Human Gene Module / Chromosome X / MAGEC3

MAGEC3MAGE family member C3

SFARI Gene Score
1
High Confidence Criteria 1.1
Autism Reports / Total Reports
6 / 6
Rare Variants / Common Variants
6 / 0
Aliases
-
Associated Syndromes
-
Chromosome Band
Xq27.2
Associated Disorders
-
Relevance to Autism

Application of a modified transmission disequilibrium test to 13,052 male ASD probands from the Simons Simplex Collection and the SPARK cohort and 2,295 male sibling controls in Wang et al., 2023 identified MAGEC3 as a gene displaying significant overtransmission of rare X-linked damaging variants to ASD probands versus male sibling controls (P = 2.10E-07, chromosome-X-wide Bonferroni corrected P = 0.00017); this gene also passed exome-wide significance (exome-wide Bonferroni corrected P = 0.0041). A study examining rare hemizygous knockouts in male ASD probands had previously identified the same MAGEC3 nonsense variant (p.Gln193Ter) in two separate male probands; this variant was not observed in female ASD probands or in either male or female controls in this study (Lim et al., 2013). Additional hemizygous variants in MAGEC3 have also been identified in male ASD probands from the AGRE cohort, including a frameshift variant identified in both ASD-affected brothers in a multiplex family (Chahrour et al., 2012; Cirnigliaro et al., 2023).

Molecular Function

This gene is a member of the MAGEC gene family. The members of this family are not expressed in normal tissues, except for testis, and are expressed in tumors of various histological types. The MAGEC genes are clustered on chromosome Xq26-q27.

External Links
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Reports related to MAGEC3 (6 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support Whole-exome sequencing and homozygosity analysis implicate depolarization-regulated neuronal genes in autism Chahrour MH , et al. (2012) Yes -
2 Support Rare complete knockouts in humans: population distribution and significant role in autism spectrum disorders Lim ET , et al. (2013) Yes -
3 Support - Cirnigliaro M et al. (2023) Yes -
4 Primary - Sheng Wang et al. (2023) Yes -
5 Support - Ashlesha Gogate et al. (2024) Yes -
6 Support - Vijay Gupta et al. (2024) Yes -
Rare Variants   (6)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.577C>T p.Gln193Ter stop_gained Unknown - Unknown 23352160 Lim ET , et al. (2013)
c.212C>A p.Ser71Ter stop_gained Familial Maternal Simplex 39769462 Vijay Gupta et al. (2024)
c.87T>A p.Tyr29Ter stop_gained Familial Maternal Multiplex 39632905 Ashlesha Gogate et al. (2024)
c.880C>G p.Leu294Val missense_variant Unknown - Extended multiplex 22511880 Chahrour MH , et al. (2012)
c.1168A>G p.Ser390Gly missense_variant Familial Maternal Multiplex 39632905 Ashlesha Gogate et al. (2024)
c.653_656dup p.Gly220HisfsTer13 frameshift_variant Familial Maternal Multiplex 37506195 Cirnigliaro M et al. (2023)
Common Variants  

No common variants reported.

SFARI Gene score
1

High Confidence

Score Delta: Score remained at 1

criteria met
See SFARI Gene'scoring criteria
1

High Confidence

See all Category 1 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.

4/1/2024
icon
1

Increased from to 1

Krishnan Probability Score

Score 0.49276186220942

Ranking 4416/25841 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 3.2490215491358E-8

Ranking 15939/18225 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 0.94590218811777

Ranking 16655/18665 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
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