Human Gene Module / Chromosome 1 / SAMD11

SAMD11sterile alpha motif domain containing 11

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
4 / 4
Rare Variants / Common Variants
10 / 0
Aliases
SAMD11, MRS
Associated Syndromes
-
Chromosome Band
1p36.33
Associated Disorders
-
Relevance to Autism

Linkage analysis and follow-up exome sequencing in seven large families with ASD identified a missense variant in the SAMD11 gene (rs200195897) that was transmitted to four affected individuals in one family (Chapman et al., 2015). Subsequent analysis of whole-genome sequencing data from individuals with ASD and family members in the MSSNG database replicated transmission of rs200195897 to four affected individuals in three additional families; this variant was also present in three singleton affected individuals and no unaffected individuals other than transmitting parents (Chapman et al., 2018).

Molecular Function

May play a role in photoreceptor development.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to SAMD11 (4 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary Whole exome sequencing in extended families with autism spectrum disorder implicates four candidate genes Chapman NH , et al. (2015) Yes -
2 Recent Recommendation Replication of a rare risk haplotype on 1p36.33 for autism spectrum disorder Chapman NH , et al. (2018) Yes -
3 Support - Zhou X et al. (2022) Yes -
4 Support - Cirnigliaro M et al. (2023) Yes -
Rare Variants   (10)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.683C>T p.Pro228Leu missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.1605A>T p.Pro535= synonymous_variant De novo - Simplex 35982159 Zhou X et al. (2022)
c.1890del p.Asp632ThrfsTer57 frameshift_variant De novo - - 35982159 Zhou X et al. (2022)
c.877C>G p.Pro293Ala missense_variant Unknown - Simplex 30276537 Chapman NH , et al. (2018)
c.877C>G p.Pro293Ala missense_variant Unknown - Multiplex 30276537 Chapman NH , et al. (2018)
c.2181+2T>C - splice_site_variant Familial Paternal Multiplex 37506195 Cirnigliaro M et al. (2023)
c.877C>G p.Pro293Ala missense_variant Familial Maternal Simplex 30276537 Chapman NH , et al. (2018)
c.877C>G p.Pro293Ala missense_variant Familial Paternal Simplex 30276537 Chapman NH , et al. (2018)
c.877C>G p.Pro293Ala missense_variant Familial Paternal Multiplex 30276537 Chapman NH , et al. (2018)
c.877C>G p.Pro293Ala missense_variant Familial - Extended multiplex 26204995 Chapman NH , et al. (2015)
Common Variants  

No common variants reported.

SFARI Gene score
2

Strong Candidate

Linkage analysis and follow-up exome sequencing in seven large families with ASD identified a missense variant in the SAMD11 gene (rs200195897) that was transmitted to four affected individuals in one family (Chapman et al., 2015). Subsequent analysis of whole-genome sequencing data from individuals with ASD and family members in the MSSNG database replicated transmission of rs200195897 to four affected individuals in three additional families; this variant was also present in three singleton affected individuals and no unaffected individuals other than transmitting parents (Chapman et al., 2018).

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

Linkage analysis and follow-up exome sequencing in seven large families with ASD identified a missense variant in the SAMD11 gene (rs200195897) that was transmitted to four affected individuals in one family (Chapman et al., 2015). Subsequent analysis of whole-genome sequencing data from individuals with ASD and family members in the MSSNG database replicated transmission of rs200195897 to four affected individuals in three additional families; this variant was also present in three singleton affected individuals and no unaffected individuals other than transmitting parents (Chapman et al., 2018).

10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

Linkage analysis and follow-up exome sequencing in seven large families with ASD identified a missense variant in the SAMD11 gene (rs200195897) that was transmitted to four affected individuals in one family (Chapman et al., 2015). Subsequent analysis of whole-genome sequencing data from individuals with ASD and family members in the MSSNG database replicated transmission of rs200195897 to four affected individuals in three additional families; this variant was also present in three singleton affected individuals and no unaffected individuals other than transmitting parents (Chapman et al., 2018).

Reports Added
[New Scoring Scheme]
10/1/2018
icon
4

Increased from to 4

Description

Linkage analysis and follow-up exome sequencing in seven large families with ASD identified a missense variant in the SAMD11 gene (rs200195897) that was transmitted to four affected individuals in one family (Chapman et al., 2015). Subsequent analysis of whole-genome sequencing data from individuals with ASD and family members in the MSSNG database replicated transmission of rs200195897 to four affected individuals in three additional families; this variant was also present in three singleton affected individuals and no unaffected individuals other than transmitting parents (Chapman et al., 2018).

Krishnan Probability Score

Score 0.45903780418098

Ranking 9606/25841 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 1.353811571292E-10

Ranking 16889/18225 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 0.69219023358897

Ranking 1109/18665 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
Zhang D Score

Score -0.34060269514222

Ranking 17723/20870 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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