SATB2

Chr 2AD

SATB homeobox 2

Also known as: C2DELq32q33, DEL2Q32Q33, GLSS

NCBI Gene: 23314ENSG00000119042UniProt: Q9UPW6

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 cognitive disability. Alternate splicing results in multiple transcript variants that encode the same protein. [provided by RefSeq, Feb 2010]

Primary Disease Associations & Inheritance

Glass syndromeMIM #612313
AD
UniProtCleft palate isolated
556
ClinVar variants
153
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— SATB2
🧬
Gene-Disease Validity (ClinGen)
SATB2 associated disorder · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
153 Pathogenic / Likely Pathogenic· 163 VUS of 556 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.09LOEUF
pLI 1.000
Z-score 5.32
OE 0.00 (0.00–0.09)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
4.05Z-score
OE missense 0.44 (0.39–0.50)
183 obs / 415.3 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.00 (0.00–0.09)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.44 (0.39–0.50)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.10
0≤1.21.6
LoF obs/exp: 0 / 32.9Missense obs/exp: 183 / 415.3Syn Z: -1.02

ClinVar Variant Classifications

556 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic104
Likely Pathogenic49
VUS163
Likely Benign201
Benign32
Conflicting7
104
Pathogenic
49
Likely Pathogenic
163
VUS
201
Likely Benign
32
Benign
7
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
39
9
56
0
104
Likely Pathogenic
16
21
12
0
49
VUS
2
146
14
1
163
Likely Benign
0
8
70
123
201
Benign
0
22
9
1
32
Conflicting
—7
Total57206161125556

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

SATB2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

SATB2-related Glass syndrome

definitive
ADLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Glass syndrome

MIM #612313

Molecular basis of disorder known

Autosomal dominant
📖
GeneReview available — SATB2
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
KDM2B-Rearranged Soft Tissue Sarcomas Expand the Concept of BCOR-Associated Sarcoma.
Motoi T et al.·Mod Pathol
2023
Pathogenic SATB2 missense variants affecting p.Gly392 have variable functional implications and result in diverse clinical phenotypes.
den Hoed J et al.·J Med Genet
2024Functional
SATB2-associated syndrome: Mechanisms, phenotype, and practical recommendations.
Zarate YA et al.·Am J Med Genet A
2017Review
Immunohistochemical Characterization of Gingival Fibromas.
Darling M et al.·Head Neck Pathol
2023
Mendelian etiologies identified with whole exome sequencing in cerebral palsy.
Chopra M et al.·Ann Clin Transl Neurol
2022
Individuals with SATB2-associated syndrome have impaired vitamin and energy metabolism pathways.
Collu R et al.·Metab Brain Dis
2024
Bone health and SATB2-associated syndrome.
Zarate YA et al.·Clin Genet
2018Review
EWSR1::POU2AF3(COLCA2) Sarcoma: An Aggressive, Polyphenotypic Sarcoma With a Head and Neck Predilection.
Koshyk O et al.·Mod Pathol
2023
SATB1 and 2 in colorectal cancer.
Brocato J et al.·Carcinogenesis
2015Review
Mutation update for the SATB2 gene.
Zarate YA et al.·Hum Mutat
2019Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
SATB2 Mediates H3K9 Delactylation by Recruiting HDAC3 to Repress LCN2 and Inhibit Lung Tumor Growth and Metastasis.
Wen T et al.·Adv Sci (Weinh)
2026
SATB2 accelerates post-traumatic stress disorder (PTSD) via increased FOXM1/STAT3/P2X7R signaling-induced inflammation in the hippocampus.
Zhao C et al.·Eur J Med Res
2026
Prioritizing topics for a Clinical Practice Guideline on SATB2-Associated Syndrome: Methodological rigor versus clinical usability.
Wilhelmina Gaasterland CM et al.·J Clin Epidemiol
2026
SATB2 Induces Malignant Transformation and Cancer Stem Cell Characteristics, and Inhibition of Its Expression Reverses Drug Resistance in Mesothelioma.
Brown C et al.·Cells
2026🔓 Open Access
Clinical and Molecular Characterization of Five Additional Individuals With SATB2-Associated Syndrome in Guangxi.
Yi S et al.·Biochem Genet
2026
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools