330	1585055	1585214
ENSE00003564100	1584540	1584677
ENSE00003594516	1578335	1578538
ENSE00003638978	1582622	1582712

Expression profiles

Bgee: expression breadth ubiquitous, 287 present calls, max score 97.32.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 18.7146 / max 137.5056, expressed in 1810 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
178049	9.5020	1710
178051	5.8378	1719
178048	2.5715	1117
178050	0.6346	336
178044	0.0670	15
178045	0.0386	14
178043	0.0379	13
178041	0.0163	7
178046	0.0069	4
178042	0.0022	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
apex of heart	UBERON:0002098	97.32	gold quality
right frontal lobe	UBERON:0002810	96.11	gold quality
cingulate cortex	UBERON:0003027	95.73	gold quality
anterior cingulate cortex	UBERON:0009835	95.69	gold quality
amygdala	UBERON:0001876	95.54	gold quality
lower esophagus mucosa	UBERON:0035834	94.82	gold quality
mucosa of transverse colon	UBERON:0004991	94.77	gold quality
adenohypophysis	UBERON:0002196	94.75	gold quality
left uterine tube	UBERON:0001303	94.43	gold quality
Brodmann (1909) area 10	UBERON:0013541	94.38	gold quality
right hemisphere of cerebellum	UBERON:0014890	94.38	gold quality
right lobe of thyroid gland	UBERON:0001119	94.36	gold quality
hindlimb stylopod muscle	UBERON:0004252	94.35	gold quality
gastrocnemius	UBERON:0001388	94.26	gold quality
right ovary	UBERON:0002118	94.19	gold quality
Brodmann (1909) area 9	UBERON:0013540	94.18	gold quality
cerebellar hemisphere	UBERON:0002245	94.10	gold quality
cerebellar cortex	UBERON:0002129	93.98	gold quality
pituitary gland	UBERON:0000007	93.87	gold quality
ganglionic eminence	UBERON:0004023	93.87	gold quality
left lobe of thyroid gland	UBERON:0001120	93.85	gold quality
putamen	UBERON:0001874	93.85	gold quality
right lobe of liver	UBERON:0001114	93.80	gold quality
metanephros cortex	UBERON:0010533	93.80	gold quality
prefrontal cortex	UBERON:0000451	93.79	gold quality
ventricular zone	UBERON:0003053	93.78	gold quality
stromal cell of endometrium	CL:0002255	93.77	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	93.76	gold quality
left ovary	UBERON:0002119	93.69	gold quality
body of uterus	UBERON:0009853	93.57	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.19

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
POU5F1	Unknown

Upstream regulators (CollecTRI, top): DNMT1, DNMT3A, DNMT3B, FOXN1, JUN, MBD2, MECOM, NCOR1, NCOR2, NR6A1, ZBTB7A

Literature-anchored findings (GeneRIF, showing 27)

