SATB1

Chr 3AD

SATB homeobox 1

Also known as: DEFDA, DHDBV, KTZSL

NCBI Gene: 6304 ENSG00000182568 UniProt: Q01826 OMIM: 602075

The protein functions as a transcriptional repressor that binds to AT-rich DNA sequences at matrix attachment regions and recruits chromatin-remodeling factors to regulate gene expression, playing essential roles in T-cell maturation, globin gene switching, and neuronal differentiation. Mutations cause den Hoed-de Boer-Voisin syndrome and developmental delay with dysmorphic facies and dental anomalies through an autosomal dominant inheritance pattern. The gene is highly intolerant to loss-of-function variants, and mutations can cause disease predominantly through haploinsufficiency mechanisms.

OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

This gene encodes a matrix protein which binds nuclear matrix and scaffold-associating DNAs through a unique nuclear architecture. The protein recruits chromatin-remodeling factors in order to regulate chromatin structure and gene expression. [provided by RefSeq, Apr 2016]

OMIM ResearchGenerating clinical summary…

LOFmechanismADLOEUF 0.292 OMIM phenotypes

Clinical Summary— SATB1

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Gene-Disease Validity (ClinGen)

complex neurodevelopmental disorder · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.99). One damaged copy is likely sufficient to cause disease.

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ClinVar Variants

37 unique Pathogenic / Likely Pathogenic· 149 VUS of 234 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Dual constrained — LoF & missense intolerant

LoF Constraint?

0.29LOEUF

pLI 0.991

Z-score 5.02

OE 0.15 (0.08–0.29)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

3.98Z-score

OE missense 0.46 (0.41–0.52)

202 obs / 436.1 exp

Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?

LoF OE?0.15 (0.08–0.29)

0≤0.351.4

Missense OE?0.46 (0.41–0.52)

0≤0.61.4

Synonymous OE?1.10

0≤1.21.6

LoF obs/exp: 6 / 40.4Missense obs/exp: 202 / 436.1Syn Z: -1.07

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

moderateSATB1-related developmental disorderLOFAD

This gene — mechanism propensity

0.3097th %ile

GOF

0.3789th %ile

LOF

0.79top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · 1 literature citation · 62% of P/LP variants are LoF · LOEUF 0.29

Literature Evidence

LOFThese findings suggested haploinsufficiency as a mechanism; however, some of the mutations were demonstrated to escape nonsense-mediated mRNA decay.1

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

References

1.PMID 33513338 ↗

ClinVar Variant Classifications

234 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic18

Likely Pathogenic19

VUS149

Likely Benign21

Benign7

Conflicting5

Pathogenic

Likely Pathogenic

149

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	13	4	1	0	18
Likely Pathogenic	10	9	0	0	19
VUS	18	124	5	2	149
Likely Benign	0	9	2	10	21
Benign	0	3	2	2	7
Conflicting	—				5
Total	41	149	10	14	219

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

View in ClinVar →

24 pathogenic / likely-pathogenic (of 27) ClinVar copy-number / structural variants overlap SATB1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →