MBD3methyl-CpG binding domain protein 3
Autism Reports / Total Reports
1 / 4Rare Variants / Common Variants
9 / 5Aliases
-Associated Syndromes
-Chromosome Band
19p13.3Associated Disorders
-Relevance to Autism
Genetic association and rare variants have been found in the MBD3 gene associated with autism in a Caucasian and African-American cohort (Cukier et al., 2010).
Molecular Function
The encoded protein is is a subunit of the NuRD, a multisubunit complex containing nucleosome remodeling and histone deacetylase activities
External Links
SFARI Genomic Platforms
Reports related to MBD3 (4 Reports)
| # | Type | Title | Author, Year | Autism Report | Associated Disorders |
|---|---|---|---|---|---|
| 1 | Highly Cited | MBD2-MBD3 complex binds to hemi-methylated DNA and forms a complex containing DNMT1 at the replication foci in late S phase | Tatematsu KI , et al. (2000) | No | - |
| 2 | Highly Cited | Closely related proteins MBD2 and MBD3 play distinctive but interacting roles in mouse development | Hendrich B , et al. (2001) | No | - |
| 3 | Recent Recommendation | Mbd3, a component of NuRD/Mi-2 complex, helps maintain pluripotency of mouse embryonic stem cells by repressing trophectoderm differentiation | Zhu D , et al. (2009) | No | - |
| 4 | Primary | Novel variants identified in methyl-CpG-binding domain genes in autistic individuals | Cukier HN , et al. (2009) | Yes | - |
Rare Variants (9)
| Status | Allele Change | Residue Change | Variant Type | Inheritance Pattern | Parental Transmission | Family Type | PubMed ID | Author, Year |
|---|---|---|---|---|---|---|---|---|
| C>T | - | intron_variant | - | - | - | 19921286 | Cukier HN , et al. (2009) | |
| G>A | - | intron_variant | - | - | - | 19921286 | Cukier HN , et al. (2009) | |
| delGAG | - | inframe_deletion | - | - | - | 19921286 | Cukier HN , et al. (2009) | |
| A>G | p.(=) | synonymous_variant | - | - | - | 19921286 | Cukier HN , et al. (2009) | |
| C>T | p.(=) | synonymous_variant | - | - | - | 19921286 | Cukier HN , et al. (2009) | |
| G>A | p.(=) | synonymous_variant | - | - | - | 19921286 | Cukier HN , et al. (2009) | |
| delGAG | p.Glu281del | inframe_deletion | - | - | - | 19921286 | Cukier HN , et al. (2009) | |
| c.68G>T | p.Arg23Met | missense_variant | Familial | - | - | 19921286 | Cukier HN , et al. (2009) | |
| del20insCTG | - | frameshift_variant | Unknown | - | Unknown | 19921286 | Cukier HN , et al. (2009) |
Common Variants (5)
| Status | Allele Change | Residue Change | Variant Type | Inheritance Pattern | Paternal Transmission | Family Type | PubMed ID | Author, Year |
|---|---|---|---|---|---|---|---|---|
| c.*955C>T | - | 3_prime_UTR_variant | - | - | - | 19921286 | Cukier HN , et al. (2009) | |
| c.*1231A>G | - | 3_prime_UTR_variant | - | - | - | 19921286 | Cukier HN , et al. (2009) | |
| c.*1239G>C | - | 3_prime_UTR_variant | - | - | - | 19921286 | Cukier HN , et al. (2009) | |
| c.*1046G>A | G/A | 3_prime_UTR_variant | - | - | - | 19921286 | Cukier HN , et al. (2009) | |
| c.*1235A>G | A/G | 3_prime_UTR_variant | - | - | - | 19921286 | Cukier HN , et al. (2009) |
SFARI Gene score
2
Strong Candidate
A single unreplicated association was reported of the R23M variant in half-brothers by Cukier et al., 2010 (PMID: 19921286). A 2005 screen of the same gene was negative (Li et al., 2005; PMID: 15967618).
Score Delta: Score remained at 2
criteria met
See SFARI Gene'scoring criteriaWe considered a rigorous statistical comparison between cases and controls, yielding genome-wide statistical significance, with independent replication, to be the strongest possible evidence for a gene. These criteria were relaxed slightly for category 2.
4/1/2022
3
2
Decreased from 3 to 2
Description
A single unreplicated association was reported of the R23M variant in half-brothers by Cukier et al., 2010 (PMID: 19921286). A 2005 screen of the same gene was negative (Li et al., 2005; PMID: 15967618).
10/1/2019
4
3
Decreased from 4 to 3
New Scoring Scheme
Description
A single unreplicated association was reported of the R23M variant in half-brothers by Cukier et al., 2010 (PMID: 19921286). A 2005 screen of the same gene was negative (Li et al., 2005; PMID: 15967618).
Reports Added
[New Scoring Scheme]7/1/2014
No data
4
Increased from No data to 4
Description
A single unreplicated association was reported of the R23M variant in half-brothers by Cukier et al., 2010 (PMID: 19921286). A 2005 screen of the same gene was negative (Li et al., 2005; PMID: 15967618).
4/1/2014
No data
4
Increased from No data to 4
Description
A single unreplicated association was reported of the R23M variant in half-brothers by Cukier et al., 2010 (PMID: 19921286). A 2005 screen of the same gene was negative (Li et al., 2005; PMID: 15967618).
Krishnan Probability Score
Score 0.3317347130292
Ranking 24699/25841 scored genes
[Show Scoring Methodology]
Krishnan and colleagues generated probability scores genome-wide by using a machine learning
approach on a human brain-specific gene network. The method was first presented in Nat
Neurosci 19, 1454-1462 (2016), and scores for more than 25,000 RefSeq genes can be accessed
in column G of supplementary table 3 (see:
http://www.nature.com/neuro/journal/v19/n11/extref/nn.4353-S5.xlsx). A searchable browser,
with the ability to view networks of associated ASD risk genes, can be found at
asd.princeton.edu.
ExAC Score
Score 0.91932388045198
Ranking 3042/18225 scored genes
[Show Scoring Methodology]
The Exome Aggregation Consortium (ExAC) is a summary database of 60,706 exomes that has
been widely used to estimate 'constraint' on mutation for individual genes. It was introduced by
Lek et al. Nature 536, 285-291 (2016), and the ExAC browser can be found at
exac.broadinstitute.org. The pLI score was developed as measure of intolerance to loss-of-
function mutation. A pLI > 0.9 is generally viewed as highly constrained, and thus any loss-of-
function mutations in autism in such a gene would be more likely to confer risk. For a full list of
pLI scores see:
ftp://ftp.broadinstitute.org/pub/ExAC_release/release0.3.1/functional_gene_constraint/fordist_cle
aned_exac_nonTCGA_z_pli_rec_null_data.txt
Sanders TADA Score
Score 0.93032151738431
Ranking 11398/18665 scored genes
[Show Scoring Methodology]
The TADA score ('Transmission and De novo Association') was introduced by He et al. PLoS Genet 9(8):e1003671 (2013),
and is a statistic that integrates evidence from both de novo and transmitted mutations.
It forms the basis for the claim of 65 individual genes being strongly associated with autism risk at a false discovery rate of 0.1 (Sanders et al. Neuron 87, 1215-1233
(2015)). The calculated TADA score for 18,665 RefSeq genes can be found in column P of Supplementary Table 6 in the Sanders et al. paper
(the column headed 'tadaFdrAscSscExomeSscAgpSmallDel'), which represents a combined analysis of exome data and small de novo deletions (see www.cell.com/cms/attachment/2038545319/2052606711/mmc7.xlsx).
Larsen Cumulative Evidence Score
Score 5
Ranking 287/461 scored genes
[Show Scoring Methodology]
Larsen and colleagues generated gene scores based on the sum of evidence for all available
ASD-associated variants in a gene, with assessments based on mode of inheritance, effect size,
and variant frequency in the general population. The approach was first presented in Mol Autism
7:44 (2016), and scores for 461 genes can be found in column I in supplementary table 4 from
that paper.
Zhang D Score
Score -0.20925218586373
Ranking 15627/20870 scored genes
[Show Scoring Methodology]
The DAMAGES score (disease-associated mutation analysis using gene expression signatures),
or D score, was developed to combine evidence from de novo loss-of- function mutation with
evidence from cell-type- specific gene expression in the mouse brain (specifically translational
profiles of 24 specific mouse CNS cell types isolated from 6 different brain regions). Genes with
positive D scores are more likely to be associated with autism risk, with higher-confidence genes
having higher D scores. This statistic was first presented by Zhang & Shen (Hum Mutat 38, 204-
215 (2017), and D scores for more than 20,000 RefSeq genes can be found in column M in
supplementary table 2 from that paper.
External PIN Data
Interactome
- Protein Binding
- DNA Binding
- RNA Binding
- Protein Modification
- Direct Regulation
- ASD-Linked Genes
Interaction Table
| Interactor Symbol | Interactor Name | Interactor Organism | Interactor Type | Entrez ID | Uniprot ID |
|---|---|---|---|---|---|
| CPNE5 | Copine-5 | Human | Protein Binding | 57699 | Q9HCH3 |
| RCN3 | reticulocalbin 3, EF-hand calcium binding domain | Human | Protein Binding | 57333 | Q96D15 |
| VAMP7 | vesicle-associated membrane protein 7 | Human | DNA Binding | 6845 | P51809 |
| ZBED1 | zinc finger, BED-type containing 1 | Human | Protein Binding | 9189 | O96006 |