Human Gene Module / Chromosome 20 / MACROD2

MACROD2MACRO domain containing 2

Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
11 / 19
Rare Variants / Common Variants
4 / 11
Aliases
MACROD2, C20orf133
Associated Syndromes
-
Genetic Category
Rare Single Gene Mutation, Genetic Association
Chromosome Band
20p12.1
Associated Disorders
ADHD
Relevance to Autism

Genetic association has been found between the MACROD2 gene and autism in AGP, AGRE and SAGE cohorts (Anney et al., 2010). However, genetic association was not found between MACROD2 and autism in a large European population cohort (Curran et al., 2011).

Molecular Function

The protein encoded by this gene is a deacetylase involved in removing ADP-ribose from mono-ADP-ribosylated proteins. The encoded protein has been shown to translocate from the nucleus to the cytoplasm upon DNA damage.

Reports related to MACROD2 (19 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Highly Cited The C20orf133 gene is disrupted in a patient with Kabuki syndrome. Maas NM , et al. (2007) No -
2 Recent Recommendation Lack of C20orf133 and FLRT3 mutations in 43 patients with Kabuki syndrome in Japan. Kuniba H , et al. (2008) No -
3 Recent Recommendation Hotspots of large rare deletions in the human genome. Bradley WE , et al. (2010) No -
4 Primary A genome-wide scan for common alleles affecting risk for autism. Anney R , et al. (2010) Yes -
5 Recent Recommendation Identification of macrodomain proteins as novel O-acetyl-ADP-ribose deacetylases. Chen D , et al. (2011) No -
6 Negative Association No association between a common single nucleotide polymorphism, rs4141463, in the MACROD2 gene and autism spectrum disorder. Curran S , et al. (2011) Yes -
7 Support Epileptic encephalopathies of the Landau-Kleffner and continuous spike and waves during slow-wave sleep types: genomic dissection makes the link wi... Lesca G , et al. (2012) No ADHD
8 Negative Association The association of rs4307059 and rs35678 markers with autism spectrum disorders is replicated in Italian families. Prandini P , et al. (2012) Yes -
9 Positive Association Individual common variants exert weak effects on the risk for autism spectrum disorderspi. Anney R , et al. (2012) Yes -
10 Support A discovery resource of rare copy number variations in individuals with autism spectrum disorder. Prasad A , et al. (2013) Yes -
11 Recent Recommendation Genome-wide scan of healthy human connectome discovers SPON1 gene variant influencing dementia severity. Jahanshad N , et al. (2013) No -
12 Support Identification of risk genes for autism spectrum disorder through copy number variation analysis in Austrian families. Egger G , et al. (2014) Yes -
13 Positive Association MACROD2 gene associated with autistic-like traits in a general population sample. Jones RM , et al. (2014) No -
14 Positive Association Phenome-wide association study (PheWAS) in EMR-linked pediatric cohorts, genetically links PLCL1 to speech language development and IL5-IL13 to Eos... Namjou B , et al. (2014) Yes -
15 Positive Association Genome-Wide Association Study for Autism Spectrum Disorder in Taiwanese Han Population. Kuo PH , et al. (2015) Yes -
16 Negative Association Lack of replication of previous autism spectrum disorder GWAS hits in European populations. Torrico B , et al. (2016) Yes -
17 Positive Association Meta-analysis of GWAS of over 16,000 individuals with autism spectrum disorder highlights a novel locus at 10q24.32 and a significant overlap with ... Autism Spectrum Disorders Working Group of The Psychiatric Genomics Consortium (2017) Yes -
18 Recent recommendation Biochemical and Morphological Characterization of a Neurodevelopmental Disorder-Related Mono-ADP-Ribosylhydrolase, MACRO Domain Containing 2. Ito H , et al. (2018) No -
19 Recent Recommendation Identification of common genetic risk variants for autism spectrum disorder. Grove J , et al. (2019) Yes -
Rare Variants   (4)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
- - copy_number_loss Unknown - - 24643514 Egger G , et al. (2014)
- - copy_number_loss Unknown - Unknown 23275889 Prasad A , et al. (2013)
- - copy_number_gain Familial Paternal Unknown 22738016 Lesca G , et al. (2012)
- - copy_number_loss Familial Paternal Unknown 22738016 Lesca G , et al. (2012)
Common Variants   (11)
Status Allele Change Residue Change Variant Type Inheritance Pattern Paternal Transmission Family Type PubMed ID Author, Year
c.418+79618A>C - intron_variant - - - 28540026 Autism Spectrum Disorders Working Group of The Psychiatric Genomics Consortium (2017)
c.418+177262A>T - intron_variant - - - 28540026 Autism Spectrum Disorders Working Group of The Psychiatric Genomics Consortium (2017)
c.164-19716G>A - intron_variant - - - 26398136 Kuo PH , et al. (2015)
c.418+81866T>C A intron_variant - - - 20663923 Anney R , et al. (2010)
c.418+197367C>T - intron_variant - - - 22843504 Anney R , et al. (2012)
c.418+199551T>C - intron_variant - - - 22843504 Anney R , et al. (2012)
c.418+201817G>T - intron_variant - - - 22843504 Anney R , et al. (2012)
c.418+243136C>T - intron_variant - - - 25477900 Namjou B , et al. (2014)
c.418+81866T>C C/T intron_variant - - - 21656903 Curran S , et al. (2011)
c.418+81866T>C Effect allele, T intron_variant - - - 25360606 Jones RM , et al. (2014)
c.418+170662_418+170668delTTTTTTT - intron_variant - - - 30804558 Grove J , et al. (2019)
SFARI Gene score
2

Strong Candidate

3

Score Delta: Increased from 3 to 4.3 + acc2

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.

