MBD3
protein-codingmethyl-CpG binding domain protein 3, the group of NuRD complex subunits|Methyl-CpG binding domain containing
Gene summary
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. [provided by RefSeq, Jul 2013]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~19.3 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to MBD3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001281453.2. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 2 | 1 | 3 | |||
| missense | 3 | 3 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 3 | 2 | 1 | 6 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001268382.1 | 6 | MANE Select | |
| Ensembl | ENSP00000412302.2 | 6 | MANE Select | |
| RefSeq | NP_001268383.1 | 6 | Standard | |
| Ensembl | ENSP00000156825.2 | 6 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| mbd3b | Danio rerio | Structure: definitive hemopoiesis Quality: decreased occurrence abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression
- Positive epigenetic regulation of rRNA expression
- Signal Transduction
- Epigenetic regulation of gene expression
- Gene expression (Transcription)
Biological Process
- negative regulation of transcription by RNA polymerase II
- in utero embryonic development
- methylation-dependent chromatin silencing
- brain development
- heart development
Molecular Function
- RNA polymerase II proximal promoter sequence-specific DNA binding
- RNA polymerase II distal enhancer sequence-specific DNA binding
- DNA binding
- histone deacetylase activity
- protein binding
Cellular Component
- nuclear chromatin
- heterochromatin
- nucleus
- nucleoplasm
- cytoplasm
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000156825
- Coding exons
- 6
- Length
- 16244
- Individuals with no LoFs
- 125041
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 6
- Defined
- 125047
- p
- 0.0000240
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.39 | 145 | 200 | 0.724 | 0.0000148 | 1902 |
| Missense (PolyPhen) | 52 | 88.832 | 0.58538 | 743 | ||
| Synonymous | -2.03 | 121 | 95.8 | 1.26 | 0.00000878 | 536 |
| Loss of Function | 3.14 | 0 | 11.5 | 0.00 | 4.96e-7 | 136 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0.00010 | 0.00010 | rare |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000033 | 0.000027 | rare |
| South Asian | 0.000039 | 0.000033 | rare |
| Other | 0.00017 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Acts as transcriptional repressor and plays a role in gene silencing. Does not bind to DNA by itself (PubMed:12124384). Binds to DNA with a preference for sites containing methylated CpG dinucleotides (in vitro). Binds to a lesser degree DNA containing unmethylated CpG dinucleotides (PubMed:24307175). Recruits histone deacetylases and DNA methyltransferases. {ECO:0000269|PubMed:10947852, ECO:0000269|PubMed:12124384, ECO:0000269|PubMed:18644863, ECO:0000269|PubMed:23361464, ECO:0000269|PubMed:24307175, ECO:0000269|PubMed:9774669}.;
Recessive Scores
- pRec
- 0.129
Intolerance Scores
- LoFtool
- 0.0475
- RVIS EVS
- -0.82
- RVIS percentile EVS
- 11.68
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.973
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |