Human Gene Module / Chromosome 18 / MBD1

MBD1methyl-CpG binding domain protein 1

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
3 / 9
Rare Variants / Common Variants
8 / 4
Aliases
MBD1, RFT,  PCM1,  CXXC3
Associated Syndromes
-
Chromosome Band
18q21.1
Associated Disorders
-
Relevance to Autism

Genetic association and rare variants have been found in the MBD1 gene associated with autism in a Caucasian and African-American cohort (Cukier et al., 2010).

Molecular Function

The encoded protein binds specifically to methylated DNA and can repress transcription

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to MBD1 (9 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Highly Cited Solution structure of the methyl-CpG binding domain of human MBD1 in complex with methylated DNA Ohki I , et al. (2001) No -
2 Primary Mutation analysis of methyl-CpG binding protein family genes in autistic patients Li H , et al. (2005) Yes -
3 Recent Recommendation The loss of methyl-CpG binding protein 1 leads to autism-like behavioral deficits Allan AM , et al. (2008) No -
4 Support Novel variants identified in methyl-CpG-binding domain genes in autistic individuals Cukier HN , et al. (2009) Yes -
5 Highly Cited DNA methylation inhibits transcription indirectly via a methyl-CpG binding protein Boyes J and Bird A (1991) No -
6 Recent Recommendation - Jobe EM , et al. (2017) No -
7 Recent Recommendation Methyl-CpG-Binding Protein MBD1 Regulates Neuronal Lineage Commitment through Maintaining Adult Neural Stem Cell Identity Jobe EM , et al. (2017) No -
8 Recent Recommendation Methyl-CpG-Binding Protein MBD1 Regulates Neuronal Lineage Commitment through Maintaining Adult Neural Stem Cell Identity Jobe EM , et al. (2017) No -
9 Support - Cirnigliaro M et al. (2023) Yes -
Rare Variants   (8)
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)
T>C - intron_variant - - - 19921286 Cukier HN , et al. (2009)
G>A p.(=) synonymous_variant - - - 19921286 Cukier HN , et al. (2009)
G>A p.Gly428His missense_variant - - - 19921286 Cukier HN , et al. (2009)
c.-26+1G>T - splice_site_variant De novo - Multiplex 37506195 Cirnigliaro M et al. (2023)
c.1674A>T p.Lys558Asn missense_variant Familial Maternal - 19921286 Cukier HN , et al. (2009)
c.805C>T p.Arg269Cys missense_variant Familial Paternal Simplex 15967618 Li H , et al. (2005)
c.440G>A p.Arg147Lys missense_variant Familial Paternal Multiplex 19921286 Cukier HN , et al. (2009)
Common Variants   (4)
Status Allele Change Residue Change Variant Type Inheritance Pattern Paternal Transmission Family Type PubMed ID Author, Year
c.1950C>T;c.*32+1822C>T;c.1629-1984C>T;c.*364C>T;c.*29C>T;c.*204C>T;c.1743C>T;c.2103C>T;c.2028C>T;c. p.(=) synonymous_variant - - - 19921286 Cukier HN , et al. (2009)
c.1201C>G;c.1276C>G;c.1273C>G;c.1108C>G;c.1051C>G;c.1033C>G;c.1132C>G;c.1054C>G;c.1354C>G;c.1279C>G; p.Pro401Ala missense_variant - - - 19921286 Cukier HN , et al. (2009)
c.*370G>T;c.*33-1596G>T;c.1629-1596G>T;c.*752G>T;c.*417G>T;c.*592G>T;c.1932-1596G>T;c.1887-1596G>T;c - 500B_downstream_variant, intron_variant, 3_prime_UTR_variant - - - 19921286 Cukier HN , et al. (2009)
c.240G>A;c.318G>A p.(=) synonymous_variant - - - 19921286 Cukier HN , et al. (2009)
SFARI Gene score
2

Strong Candidate

Candidate gene based on role in methylation. Screening of cases identified several rare missense mutations (PMIDs: 15967618, 19921286); no rigorous screening of controls. Mice knock-outs have reduced social interaction, learning deficits and anxiety (PMID: 18385101).

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

Candidate gene based on role in methylation. Screening of cases identified several rare missense mutations (PMIDs: 15967618, 19921286); no rigorous screening of controls. Mice knock-outs have reduced social interaction, learning deficits and anxiety (PMID: 18385101).

10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

Candidate gene based on role in methylation. Screening of cases identified several rare missense mutations (PMIDs: 15967618, 19921286); no rigorous screening of controls. Mice knock-outs have reduced social interaction, learning deficits and anxiety (PMID: 18385101).

Reports Added
[New Scoring Scheme]
1/1/2017
4
icon
4

Decreased from 4 to 4

Description

Candidate gene based on role in methylation. Screening of cases identified several rare missense mutations (PMIDs: 15967618, 19921286); no rigorous screening of controls. Mice knock-outs have reduced social interaction, learning deficits and anxiety (PMID: 18385101).

Reports Added
[Methyl-CpG-Binding Protein MBD1 Regulates Neuronal Lineage Commitment through Maintaining Adult Neural Stem Cell Identity.2017] [Methyl-CpG-Binding Protein MBD1 Regulates Neuronal Lineage Commitment through Maintaining Adult Neural Stem Cell Identity.2017]
7/1/2014
No data
icon
4

Increased from No data to 4

Description

Candidate gene based on role in methylation. Screening of cases identified several rare missense mutations (PMIDs: 15967618, 19921286); no rigorous screening of controls. Mice knock-outs have reduced social interaction, learning deficits and anxiety (PMID: 18385101).

4/1/2014
No data
icon
4

Increased from No data to 4

Description

Candidate gene based on role in methylation. Screening of cases identified several rare missense mutations (PMIDs: 15967618, 19921286); no rigorous screening of controls. Mice knock-outs have reduced social interaction, learning deficits and anxiety (PMID: 18385101).

Krishnan Probability Score

Score 0.44745238239814

Ranking 12359/25841 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 0.95961595147663

Ranking 2536/18225 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 0.93706481800548

Ranking 13401/18665 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 2

Ranking 396/461 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 0.47917263845751

Ranking 669/20870 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
External PIN Data
BioGRIDHuman Protein Reference Database
Interactome
Interaction Table
Interactor Symbol Interactor Name Interactor Organism Interactor Type Entrez ID Uniprot ID
LOC126075 coiled-coil domain containing 159 Human Protein Binding 126075 P0C7I6
LOC161527 golgin A6 family-like 4 Human Protein Binding 161527 A6NEF3
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