SATB2 associated disorder

Summary

SATB2 associated disorder (MONDO:0100147) is a disease caused by SATB2 (GenCC Definitive), with 1 cohort gene.

At a glance

• Prevalence: 1-9 / 100 000 (Worldwide) [Orphanet-validated]
• Causal gene: SATB2 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 9

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		667	Worldwide	Validated
Point prevalence	1-9 / 100 000	4.2	Worldwide	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	SATB2 associated disorder
Mondo ID	MONDO:0100147
Orphanet	576278
GARD	0022326
Is cancer (heuristic)	no

Also known as: SAS · SATB2 associated disorder · SATB2-associated syndrome

Data availability: 9 ClinVar variants · 2 GenCC gene-disease records.

Disease family

An umbrella term covering 1 Mondo subtype.

Classification path: disease › human disease › disease by body system or component › nervous system disorder › neurodevelopmental disorder › intellectual disability › syndromic intellectual disability › autosomal dominant syndromic intellectual disability › SATB2 associated disorder

Related subtypes (33): Myhre syndrome, KBG syndrome, Rubinstein-Taybi syndrome due to CREBBP mutations, Mowat-Wilson syndrome, Schinzel-Giedion syndrome, intellectual disability-sparse hair-brachydactyly syndrome, Pierpont syndrome, Bohring-Opitz syndrome, hereditary cryohydrocytosis with reduced stomatin, intellectual disability-severe speech delay-mild dysmorphism syndrome, Rubinstein-Taybi syndrome due to EP300 haploinsufficiency, DYRK1A-related intellectual disability syndrome, intellectual disability, autosomal dominant 13, Schuurs-Hoeijmakers syndrome, severe intellectual disability-poor language-strabismus-grimacing face-long fingers syndrome, severe intellectual disability-progressive spastic diplegia syndrome, CTCF-related neurodevelopmental disorder, Bosch-Boonstra-Schaaf optic atrophy syndrome, autism spectrum disorder due to AUTS2 deficiency, ADNP-related multiple congenital anomalies - intellectual disability - autism spectrum disorder, autosomal dominant intellectual disability-craniofacial anomalies-cardiac defects syndrome, Houge-Janssens syndrome 1, intellectual disability-microcephaly-strabismus-behavioral abnormalities syndrome, cardiac anomalies - developmental delay - facial dysmorphism syndrome, micrognathia-recurrent infections-behavioral abnormalities-mild intellectual disability syndrome, intellectual developmental disorder with dysmorphic facies and ptosis, intellectual disability, autosomal dominant 48, SETD2-related microcephaly-severe intellectual disability-multiple congenital anomalies syndrome, intellectual developmental disorder with gastrointestinal difficulties and high pain threshold, SIN3A-related intellectual disability syndrome, Ververi-Brady syndrome 1, intellectual developmental disorder with dysmorphic facies and behavioral abnormalities, intellectual developmental disorder with speech delay, dysmorphic facies, and t-cell abnormalities

Subtypes (1): chromosome 2q32-q33 deletion syndrome

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

9 retrieved; paginated sample, class counts are floors:

3 pathogenic, 2 not provided, 2 pathogenic/likely pathogenic, 1 uncertain significance, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
3062110	NM_001172509.2(SATB2):c.1976TCA[1] (p.Ile660del)	LOC126806462	Pathogenic	criteria provided, single submitter
1805643	NM_001172509.2(SATB2):c.581_584del (p.Glu194fs)	SATB2	Pathogenic	criteria provided, single submitter
208673	NM_001172509.2(SATB2):c.847C>T (p.Arg283Ter)	SATB2	Pathogenic	criteria provided, multiple submitters, no conflicts
381575	NM_001172509.2(SATB2):c.1165C>T (p.Arg389Cys)	SATB2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
662501	NM_001172509.2(SATB2):c.1195C>T (p.Arg399Cys)	SATB2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
657251	NM_001172509.2(SATB2):c.597+4A>G	SATB2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1693293	NM_001172509.2(SATB2):c.334G>A (p.Ala112Thr)	SATB2	Uncertain significance	criteria provided, single submitter
2578385	GRCh37/hg19 2q33.1(chr2:200188260-200214121)x1	SATB2	not provided	no classification provided
2672080	NM_001172509.2(SATB2):c.1476A>T (p.Gln492His)	SATB2	not provided	no classification provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 3 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
SATB2	Definitive	Autosomal dominant	SATB2 associated disorder	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SATB2	Orphanet:251019	2q32q33 deletion syndrome
SATB2	Orphanet:251028	SATB2-associated syndrome due to a chromosomal rearrangement
SATB2	Orphanet:576283	SATB2-associated syndrome due to a pathogenic variant

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SATB2	HGNC:21637	ENSG00000119042	Q9UPW6	DNA-binding protein SATB2	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SATB2	DNA-binding protein SATB2	Binds to DNA, at nuclear matrix- or scaffold-associated regions.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 0 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Transcription factor	1	8.3×	0.121

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SATB2	Transcription factor	no		HD, CUT_dom, Homeodomain-like_sf

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
cortical plate	1
mucosa of sigmoid colon	1
periodontal ligament	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SATB2	235	ubiquitous	marker	periodontal ligament, cortical plate, mucosa of sigmoid colon

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SATB2	2,254

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SATB2	Q9UPW6	3

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 11. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
RUNX2 regulates bone development	1	815.7×	0.012	SATB2
RUNX2 regulates osteoblast differentiation	1	456.8×	0.012	SATB2
Transcriptional regulation by RUNX2	1	253.8×	0.012	SATB2
SUMO E3 ligases SUMOylate target proteins	1	178.4×	0.012	SATB2
SUMOylation	1	163.1×	0.012	SATB2
SUMOylation of chromatin organization proteins	1	158.6×	0.012	SATB2
RNA Polymerase II Transcription	1	22.5×	0.068	SATB2
Post-translational protein modification	1	19.2×	0.068	SATB2
Gene expression (Transcription)	1	17.8×	0.068	SATB2
Generic Transcription Pathway	1	15.1×	0.073	SATB2
Metabolism of proteins	1	12.4×	0.081	SATB2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
osteoblast development	1	991.3×	0.008	SATB2
embryonic pattern specification	1	543.6×	0.008	SATB2
embryonic skeletal system morphogenesis	1	391.9×	0.008	SATB2
cartilage development	1	251.5×	0.008	SATB2
roof of mouth development	1	247.8×	0.008	SATB2
neuron migration	1	133.8×	0.012	SATB2
chromatin remodeling	1	73.0×	0.020	SATB2
negative regulation of transcription by RNA polymerase II	1	17.7×	0.071	SATB2
positive regulation of transcription by RNA polymerase II	1	14.9×	0.075	SATB2
regulation of transcription by RNA polymerase II	1	11.7×	0.086	SATB2

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SATB2	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
SATB2	6	Binding:6

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	SATB2

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
SATB2	6	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.