• MBD3 is highly expressed in glioblastome multiforme compared to astrocytoma and anaplastic astrocytoma (PMID:11836615)
• interaction with two highly related p66 proteins (PMID:12183469)
• localization in Aurora-A-positive centrosomes in M phase (PMID:12354758)
• MBD3L2 interacts with MBD3 and components of the NuRD complex and can oppose MBD2-MeCP1-mediated methylation silencing (PMID:15701600)
• MBD3 assembles into mutually exclusive distinct Mi-2/NuRD-like complex, called MBD3/NuRD. (PMID:16428440)
• This is the first demonstration that MBD3 is involved in inducing and maintaining the demethylated state of a specific promoter. (PMID:17452452)
• data demonstrate a causal relationship between MBD3 and DNA demethylation of genomic targets in cells. (PMID:18602768)
• Study demonstrates a direct role of the MBD3, a subunit of nucleosome remodeling and deacetylase corepressor complex complex in aberrant gene repression and transmission of epigenetic repressive marks in acute promyelocytic leukemia. (PMID:18644863)
• These findings collectively support a role for MBD3 in cell cycle progression and cell death as a modulator of HDAC-mediated transcription. (PMID:19041848)
• MBD3 mutations are not responsible for ICR1 hypomethylation in Silver-Russell syndrome. (PMID:20004753)
• These factors lead to a binding affinity hierarchy of p66alpha for the different MBD2 homologues (MBD2 approximately MBD3 > MBD3L1 approximately MBD3L2). (PMID:23239876)
• MBD3 is enriched at active promoters, whereas MBD2 is bound at methylated promoters and enriched at exon sequences of active genes. (PMID:23361464)
• reduced mRNA expression of MBD2 and MBD3 is implicated in gastric carcinogenesis. (PMID:24338710)
• These data suggest that MBD3, and by extension the NuRD complex, may have multiple roles in fine tuning expression for both active and silent genes, representing an important step in defining regulatory mechanisms (PMID:24385926)
• This study investigates the genetic association between methyl-CpG-binding domain (MBD) gene polymorphisms and schizophrenia. (PMID:24849540)
• Insufficient MBD3 induced by small interfering RNA (siRNA) was found to result in a global DNA hypermethylation as well as increased methylation in the promoter CpG islands (CGIs) of a number of cell cycle related genes. (PMID:25753672)
• Overexpression of MBD3 is associated with neoplasms. (PMID:27465550)
• Suggest that MBD3 exerts influences on both active and silenced genes in glioma cells. (PMID:27835581)
• Study have demonstrated that MBD3/ NuRD inhibits formation of liver induced cancer stem cells (iCSCs). In addition, MBD3 suppression induces c-JUN, resulting in the induction of pluripotent genes in iCSCs. (PMID:27894081)
• MBD3 inhibits epithelial-mesenchymal transition in pancreatic cancer cells probably via TGF-beta/Smad signaling and may be a candidate for diagnostics and prognosis of pancreatic cancer. (PMID:27898661)
• the interplay of the Zalpha domain from ADAR1 and MBD3 may regulate the transition of the DNA conformation between B- and Z-DNA and thereby modulate chromatin accessibility, resulting in alterations in gene expression (PMID:30304469)
• our results demonstrate that mCG-binding arginine fingers embedded into a conserved structural fold are essential structural features for MBD2/3s binding to methylated DNA among metazoans. (PMID:30980593)
• Histone deacetylases, Mbd3/NuRD, and Tet2 hydroxylase are crucial regulators of epithelial-mesenchymal plasticity and tumor metastasis. (PMID:31666683)
• Glioma stem-like cells evade interferon suppression through MBD3/NuRD complex-mediated STAT1 downregulation. (PMID:32181805)
• Methyl-CpG binding domain protein 3: a new diagnostic marker and potential therapeutic target of melanoma. (PMID:32963182)
• MBD3 promotes hepatocellular carcinoma progression and metastasis through negative regulation of tumour suppressor TFPI2. (PMID:35501390)
• Densely methylated DNA traps Methyl-CpG-binding domain protein 2 but permits free diffusion by Methyl-CpG-binding domain protein 3. (PMID:36037972)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	mbd3a	ENSDARG00000061774
mus_musculus	Mbd3	ENSMUSG00000035478
rattus_norvegicus	Mbd3	ENSRNOG00000028956
drosophila_melanogaster	MBD-like	FBGN0027950

Paralogs (8): MBD2 (ENSG00000134046), MBD1 (ENSG00000141644), MBD3L1 (ENSG00000170948), MBD3L3 (ENSG00000182315), MBD3L2B (ENSG00000196589), MBD3L4 (ENSG00000205718), MBD3L2 (ENSG00000230522), MBD3L5 (ENSG00000237247)

Protein

Protein identifiers

Methyl-CpG-binding domain protein 3 — O95983 (reviewed: O95983)

Alternative names: Methyl-CpG-binding protein MBD3

All UniProt accessions (7): O95983, A0A087WT34, A0A087WVG6, A0A087WZ12, A0A087X1H1, A0A0A0MTS6, K7EIE8

UniProt curated annotations — full annotation on UniProt →

Function. Acts as a component of the histone deacetylase NuRD complex which participates in the remodeling of chromatin. Acts as transcriptional repressor and plays a role in gene silencing. Does not bind to methylated DNA by itself. Binds to a lesser degree DNA containing unmethylated CpG dinucleotides. Recruits histone deacetylases and DNA methyltransferases.

Subunit / interactions. Heterodimer (via N-terminus) with MBD2. Component of the MeCP1 histone deacetylase complex. 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 MBD3L2 (via N-terminus); the interaction is direct. Interacts with BCL6. Interacts with CDK2AP1. Interacts with HDAC1. Interacts with MTA2. Interacts with DNMT1. Interacts with GATAD2A. Interacts with GATAD2B. Does not interact with PWWP2A. Does not interact with PWWP2B.

Subcellular location. Nucleus. Chromosome.

Isoforms (2)

UniProt ID	Names	Canonical?
O95983-1	1	yes
O95983-2	2

RefSeq proteins (2): NP_001268382, NP_001268383 (=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 (25 total): modified residue 3, cross-link 3, mutagenesis site 3, strand 3, region of interest 3, turn 3, compositionally biased region 2, chain 1, domain 1, splice variant 1, helix 1, coiled-coil region 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
6CCG	X-RAY DIFFRACTION	1.9
6CC8	X-RAY DIFFRACTION	1.95
6CEU	X-RAY DIFFRACTION	2
6CEV	X-RAY DIFFRACTION	2
2MB7	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O95983-F1	78.83	0.42

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 (6): 144, 73, 90, 92, 56, 85

Mutagenesis-validated functional residues (3):

Position	Phenotype
30	no effect. confers strong binding to methylated cpg (in vitro); when associated with y-34.
34	augments dna binding activity, irrespective of dna methylation.
34	confers weak binding to methylated cpg (in vitro). confers strong binding to methylated cpg (in vitro); when associated

Function

Pathways and Gene Ontology

Reactome pathways

35 pathways

ID	Pathway
R-HSA-3214815	HDACs deacetylate histones
R-HSA-427389	ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression
R-HSA-6804758	Regulation of TP53 Activity through Acetylation
R-HSA-73762	RNA Polymerase I Transcription Initiation
R-HSA-8943724	Regulation of PTEN gene transcription
R-HSA-9679191	Potential therapeutics for SARS
R-HSA-9843940	Regulation of endogenous retroelements by KRAB-ZFP proteins
R-HSA-9844594	Transcriptional regulation of brown and beige adipocyte differentiation by EBF2
R-HSA-9845323	Regulation of endogenous retroelements by Piwi-interacting RNAs (piRNAs)
R-HSA-9937850	NuRD complex assembly
R-HSA-9940951	Interaction of NuRD complexes with transcription factors
R-HSA-9976102	Differentiation of naive CD4+ T cells to T helper 2 cells (Th2 cells)
R-HSA-1257604	PIP3 activates AKT signaling
R-HSA-1266738	Developmental Biology
R-HSA-162582	Signal Transduction
R-HSA-1643685	Disease
R-HSA-212165	Epigenetic regulation of gene expression
R-HSA-212436	Generic Transcription Pathway
R-HSA-3247509	Chromatin modifying enzymes
R-HSA-3700989	Transcriptional Regulation by TP53
R-HSA-4839726	Chromatin organization
R-HSA-5250913	Positive epigenetic regulation of rRNA expression
R-HSA-5633007	Regulation of TP53 Activity
R-HSA-5663205	Infectious disease
R-HSA-6807070	PTEN Regulation
R-HSA-73854	RNA Polymerase I Promoter Clearance
R-HSA-73857	RNA Polymerase II Transcription
R-HSA-73864	RNA Polymerase I Transcription
R-HSA-74160	Gene expression (Transcription)
R-HSA-9006925	Intracellular signaling by second messengers

MSigDB gene sets: 176 (showing top): PID_HDAC_CLASSI_PATHWAY, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_MUSCLE_TISSUE_DEVELOPMENT, GOBP_RESPONSE_TO_ESTRADIOL, REACTOME_RNA_POLYMERASE_I_TRANSCRIPTION_INITIATION, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, KAUFFMANN_DNA_REPAIR_GENES, GGGTGGRR_PAX4_03, OHASHI_AURKA_TARGETS, GOBP_NEGATIVE_REGULATION_OF_GENE_EXPRESSION_EPIGENETIC, GOBP_DNA_METHYLATION_DEPENDENT_CONSTITUTIVE_HETEROCHROMATIN_FORMATION, GOBP_VENTRICULAR_CARDIAC_MUSCLE_TISSUE_DEVELOPMENT, GOBP_IN_UTERO_EMBRYONIC_DEVELOPMENT, BLALOCK_ALZHEIMERS_DISEASE_UP

GO Biological Process (15): negative regulation of transcription by RNA polymerase II (GO:0000122), in utero embryonic development (GO:0001701), ventricular cardiac muscle tissue development (GO:0003229), chromatin remodeling (GO:0006338), DNA methylation-dependent constitutive heterochromatin formation (GO:0006346), response to nutrient levels (GO:0031667), response to estradiol (GO:0032355), regulation of cell fate specification (GO:0042659), 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), regulation of stem cell differentiation (GO:2000736), tissue development (GO:0009888), epigenetic regulation of gene expression (GO:0040029)

GO Molecular Function (4): DNA binding (GO:0003677), methyl-CpG binding (GO:0008327), protein binding (GO:0005515), nucleosomal DNA binding (GO:0031492)

GO Cellular Component (8): chromatin (GO:0000785), heterochromatin (GO:0000792), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), NuRD complex (GO:0016581), protein-containing complex (GO:0032991), chromosome (GO:0005694)

Reactome top-level categories

Rollup of top-16 pathways:

Category	Pathways
Regulation of endogenous retroelements	2
Chromatin modifying enzymes	1
Positive epigenetic regulation of rRNA expression	1
Regulation of TP53 Activity	1
RNA Polymerase I Promoter Clearance	1
PTEN Regulation	1
SARS-CoV Infections	1
Transcriptional regulation of brown and beige adipocyte differentiation	1
CHD3, CHD4, CHD5 subfamily	1
NuRD complex assembly	1
Differentiation of T cells	1
Intracellular signaling by second messengers	1
Gene expression (Transcription)	1
RNA Polymerase II Transcription	1
Chromatin organization	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
response to oxygen-containing compound	2
DNA-templated transcription	2
regulation of DNA-templated transcription	2
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
chordate embryonic development	1
cardiac muscle tissue development	1
chromatin organization	1
constitutive heterochromatin formation	1
response to stimulus	1
response to lipid	1
cell fate specification	1
regulation of cell fate commitment	1
negative regulation of RNA biosynthetic process	1
positive regulation of RNA biosynthetic process	1
embryo development	1
animal organ development	1
regulation of cell differentiation	1
stem cell differentiation	1
anatomical structure development	1
chromatin remodeling	1
regulation of gene expression	1
nucleic acid binding	1
nucleotide binding	1
sequence-specific DNA binding	1
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
intracellular membraneless organelle	1

Protein interactions and networks

STRING

1136 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MBD3	CHD4	Q14839	838
MBD3	HDAC1	Q13547	828
MBD3	RBBP7	Q16576	808
MBD3	MTA2	O94776	791
MBD3	MTA1	Q13330	789
MBD3	RBBP4	P31149	766
MBD3	LGR5	O75473	668
MBD3	CHD3	Q12873	622
MBD3	MTA3	Q9BTC8	601
MBD3	HDAC2	Q92769	580
MBD3	WDR5	P61964	520
MBD3	KDM1A	O60341	483
MBD3	DNMT1	P26358	412
MBD3	GATAD2B	Q8WXI9	404
MBD3	TET1	Q8NFU7	398

IntAct

182 interactions, top by confidence:

A	B	Type	Score
MBD3	HDAC1	psi-mi:“MI:0915”(physical association)	0.910
HDAC1	KDM1A	psi-mi:“MI:0914”(association)	0.910
HDAC2	KDM1A	psi-mi:“MI:0914”(association)	0.890
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
RBBP4	CDK2AP1	psi-mi:“MI:0914”(association)	0.790
HDAC1	TNRC18	psi-mi:“MI:0914”(association)	0.790
GATAD2B	CDK2AP1	psi-mi:“MI:0914”(association)	0.790
MBD3	GATAD2B	psi-mi:“MI:0915”(physical association)	0.740
GATAD2B	MBD3	psi-mi:“MI:0915”(physical association)	0.740
CHD4	CDK2AP1	psi-mi:“MI:0914”(association)	0.730
RBBP7	HAT1	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
MBD3	CDK2AP1	psi-mi:“MI:0914”(association)	0.730
MTA3	MBD3	psi-mi:“MI:0914”(association)	0.690
ZGPAT	DHX15	psi-mi:“MI:0914”(association)	0.670
ZNF219	CDK2AP1	psi-mi:“MI:0914”(association)	0.640

BioGRID (526): MBD3 (Two-hybrid), MBD3 (Two-hybrid), MBD3 (Two-hybrid), MBD3 (Two-hybrid), MBD3 (Two-hybrid), TRIM54 (Two-hybrid), RCN3 (Two-hybrid), GATAD2B (Two-hybrid), CEP76 (Two-hybrid), MBD3 (Affinity Capture-MS), MBD3 (Affinity Capture-MS), MBD3 (Affinity Capture-MS), MBD3 (Affinity Capture-MS), MBD3 (Affinity Capture-MS), MBD3 (Affinity Capture-MS)

ESM2 similar proteins: A0A088MLT8, A2AQ19, A4FV29, A4IFK9, B3KU38, O14795, O70166, O93388, O95983, P21818, P31395, P50751, P54227, P55821, P63042, P63043, Q09001, Q09002, Q09004, Q09006, Q2KJ58, Q32L68, Q4KUS2, Q4R4N5, Q5F3L9, Q5FVJ5, Q5PSV4, Q5R4C5, Q5R562, Q5R8C6, Q5RAD5, Q62768, Q6GQB5, Q8IVM0, Q8IW50, Q8TBN0, Q8VDV3, Q90987, Q92541, Q93045

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

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
MBD3	“form complex”	“MBD3/NuRD complex”	binding
AURKA	up-regulates	MBD3	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 139 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
Transcriptional regulation of brown and beige adipocyte differentiation by EBF2	11	41.9×	8e-14
Regulation of TP53 Activity through Acetylation	9	41.1×	3e-11
RNA Polymerase I Transcription Initiation	13	29.1×	4e-14
Transcriptional regulation of pluripotent stem cells	5	27.2×	4e-05
Regulation of PTEN gene transcription	14	25.0×	4e-14
NuRD complex assembly	16	22.6×	2e-15
Interaction of NuRD complexes with transcription factors	17	21.6×	9e-16
ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression	14	21.3×	2e-13

GO biological processes:

GO term	Partners	Fold	FDR
regulation of stem cell differentiation	11	66.9×	6e-16
NLS-bearing protein import into nucleus	5	31.8×	5e-05
negative regulation of proteasomal ubiquitin-dependent protein catabolic process	5	15.9×	1e-03
circadian regulation of gene expression	6	11.2×	1e-03
chromatin remodeling	18	10.4×	3e-11
double-strand break repair	6	9.7×	3e-03
protein import into nucleus	8	9.2×	3e-04
nucleosome assembly	6	6.7×	1e-02

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

1544 predictions. Top by Δscore:

Variant	Effect	Δscore
19:1578377:T:TA	donor_gain	1.0000
19:1578386:T:TA	donor_gain	1.0000
19:1578389:T:TA	donor_gain	1.0000
19:1578398:T:TA	donor_gain	1.0000
19:1578535:CTTC:C	acceptor_gain	1.0000
19:1578536:TTC:T	acceptor_gain	1.0000
19:1578537:TC:T	acceptor_gain	1.0000
19:1578538:CC:C	acceptor_gain	1.0000
19:1578539:C:CC	acceptor_gain	1.0000
19:1581087:GCTA:G	donor_loss	1.0000
19:1581087:GCTAC:G	donor_loss	1.0000
19:1581088:CTA:C	donor_loss	1.0000
19:1581088:CTAC:C	donor_loss	1.0000
19:1581089:TA:T	donor_loss	1.0000
19:1581089:TACCT:T	donor_loss	1.0000
19:1581090:ACCT:A	donor_loss	1.0000
19:1581091:C:CG	donor_loss	1.0000
19:1581091:C:T	donor_loss	1.0000
19:1581267:CCC:C	acceptor_gain	1.0000
19:1581268:CCC:C	acceptor_gain	1.0000
19:1584535:CTCA:C	donor_loss	1.0000
19:1584538:A:AC	donor_gain	1.0000
19:1584538:A:AT	donor_loss	1.0000
19:1584539:C:A	donor_loss	1.0000
19:1584539:C:CC	donor_gain	1.0000
19:1584673:TTGCC:T	acceptor_gain	1.0000
19:1584674:TGCC:T	acceptor_gain	1.0000
19:1584675:GCC:G	acceptor_gain	1.0000
19:1584676:CC:C	acceptor_gain	1.0000
19:1584676:CCC:C	acceptor_gain	1.0000

