SATB2

SATB homeobox 2, the group of CUT class homeoboxes and pseudogenes

Basic information

Region (hg38): 2:199269504-199471266

Links

ENSG00000119042 ∙ NCBI:23314 ∙ OMIM:608148 ∙ HGNC:21637 ∙ Uniprot:Q9UPW6 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• chromosome 2q32-q33 deletion syndrome (Definitive), mode of inheritance: AD
• chromosome 2q32-q33 deletion syndrome (Moderate), mode of inheritance: AD
• chromosome 2q32-q33 deletion syndrome (Strong), mode of inheritance: AD
• SATB2 associated disorder (Definitive), mode of inheritance: AD
• SATB2 associated disorder (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Glass syndrome	AD	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Craniofacial; Dental; Musculoskeletal; Neurologic	17377962; 19170718; 19668335; 22521361; 23925499; 24301056; 24363063; 25118029

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SATB2 gene.

• Chromosome 2q32-q33 deletion syndrome (483 variants)
• not provided (167 variants)
• Inborn genetic diseases (71 variants)
• SATB2-related condition (10 variants)
• Intellectual disability (7 variants)
• SATB2 associated disorder (6 variants)
• not specified (6 variants)
• Neurodevelopmental disorder (2 variants)
• See cases (2 variants)
• Cleft palate (1 variants)
• Intellectual disability;Dystonic disorder (1 variants)
• Global developmental delay (1 variants)
• 7 conditions (1 variants)
• Cerebellar ataxia (1 variants)
• Developmental disorder (1 variants)
• SATB2-associated syndrome (1 variants)
• 6 conditions (1 variants)
• SATB2-Related Disorder (1 variants)
• Isolated cleft palate (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SATB2 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			3	164	5	172
missense	11	24	143	24	28	230
nonsense	26	8				34
start loss		1				1
frameshift	43	11				54
inframe indel			3			3
splice donor/acceptor (+/-2bp)	7	6				13
splice region			4	15	4	23
non coding			3	42	24	69
Total	87	50	152	230	57

Highest pathogenic variant AF is 0.00000657

Variants in SATB2

This is a list of pathogenic ClinVar variants found in the SATB2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
2-199272217-C-A		Chromosome 2q32-q33 deletion syndrome	Uncertain significance (Nov 24, 2023)
2-199272223-A-T		Chromosome 2q32-q33 deletion syndrome	Likely benign (Oct 03, 2023)
2-199272224-A-G		Chromosome 2q32-q33 deletion syndrome	Uncertain significance (Aug 02, 2018)
2-199272228-C-T		Chromosome 2q32-q33 deletion syndrome	Uncertain significance (Feb 03, 2022)
2-199272229-G-T		Chromosome 2q32-q33 deletion syndrome	Likely benign (Nov 06, 2023)
2-199272230-G-C		Chromosome 2q32-q33 deletion syndrome	Uncertain significance (Jun 27, 2022)
2-199272231-C-G		Chromosome 2q32-q33 deletion syndrome	Uncertain significance (Mar 12, 2022)
2-199272235-T-C		Chromosome 2q32-q33 deletion syndrome	Likely benign (Jul 12, 2020)
2-199272236-G-A		Chromosome 2q32-q33 deletion syndrome • Inborn genetic diseases	Conflicting classifications of pathogenicity (Feb 05, 2024)
2-199272237-C-T		Chromosome 2q32-q33 deletion syndrome • Inborn genetic diseases	Benign/Likely benign (Jan 17, 2024)
2-199272239-G-A		Chromosome 2q32-q33 deletion syndrome • Inborn genetic diseases	Uncertain significance (Nov 12, 2021)
2-199272241-C-G		Chromosome 2q32-q33 deletion syndrome • Inborn genetic diseases	Benign/Likely benign (Dec 11, 2023)
2-199272241-C-T		Chromosome 2q32-q33 deletion syndrome	Likely benign (Mar 07, 2020)
2-199272245-CT-C		Chromosome 2q32-q33 deletion syndrome	Uncertain significance (Dec 20, 2022)
2-199272249-T-G		Chromosome 2q32-q33 deletion syndrome	Uncertain significance (Sep 01, 2022)
2-199272252-C-T		Inborn genetic diseases	Uncertain significance (Jun 29, 2022)
2-199272255-C-T		Inborn genetic diseases • Chromosome 2q32-q33 deletion syndrome	Uncertain significance (May 15, 2023)
2-199272262-C-T		Inborn genetic diseases • Chromosome 2q32-q33 deletion syndrome	Likely benign (Nov 13, 2023)
2-199272268-A-G		Chromosome 2q32-q33 deletion syndrome	Likely benign (Nov 01, 2018)
2-199272276-C-T			Uncertain significance (Jan 29, 2020)
2-199272278-T-C		Chromosome 2q32-q33 deletion syndrome	Benign (Aug 09, 2022)
2-199272283-C-G		Chromosome 2q32-q33 deletion syndrome	Uncertain significance (Aug 17, 2023)
2-199272284-A-T		not specified	Uncertain significance (Sep 22, 2023)
2-199272287-T-C		Chromosome 2q32-q33 deletion syndrome	Uncertain significance (Oct 25, 2022)
2-199272288-C-T		Chromosome 2q32-q33 deletion syndrome	Uncertain significance (Nov 27, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SATB2	protein_coding	protein_coding	ENST00000417098	10	201767

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.00000809	125389	0	1	125390	0.00000399

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	4.05	183	415	0.441	0.0000247	4816
Missense in Polyphen		26	152.54	0.17044		1846
Synonymous	-1.02	188	171	1.10	0.0000114	1436
Loss of Function	5.32	0	32.9	0.00	0.00000179	357

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00000883	0.00000883
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Binds to DNA, at nuclear matrix- or scaffold-associated regions. Thought to recognize the sugar-phosphate structure of double-stranded DNA. Transcription factor controlling nuclear gene expression, by binding to matrix attachment regions (MARs) of DNA and inducing a local chromatin-loop remodeling. Acts as a docking site for several chromatin remodeling enzymes and also by recruiting corepressors (HDACs) or coactivators (HATs) directly to promoters and enhancers. Required for the initiation of the upper- layer neurons (UL1) specific genetic program and for the inactivation of deep-layer neurons (DL) and UL2 specific genes, probably by modulating BCL11B expression. Repressor of Ctip2 and regulatory determinant of corticocortical connections in the developing cerebral cortex. May play an important role in palate formation. Acts as a molecular node in a transcriptional network regulating skeletal development and osteoblast differentiation. {ECO:0000269|PubMed:14701874}.
• Disease: DISEASE: Note=Chromosomal aberrations involving SATB2 are found in isolated cleft palate. Translocation t(2;7); translocation t(2;11). {ECO:0000269|PubMed:12915443}.; DISEASE: Cleft palate isolated (CPI) [MIM:119540]: A congenital fissure of the soft and/or hard palate, due to faulty fusion. Isolated cleft palate is not associated with cleft lips. Some patients may manifest other craniofacial dysmorphic features, mental retardation, and osteoporosis. {ECO:0000269|PubMed:12915443, ECO:0000269|PubMed:17377962}. Note=The disease may be caused by mutations affecting the gene represented in this entry.; DISEASE: Note=A chromosomal aberration involving SATB2 is found in a patient with classical features of Toriello-Carey syndrome. Translocation t(2;14)(q33;q22). {ECO:0000269|PubMed:19170718}.
• Pathway: RUNX2 regulates osteoblast differentiation;RUNX2 regulates bone development;Transcriptional regulation by RUNX2;Gene expression (Transcription);Generic Transcription Pathway;SUMOylation of chromatin organization proteins;Post-translational protein modification;SUMO E3 ligases SUMOylate target proteins;Metabolism of proteins;RNA Polymerase II Transcription;SUMOylation (Consensus)

Intolerance Scores

• loftool: 0.0340
• rvis_EVS: -0.87
• rvis_percentile_EVS: 10.65

Haploinsufficiency Scores

• pHI: 0.908
• hipred: Y
• hipred_score: 0.806
• ghis: 0.489

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.919

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Satb2
• Phenotype: respiratory system phenotype; embryo phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); limbs/digits/tail phenotype; digestive/alimentary phenotype; skeleton phenotype; cellular phenotype; endocrine/exocrine gland phenotype; growth/size/body region phenotype; craniofacial phenotype

Zebrafish Information Network

• Gene name: satb2
• Affected structure: whole organism
• Phenotype tag: abnormal
• Phenotype quality: dead

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;neuron migration;osteoblast development;chromatin remodeling;embryonic pattern specification;commitment of neuronal cell to specific neuron type in forebrain;positive regulation of transcription by RNA polymerase II;embryonic skeletal system morphogenesis;cartilage development;roof of mouth development;cellular response to organic substance
• Cellular component: histone deacetylase complex;nucleus;nucleoplasm;transcription factor complex;nuclear matrix
• Molecular function: RNA polymerase II proximal promoter sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;DNA-binding transcription activator activity, RNA polymerase II-specific;chromatin binding;protein binding;sequence-specific DNA binding