SATB2SATB homeobox 2

SFARI Gene Score

Strong Candidate, Syndromic Criteria 2.1, Syndromic

Autism Reports / Total Reports

13 / 49

Rare Variants / Common Variants

169 / 1

EAGLE Score

24.95

Strong Learn More

Aliases

SATB2, FLJ21474, FLJ32076, KIAA1034, MGC119474, MGC119477

Associated Syndromes

SATB2-associated syndrome, Glass syndrome, Glass syndrome, DD/ID, Glass syndrome, DD, ID

Chromosome Band

2q33.1

Associated Disorders

DD/NDD, ID, EP, EPS, ASD

Genetic Category

Rare Single Gene Mutation, Syndromic, Genetic Association, Functional

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.

External Links

Gene Card Open Targets Platform gnomAD browser PubMed

Human

Entrez Gene OMIM UniProt HumanBase VariCarta

SFARI Genomic Platforms

GPF browser SFARI genome browser

Reports (49)
Variants (170)
Gene Score
Protein Interactions (6)

Reports related to SATB2 (49 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 2 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 developmental disorders	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	-
29	Support	Astrocyte layers in the mammalian cerebral cortex revealed by a single-cell in situ transcriptomic map	Bayraktar OA et al. (2020)	No	-
30	Support	Large-scale targeted sequencing identifies risk genes for neurodevelopmental disorders	Wang T et al. (2020)	Yes	ID
31	Support	-	Zarate YA et al. (2021)	No	Epilepsy/seizures
32	Support	-	Abe-Hatano C et al. (2021)	No	-
33	Support	-	Hiraide T et al. (2021)	No	-
34	Support	-	Zarate YA et al. (2021)	No	ASD
35	Support	-	Pode-Shakked B et al. (2021)	Yes	-
36	Support	-	Mahjani B et al. (2021)	Yes	-
37	Support	-	Aguilera C et al. (2021)	No	-
38	Support	-	MouillÃÂ© M et al. (2022)	No	ASD
39	Support	-	Bissell S et al. (2022)	No	-
40	Support	-	Levchenko O et al. (2022)	No	Epilepsy/seizures
41	Support	-	Zhou X et al. (2022)	Yes	-
42	Support	-	Shimelis H et al. (2023)	No	-
43	Support	-	Copelli MM et al. (2023)	No	Autistic features
44	Support	-	Sanchis-Juan A et al. (2023)	No	-
45	Support	-	Nico Wahl et al. (2024)	No	-
46	Support	-	Alistair T Pagnamenta et al. (2024)	No	-
47	Support	-	Axel Schmidt et al. (2024)	No	ID, cognitive impairment
48	Support	-	Jianfen Yang et al. (2024)	No	-
49	Support	-	Karen Lob et al. ()	Yes	DD, ID

Rare Variants (169)

Allele Change	Residue Change	Variant Type	Inheritance Pattern	Parental Transmission	Family Type	PubMed ID	Author, Year
-	-	inversion	De novo	-	-	27841880	Redin C , et al. (2016)
-	-	translocation	De novo	-	-	27841880	Redin C , et al. (2016)
-	-	copy_number_loss	De novo	-	-	33381861	Zarate YA et al. (2021)
-	-	copy_number_loss	Unknown	-	-	33381861	Zarate YA et al. (2021)
-	-	copy_number_loss	Unknown	-	-	29436146	Zarate YA , et al. (2018)
-	-	copy_number_loss	De novo	-	-	31021519	Zarate YA , et al. (2019)
-	-	copy_number_loss	Unknown	-	-	31021519	Zarate YA , et al. (2019)
-	-	translocation	De novo	-	-	22521361	Talkowski ME , et al. (2012)
-	-	frameshift_variant	De novo	-	-	31021519	Zarate YA , et al. (2019)
-	-	copy_number_gain	-	-	Multiplex	29436146	Zarate YA , et al. (2018)
-	-	copy_number_loss	De novo	-	-	35241104	MouillÃÂ© M et al. (2022)
c.-313C>T	-	stop_gained	De novo	-	-	29436146	Zarate YA , et al. (2018)
c.-561T>G	-	missense_variant	Unknown	-	-	31021519	Zarate YA , et al. (2019)
c.-2del	-	frameshift_variant	De novo	-	-	28139846	Zarate YA , et al. (2017)
c.1174-2A>G	-	splice_site_variant	De novo	-	-	33004838	Wang T et al. (2020)
c.347-16019C>T	-	missense_variant	De novo	-	-	30945278	Jiao Q , et al. (2019)
-	-	complex_structural_alteration	De novo	-	-	27841880	Redin C , et al. (2016)
c.-336del	-	frameshift_variant	De novo	-	-	28139846	Zarate YA , et al. (2017)
c.-418del	-	frameshift_variant	De novo	-	-	28139846	Zarate YA , et al. (2017)
c.-484del	-	frameshift_variant	De novo	-	-	31021519	Zarate YA , et al. (2019)
-	-	inversion	De novo	-	Simplex	38776926	Alistair T Pagnamenta et al. (2024)
c.-342del	-	splice_site_variant	Unknown	-	-	31021519	Zarate YA , et al. (2019)
c.124G>T	p.Gly42Ter	stop_gained	De novo	-	-	28139846	Zarate YA , et al. (2017)
c.-10_-9del	-	frameshift_variant	De novo	-	-	29436146	Zarate YA , et al. (2018)
c.181C>T	p.Pro61Ser	missense_variant	De novo	-	-	35982159	Zhou X et al. (2022)
c.847C>T	p.Arg283Ter	stop_gained	De novo	-	-	28139846	Zarate YA , et al. (2017)
c.390T>A	p.Tyr130Ter	stop_gained	De novo	-	-	28151491	Bengani H , et al. (2017)
c.346G>T	p.Gly116Ter	stop_gained	De novo	-	-	29436146	Zarate YA , et al. (2018)
c.715C>T	p.Arg239Ter	stop_gained	Unknown	-	-	29436146	Zarate YA , et al. (2018)
c.715C>T	p.Arg239Ter	stop_gained	De novo	-	-	31021519	Zarate YA , et al. (2019)
c.715C>T	p.Arg239Ter	stop_gained	Unknown	-	-	31021519	Zarate YA , et al. (2019)
c.847C>T	p.Arg283Ter	stop_gained	De novo	-	-	31021519	Zarate YA , et al. (2019)
c.868C>T	p.Gln290Ter	stop_gained	De novo	-	-	31021519	Zarate YA , et al. (2019)
c.868C>T	p.Gln290Ter	stop_gained	Unknown	-	-	31021519	Zarate YA , et al. (2019)
c.988C>T	p.Gln330Ter	stop_gained	De novo	-	-	31021519	Zarate YA , et al. (2019)
c.997C>T	p.Gln333Ter	stop_gained	De novo	-	-	31021519	Zarate YA , et al. (2019)
c.715C>T	p.Arg239Ter	stop_gained	De novo	-	-	37107640	Copelli MM et al. (2023)
c.347-15097C>T	-	missense_variant	De novo	-	-	31021519	Zarate YA , et al. (2019)
c.347-15107T>G	-	missense_variant	De novo	-	-	31021519	Zarate YA , et al. (2019)
c.347-15120A>G	-	missense_variant	De novo	-	-	31021519	Zarate YA , et al. (2019)
c.1174-2A>G	-	splice_site_variant	De novo	-	-	29436146	Zarate YA , et al. (2018)
c.962T>C	p.Ile321Thr	missense_variant	De novo	-	-	35982159	Zhou X et al. (2022)
c.1255C>T	p.Gln419Ter	stop_gained	De novo	-	-	28139846	Zarate YA , et al. (2017)
c.1285C>T	p.Arg429Ter	stop_gained	De novo	-	-	28151491	Bengani H , et al. (2017)
c.2074G>T	p.Glu692Ter	stop_gained	De novo	-	-	28151491	Bengani H , et al. (2017)
c.1285C>T	p.Arg429Ter	stop_gained	De novo	-	-	29436146	Zarate YA , et al. (2018)
c.1375C>T	p.Arg459Ter	stop_gained	Unknown	-	-	29436146	Zarate YA , et al. (2018)
c.1495A>T	p.Lys499Ter	stop_gained	De novo	-	-	29436146	Zarate YA , et al. (2018)
c.1135C>T	p.Gln379Ter	stop_gained	De novo	-	-	31021519	Zarate YA , et al. (2019)
c.1285C>T	p.Arg429Ter	stop_gained	De novo	-	-	31021519	Zarate YA , et al. (2019)
c.1375C>T	p.Arg459Ter	stop_gained	De novo	-	-	31021519	Zarate YA , et al. (2019)
c.1756C>T	p.Gln586Ter	stop_gained	Unknown	-	-	31021519	Zarate YA , et al. (2019)
c.688A>T	p.Lys230Ter	stop_gained	De novo	-	-	28333917	Vissers LE , et al. (2017)
c.225T>A	p.Tyr75Ter	stop_gained	De novo	-	-	39039281	Axel Schmidt et al. (2024)
c.1166G>A	p.Arg389His	missense_variant	Unknown	-	-	33004838	Wang T et al. (2020)
c.1214G>A	p.Arg405Gln	missense_variant	Unknown	-	-	33004838	Wang T et al. (2020)
c.1286G>A	p.Arg429Gln	missense_variant	De novo	-	-	33004838	Wang T et al. (2020)
c.1595G>A	p.Arg532His	missense_variant	Unknown	-	-	33004838	Wang T et al. (2020)
c.1627C>T	p.Arg543Cys	missense_variant	Unknown	-	-	33004838	Wang T et al. (2020)
c.1195C>G	p.Arg399Gly	missense_variant	De novo	-	-	35982159	Zhou X et al. (2022)
c.1321A>G	p.Met441Val	missense_variant	De novo	-	-	35982159	Zhou X et al. (2022)
c.1637A>T	p.Asn546Ile	missense_variant	De novo	-	-	35982159	Zhou X et al. (2022)
c.347-14931del	-	frameshift_variant	Unknown	-	-	28139846	Zarate YA , et al. (2017)
c.347-14632del	-	frameshift_variant	De novo	-	-	29436146	Zarate YA , et al. (2018)
c.347-15067dup	-	frameshift_variant	Unknown	-	-	29436146	Zarate YA , et al. (2018)
c.347-15146del	-	frameshift_variant	De novo	-	-	29436146	Zarate YA , et al. (2018)
c.-573_-555del	-	frameshift_variant	De novo	-	-	31021519	Zarate YA , et al. (2019)
c.347-15004del	-	frameshift_variant	Unknown	-	-	31021519	Zarate YA , et al. (2019)
c.347-15019del	-	frameshift_variant	De novo	-	-	31021519	Zarate YA , et al. (2019)
c.347-15163del	-	frameshift_variant	De novo	-	-	31021519	Zarate YA , et al. (2019)
c.347-15988del	-	frameshift_variant	De novo	-	-	31021519	Zarate YA , et al. (2019)
c.1495A>T	p.Lys499Ter	stop_gained	De novo	-	-	28554332	Bowling KM , et al. (2017)
c.715C>T	p.Arg239Ter	stop_gained	De novo	-	-	17377962	Leoyklang P , et al. (2007)
c.688A>T	p.Lys230Ter	stop_gained	De novo	-	-	27479843	Lelieveld SH et al. (2016)
c.658C>T	p.Gln220Ter	stop_gained	De novo	-	-	35241104	MouillÃÂ© M et al. (2022)
c.703G>T	p.Glu235Ter	stop_gained	De novo	-	-	35241104	MouillÃÂ© M et al. (2022)
c.715C>T	p.Arg239Ter	stop_gained	De novo	-	-	35241104	MouillÃÂ© M et al. (2022)
c.955C>T	p.Gln319Ter	stop_gained	De novo	-	-	35241104	MouillÃÂ© M et al. (2022)
c.562C>T	p.Gln188Ter	stop_gained	Unknown	-	Simplex	33004838	Wang T et al. (2020)
c.1285C>T	p.Arg429Ter	stop_gained	De novo	-	-	35241104	MouillÃÂ© M et al. (2022)
-	-	copy_number_loss	1 de novo, 12 unknown	-	Unknown	25217958	Coe BP , et al. (2014)
c.607T>G	p.Ser203Ala	missense_variant	Unknown	-	-	34615535	Mahjani B et al. (2021)
c.185T>A	p.Val62Asp	missense_variant	De novo	-	-	29436146	Zarate YA , et al. (2018)
c.287T>G	p.Leu96Arg	missense_variant	De novo	-	-	29436146	Zarate YA , et al. (2018)
c.285G>T	p.Gln95His	missense_variant	De novo	-	-	31021519	Zarate YA , et al. (2019)
c.715C>T	p.Arg239Ter	stop_gained	De novo	-	-	31209962	Aspromonte MC , et al. (2019)
c.715C>T	p.Arg239Ter	stop_gained	De novo	-	Simplex	24301056	Dcker D , et al. (2013)
c.392T>A	p.Val131Glu	missense_variant	De novo	-	-	29436146	Zarate YA , et al. (2018)
c.760C>T	p.His254Tyr	missense_variant	De novo	-	-	31021519	Zarate YA , et al. (2019)
c.868C>T	p.Gln290Ter	stop_gained	De novo	-	Simplex	33644862	Hiraide T et al. (2021)
c.1286G>A	p.Arg429Gln	missense_variant	De novo	-	-	28139846	Zarate YA , et al. (2017)
c.1964C>T	p.Pro655Leu	missense_variant	De novo	-	-	28139846	Zarate YA , et al. (2017)
c.1157C>T	p.Ala386Val	missense_variant	De novo	-	-	28151491	Bengani H , et al. (2017)
c.1165C>T	p.Arg389Cys	missense_variant	De novo	-	-	28151491	Bengani H , et al. (2017)
c.1181T>C	p.Leu394Ser	missense_variant	De novo	-	-	28151491	Bengani H , et al. (2017)
c.1696G>A	p.Glu566Lys	missense_variant	De novo	-	-	28151491	Bengani H , et al. (2017)
c.1165C>T	p.Arg389Cys	missense_variant	De novo	-	-	29436146	Zarate YA , et al. (2018)
c.1196G>A	p.Arg399His	missense_variant	De novo	-	-	29436146	Zarate YA , et al. (2018)
c.1286G>A	p.Arg429Gln	missense_variant	De novo	-	-	29436146	Zarate YA , et al. (2018)
c.1136A>C	p.Gln379Pro	missense_variant	De novo	-	-	31021519	Zarate YA , et al. (2019)
c.1165C>T	p.Arg389Cys	missense_variant	De novo	-	-	31021519	Zarate YA , et al. (2019)
c.1166G>T	p.Arg389Leu	missense_variant	De novo	-	-	31021519	Zarate YA , et al. (2019)
c.1169C>T	p.Thr390Ile	missense_variant	De novo	-	-	31021519	Zarate YA , et al. (2019)
c.1175G>A	p.Gly392Glu	missense_variant	De novo	-	-	31021519	Zarate YA , et al. (2019)
c.1196G>A	p.Arg399His	missense_variant	De novo	-	-	31021519	Zarate YA , et al. (2019)
c.1196G>A	p.Arg399His	missense_variant	Unknown	-	-	31021519	Zarate YA , et al. (2019)
c.1196G>T	p.Arg399Leu	missense_variant	De novo	-	-	31021519	Zarate YA , et al. (2019)
c.1253T>G	p.Met418Arg	missense_variant	De novo	-	-	31021519	Zarate YA , et al. (2019)