AlphaMissense

1933 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:1578488:A:G	L243P	1.000
19:1578492:C:G	A242P	1.000
19:1578500:A:G	L239P	1.000
19:1578509:C:G	R236P	1.000
19:1581131:G:C	P213R	1.000
19:1581131:G:T	P213H	1.000
19:1581188:C:A	G194V	1.000
19:1581188:C:T	G194E	1.000
19:1581189:C:G	G194R	1.000
19:1581189:C:T	G194R	1.000
19:1581215:A:G	L185P	1.000
19:1581224:G:T	A182D	1.000
19:1582693:A:G	L143P	1.000
19:1584613:A:T	V112E	1.000
19:1584621:C:A	K109N	1.000
19:1584621:C:G	K109N	1.000
19:1584624:G:C	F108L	1.000
19:1584624:G:T	F108L	1.000
19:1584625:A:C	F108C	1.000
19:1584625:A:G	F108S	1.000
19:1584626:A:C	F108V	1.000
19:1584626:A:G	F108L	1.000
19:1584628:A:C	I107S	1.000
19:1584628:A:G	I107T	1.000
19:1584628:A:T	I107N	1.000
19:1584631:G:A	S106F	1.000
19:1584634:G:T	A105E	1.000
19:1584643:C:G	R102P	1.000
19:1584644:G:C	R102G	1.000
19:1584644:G:T	R102S	1.000

dbSNP variants (sampled 300 via entrez): RS1000017302 (19:1581573 G>C), RS1000038261 (19:1576332 G>A), RS1000069712 (19:1581734 C>G), RS1000169938 (19:1588208 C>T), RS1000257214 (19:1591595 C>T), RS1000285138 (19:1573932 G>A,C), RS1000300720 (19:1578111 G>A), RS1000529977 (19:1577904 C>T), RS1000530401 (19:1585174 G>A), RS1000575568 (19:1587114 C>G), RS1000709114 (19:1590455 C>T), RS1000899682 (19:1577409 C>T), RS1000964681 (19:1579211 C>A,G), RS1000969175 (19:1575863 G>A), RS1000985833 (19:1585458 G>A)

Disease associations

OMIM: gene MIM:603573 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression	3
Valproic Acid	affects expression, decreases expression, increases methylation	3
sodium arsenite	increases expression	2
FR900359	affects phosphorylation	1
Batroxase, Bothrops atrox	decreases expression	1
TAK-243	decreases sumoylation	1
2,4,6-tribromophenol	decreases expression	1
lead acetate	increases expression	1
pyrimidin-2-one beta-ribofuranoside	decreases expression	1
decabromobiphenyl ether	decreases expression	1
sulforaphane	increases expression	1
zinc chromate	decreases expression, increases abundance	1
benzo(e)pyrene	increases methylation	1
ferrous chloride	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
chromium hexavalent ion	decreases expression, increases abundance	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
bisphenol S	affects cotreatment, decreases methylation	1
NSC 689534	decreases expression, affects binding	1
Decitabine	increases expression	1
Arsenic Trioxide	decreases expression	1
Fulvestrant	decreases methylation, affects cotreatment	1
Vorinostat	decreases expression	1
Vehicle Emissions	increases expression	1
Benzophenoneidum	increases expression	1
Cadmium	increases abundance, increases expression	1
Cisplatin	decreases expression	1
Copper	affects binding, decreases expression	1
Doxorubicin	affects expression	1

Cellosaurus cell lines

9 cell lines: 6 cancer cell line, 3 embryonic stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_A4B0	SEES3-1V human MBD3, clone1	Embryonic stem cell	Male
CVCL_A4B1	SEES3-1V human MBD3, clone2	Embryonic stem cell	Male
CVCL_A4B2	SEES3-1V human MBD3, clone3	Embryonic stem cell	Male
CVCL_B7Y8	Abcam Raji MBD3 KO	Cancer cell line	Male
CVCL_B9YY	Abcam THP-1 MBD3 KO	Cancer cell line	Male
CVCL_C7AP	Abcam PC-3 MBD3 KO	Cancer cell line	Male
CVCL_SX45	HAP1 MBD3 (-) 1	Cancer cell line	Male
CVCL_SX46	HAP1 MBD3 (-) 2	Cancer cell line	Male
CVCL_SX47	HAP1 MBD3 (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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