4/1/2018
3
icon
4.3 + acc2

Increased from 3 to 4.3 + acc2

Description

3

4/1/2017
3
icon
3

Increased from 3 to 3

Description

Inconsistent genetic association has been reported between the MACROD2 gene and autism in AGP, AGRE and SAGE cohorts (Anney et al., 2010). However, genetic association was not found between MACROD2 and autism in a large European population cohort (Curran et al., 2011).

Reports Added
[MACROD2 gene associated with autistic-like traits in a general population sample.2014] [A genome-wide scan for common alleles affecting risk for autism.2010] [No association between a common single nucleotide polymorphism, rs4141463, in the MACROD2 gene and autism spectrum disorder.2011] [The association of rs4307059 and rs35678 markers with autism spectrum disorders is replicated in Italian families.2012] [Individual common variants exert weak effects on the risk for autism spectrum disorderspi.2012] [A discovery resource of rare copy number variations in individuals with autism spectrum disorder.2013] [Identification of risk genes for autism spectrum disorder through copy number variation analysis in Austrian families.2014] [Phenome-wide association study (PheWAS) in EMR-linked pediatric cohorts, genetically links PLCL1 to speech language development and IL5-IL13 to Eos...2014] [Epileptic encephalopathies of the Landau-Kleffner and continuous spike and waves during slow-wave sleep types: genomic dissection makes the link wi...2012] [The C20orf133 gene is disrupted in a patient with Kabuki syndrome.2007] [Lack of C20orf133 and FLRT3 mutations in 43 patients with Kabuki syndrome in Japan.2008] [Hotspots of large rare deletions in the human genome.2010] [Identification of macrodomain proteins as novel O-acetyl-ADP-ribose deacetylases.2011] [Genome-wide scan of healthy human connectome discovers SPON1 gene variant influencing dementia severity.2013] [Genome-Wide Association Study for Autism Spectrum Disorder in Taiwanese Han Population.2015] [Lack of replication of previous autism spectrum disorder GWAS hits in European populations.2016] [Meta-analysis of GWAS of over 16,000 individuals with autism spectrum disorder highlights a novel locus at 10q24.32 and a significant overlap with ...2017]
7/1/2016
3
icon
3

Increased from 3 to 3

Description

Inconsistent genetic association has been reported between the MACROD2 gene and autism in AGP, AGRE and SAGE cohorts (Anney et al., 2010). However, genetic association was not found between MACROD2 and autism in a large European population cohort (Curran et al., 2011).

1/1/2016
3
icon
3

Increased from 3 to 3

Description

Inconsistent genetic association has been reported between the MACROD2 gene and autism in AGP, AGRE and SAGE cohorts (Anney et al., 2010). However, genetic association was not found between MACROD2 and autism in a large European population cohort (Curran et al., 2011).

Reports Added
[MACROD2 gene associated with autistic-like traits in a general population sample.2014] [A genome-wide scan for common alleles affecting risk for autism.2010] [No association between a common single nucleotide polymorphism, rs4141463, in the MACROD2 gene and autism spectrum disorder.2011] [The association of rs4307059 and rs35678 markers with autism spectrum disorders is replicated in Italian families.2012] [Individual common variants exert weak effects on the risk for autism spectrum disorderspi.2012] [A discovery resource of rare copy number variations in individuals with autism spectrum disorder.2013] [Identification of risk genes for autism spectrum disorder through copy number variation analysis in Austrian families.2014] [Phenome-wide association study (PheWAS) in EMR-linked pediatric cohorts, genetically links PLCL1 to speech language development and IL5-IL13 to Eos...2014] [Epileptic encephalopathies of the Landau-Kleffner and continuous spike and waves during slow-wave sleep types: genomic dissection makes the link wi...2012] [The C20orf133 gene is disrupted in a patient with Kabuki syndrome.2007] [Lack of C20orf133 and FLRT3 mutations in 43 patients with Kabuki syndrome in Japan.2008] [Hotspots of large rare deletions in the human genome.2010] [Identification of macrodomain proteins as novel O-acetyl-ADP-ribose deacetylases.2011] [Genome-wide scan of healthy human connectome discovers SPON1 gene variant influencing dementia severity.2013] [Genome-Wide Association Study for Autism Spectrum Disorder in Taiwanese Han Population.2015]
1/1/2015
3
icon
3

Increased from 3 to 3

Description

Inconsistent genetic association has been reported between the MACROD2 gene and autism in AGP, AGRE and SAGE cohorts (Anney et al., 2010). However, genetic association was not found between MACROD2 and autism in a large European population cohort (Curran et al., 2011).

7/1/2014
No data
icon
3

Increased from No data to 3

Description

Inconsistent genetic association has been reported between the MACROD2 gene and autism in AGP, AGRE and SAGE cohorts (Anney et al., 2010). However, genetic association was not found between MACROD2 and autism in a large European population cohort (Curran et al., 2011).

4/1/2014
No data
icon
3

Increased from No data to 3

Description

Inconsistent genetic association has been reported between the MACROD2 gene and autism in AGP, AGRE and SAGE cohorts (Anney et al., 2010). However, genetic association was not found between MACROD2 and autism in a large European population cohort (Curran et al., 2011).

Krishnan Probability Score

Score 0.49479938016342

Ranking 3418/25841 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 0.011356747021034

Ranking 9904/18225 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 0.95078348633128

Ranking 18627/18665 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 33

Ranking 66/461 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 -0.24859005982104

Ranking 16353/20870 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.
CNVs associated with MACROD2(1 CNVs)
20p12.1 34 Deletion-Duplication 53  /  279
Submit New Gene

Report an Error