Human Gene Module / Chromosome 7 / MUC12

MUC12mucin 12, cell surface associated

Score
3
Suggestive Evidence Criteria 3.1
Autism Reports / Total Reports
2 / 2
Rare Variants / Common Variants
8 / 0
Aliases
MUC12, MUC-11,  MUC-12,  MUC11
Associated Syndromes
-
Genetic Category
Rare Single Gene Mutation
Chromosome Band
7q22.1
Associated Disorders
-
Relevance to Autism

A de novo nonsense variant in the MUC12 gene was identified in an ASD proband from the Autism Sequencing Consortium in De Rubeis et al., 2014. Six non-synonymous postzygotic mosaic mutations (PZMs) in this gene were identified in ASD probands in Lim et al., 2017; comparison with a background set of 84,448 privately inherited variants demonstrated that this gene harbored more PZMs than expected based on background rates (6/571 observed vs. 233/84,448 expected; hypergeometric P-value of 5.3E-03).

Molecular Function

This gene encodes an integral membrane glycoprotein that is a member of the mucin family. Mucins are O-glycosylated proteins that play an essential role in forming protective mucous barriers on epithelial surfaces and have been implicated in epithelial renewal and differentiation. These glycoproteins also play a role in intracellular signaling.

Reports related to MUC12 (2 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary Synaptic, transcriptional and chromatin genes disrupted in autism. De Rubeis S , et al. (2014) Yes -
2 Recent Recommendation Rates, distribution and implications of postzygotic mosaic mutations in autism spectrum disorder. Lim ET , et al. (2017) Yes -
Rare Variants   (8)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.2296G>T p.Glu766Ter stop_gained De novo NA - 25363760 De Rubeis S , et al. (2014)
c.9547T>G p.Ser3183Ala missense_variant De novo NA - 28714951 Lim ET , et al. (2017)
c.9874T>G p.Leu3292Val missense_variant De novo NA - 28714951 Lim ET , et al. (2017)
c.11900C>T p.Thr3967Ile missense_variant De novo NA - 28714951 Lim ET , et al. (2017)
c.11947A>C p.Ser3983Arg missense_variant De novo NA - 28714951 Lim ET , et al. (2017)
c.12019C>A p.Leu4007Met missense_variant De novo NA - 28714951 Lim ET , et al. (2017)
c.13043C>G p.Ala4348Gly missense_variant De novo NA - 28714951 Lim ET , et al. (2017)
c.11991C>T p.His3997%3D synonymous_variant De novo NA - 28714951 Lim ET , et al. (2017)
Common Variants  

No common variants reported.

SFARI Gene score
3

Suggestive Evidence

A de novo nonsense variant in the MUC12 gene was identified in an ASD proband from the Autism Sequencing Consortium in De Rubeis et al., 2014. Six non-synonymous postzygotic mosaic mutations (PZMs) in this gene were identified in ASD probands in Lim et al., 2017; comparison with a background set of 84,448 privately inherited variants demonstrated that this gene harbored more PZMs than expected based on background rates (6/571 observed vs. 233/84,448 expected; hypergeometric P-value of 5.3E-03).

Score Delta: Decreased from 4 to 3

3

Suggestive Evidence

See all Category 3 Genes

The literature is replete with relatively small studies of candidate genes, using either common or rare variant approaches, which do not reach the criteria set out for categories 1 and 2. Genes that had two such lines of supporting evidence were placed in category 3, and those with one line of evidence were placed in category 4. Some additional lines of "accessory evidence" (indicated as "acc" in the score cards) could also boost a gene from category 4 to 3.

10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

A de novo nonsense variant in the MUC12 gene was identified in an ASD proband from the Autism Sequencing Consortium in De Rubeis et al., 2014. Six non-synonymous postzygotic mosaic mutations (PZMs) in this gene were identified in ASD probands in Lim et al., 2017; comparison with a background set of 84,448 privately inherited variants demonstrated that this gene harbored more PZMs than expected based on background rates (6/571 observed vs. 233/84,448 expected; hypergeometric P-value of 5.3E-03).

Reports Added
[New Scoring Scheme]
7/1/2017
icon
4

Increased from to 4

Description

A de novo nonsense variant in the MUC12 gene was identified in an ASD proband from the Autism Sequencing Consortium in De Rubeis et al., 2014. Six non-synonymous postzygotic mosaic mutations (PZMs) in this gene were identified in ASD probands in Lim et al., 2017; comparison with a background set of 84,448 privately inherited variants demonstrated that this gene harbored more PZMs than expected based on background rates (6/571 observed vs. 233/84,448 expected; hypergeometric P-value of 5.3E-03).

Krishnan Probability Score

Score 0.44728122810044

Ranking 13077/25841 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.
Sanders TADA Score

Score 0.94152817867146

Ranking 14966/18665 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).
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SFARI Gene Update

We are pleased to announce some changes to the ongoing curation of the data in SFARI Gene. In the context of a continued effort to develop the human gene module and its manually curated list of autism risk genes, we are modifying other aspects of the site to focus on the information that is of greatest interest to the research community. The version of SFARI Gene that has been developed until now will be frozen and will remain available as “SFARI Gene Archive”. Please see the announcement for more details.
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