c.1286G>A	p.Arg429Gln	missense_variant	Unknown	-	-	31021519	Zarate YA , et al. (2019)
c.1903G>T	p.Asp635Tyr	missense_variant	De novo	-	-	31021519	Zarate YA , et al. (2019)
c.346+2T>G	-	splice_site_variant	De novo	-	Simplex	25885067	Zarate YA , et al. (2015)
-	-	complex_structural_alteration	De novo	-	-	30923172	Schluth-Bolard C , et al. (2019)
c.748C>T	p.Gln250Ter	stop_gained	De novo	-	Simplex	25885067	Zarate YA , et al. (2015)
c.847C>T	p.Arg283Ter	stop_gained	De novo	-	Simplex	25885067	Zarate YA , et al. (2015)
c.1298A>C	p.Tyr433Ser	missense_variant	De novo	-	-	31452935	Feliciano P et al. (2019)
c.346G>C	p.Gly116Arg	splice_site_variant	De novo	-	-	28139846	Zarate YA , et al. (2017)
c.1171C>T	p.Gln391Ter	stop_gained	De novo	-	Simplex	25885067	Zarate YA , et al. (2015)
c.1165C>T	p.Arg389Cys	missense_variant	De novo	-	-	35241104	MouillÃÂ© M et al. (2022)
c.1198A>G	p.Lys400Glu	missense_variant	De novo	-	-	35241104	MouillÃÂ© M et al. (2022)
c.1538G>A	p.Ser513Asn	missense_variant	De novo	-	-	35241104	MouillÃÂ© M et al. (2022)
c.1696G>A	p.Glu566Lys	missense_variant	De novo	-	-	35241104	MouillÃÂ© M et al. (2022)
c.1861A>T	p.Ile621Phe	missense_variant	De novo	-	Simplex	30504930	Guo H , et al. (2018)
c.1109A>T	p.Asp370Val	missense_variant	Unknown	-	-	28628100	Geisheker MR , et al. (2017)
c.1184C>T	p.Ser395Phe	missense_variant	De novo	-	-	28628100	Geisheker MR , et al. (2017)
c.1214G>A	p.Arg405Gln	missense_variant	Unknown	-	-	28628100	Geisheker MR , et al. (2017)
c.1639dup	p.Leu547ProfsTer5	frameshift_variant	De novo	-	-	35982159	Zhou X et al. (2022)
c.1197dup	p.Lys400Ter	frameshift_variant	De novo	-	-	35241104	MouillÃÂ© M et al. (2022)
c.1148del	p.Ala383GlufsTer30	frameshift_variant	Unknown	-	-	33004838	Wang T et al. (2020)
c.1728del	p.Glu577SerfsTer47	frameshift_variant	Unknown	-	-	33004838	Wang T et al. (2020)
c.1142T>G	p.Val381Gly	missense_variant	De novo	-	Simplex	23020937	Rauch A , et al. (2012)
c.15del	p.Ser5ArgfsTer25	frameshift_variant	Unknown	-	-	31021519	Zarate YA , et al. (2019)
c.83del	p.Pro28GlnfsTer2	frameshift_variant	Unknown	-	-	36475376	Shimelis H et al. (2023)
c.1627del	p.Arg543AlafsTer3	frameshift_variant	De novo	-	-	28708303	Chrot E , et al. (2017)
c.347-14689_347-14688del	-	frameshift_variant	De novo	-	-	29436146	Zarate YA , et al. (2018)
c.1285C>T	p.Arg429Ter	stop_gained	De novo	-	Simplex	34580403	Pode-Shakked B et al. (2021)
c.1375C>T	p.Arg459Ter	stop_gained	Unknown	-	Simplex	37541188	Sanchis-Juan A et al. (2023)
c.347-15118G>A	-	splice_site_variant	De novo	-	Simplex	27848944	Trujillano D , et al. (2016)
c.1536_1537del	p.Gln514GlyfsTer5	frameshift_variant	Unknown	-	-	39136901	Karen Lob et al. ()
c.583dup	p.Cys195LeufsTer14	frameshift_variant	De novo	-	-	28139846	Zarate YA , et al. (2017)
c.583dup	p.Cys195LeufsTer14	frameshift_variant	De novo	-	-	28151491	Bengani H , et al. (2017)
c.1203dup	p.Glu402ArgfsTer35	frameshift_variant	De novo	-	-	28151491	Bengani H , et al. (2017)
c.1575del	p.Asn526ThrfsTer20	frameshift_variant	De novo	-	-	28151491	Bengani H , et al. (2017)
c.1646del	p.Gln549ArgfsTer75	frameshift_variant	De novo	-	-	28151491	Bengani H , et al. (2017)
c.1826del	p.Asp609AlafsTer15	frameshift_variant	De novo	-	-	34653234	Aguilera C et al. (2021)
c.1657del	p.Asp553MetfsTer71	frameshift_variant	Unknown	-	-	36475376	Shimelis H et al. (2023)
c.696dup	p.Lys233Ter	frameshift_variant	De novo	-	Simplex	35887114	Levchenko O et al. (2022)
c.1174G>A	p.Gly392Arg	missense_variant	De novo	-	Simplex	33624935	Abe-Hatano C et al. (2021)
c.347-15873_347-15872insTGGT	-	frameshift_variant	Unknown	-	-	29436146	Zarate YA , et al. (2018)
c.1610del	p.Asn537ThrfsTer9	frameshift_variant	De novo	-	-	35241104	MouillÃÂ© M et al. (2022)
c.1627del	p.Arg543AlafsTer3	frameshift_variant	De novo	-	-	35241104	MouillÃÂ© M et al. (2022)
c.1010dup	p.Gln338AlafsTer13	frameshift_variant	De novo	-	-	35241104	MouillÃÂ© M et al. (2022)
c.347-15150_347-15149insCAAGCCT	-	frameshift_variant	De novo	-	-	31021519	Zarate YA , et al. (2019)
c.1131_1132del	p.Ser378ProfsTer18	frameshift_variant	Unknown	-	-	29436146	Zarate YA , et al. (2018)
c.315_316insAC	p.Tyr106ThrfsTer13	frameshift_variant	De novo	-	-	31021519	Zarate YA , et al. (2019)
c.1963C>T	p.Pro655Ser	missense_variant	Familial	Paternal	Simplex	23849776	Jiang YH , et al. (2013)
c.1131_1132del	p.Ser378ProfsTer18	frameshift_variant	Unknown	-	-	28554332	Bowling KM , et al. (2017)
c.553_554insT	p.Glu185ValfsTer24	frameshift_variant	De novo	-	-	39039281	Axel Schmidt et al. (2024)
c.1103_1106del	p.Val368GlufsTer4	frameshift_variant	De novo	-	-	39039281	Axel Schmidt et al. (2024)
c.411_412insGACAGTGG	p.Thr138AspfsTer16	frameshift_variant	Unknown	-	-	33004838	Wang T et al. (2020)
c.1945dup	p.Ser649PhefsTer40	frameshift_variant	De novo	-	Simplex	25885067	Zarate YA , et al. (2015)
c.414_415del	p.Val139GlyfsTer69	frameshift_variant	De novo	-	Simplex	35887114	Levchenko O et al. (2022)
c.598-2A>G	-	splice_site_variant	De novo (germline mosaicism)	-	Multiplex	28151491	Bengani H , et al. (2017)
c.1173+2T>C	-	splice_site_variant	De novo	-	Unknown	25533962	Deciphering Developmental Disorders Study (2014)
c.1375C>T	p.Arg459Ter	stop_gained	De novo	-	Simplex	25533962	Deciphering Developmental Disorders Study (2014)
c.1166G>T	p.Arg389Leu	missense_variant	De novo	-	Simplex	25533962	Deciphering Developmental Disorders Study (2014)
c.1196G>A	p.Arg399His	missense_variant	De novo	-	Simplex	25533962	Deciphering Developmental Disorders Study (2014)
c.1204G>A	p.Glu402Lys	missense_variant	De novo	-	Simplex	25533962	Deciphering Developmental Disorders Study (2014)
c.1543G>A	p.Gly515Ser	missense_variant	De novo	-	Simplex	25533962	Deciphering Developmental Disorders Study (2014)
c.594_595del	p.Gln199GlufsTer9	frameshift_variant	De novo	-	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)

Current Score
Scoring History
3rd Party Scoring

SFARI Gene score

Strong Candidate, 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 2S

criteria met

See SFARI Gene'scoring criteria

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.

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

Decreased from 3S to 2S

Description

4/1/2021

Decreased from 3S to 3S

Description

Reports Added

[SATB2-associated syndrome in adolescents and adults2021]

1/1/2021

Decreased from 3S to 3S

Description

Reports Added

[Growth, development, and phenotypic spectrum of individuals with deletions of 2q33.1 involving SATB22021] [Whole genome sequencing of 45 Japanese patients with intellectual disability2021] [Genetic and phenotypic analysis of 101 patients with developmental delay or intellectual disability using whole-exome sequencing2021]

10/1/2020

Decreased from 3S to 3S

Description

Reports Added

[Large-scale targeted sequencing identifies risk genes for neurodevelopmental disorders2020]

4/1/2020

Decreased from 3S to 3S

Description

Reports Added

[Astrocyte layers in the mammalian cerebral cortex revealed by a single-cell in situ transcriptomic map2020]

10/1/2019

Decreased from 4S to 3S

New Scoring Scheme

Description

Reports Added

[Exome sequencing of 457 autism families recruited online provides evidence for autism risk genes2019] [New Scoring Scheme]

7/1/2019

Decreased from 4S to 4S

Description

Reports Added

[Characterization of intellectual disability and autism comorbidity through gene panel sequencing.2019]

4/1/2019

Decreased from 4S to 4S

Description

Reports Added

[Whole genome paired-end sequencing elucidates functional and phenotypic consequences of balanced chromosomal rearrangement in patients with develop...2019] [The combination of whole-exome sequencing and copy number variation sequencing enables the diagnosis of rare neurological disorders.2019] [Mutation update for the SATB2 gene.2019]

10/1/2018

Decreased from 4S to 4S

Description

Reports Added

[Genome sequencing identifies multiple deleterious variants in autism patients with more severe phenotypes.2018]

7/1/2018

Decreased from 4S to 4S

Description

Reports Added

[Genes regulated by SATB2 during neurodevelopment contribute to schizophrenia and educational attainment.2018]

7/1/2017

Decreased from 4S to 4S

Description

Reports Added

[Hotspots of missense mutation identify neurodevelopmental disorder genes and functional domains.2017] [Using medical exome sequencing to identify the causes of neurodevelopmental disorders: experience of two clinical units and 216 patients.2017]

4/1/2017

Decreased from 4S to 4S

Description

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 disability2016] [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

Decreased from 4S to 4S

Description

Reports Added

[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]

10/1/2016

Decreased from 4 to 4S

Description

Reports Added

[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]

7/1/2016

Decreased from 4 to 4

Description

Reports Added

[Meta-analysis of 2,104 trios provides support for 10 new genes for intellectual disability2016]

4/1/2015

Decreased from 4 to 4

Description

Reports Added

[Further supporting evidence for the SATB2-associated syndrome found through whole exome sequencing.2015] [A molecular model for neurodevelopmental disorders.2015]

1/1/2015

Decreased from 4 to 4

Description

Reports Added

[Large-scale discovery of novel genetic causes of developmental disorders.2014]

10/1/2014

Decreased from 4 to 4

Description

Reports Added

[Refining analyses of copy number variation identifies specific genes associated with developmental delay.2014]

7/1/2014

No data

Increased from No data to 4

Description

4/1/2014

No data

Increased from No data to 4

Description

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.

Original Source

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

Original Source

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).

Original Source

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.

Original Source

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.

Original Source

External PIN Data

BioGRID Human Protein Reference Database

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

Human Gene Module / Chromosome 2 / SATB2

SATB2SATB homeobox 2

SFARI Gene Score

Autism Reports / Total Reports

Rare Variants / Common Variants

EAGLE Score

Aliases

Associated Syndromes

Chromosome Band

Associated Disorders

Genetic Category

Relevance to Autism

Molecular Function

External Links

Human

SFARI Genomic Platforms

Reports related to SATB2 (49 Reports)

Rare Variants (169)

Common Variants (1)

SFARI Gene score

Strong Candidate, Syndromic

Score Delta: Score remained at 2S

criteria met

Strong Candidate

Syndromic

4/1/2022

Decreased from 3S to 2S

Description

4/1/2021

Decreased from 3S to 3S

Description

Reports Added

1/1/2021

Decreased from 3S to 3S

Description

Reports Added

10/1/2020

Decreased from 3S to 3S

Description

Reports Added

4/1/2020

Decreased from 3S to 3S

Description

Reports Added

10/1/2019

Decreased from 4S to 3S

New Scoring Scheme

Description

Reports Added

7/1/2019

Decreased from 4S to 4S

Description

Reports Added

4/1/2019

Decreased from 4S to 4S

Description

Reports Added

10/1/2018

Decreased from 4S to 4S

Description

Reports Added

7/1/2018

Decreased from 4S to 4S

Description

Reports Added

7/1/2017

Decreased from 4S to 4S

Description

Reports Added

4/1/2017

Decreased from 4S to 4S

Description

Reports Added

1/1/2017

Decreased from 4S to 4S

Description

Reports Added

10/1/2016

Decreased from 4 to 4S

Description