SATB2

Chr 2AD

SATB homeobox 2

Also known as: C2DELq32q33, DEL2Q32Q33, GLSS

NCBI Gene: 23314 ENSG00000119042 UniProt: Q9UPW6 OMIM: 608148

The protein binds nuclear matrix attachment regions and regulates transcription and chromatin remodeling. Mutations cause Glass syndrome, characterized by isolated cleft palate and cognitive disability, with autosomal dominant inheritance. The mechanism involves loss of function, as the gene is highly intolerant to loss-of-function variants.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

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]

GeneReviews OMIM ResearchGenerating clinical summary…

LOFmechanismAD1 OMIM phenotype

Clinical Summary— SATB2

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Gene-Disease Validity (ClinGen)

SATB2 associated disorder · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

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ClinVar Variants

209 unique Pathogenic / Likely Pathogenic· 236 VUS of 927 total submissions

Explore recent and relevant literature in Research Assistant →

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GeneReview available — SATB2

Authoritative clinical overview · Recommended first read

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Some data sources returned errors (1)

gnomad: TimeoutError: The operation was aborted due to timeout

Population Genetics & Constraint

gnomAD

Constraint data not available from gnomAD.

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveSATB2-related Glass syndromeLOFAD

This gene — mechanism propensity

0.16100th %ile

GOF

0.2497th %ile

LOF

0.88top 5%

This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to loss-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

LOFprediction above median · 1 literature citation · 70% of P/LP variants are LoF · ClinGen HI: Sufficient evidence for dosage pathogenicity

DN1 literature citation

Literature Evidence

DNThis phenotype was accompanied by osteoporosis, fractures, and tibial bowing in two previously reported adult patients; each possessed SATB2 mutations either predicted or demonstrated to escape nonsense-mediated decay, suggesting that the additional bone defects result from a dominant negative effec1

LOFThe recent identification of SATB2 as a candidate gene responsible for the craniofacial dysmorphologies associated with deletions and translocations at 2q32-q33, one of only three regions of the genome for which haploinsufficiency has been significantly associated with isolated cleft palate, led us 2

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

References

ClinVar Variant Classifications

927 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic129

Likely Pathogenic80

VUS236

Likely Benign346

Benign80

Conflicting31

129

Pathogenic

Likely Pathogenic

236

VUS

346

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	107	15	7	0	129
Likely Pathogenic	39	38	3	0	80
VUS	2	217	16	1	236
Likely Benign	0	29	88	229	346
Benign	0	44	31	5	80
Conflicting	—				31
Total	148	343	145	235	902

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

View in ClinVar →

49 pathogenic / likely-pathogenic (of 54) ClinVar copy-number / structural variants overlap SATB2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →