Human Gene Module / Chromosome 12 / MBD6

MBD6Methyl-CpG binding domain protein 6

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
3 / 3
Rare Variants / Common Variants
17 / 0
Aliases
MBD6, KIAA1887
Associated Syndromes
-
Chromosome Band
12q13.3
Associated Disorders
-
Relevance to Autism

A total of 11 ASD-specific variants, seven of which were non-synonymous, in the MBD6 gene were identified in cases but not controls. One of these variants, MBD6 Arg883Trp, segregated with disease in a multiplex ASD family (Cukier et al., 2012).

Molecular Function

Binds to heterochromatin. Does not interact with either methylated or unmethylated DNA (in vitro)

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to MBD6 (3 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary The expanding role of MBD genes in autism: identification of a MECP2 duplication and novel alterations in MBD5, MBD6, and SETDB1 Cukier HN , et al. (2012) Yes -
2 Support - Alonso-Gonzalez A et al. (2021) Yes -
3 Support - Zhou X et al. (2022) Yes -
Rare Variants   (17)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.1239G>T p.Leu413%3D synonymous_variant De novo - - 35982159 Zhou X et al. (2022)
c.1880C>T p.Pro627Leu missense_variant De novo - Simplex 35982159 Zhou X et al. (2022)
c.2569C>T p.Arg857Trp missense_variant De novo - Simplex 35982159 Zhou X et al. (2022)
c.114-23C>T - intron_variant Unknown Unknown Unknown 23055267 Cukier HN , et al. (2012)
c.2236+28C>T - intron_variant Unknown Unknown Unknown 23055267 Cukier HN , et al. (2012)
c.2829_2830delinsT p.Gly944GlufsTer2 frameshift_variant De novo - - 35982159 Zhou X et al. (2022)
c.826A>C p.Asn276His missense_variant De novo - Simplex 33431980 Alonso-Gonzalez A et al. (2021)
c.831T>A p.Asn277Lys missense_variant De novo - Simplex 33431980 Alonso-Gonzalez A et al. (2021)
c.1882C>T p.Leu628= synonymous_variant Unknown Unknown Unknown 23055267 Cukier HN , et al. (2012)
c.2415A>G p.Pro805= synonymous_variant Unknown Unknown Unknown 23055267 Cukier HN , et al. (2012)
c.916G>A p.Gly306Arg missense_variant Familial Maternal Simplex 23055267 Cukier HN , et al. (2012)
c.2446G>A p.Glu816Lys missense_variant Familial Maternal Simplex 23055267 Cukier HN , et al. (2012)
c.2827C>G p.Pro943Ala missense_variant Familial Paternal Simplex 23055267 Cukier HN , et al. (2012)
c.2899C>T p.Arg967Cys missense_variant Familial Maternal Simplex 23055267 Cukier HN , et al. (2012)
c.1379C>G p.Ser460Cys missense_variant Familial Paternal Multiplex 23055267 Cukier HN , et al. (2012)
c.1414G>T p.Val472Leu missense_variant Familial Maternal Multiplex 23055267 Cukier HN , et al. (2012)
c.2647C>T p.Arg883Trp missense_variant Familial Maternal Multiplex 23055267 Cukier HN , et al. (2012)
Common Variants  

No common variants reported.

SFARI Gene score
2

Strong Candidate

A total of 11 ASD-specific variants, seven of which were non-synonymous, in the MBD6 gene were identified in cases but not controls in Cukier et al., 2012; one of these variants (p.Arg883Trp) segregated with disease in a multiplex ASD family.

Score Delta: Score remained at 2

criteria met
See SFARI Gene'scoring criteria
2

Strong Candidate

See all Category 2 Genes

We 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
icon
2

Decreased from 3 to 2

Description

A total of 11 ASD-specific variants, seven of which were non-synonymous, in the MBD6 gene were identified in cases but not controls in Cukier et al., 2012; one of these variants (p.Arg883Trp) segregated with disease in a multiplex ASD family.

1/1/2021
3
icon
3

Decreased from 3 to 3

Description

A total of 11 ASD-specific variants, seven of which were non-synonymous, in the MBD6 gene were identified in cases but not controls in Cukier et al., 2012; one of these variants (p.Arg883Trp) segregated with disease in a multiplex ASD family.

Reports Added
[Exploring the biological role of postzygotic and germinal de novo mutations in ASD2021]
10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

A total of 11 ASD-specific variants, seven of which were non-synonymous, in the MBD6 gene were identified in cases but not controls in Cukier et al., 2012; one of these variants (p.Arg883Trp) segregated with disease in a multiplex ASD family.

Reports Added
[New Scoring Scheme]
7/1/2018
icon
4

Increased from to 4

Description

A total of 11 ASD-specific variants, seven of which were non-synonymous, in the MBD6 gene were identified in cases but not controls in Cukier et al., 2012; one of these variants (p.Arg883Trp) segregated with disease in a multiplex ASD family.

Krishnan Probability Score

Score 0.48781009636775

Ranking 6894/25841 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.
Original Source
ExAC Score

Score 0.96365750042042

Ranking 2475/18225 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
Original Source
Sanders TADA Score

Score 0.87509859211398

Ranking 4565/18665 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).
Original Source
Larsen Cumulative Evidence Score

Score 28

Ranking 76/461 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.
Original Source
Zhang D Score

Score 0.16922155157517

Ranking 4824/20870 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.
Original Source
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