Chromosome 2q32-q33 deletion syndrome

Summary

Chromosome 2q32-q33 deletion syndrome (MONDO:0012864) is a disease caused by SATB2 (GenCC Definitive), with 5 cohort genes.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: SATB2 (GenCC Definitive)
• Cohort genes: 5
• ClinVar variants: 738
• Phenotypes (HPO): 43

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		25	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

43 HPO clinical features (Orphanet curated; top 43 by frequency):

HPO ID	Term	Frequency
HP:0000750	Delayed speech and language development	Very frequent (80-99%)
HP:0001263	Global developmental delay	Very frequent (80-99%)
HP:0004322	Short stature	Very frequent (80-99%)
HP:0010864	Intellectual disability, severe	Very frequent (80-99%)
HP:0000175	Cleft palate	Frequent (30-79%)
HP:0000218	High palate	Frequent (30-79%)
HP:0000233	Thin vermilion border	Frequent (30-79%)
HP:0000347	Micrognathia	Frequent (30-79%)
HP:0000348	High forehead	Frequent (30-79%)
HP:0000369	Low-set ears	Frequent (30-79%)
HP:0000426	Prominent nasal bridge	Frequent (30-79%)
HP:0000678	Dental crowding	Frequent (30-79%)
HP:0001252	Hypotonia	Frequent (30-79%)
HP:0001510	Growth delay	Frequent (30-79%)
HP:0002213	Fine hair	Frequent (30-79%)
HP:0011968	Feeding difficulties	Frequent (30-79%)
HP:0000160	Narrow mouth	Occasional (5-29%)
HP:0000248	Brachycephaly	Occasional (5-29%)
HP:0000252	Microcephaly	Occasional (5-29%)
HP:0000276	Long face	Occasional (5-29%)
HP:0000324	Facial asymmetry	Occasional (5-29%)
HP:0000343	Long philtrum	Occasional (5-29%)
HP:0000444	Convex nasal ridge	Occasional (5-29%)
HP:0000463	Anteverted nares	Occasional (5-29%)
HP:0000486	Strabismus	Occasional (5-29%)
HP:0000494	Downslanted palpebral fissures	Occasional (5-29%)
HP:0000677	Oligodontia	Occasional (5-29%)
HP:0000717	Autism	Occasional (5-29%)
HP:0000718	Aggressive behavior	Occasional (5-29%)
HP:0000739	Anxiety	Occasional (5-29%)
HP:0001166	Arachnodactyly	Occasional (5-29%)
HP:0001762	Talipes equinovarus	Occasional (5-29%)
HP:0001863	Toe clinodactyly	Occasional (5-29%)
HP:0002360	Sleep abnormality	Occasional (5-29%)
HP:0002546	Incomprehensible speech	Occasional (5-29%)
HP:0004209	Clinodactyly of the 5th finger	Occasional (5-29%)
HP:0007018	Attention deficit hyperactivity disorder	Occasional (5-29%)
HP:0008070	Sparse hair	Occasional (5-29%)
HP:0008734	Decreased testicular size	Occasional (5-29%)
HP:0010059	Broad hallux phalanx	Occasional (5-29%)
HP:0011304	Broad thumb	Occasional (5-29%)
HP:0100024	Conspicuously happy disposition	Occasional (5-29%)
HP:0001382	Joint hypermobility	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	chromosome 2q32-q33 deletion syndrome
Mondo ID	MONDO:0012864
MeSH	C567350
OMIM	612313
Orphanet	251019, 576283
DOID	DOID:0060428
SNOMED CT	719659003
UMLS	C2676739
MedGen	436765
GARD	0013206
Is cancer (heuristic)	no

Also known as: 2q32q33 microdeletion syndromes · chromosome 2q32-q33 deletion syndrome · Del(2)(q32) · Del(2)(q32q33) · glass · glass syndrome · monosomy 2q32-q33 · monosomy 2q32q33 · SAS · SATB2 syndrome · SATB2-associated syndrome

Data availability: 738 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › chromosomal disorder › syndrome caused by partial chromosomal deletion › partial deletion of chromosome 2 › partial deletion of the long arm of chromosome 2 › chromosome 2q32-q33 deletion syndrome

Related subtypes (8): 2q37 microdeletion syndrome, chromosome 2q31.2 deletion syndrome, 2q24 microdeletion syndrome, 2q23.1 microdeletion syndrome, 2q31.1 microdeletion syndrome, 2q33.1 microdeletion syndrome, Mowat-Wilson syndrome due to monosomy 2q22, 2q13 microdeletion 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

600 retrieved; paginated sample, class counts are floors:

269 likely benign, 152 uncertain significance, 60 pathogenic, 47 benign, 35 likely pathogenic, 18 conflicting classifications of pathogenicity, 12 benign/likely benign, 7 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1703524	GRCh37/hg19 2q32.1-34(chr2:185697659-213002074)	COL5A2	Pathogenic	no assertion criteria provided
2576537	NM_001172509.2(SATB2):c.2104del (p.Asp702fs)	LOC126806462	Pathogenic	no assertion criteria provided
3370478	NM_001172509.2(SATB2):c.1763dup (p.Pro589fs)	LOC126806462	Pathogenic	criteria provided, single submitter
3777182	NM_001172509.2(SATB2):c.1972_1973del (p.Thr658fs)	LOC126806462	Pathogenic	criteria provided, single submitter
436636	NM_001172509.2(SATB2):c.1964C>T (p.Pro655Leu)	LOC126806462	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1032667	NM_001172509.2(SATB2):c.1135C>T (p.Gln379Ter)	SATB2	Pathogenic	criteria provided, single submitter
1076235	NC_000002.11:g.(?200136914)(200320780_?)del	SATB2	Pathogenic	criteria provided, single submitter
1208890	NM_001172509.2(SATB2):c.1564C>T (p.Arg522Cys)	SATB2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1308668	NM_001172509.2(SATB2):c.1153del (p.Val385fs)	SATB2	Pathogenic	criteria provided, single submitter
1320122	NM_001172509.2(SATB2):c.150del (p.Val51fs)	SATB2	Pathogenic	criteria provided, single submitter
1323551	NM_001172509.2(SATB2):c.1705dup (p.Gln569fs)	SATB2	Pathogenic	criteria provided, single submitter
1338898	NM_001172509.2(SATB2):c.1544G>A (p.Gly515Asp)	SATB2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1343141	NM_001172509.2(SATB2):c.1174G>C (p.Gly392Arg)	SATB2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1373974	NM_001172509.2(SATB2):c.554del (p.Glu185fs)	SATB2	Pathogenic	criteria provided, single submitter
1411669	NM_001172509.2(SATB2):c.588_595del (p.Leu197fs)	SATB2	Pathogenic	criteria provided, single submitter
1453296	NM_001172509.2(SATB2):c.346+2T>A	SATB2	Pathogenic	criteria provided, single submitter
1453490	NM_001172509.2(SATB2):c.282_289dup (p.Val97fs)	SATB2	Pathogenic	criteria provided, single submitter
1457171	NM_001172509.2(SATB2):c.346+1G>A	SATB2	Pathogenic	criteria provided, single submitter
1526096	NM_001172509.2(SATB2):c.1166G>T (p.Arg389Leu)	SATB2	Pathogenic	criteria provided, multiple submitters, no conflicts
1805641	NM_001172509.2(SATB2):c.728C>G (p.Ser243Ter)	SATB2	Pathogenic	criteria provided, single submitter
1809701	NM_001172509.2(SATB2):c.344_346+1dup	SATB2	Pathogenic	criteria provided, single submitter
1809703	NM_001172509.2(SATB2):c.138del (p.Arg46fs)	SATB2	Pathogenic	criteria provided, single submitter
1809704	NM_001172509.2(SATB2):c.622dup (p.Ser208fs)	SATB2	Pathogenic	criteria provided, single submitter
208673	NM_001172509.2(SATB2):c.847C>T (p.Arg283Ter)	SATB2	Pathogenic	criteria provided, multiple submitters, no conflicts
2101013	NM_001172509.2(SATB2):c.1569G>A (p.Trp523Ter)	SATB2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
217315	NC_000002.12:g.(199364049_199364051)_(199399060_199399062)dup	SATB2	Pathogenic	no assertion criteria provided
218098	NM_001172509.1(SATB2):c.170_346dup	SATB2	Pathogenic	no assertion criteria provided
2203243	NM_001172509.2(SATB2):c.1204G>A (p.Glu402Lys)	SATB2	Pathogenic	criteria provided, multiple submitters, no conflicts
224131	NM_001172509.2(SATB2):c.1131_1132del (p.Ser378fs)	SATB2	Pathogenic	criteria provided, single submitter
235893	NM_001172509.2(SATB2):c.1495A>T (p.Lys499Ter)	SATB2	Pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 6 · 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	chromosome 2q32-q33 deletion syndrome	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
COL5A2	Orphanet:287	Classical Ehlers-Danlos syndrome
PGAP1	Orphanet:401820	Autosomal recessive spastic paraplegia type 67
PGAP1	Orphanet:88616	Autosomal recessive non-syndromic intellectual disability

Cohort genes → proteins

5 cohort genes, 5 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	5

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SATB2	HGNC:21637	ENSG00000119042	Q9UPW6	DNA-binding protein SATB2	gencc,clinvar
COL5A2	HGNC:2210	ENSG00000204262	P05997	Collagen alpha-2(V) chain	clinvar
PGAP1	HGNC:25712	ENSG00000197121	Q75T13	GPI inositol-deacylase	clinvar
ANKAR	HGNC:26350	ENSG00000151687	Q7Z5J8	Ankyrin and armadillo repeat-containing protein	clinvar
GTF3C3	HGNC:4666	ENSG00000119041	Q9Y5Q9	General transcription factor 3C polypeptide 3	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.
COL5A2	Collagen alpha-2(V) chain	Type V collagen is a member of group I collagen (fibrillar forming collagen).
PGAP1	GPI inositol-deacylase	GPI inositol-deacylase that catalyzes the remove of the acyl chain linked to the 2-OH position of inositol ring from the GPI-anchored protein (GPI-AP) in the endoplasmic reticulum.
GTF3C3	General transcription factor 3C polypeptide 3	Involved in RNA polymerase III-mediated transcription.

Protein-family classification

Druggable: 0 · Difficult: 2 · Unknown: 3 · 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
Scaffold/PPI	1	3.5×	0.608
Transcription factor	1	1.6×	0.608
Other/Unknown	3	1.1×	0.608

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SATB2	Transcription factor	no		HD, CUT_dom, Homeodomain-like_sf
COL5A2	Other/Unknown	no		Fib_collagen_C, VWF_dom, Collagen
PGAP1	Other/Unknown	no		PGAP1-ab_dom-like, AB_hydrolase_fold, PGAP1/BST1
ANKAR	Scaffold/PPI	no		Armadillo, Ankyrin_rpt, ARM-like
GTF3C3	Other/Unknown	no		TPR-like_helical_dom_sf, TPR_rpt, Tfc4/TFIIIC-102/Sfc4

Expression context

Cohort genes with no expression data: 0.

4 cohort genes 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)	5
unknown	0

Top tissues across cohort

Tissue	Cohort genes
periodontal ligament	2
calcaneal tendon	2
cortical plate	1
mucosa of sigmoid colon	1
stromal cell of endometrium	1
tendon of biceps brachii	1
endothelial cell	1
ganglionic eminence	1
upper leg skin	1
left ovary	1
male germ line stem cell (sensu Vertebrata) in testis	1
adrenal tissue	1
colonic epithelium	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
COL5A2	266	ubiquitous	marker	tendon of biceps brachii, periodontal ligament, stromal cell of endometrium
PGAP1	271	ubiquitous	marker	endothelial cell, ganglionic eminence, upper leg skin
ANKAR	163	ubiquitous	yes	calcaneal tendon, male germ line stem cell (sensu Vertebrata) in testis, left ovary
GTF3C3	279	ubiquitous	marker	calcaneal tendon, adrenal tissue, colonic epithelium

Protein interactions among cohort

Intra-cohort edges: 2.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
GTF3C3	2,461
COL5A2	2,286
SATB2	2,254
PGAP1	882
ANKAR	573

Intra-cohort edges

A	B	Sources
COL5A2	GTF3C3	string_interaction
GTF3C3	SATB2	string_interaction

Structural data

PDB: 2 · AlphaFold-only: 3 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SATB2	Q9UPW6	3
GTF3C3	Q9Y5Q9	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
PGAP1	Q75T13	89.15
ANKAR	Q7Z5J8	84.79
COL5A2	P05997	53.15

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 31. Enrichment computed across 5 evidence-associated genes (4 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 4 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Attachment of GPI anchor to uPAR	1	317.2×	0.030	PGAP1
RUNX2 regulates bone development	1	203.9×	0.030	SATB2
Fibronectin matrix formation	1	142.8×	0.030	COL5A2
Attachment of bacteria to epithelial cells	1	124.1×	0.030	COL5A2
RUNX2 regulates osteoblast differentiation	1	114.2×	0.030	SATB2
Syndecan interactions	1	105.7×	0.030	COL5A2
RNA Polymerase III Transcription Initiation From Type 2 Promoter	1	105.7×	0.030	GTF3C3
RNA Polymerase III Transcription Initiation From Type 1 Promoter	1	102.0×	0.030	GTF3C3
MET activates PTK2 signaling	1	95.2×	0.030	COL5A2
RNA Polymerase III Transcription Initiation	1	84.0×	0.030	GTF3C3
RNA Polymerase III Transcription	1	81.6×	0.030	GTF3C3
RNA Polymerase III Abortive And Retractive Initiation	1	69.6×	0.030	GTF3C3
Collagen chain trimerization	1	64.9×	0.030	COL5A2
Signaling by PDGF	1	63.4×	0.030	COL5A2
Transcriptional regulation by RUNX2	1	63.4×	0.030	SATB2
NCAM1 interactions	1	62.1×	0.030	COL5A2
Developmental Lineage of Pancreatic Ductal Cells	1	57.1×	0.030	COL5A2
Gene expression (Transcription)	2	8.9×	0.030	SATB2, GTF3C3
Assembly of collagen fibrils and other multimeric structures	1	50.1×	0.031	COL5A2
SUMO E3 ligases SUMOylate target proteins	1	44.6×	0.031	SATB2
Collagen degradation	1	43.9×	0.031	COL5A2
Collagen biosynthesis and modifying enzymes	1	42.6×	0.031	COL5A2
SUMOylation	1	40.8×	0.031	SATB2
SUMOylation of chromatin organization proteins	1	39.6×	0.031	SATB2
Non-integrin membrane-ECM interactions	1	38.6×	0.031	COL5A2
ECM proteoglycans	1	37.6×	0.031	COL5A2
Integrin cell surface interactions	1	33.6×	0.034	COL5A2
RNA Polymerase II Transcription	1	5.6×	0.184	SATB2
Post-translational protein modification	1	4.8×	0.206	SATB2
Generic Transcription Pathway	1	3.8×	0.248	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 4 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
embryonic pattern specification	2	271.8×	5e-04	SATB2, PGAP1
negative regulation of endodermal cell differentiation	1	2106.5×	0.006	COL5A2
eye morphogenesis	1	1053.2×	0.006	COL5A2
forebrain regionalization	1	842.6×	0.006	PGAP1
positive regulation of ER to Golgi vesicle-mediated transport	1	842.6×	0.006	PGAP1
5S class rRNA transcription by RNA polymerase III	1	702.2×	0.006	GTF3C3
attachment of GPI anchor to protein	1	526.6×	0.007	PGAP1
tRNA transcription by RNA polymerase III	1	383.0×	0.008	GTF3C3
osteoblast development	1	247.8×	0.012	SATB2
transcription by RNA polymerase III	1	191.5×	0.013	GTF3C3
anterior/posterior axis specification	1	183.2×	0.013	PGAP1
GPI anchor biosynthetic process	1	123.9×	0.017	PGAP1
skin development	1	110.9×	0.018	COL5A2
embryonic skeletal system morphogenesis	1	98.0×	0.019	SATB2
cellular response to amino acid stimulus	1	76.6×	0.023	COL5A2
cartilage development	1	62.9×	0.025	SATB2
roof of mouth development	1	62.0×	0.025	SATB2
collagen fibril organization	1	56.2×	0.026	COL5A2
neuron migration	1	33.4×	0.040	SATB2
skeletal system development	1	31.4×	0.041	COL5A2
sensory perception of sound	1	25.2×	0.048	PGAP1
chromatin remodeling	1	18.2×	0.063	SATB2
protein transport	1	11.0×	0.100	PGAP1
negative regulation of transcription by RNA polymerase II	1	4.4×	0.225	SATB2
positive regulation of transcription by RNA polymerase II	1	3.7×	0.253	SATB2
regulation of transcription by RNA polymerase II	1	2.9×	0.302	SATB2

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 5

Druggability breadth: 3 of 5 evidence-associated genes (60%) 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
COL5A2	0	0
PGAP1	0	0
ANKAR	0	0
GTF3C3	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
GTF3C3	1	Binding:1

Pharmacogenomics

Cohort genes with a PharmGKB record: 5; 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	5	SATB2, COL5A2, PGAP1, ANKAR, GTF3C3

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
SATB2	6	—
COL5A2	0	—
PGAP1	0	—
ANKAR	0	—
GTF3C3	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.