Human Gene Module / Chromosome 3 / SATB1

SATB1SATB homeobox 1

SFARI Gene Score
1S
High Confidence, Syndromic Criteria 1.1, Syndromic
Autism Reports / Total Reports
2 / 4
Rare Variants / Common Variants
35 / 0
EAGLE Score
2.5
Limited Learn More
Aliases
-
Associated Syndromes
-
Chromosome Band
3p24.3
Associated Disorders
ASD, EPS
Genetic Category
Rare Single Gene Mutation, Syndromic
Relevance to Autism

Two de novo variants in the SATB1 gene (one protein-truncating, one missense) were identified in ASD probands from the Autism Sequencing Consortium, while three additional protein-truncating variants in this gene were observed in case samples from the Danish iPSYCH study (Satterstrom et al., 2020). TADA analysis of de novo variants from the Simons Simplex Collection and the Autism Sequencing Consortium and protein-truncating variants from iPSYCH in Satterstrom et al., 2020 identified SATB1 as a candidate gene with a false discovery rate (FDR) between 0.01 and 0.05 (0.01 < FDR 0.05).

Molecular Function

This gene encodes a matrix protein which binds nuclear matrix and scaffold-associating DNAs through a unique nuclear architecture. The protein recruits chromatin-remodeling factors in order to regulate chromatin structure and gene expression.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to SATB1 (4 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary Large-Scale Exome Sequencing Study Implicates Both Developmental and Functional Changes in the Neurobiology of Autism Satterstrom FK et al. (2020) Yes -
2 Support Excess of de novo variants in genes involved in chromatin remodelling in patients with marfanoid habitus and intellectual disability Chevarin M et al. (2020) No Marfanoid habitus
3 Recent recommendation - den Hoed J et al. (2021) No ASD or autistic features, stereotypy, epilepsy/sei
4 Support - Mahjani B et al. (2021) Yes -
Rare Variants   (35)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
- - copy_number_loss De novo - Simplex 33513338 den Hoed J et al. (2021)
c.41C>A p.Ser14Ter stop_gained Unknown - - 34615535 Mahjani B et al. (2021)
c.1228C>T p.Arg410Ter stop_gained De novo - - 33513338 den Hoed J et al. (2021)
- - copy_number_loss Familial Paternal Simplex 33513338 den Hoed J et al. (2021)
c.590T>G p.Leu197Arg missense_variant Unknown - - 34615535 Mahjani B et al. (2021)
c.1588G>A p.Glu530Lys missense_variant Unknown - - 34615535 Mahjani B et al. (2021)
c.2135C>T p.Ala712Val missense_variant Unknown - - 34615535 Mahjani B et al. (2021)
c.1588G>A p.Glu530Lys missense_variant De novo - - 33513338 den Hoed J et al. (2021)
c.2080C>T p.Gln694Ter stop_gained De novo - Simplex 33513338 den Hoed J et al. (2021)
c.967A>G p.Met323Val missense_variant De novo - Unknown 33513338 den Hoed J et al. (2021)
c.1219G>C p.Glu407Gln missense_variant De novo - Simplex 33513338 den Hoed J et al. (2021)
c.1237G>A p.Glu413Lys missense_variant De novo - Simplex 33513338 den Hoed J et al. (2021)
c.1259A>G p.Gln420Arg missense_variant De novo - Simplex 33513338 den Hoed J et al. (2021)
c.1588G>A p.Glu530Lys missense_variant De novo - Simplex 33513338 den Hoed J et al. (2021)
c.1588G>C p.Glu530Gln missense_variant De novo - Simplex 33513338 den Hoed J et al. (2021)
c.1589A>G p.Glu530Gly missense_variant De novo - Simplex 33513338 den Hoed J et al. (2021)
c.1639G>A p.Glu547Lys missense_variant De novo - Simplex 33513338 den Hoed J et al. (2021)
c.1730A>G p.His577Arg missense_variant De novo - Simplex 33513338 den Hoed J et al. (2021)
c.2044C>G p.Leu682Val missense_variant De novo - Simplex 33513338 den Hoed J et al. (2021)
c.1588G>A p.Glu530Lys missense_variant De novo - Unknown 33513338 den Hoed J et al. (2021)
c.1856A>G p.Gln619Arg missense_variant De novo - Unknown 33513338 den Hoed J et al. (2021)
c.1574A>G p.Gln525Arg missense_variant Unknown - Multiplex 33513338 den Hoed J et al. (2021)
c.1588G>A p.Glu530Lys missense_variant De novo - Multiplex 33513338 den Hoed J et al. (2021)
c.1782del p.Gln594HisfsTer113 frameshift_variant De novo - - 33513338 den Hoed J et al. (2021)
c.1576G>A p.Gly526Arg splice_site_variant De novo - Simplex 33513338 den Hoed J et al. (2021)
c.1205A>G p.Gln402Arg missense_variant De novo - Simplex 31981491 Satterstrom FK et al. (2020)
c.1004_1005del p.Arg335ThrfsTer20 frameshift_variant De novo - - 33513338 den Hoed J et al. (2021)
c.542C>T p.Pro181Leu missense_variant Familial Maternal Multiplex 33513338 den Hoed J et al. (2021)
c.1220A>G p.Glu407Gly missense_variant Familial Maternal Multiplex 33513338 den Hoed J et al. (2021)
c.1205A>G p.Gln402Arg missense_variant Unknown Not maternal Simplex 33513338 den Hoed J et al. (2021)
c.607_608del p.Ser203PhefsTer49 frameshift_variant De novo - Simplex 33513338 den Hoed J et al. (2021)
c.1460del p.Pro487GlnfsTer6 frameshift_variant De novo - Simplex 31981491 Satterstrom FK et al. (2020)
c.1004_1005del p.Arg335ThrfsTer20 frameshift_variant De novo - Unknown 32277047 Chevarin M et al. (2020)
c.2111del p.Gly704AlafsTer3 frameshift_variant Familial Maternal Simplex 33513338 den Hoed J et al. (2021)
c.1936_1937del p.Arg646AlafsTer25 frameshift_variant Familial Paternal Simplex 33513338 den Hoed J et al. (2021)
Common Variants  

No common variants reported.

SFARI Gene score
1S

High Confidence, Syndromic

Score Delta: Score remained at 1S

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.

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."

4/1/2022
icon
1

Increased from to 1

Krishnan Probability Score

Score 0.56639835894169

Ranking 1214/25841 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 0.85661387202016

Ranking 3572/18225 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 0.93745632410578

Ranking 13531/18665 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 0.3579146485949

Ranking 1918/20870 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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