Human Gene Module / Chromosome 2 / SATB2

SATB2SATB homeobox 2

Score
3S
Suggestive Evidence, Syndromic Criteria 3.1, Syndromic
Autism Reports / Total Reports
8 / 28
Rare Variants / Common Variants
121 / 1
Aliases
SATB2, FLJ21474,  FLJ32076,  KIAA1034,  MGC119474,  MGC119477
Associated Syndromes
SATB2-associated syndrome, Glass syndrome
Genetic Category
Rare Single Gene Mutation, Syndromic, Genetic Association
Chromosome Band
2q33.1
Associated Disorders
DD/NDD, ASD, EP, EPS, ID
Relevance to Autism

This gene was identified as an ASD candidate gene following the identification of a balanced chromosomal abnormality (BCA) leading to gene disruption in an ASD case (Talkowski et al., 2012). This BCA-disrupted gene was also individually implicated by case-control CNV burden or by a minimum of 3 CNVs in neuodevelopmental disorder (NDD) cases with none in controls in a follow-up study in the same report.

Molecular Function

This gene encodes a DNA binding protein that specifically binds nuclear matrix attachment regions. The encoded protein is involved in transcription regulation and chromatin remodeling. Defects in this gene are associated with isolated cleft palate and mental retardation.

Reports related to SATB2 (28 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support Heterozygous nonsense mutation SATB2 associated with cleft palate, osteoporosis, and cognitive defects. Leoyklang P , et al. (2007) No Epilepsy
2 Primary Sequencing chromosomal abnormalities reveals neurodevelopmental loci that confer risk across diagnostic boundaries. Talkowski ME , et al. (2012) Yes -
3 Support Range of genetic mutations associated with severe non-syndromic sporadic intellectual disability: an exome sequencing study. Rauch A , et al. (2012) No Epilepsy, ASD
4 Support Detection of clinically relevant genetic variants in autism spectrum disorder by whole-genome sequencing. Jiang YH , et al. (2013) Yes -
5 Support Further delineation of the SATB2 phenotype. Dcker D , et al. (2013) No -
6 Support Refining analyses of copy number variation identifies specific genes associated with developmental delay. Coe BP , et al. (2014) Yes -
7 Support Large-scale discovery of novel genetic causes of developmental disorders. Deciphering Developmental Disorders Study (2014) No Epilpesy/seizures, delayed or absent speech
8 Support Further supporting evidence for the SATB2-associated syndrome found through whole exome sequencing. Zarate YA , et al. (2015) No DD, ID
9 Recent Recommendation A molecular model for neurodevelopmental disorders. Gigek CO , et al. (2015) No -
10 Support Meta-analysis of 2,104 trios provides support for 10 new genes for intellectual disability. Lelieveld SH , et al. (2016) No -
11 Recent Recommendation SATB2-associated syndrome: Mechanisms, phenotype, and practical recommendations. Zarate YA and Fish JL (2016) No -
12 Support The genomic landscape of balanced cytogenetic abnormalities associated with human congenital anomalies. Redin C , et al. (2016) Yes -
13 Support Clinical exome sequencing: results from 2819 samples reflecting 1000 families. Trujillano D , et al. (2016) No ASD, DD, epilepsy/seizures
14 Support Genotype and phenotype in 12 additional individuals with SATB2-associated syndrome. Zarate YA , et al. (2017) No DD, ID
15 Support Clinical and molecular consequences of disease-associated de novo mutations in SATB2. Bengani H , et al. (2017) No -
16 Support A clinical utility study of exome sequencing versus conventional genetic testing in pediatric neurology. Vissers LE , et al. (2017) No -
17 Support Genomic diagnosis for children with intellectual disability and/or developmental delay. Bowling KM , et al. (2017) No -
18 Support Hotspots of missense mutation identify neurodevelopmental disorder genes and functional domains. Geisheker MR , et al. (2017) Yes -
19 Support Using medical exome sequencing to identify the causes of neurodevelopmental disorders: experience of two clinical units and 216 patients. Chrot E , et al. (2017) No -
20 Recent Recommendation Natural history and genotype-phenotype correlations in 72 individuals with SATB2-associated syndrome. Zarate YA , et al. (2018) No DD
21 Positive Association Common schizophrenia alleles are enriched in mutation-intolerant genes and in regions under strong background selection. Pardias AF , et al. (2018) No -
22 Support Genes regulated by SATB2 during neurodevelopment contribute to schizophrenia and educational attainment. Whitton L , et al. (2018) No -
23 Support Genome sequencing identifies multiple deleterious variants in autism patients with more severe phenotypes. Guo H , et al. (2018) Yes -
24 Support Whole genome paired-end sequencing elucidates functional and phenotypic consequences of balanced chromosomal rearrangement in patients with develop... Schluth-Bolard C , et al. (2019) No -
25 Support The combination of whole-exome sequencing and copy number variation sequencing enables the diagnosis of rare neurological disorders. Jiao Q , et al. (2019) No -
26 Recent Recommendation Mutation update for the SATB2 gene. Zarate YA , et al. (2019) No Autistic behavior
27 Support Characterization of intellectual disability and autism comorbidity through gene panel sequencing. Aspromonte MC , et al. (2019) Yes -
28 Support Exome sequencing of 457 autism families recruited online provides evidence for autism risk genes. Feliciano P , et al. (2019) Yes -
Rare Variants   (121)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
- - inversion De novo NA - 27841880 Redin C , et al. (2016)
- - translocation De novo NA - 27841880 Redin C , et al. (2016)
- - copy_number_loss Unknown - - 29436146 Zarate YA , et al. (2018)
- - copy_number_loss Unknown - - 31021519 Zarate YA , et al. (2019)
- - copy_number_loss De novo NA - 31021519 Zarate YA , et al. (2019)
- - copy_number_gain - - Multiplex 29436146 Zarate YA , et al. (2018)
- - translocation De novo NA - 22521361 Talkowski ME , et al. (2012)
- - frameshift_variant De novo NA - 31021519 Zarate YA , et al. (2019)
c.-313C>T - stop_gained De novo NA - 29436146 Zarate YA , et al. (2018)
c.-561T>G - missense_variant Unknown - - 31021519 Zarate YA , et al. (2019)
c.-2del - frameshift_variant De novo NA - 28139846 Zarate YA , et al. (2017)
c.-342del - splice_site_variant Unknown - - 31021519 Zarate YA , et al. (2019)
c.347-16019C>T - missense_variant De novo NA - 30945278 Jiao Q , et al. (2019)
- - complex_structural_alteration De novo NA - 27841880 Redin C , et al. (2016)
c.-336del - frameshift_variant De novo NA - 28139846 Zarate YA , et al. (2017)
c.-418del - frameshift_variant De novo NA - 28139846 Zarate YA , et al. (2017)
c.-484del - frameshift_variant De novo NA - 31021519 Zarate YA , et al. (2019)
c.715C>T p.Arg239Ter stop_gained Unknown - - 29436146 Zarate YA , et al. (2018)
c.715C>T p.Arg239Ter stop_gained Unknown - - 31021519 Zarate YA , et al. (2019)
c.868C>T p.Gln290Ter stop_gained Unknown - - 31021519 Zarate YA , et al. (2019)
c.124G>T p.Gly42Ter stop_gained De novo NA - 28139846 Zarate YA , et al. (2017)
c.1375C>T p.Arg459Ter stop_gained Unknown - - 29436146 Zarate YA , et al. (2018)
c.1756C>T p.Gln586Ter stop_gained Unknown - - 31021519 Zarate YA , et al. (2019)
c.-10_-9del - frameshift_variant De novo NA - 29436146 Zarate YA , et al. (2018)
c.847C>T p.Arg283Ter stop_gained De novo NA - 28139846 Zarate YA , et al. (2017)
c.390T>A p.Tyr130Ter stop_gained De novo NA - 28151491 Bengani H , et al. (2017)
c.346G>T p.Gly116Ter stop_gained De novo NA - 29436146 Zarate YA , et al. (2018)
c.715C>T p.Arg239Ter stop_gained De novo NA - 31021519 Zarate YA , et al. (2019)
c.847C>T p.Arg283Ter stop_gained De novo NA - 31021519 Zarate YA , et al. (2019)
c.868C>T p.Gln290Ter stop_gained De novo NA - 31021519 Zarate YA , et al. (2019)
c.988C>T p.Gln330Ter stop_gained De novo NA - 31021519 Zarate YA , et al. (2019)
c.997C>T p.Gln333Ter stop_gained De novo NA - 31021519 Zarate YA , et al. (2019)
c.347-15097C>T - missense_variant De novo NA - 31021519 Zarate YA , et al. (2019)
c.347-15107T>G - missense_variant De novo NA - 31021519 Zarate YA , et al. (2019)
c.347-15120A>G - missense_variant De novo NA - 31021519 Zarate YA , et al. (2019)
c.347-14931del - frameshift_variant Unknown - - 28139846 Zarate YA , et al. (2017)
c.347-15067dup - frameshift_variant Unknown - - 29436146 Zarate YA , et al. (2018)
c.347-15004del - frameshift_variant Unknown - - 31021519 Zarate YA , et al. (2019)
c.1174-2A>G - splice_site_variant De novo NA - 29436146 Zarate YA , et al. (2018)
c.1255C>T p.Gln419Ter stop_gained De novo NA - 28139846 Zarate YA , et al. (2017)
c.1285C>T p.Arg429Ter stop_gained De novo NA - 28151491 Bengani H , et al. (2017)
c.2074G>T p.Glu692Ter stop_gained De novo NA - 28151491 Bengani H , et al. (2017)
c.1285C>T p.Arg429Ter stop_gained De novo NA - 29436146 Zarate YA , et al. (2018)
c.1495A>T p.Lys499Ter stop_gained De novo NA - 29436146 Zarate YA , et al. (2018)
c.1135C>T p.Gln379Ter stop_gained De novo NA - 31021519 Zarate YA , et al. (2019)
c.1285C>T p.Arg429Ter stop_gained De novo NA - 31021519 Zarate YA , et al. (2019)
c.1375C>T p.Arg459Ter stop_gained De novo NA - 31021519 Zarate YA , et al. (2019)
c.688A>T p.Lys230Ter stop_gained De novo NA - 28333917 Vissers LE , et al. (2017)
- - copy_number_loss 1 de novo, 12 unknown - Unknown 25217958 Coe BP , et al. (2014)
c.347-14632del - frameshift_variant De novo NA - 29436146 Zarate YA , et al. (2018)
c.347-15146del - frameshift_variant De novo NA - 29436146 Zarate YA , et al. (2018)
c.-573_-555del - frameshift_variant De novo NA - 31021519 Zarate YA , et al. (2019)
c.347-15019del - frameshift_variant De novo NA - 31021519 Zarate YA , et al. (2019)
c.347-15163del - frameshift_variant De novo NA - 31021519 Zarate YA , et al. (2019)
c.347-15988del - frameshift_variant De novo NA - 31021519 Zarate YA , et al. (2019)
c.1495A>T p.Lys499Ter stop_gained De novo NA - 28554332 Bowling KM , et al. (2017)
c.715C>T p.Arg239Ter stop_gained De novo NA - 17377962 Leoyklang P , et al. (2007)
c.688A>T p.Lys230Ter stop_gained De novo NA - 27479843 Lelieveld SH , et al. (2016)
c.185T>A p.Val62Asp missense_variant De novo NA - 29436146 Zarate YA , et al. (2018)
c.287T>G p.Leu96Arg missense_variant De novo NA - 29436146 Zarate YA , et al. (2018)
c.285G>T p.Gln95His missense_variant De novo NA - 31021519 Zarate YA , et al. (2019)
c.1196G>A p.Arg399His missense_variant Unknown - - 31021519 Zarate YA , et al. (2019)
c.1286G>A p.Arg429Gln missense_variant Unknown - - 31021519 Zarate YA , et al. (2019)
c.715C>T p.Arg239Ter stop_gained De novo NA - 31209962 Aspromonte MC , et al. (2019)
c.715C>T p.Arg239Ter stop_gained De novo NA Simplex 24301056 Dcker D , et al. (2013)
c.392T>A p.Val131Glu missense_variant De novo NA - 29436146 Zarate YA , et al. (2018)
c.760C>T p.His254Tyr missense_variant De novo NA - 31021519 Zarate YA , et al. (2019)
c.1286G>A p.Arg429Gln missense_variant De novo NA - 28139846 Zarate YA , et al. (2017)
c.1964C>T p.Pro655Leu missense_variant De novo NA - 28139846 Zarate YA , et al. (2017)
c.1157C>T p.Ala386Val missense_variant De novo NA - 28151491 Bengani H , et al. (2017)
c.1165C>T p.Arg389Cys missense_variant De novo NA - 28151491 Bengani H , et al. (2017)
c.1181T>C p.Leu394Ser missense_variant De novo NA - 28151491 Bengani H , et al. (2017)
c.1696G>A p.Glu566Lys missense_variant De novo NA - 28151491 Bengani H , et al. (2017)
c.1165C>T p.Arg389Cys missense_variant De novo NA - 29436146 Zarate YA , et al. (2018)
c.1196G>A p.Arg399His missense_variant De novo NA - 29436146 Zarate YA , et al. (2018)
c.1286G>A p.Arg429Gln missense_variant De novo NA - 29436146 Zarate YA , et al. (2018)
c.1136A>C p.Gln379Pro missense_variant De novo NA - 31021519 Zarate YA , et al. (2019)
c.1165C>T p.Arg389Cys missense_variant De novo NA - 31021519 Zarate YA , et al. (2019)
c.1166G>T p.Arg389Leu missense_variant De novo NA - 31021519 Zarate YA , et al. (2019)
c.1169C>T p.Thr390Ile missense_variant De novo NA - 31021519 Zarate YA , et al. (2019)
c.1175G>A p.Gly392Glu missense_variant De novo NA - 31021519 Zarate YA , et al. (2019)
c.1196G>A p.Arg399His missense_variant De novo NA - 31021519 Zarate YA , et al. (2019)
c.1196G>T p.Arg399Leu missense_variant De novo NA - 31021519 Zarate YA , et al. (2019)
c.1253T>G p.Met418Arg missense_variant De novo NA - 31021519 Zarate YA , et al. (2019)
c.1903G>T p.Asp635Tyr missense_variant De novo NA - 31021519 Zarate YA , et al. (2019)
c.346+2T>G - splice_site_variant De novo NA Simplex 25885067 Zarate YA , et al. (2015)
- - complex_structural_alteration De novo NA - 30923172 Schluth-Bolard C , et al. (2019)
c.748C>T p.Gln250Ter stop_gained De novo NA Simplex 25885067 Zarate YA , et al. (2015)
c.847C>T p.Arg283Ter stop_gained De novo NA Simplex 25885067 Zarate YA , et al. (2015)
c.1109A>T p.Asp370Val missense_variant Unknown - - 28628100 Geisheker MR , et al. (2017)
c.1214G>A p.Arg405Gln missense_variant Unknown - - 28628100 Geisheker MR , et al. (2017)
c.346G>C p.Gly116Arg splice_site_variant De novo NA - 28139846 Zarate YA , et al. (2017)
c.1171C>T p.Gln391Ter stop_gained De novo NA Simplex 25885067 Zarate YA , et al. (2015)
c.1298A>C p.Tyr433Ser missense_variant De novo NA - 31452935 Feliciano P , et al. (2019)
c.1861A>T p.Ile621Phe missense_variant De novo NA Simplex 30504930 Guo H , et al. (2018)
c.15del p.Ser5ArgfsTer25 frameshift_variant Unknown - - 31021519 Zarate YA , et al. (2019)
c.1184C>T p.Ser395Phe missense_variant De novo NA - 28628100 Geisheker MR , et al. (2017)
c.1142T>G p.Val381Gly missense_variant De novo NA Simplex 23020937 Rauch A , et al. (2012)
c.1627del p.Arg543AlafsTer3 frameshift_variant De novo NA - 28708303 Chrot E , et al. (2017)
c.347-14689_347-14688del - frameshift_variant De novo NA - 29436146 Zarate YA , et al. (2018)
c.347-15118G>A - splice_site_variant De novo NA Simplex 27848944 Trujillano D , et al. (2016)
c.583dup p.Cys195LeufsTer14 frameshift_variant De novo NA - 28139846 Zarate YA , et al. (2017)
c.583dup p.Cys195LeufsTer14 frameshift_variant De novo NA - 28151491 Bengani H , et al. (2017)
c.347-15873_347-15872insTGGT - frameshift_variant Unknown - - 29436146 Zarate YA , et al. (2018)
c.1203dup p.Glu402ArgfsTer35 frameshift_variant De novo NA - 28151491 Bengani H , et al. (2017)
c.1575del p.Asn526ThrfsTer20 frameshift_variant De novo NA - 28151491 Bengani H , et al. (2017)
c.1646del p.Gln549ArgfsTer75 frameshift_variant De novo NA - 28151491 Bengani H , et al. (2017)
c.1131_1132del p.Ser378ProfsTer18 frameshift_variant Unknown - - 29436146 Zarate YA , et al. (2018)
c.1963C>T p.Pro655Ser missense_variant Familial Paternal Simplex 23849776 Jiang YH , et al. (2013)
c.347-15150_347-15149insCAAGCCT - frameshift_variant De novo NA - 31021519 Zarate YA , et al. (2019)
c.1131_1132del p.Ser378ProfsTer18 frameshift_variant Unknown - - 28554332 Bowling KM , et al. (2017)
c.315_316insAC p.Tyr106ThrfsTer13 frameshift_variant De novo NA - 31021519 Zarate YA , et al. (2019)
c.1945dup p.Ser649PhefsTer40 frameshift_variant De novo NA Simplex 25885067 Zarate YA , et al. (2015)
c.598-2A>G - splice_site_variant De novo (gonadal mosaicism) - Multiplex 28151491 Bengani H , et al. (2017)
c.1173+2T>C - splice_site_variant De novo NA Unknown 25533962 Deciphering Developmental Disorders Study (2014)
c.1375C>T p.Arg459Ter stop_gained De novo NA Simplex 25533962 Deciphering Developmental Disorders Study (2014)
c.1166G>T p.Arg389Leu missense_variant De novo NA Simplex 25533962 Deciphering Developmental Disorders Study (2014)
c.1196G>A p.Arg399His missense_variant De novo NA Simplex 25533962 Deciphering Developmental Disorders Study (2014)
c.1204G>A p.Glu402Lys missense_variant De novo NA Simplex 25533962 Deciphering Developmental Disorders Study (2014)
c.1543G>A p.Gly515Ser missense_variant De novo NA Simplex 25533962 Deciphering Developmental Disorders Study (2014)
c.594_595del p.Gln199GlufsTer9 frameshift_variant De novo NA Simplex 25533962 Deciphering Developmental Disorders Study (2014)
Common Variants   (1)
Status Allele Change Residue Change Variant Type Inheritance Pattern Paternal Transmission Family Type PubMed ID Author, Year
A>G - intergenic_variant - - - 29483656 Pardias AF , et al. (2018)
SFARI Gene score
3S

Suggestive Evidence, Syndromic

This gene was identified as an ASD candidate gene following the identification of a balanced chromosomal abnormality (BCA) leading to gene disruption in an ASD case (PMID 22521361). This report also showed significant burden (P=0.001) of SATB2 CNVs in individuals with neurodevelopmental disorder (NDD; ~25% of cases with ASD). Delineation of the phenotypes associated with SATB2-associated syndrome, also referred to as Glass syndrome (OMIM 612313), determined that autistic/repetitive behaviors were observed in 7 out of 35 cases (20%) described in Zarate and Fish, 2016, whereas 4/12 (33%) additional cases in Zarate et al., 2017 were reported to present with autistic tendencies. Phenotypic characterization of 72 individuals enrolled through the SAS clinical registry, 46 of whom had not been previously published, in Zarate et al., 2018 reported that while behavioral abnormalities were observed in over 80% of cases for whom such data was available, autistic behaviors were observed in approximately 20% of individuals. A review of 158 patients with SATB2-associated syndrome, including 57 previously unreported patients, in Zarate et al., 2019 found that 20% (29/145) displayed autistic behavior.

Score Delta: Score remained at 4S

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.

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."

10/1/2019
4S
icon
3S

Decreased from 4S to 3S

New Scoring Scheme
Description

This gene was identified as an ASD candidate gene following the identification of a balanced chromosomal abnormality (BCA) leading to gene disruption in an ASD case (PMID 22521361). This report also showed significant burden (P=0.001) of SATB2 CNVs in individuals with neurodevelopmental disorder (NDD; ~25% of cases with ASD). Delineation of the phenotypes associated with SATB2-associated syndrome, also referred to as Glass syndrome (OMIM 612313), determined that autistic/repetitive behaviors were observed in 7 out of 35 cases (20%) described in Zarate and Fish, 2016, whereas 4/12 (33%) additional cases in Zarate et al., 2017 were reported to present with autistic tendencies. Phenotypic characterization of 72 individuals enrolled through the SAS clinical registry, 46 of whom had not been previously published, in Zarate et al., 2018 reported that while behavioral abnormalities were observed in over 80% of cases for whom such data was available, autistic behaviors were observed in approximately 20% of individuals. A review of 158 patients with SATB2-associated syndrome, including 57 previously unreported patients, in Zarate et al., 2019 found that 20% (29/145) displayed autistic behavior.

7/1/2019
4S
icon
4S

Decreased from 4S to 4S

Description

This gene was identified as an ASD candidate gene following the identification of a balanced chromosomal abnormality (BCA) leading to gene disruption in an ASD case (PMID 22521361). This report also showed significant burden (P=0.001) of SATB2 CNVs in individuals with neurodevelopmental disorder (NDD; ~25% of cases with ASD). Delineation of the phenotypes associated with SATB2-associated syndrome, also referred to as Glass syndrome (OMIM 612313), determined that autistic/repetitive behaviors were observed in 7 out of 35 cases (20%) described in Zarate and Fish, 2016, whereas 4/12 (33%) additional cases in Zarate et al., 2017 were reported to present with autistic tendencies. Phenotypic characterization of 72 individuals enrolled through the SAS clinical registry, 46 of whom had not been previously published, in Zarate et al., 2018 reported that while behavioral abnormalities were observed in over 80% of cases for whom such data was available, autistic behaviors were observed in approximately 20% of individuals. A review of 158 patients with SATB2-associated syndrome, including 57 previously unreported patients, in Zarate et al., 2019 found that 20% (29/145) displayed autistic behavior.

4/1/2019
4S
icon
4S

Decreased from 4S to 4S

Description

This gene was identified as an ASD candidate gene following the identification of a balanced chromosomal abnormality (BCA) leading to gene disruption in an ASD case (PMID 22521361). This report also showed significant burden (P=0.001) of SATB2 CNVs in individuals with neurodevelopmental disorder (NDD; ~25% of cases with ASD). Delineation of the phenotypes associated with SATB2-associated syndrome, also referred to as Glass syndrome (OMIM 612313), determined that autistic/repetitive behaviors were observed in 7 out of 35 cases (20%) described in Zarate and Fish, 2016, whereas 4/12 (33%) additional cases in Zarate et al., 2017 were reported to present with autistic tendencies. Phenotypic characterization of 72 individuals enrolled through the SAS clinical registry, 46 of whom had not been previously published, in Zarate et al., 2018 reported that while behavioral abnormalities were observed in over 80% of cases for whom such data was available, autistic behaviors were observed in approximately 20% of individuals.

10/1/2018
4S
icon
4S

Decreased from 4S to 4S

Description

This gene was identified as an ASD candidate gene following the identification of a balanced chromosomal abnormality (BCA) leading to gene disruption in an ASD case (PMID 22521361). This report also showed significant burden (P=0.001) of SATB2 CNVs in individuals with neurodevelopmental disorder (NDD; ~25% of cases with ASD). Delineation of the phenotypes associated with SATB2-associated syndrome, also referred to as Glass syndrome (OMIM 612313), determined that autistic/repetitive behaviors were observed in 7 out of 35 cases (20%) described in Zarate and Fish, 2016, whereas 4/12 (33%) additional cases in Zarate et al., 2017 were reported to present with autistic tendencies. Phenotypic characterization of 72 individuals enrolled through the SAS clinical registry, 46 of whom had not been previously published, in Zarate et al., 2018 reported that while behavioral abnormalities were observed in over 80% of cases for whom such data was available, autistic behaviors were observed in approximately 20% of individuals.

7/1/2018
4.3 + S
icon
4S

Decreased from 4.3 + S to 4S

Description

This gene was identified as an ASD candidate gene following the identification of a balanced chromosomal abnormality (BCA) leading to gene disruption in an ASD case (PMID 22521361). This report also showed significant burden (P=0.001) of SATB2 CNVs in individuals with neurodevelopmental disorder (NDD; ~25% of cases with ASD). Delineation of the phenotypes associated with SATB2-associated syndrome, also referred to as Glass syndrome (OMIM 612313), determined that autistic/repetitive behaviors were observed in 7 out of 35 cases (20%) described in Zarate and Fish, 2016, whereas 4/12 (33%) additional cases in Zarate et al., 2017 were reported to present with autistic tendencies. Phenotypic characterization of 72 individuals enrolled through the SAS clinical registry, 46 of whom had not been previously published, in Zarate et al., 2018 reported that while behavioral abnormalities were observed in over 80% of cases for whom such data was available, autistic behaviors were observed in approximately 20% of individuals.

7/1/2017
4S
icon
4S

Decreased from 4S to 4S

Description

This gene was identified as an ASD candidate gene following the identification of a balanced chromosomal abnormality (BCA) leading to gene disruption in an ASD case (PMID 22521361). This report also showed significant burden (P=0.001) of SATB2 CNVs in individuals with neurodevelopmental disorder (NDD; ~25% of cases with ASD). Delineation of the phenotypes associated with SATB2-associated syndrome, also referred to as Glass syndrome (OMIM 612313), determined that autistic/repetitive behaviors were observed in 7 out of 35 cases (20%) described in Zarate and Fish, 2016, whereas 4/12 (33%) additional cases in Zarate et al., 2017 were reported to present with autistic tendencies.

4/1/2017
4S
icon
4S

Decreased from 4S to 4S

Description

This gene was identified as an ASD candidate gene following the identification of a balanced chromosomal abnormality (BCA) leading to gene disruption in an ASD case (PMID 22521361). This report also showed significant burden (P=0.001) of SATB2 CNVs in individuals with neurodevelopmental disorder (NDD; ~25% of cases with ASD). Delineation of the phenotypes associated with SATB2-associated syndrome, also referred to as Glass syndrome (OMIM 612313), determined that autistic/repetitive behaviors were observed in 7 out of 35 cases (20%) described in Zarate and Fish, 2016, whereas 4/12 (33%) additional cases in Zarate et al., 2017 were reported to present with autistic tendencies.

Reports Added
[Sequencing chromosomal abnormalities reveals neurodevelopmental loci that confer risk across diagnostic boundaries.2012] [Detection of clinically relevant genetic variants in autism spectrum disorder by whole-genome sequencing.2013] [Refining analyses of copy number variation identifies specific genes associated with developmental delay.2014] [Further delineation of the SATB2 phenotype.2013] [Large-scale discovery of novel genetic causes of developmental disorders.2014] [Heterozygous nonsense mutation SATB2 associated with cleft palate, osteoporosis, and cognitive defects.2007] [Range of genetic mutations associated with severe non-syndromic sporadic intellectual disability: an exome sequencing study.2012] [Further supporting evidence for the SATB2-associated syndrome found through whole exome sequencing.2015] [A molecular model for neurodevelopmental disorders.2015] [Meta-analysis of 2,104 trios provides support for 10 new genes for intellectual disability.2016] [SATB2-associated syndrome: Mechanisms, phenotype, and practical recommendations.2016] [Clinical exome sequencing: results from 2819 samples reflecting 1000 families.2016] [The genomic landscape of balanced cytogenetic abnormalities associated with human congenital anomalies.2016] [Genotype and phenotype in 12 additional individuals with SATB2-associated syndrome.2017] [Clinical and molecular consequences of disease-associated de novo mutations in SATB2.2017] [A clinical utility study of exome sequencing versus conventional genetic testing in pediatric neurology.2017] [Genomic diagnosis for children with intellectual disability and/or developmental delay.2017]
1/1/2017
4S
icon
4S

Decreased from 4S to 4S

Description

This gene was identified as an ASD candidate gene following the identification of a balanced chromosomal abnormality (BCA) leading to gene disruption in an ASD case (PMID 22521361). This report also showed significant burden (P=0.001) of SATB2 CNVs in individuals with neurodevelopmental disorder (NDD; ~25% of cases with ASD). Delineation of the phenotypes associated with SATB2-associated syndrome, also referred to as Glass syndrome (OMIM 612313), determined that autistic/repetitive behaviors were observed in 7 out of 35 cases (20%) described in Zarate and Fish, 2016, whereas 4/12 (33%) additional cases in Zarate et al., 2017 were reported to present with autistic tendencies.

