Human Gene Module / Chromosome 3 / STAG1

STAG1stromal antigen 1

SFARI Gene Score
S
Syndromic Syndromic
Autism Reports / Total Reports
4 / 10
Rare Variants / Common Variants
23 / 0
Aliases
STAG1, SA1,  SCC3A
Associated Syndromes
-
Chromosome Band
3q22.3
Associated Disorders
ASD, EPS
Relevance to Autism

Phenotypic characterization of 17 individuals from 16 families with either deletions or point mutations affecting the STAG1 gene demonstrated that STAG1 mutations were responsible for a form of syndromic intellectual disability (Lehalle et al., 2017). In addition to frequently observed phenotypes such as epilepsy and dysmorphic facial features, seven of the 17 individuals described in this report presented with autistic features, with one individual formally diagnosed with autistic disorder.

Molecular Function

This gene is a member of the SCC3 family and encodes a component of cohesin, a multisubunit protein complex that provides sister chromatid cohesion along the length of a chromosome from DNA replication through prophase and prometaphase, after which it is dissociated in preparation for segregation during anaphase.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to STAG1 (10 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary STAG1 mutations cause a novel cohesinopathy characterised by unspecific syndromic intellectual disability Lehalle D , et al. (2017) No Autistic features, epilepsy/seizures
2 Support Integrative Analyses of De Novo Mutations Provide Deeper Biological Insights into Autism Spectrum Disorder Takata A , et al. (2018) Yes -
3 Support Increased diagnostic and new genes identification outcome using research reanalysis of singleton exome sequencing Bruel AL , et al. (2019) No -
4 Support A recurrent PJA1 variant in trigonocephaly and neurodevelopmental disorders Suzuki T et al. (2020) No -
5 Support - Di Muro E et al. (2021) No -
6 Support - Singh T et al. (2022) No -
7 Support - Krgovic D et al. (2022) Yes ID
8 Support - Zhou X et al. (2022) Yes -
9 Support - Spataro N et al. (2023) No -
10 Support - Mona Abdi et al. (2023) Yes ID
Rare Variants   (23)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
- - copy_number_loss De novo - Simplex 28119487 Lehalle D , et al. (2017)
- - copy_number_loss Unknown - Simplex 28119487 Lehalle D , et al. (2017)
- - copy_number_loss Familial - Multiplex 28119487 Lehalle D , et al. (2017)
- - copy_number_loss Unknown Not maternal - 28119487 Lehalle D , et al. (2017)
c.1117C>T p.Arg373Ter stop_gained De novo - - 36980980 Spataro N et al. (2023)
c.1433A>C p.His478Pro missense_variant De novo - - 31231135 Bruel AL , et al. (2019)
c.2672A>C p.Lys891Thr missense_variant Unknown - - 35813072 Krgovic D et al. (2022)
c.1118G>A p.Arg373Gln missense_variant De novo - - 28119487 Lehalle D , et al. (2017)
c.3580G>A p.Ala1194Thr missense_variant De novo - Simplex 32530565 Suzuki T et al. (2020)
c.2090G>T p.Arg697Leu missense_variant De novo - Simplex 29346770 Takata A , et al. (2018)
c.1118G>A p.Arg373Gln missense_variant De novo - Simplex 37805537 Mona Abdi et al. (2023)
c.641A>G p.Gln214Arg missense_variant De novo - Simplex 28119487 Lehalle D , et al. (2017)
c.646A>G p.Arg216Gly missense_variant De novo - Simplex 28119487 Lehalle D , et al. (2017)
c.659A>G p.His220Arg missense_variant De novo - Simplex 28119487 Lehalle D , et al. (2017)
c.997A>C p.Lys333Gln missense_variant De novo - Simplex 28119487 Lehalle D , et al. (2017)
c.1052T>G p.Leu351Trp missense_variant De novo - Simplex 28119487 Lehalle D , et al. (2017)
c.1155A>C p.Lys385Asn missense_variant De novo - Simplex 28119487 Lehalle D , et al. (2017)
c.2936A>G p.Lys979Arg missense_variant De novo - Simplex 28119487 Lehalle D , et al. (2017)
c.1891_1892del p.Asp631CysfsTer7 frameshift_variant De novo - - 35982159 Zhou X et al. (2022)
c.1458dup p.Ser487GlnfsTer33 frameshift_variant De novo - Simplex 28119487 Lehalle D , et al. (2017)
c.2769_2770del p.Ile924SerfsTer8 frameshift_variant De novo - Simplex 34440290 Di Muro E et al. (2021)
c.3568_3569insATG p.Met1190delinsAsnVal inframe_insertion De novo - Simplex 35982159 Zhou X et al. (2022)
c.1182_1183insTCGAT p.Arg395SerfsTer7 frameshift_variant De novo - Multiplex 28119487 Lehalle D , et al. (2017)
Common Variants  

No common variants reported.

SFARI Gene score
S

Syndromic

Phenotypic characterization of 17 individuals from 16 families with either deletions or point mutations affecting the STAG1 gene demonstrated that STAG1 mutations were responsible for a form of syndromic intellectual disability (Lehalle et al., 2017). In addition to frequently observed phenotypes such as epilepsy and dysmorphic facial features, seven of the 17 individuals described in this report presented with autistic features, with one individual formally diagnosed with autistic disorder.

Score Delta: Score remained at S

criteria met
See SFARI Gene'scoring criteria
S

Syndromic

See all Category S Genes

The syndromic category includes mutations that are associated with a substantial degree of increased risk and consistently linked to additional characteristics not required for an ASD diagnosis. If there is independent evidence implicating a gene in idiopathic ASD, it will be listed as "#S" (e.g., 2S, 3S, etc.). If there is no such independent evidence, the gene will be listed simply as "S."

7/1/2020
S
icon
S

Score remained at S

Description

Phenotypic characterization of 17 individuals from 16 families with either deletions or point mutations affecting the STAG1 gene demonstrated that STAG1 mutations were responsible for a form of syndromic intellectual disability (Lehalle et al., 2017). In addition to frequently observed phenotypes such as epilepsy and dysmorphic facial features, seven of the 17 individuals described in this report presented with autistic features, with one individual formally diagnosed with autistic disorder.

Reports Added
[A recurrent PJA1 variant in trigonocephaly and neurodevelopmental disorders2020]
10/1/2019
S
icon
S

Score remained at S

New Scoring Scheme
Description

Phenotypic characterization of 17 individuals from 16 families with either deletions or point mutations affecting the STAG1 gene demonstrated that STAG1 mutations were responsible for a form of syndromic intellectual disability (Lehalle et al., 2017). In addition to frequently observed phenotypes such as epilepsy and dysmorphic facial features, seven of the 17 individuals described in this report presented with autistic features, with one individual formally diagnosed with autistic disorder.

Reports Added
[New Scoring Scheme]
7/1/2019
S
icon
S

Score remained at S

Description

Phenotypic characterization of 17 individuals from 16 families with either deletions or point mutations affecting the STAG1 gene demonstrated that STAG1 mutations were responsible for a form of syndromic intellectual disability (Lehalle et al., 2017). In addition to frequently observed phenotypes such as epilepsy and dysmorphic facial features, seven of the 17 individuals described in this report presented with autistic features, with one individual formally diagnosed with autistic disorder.

Reports Added
[Increased diagnostic and new genes identification outcome using research reanalysis of singleton exome sequencing.2019]
Krishnan Probability Score

Score 0.52589287815804

Ranking 1612/25841 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 0.9999999100229

Ranking 194/18225 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 0.94535794532247

Ranking 16438/18665 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 0.32332336355278

Ranking 2385/20870 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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