10/1/2016
4
icon
4S

Decreased from 4 to 4S

Description

This gene was identified as an ASD candidate gene following the identification of a balanced chromosomal abnormality (BCA) leading to gene disruption in an ASD case (PMID 22521361). This report also showed significant burden (P=0.001) of SATB2 CNVs in individuals with neurodevelopmental disorder (NDD; ~25% of cases with ASD). Delineation of the phenotypes associated with SATB2-associated syndrome, also referred to as Glass syndrome (OMIM 612313), determined that autistic/repetitive behaviors were observed in 7 out of 35 cases (20%) described in Zarate and Fish, 2016.

7/1/2016
4
icon
4

Decreased from 4 to 4

Description

This gene was identified as an ASD candidate gene following the identification of a balanced chromosomal abnormality (BCA) leading to gene disruption in an ASD case (PMID 22521361). This report also showed significant burden (P=0.001) of SATB2 CNVs in individuals with neurodevelopmental disorder (NDD; ~25% of cases with ASD).

4/1/2015
4
icon
4

Decreased from 4 to 4

Description

This gene was identified as an ASD candidate gene following the identification of a balanced chromosomal abnormality (BCA) leading to gene disruption in an ASD case (PMID 22521361). This report also showed significant burden (P=0.001) of SATB2 CNVs in individuals with neurodevelopmental disorder (NDD; ~25% of cases with ASD).

1/1/2015
4
icon
4

Decreased from 4 to 4

Description

This gene was identified as an ASD candidate gene following the identification of a balanced chromosomal abnormality (BCA) leading to gene disruption in an ASD case (PMID 22521361). This report also showed significant burden (P=0.001) of SATB2 CNVs in individuals with neurodevelopmental disorder (NDD; ~25% of cases with ASD).

10/1/2014
4
icon
4

Decreased from 4 to 4

Description

This gene was identified as an ASD candidate gene following the identification of a balanced chromosomal abnormality (BCA) leading to gene disruption in an ASD case (PMID 22521361). This report also showed significant burden (P=0.001) of SATB2 CNVs in individuals with neurodevelopmental disorder (NDD; ~25% of cases with ASD).

7/1/2014
No data
icon
4

Increased from No data to 4

Description

This gene was identified as an ASD candidate gene following the identification of a balanced chromosomal abnormality (BCA) leading to gene disruption in an ASD case (PMID 22521361). This report also showed significant burden (P=0.001) of SATB2 CNVs in individuals with neurodevelopmental disorder (NDD; ~25% of cases with ASD).

4/1/2014
No data
icon
4

Increased from No data to 4

Description

This gene was identified as an ASD candidate gene following the identification of a balanced chromosomal abnormality (BCA) leading to gene disruption in an ASD case (PMID 22521361). This report also showed significant burden (P=0.001) of SATB2 CNVs in individuals with neurodevelopmental disorder (NDD; ~25% of cases with ASD).

Krishnan Probability Score

Score 0.61589361421768

Ranking 108/25841 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.
ExAC Score

Score 0.99956300698079

Ranking 906/18225 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
Sanders TADA Score

Score 0.9392038501763

Ranking 14128/18665 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).
Larsen Cumulative Evidence Score

Score 10

Ranking 191/461 scored genes


[Show Scoring Methodology]
Larsen and colleagues generated gene scores based on the sum of evidence for all available ASD-associated variants in a gene, with assessments based on mode of inheritance, effect size, and variant frequency in the general population. The approach was first presented in Mol Autism 7:44 (2016), and scores for 461 genes can be found in column I in supplementary table 4 from that paper.
Zhang D Score

Score 0.39892754689767

Ranking 1476/20870 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.
Interaction Table
Interactor Symbol Interactor Name Interactor Organism Interactor Type Entrez ID Uniprot ID
Bglap bone gamma carboxyglutamate protein Mouse DNA Binding 12096 P86546
HBG1 hemoglobin, gamma A Human DNA Binding 3047 D9YZU8
HSFY1 Heat shock transcription factor, Y-linked Human Protein Binding 159119 Q96LI6
Mir24-2 microRNA 24-2 Mouse RNA Binding 723960 N/A
Mir27a microRNA 27a Mouse RNA Binding 387220 N/A
TP63 tumor protein p63 Human Protein Binding 8626 Q9H3D4
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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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