Xq25 microduplication syndrome

Summary

Xq25 microduplication syndrome (MONDO:0010507) is a disease with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 1
• ClinVar variants: 3
• Phenotypes (HPO): 20

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		28	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

20 HPO clinical features (Orphanet curated; top 20 by frequency):

HPO ID	Term	Frequency
HP:0000272	Malar flattening	Frequent (30-79%)
HP:0000286	Epicanthus	Frequent (30-79%)
HP:0000297	Facial hypotonia	Frequent (30-79%)
HP:0000303	Mandibular prognathia	Frequent (30-79%)
HP:0000729	Autistic behavior	Frequent (30-79%)
HP:0000739	Anxiety	Frequent (30-79%)
HP:0000752	Hyperactivity	Frequent (30-79%)
HP:0001250	Seizure	Frequent (30-79%)
HP:0001263	Global developmental delay	Frequent (30-79%)
HP:0001290	Generalized hypotonia	Frequent (30-79%)
HP:0001321	Cerebellar hypoplasia	Frequent (30-79%)
HP:0002079	Hypoplasia of the corpus callosum	Frequent (30-79%)
HP:0002342	Intellectual disability, moderate	Frequent (30-79%)
HP:0002360	Sleep abnormality	Frequent (30-79%)
HP:0002553	Highly arched eyebrow	Frequent (30-79%)
HP:0008050	Abnormality of the palpebral fissures	Frequent (30-79%)
HP:0009088	Speech articulation difficulties	Frequent (30-79%)
HP:0012471	Thick vermilion border	Frequent (30-79%)
HP:0045075	Sparse eyebrow	Frequent (30-79%)
HP:0004322	Short stature	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	Xq25 microduplication syndrome
Mondo ID	MONDO:0010507
OMIM	300979
Orphanet	521258
NCIT	C177544
UMLS	C4311049
MedGen	935016
GARD	0017955
Is cancer (heuristic)	no

Also known as: Xq25 duplication syndrome

Data availability: 3 ClinVar variants · 1 GenCC gene-disease record · 1 cell line.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › chromosomal disorder › syndrome caused by partial chromosomal duplication › partial duplication of chromosome X › partial duplication of the long arm of chromosome X › Xq25 microduplication syndrome

Related subtypes (4): syndromic X-linked intellectual disability Lubs type, Xq27.3q28 duplication syndrome, X-linked acrogigantism due to Xq26 microduplication, Xq12-q13.3 duplication 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

3 retrieved; paginated sample, class counts are floors:

3 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1701783	Single allele	LOC130068630	Pathogenic	criteria provided, single submitter
1703598	GRCh37/hg19 Xq25(chrX:122855926-123438005)	STAG2	Pathogenic	no assertion criteria provided
1703599	GRCh37/hg19 Xq25(chrX:122845829-123288831)	STAG2	Pathogenic	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · 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
STAG2	Limited	X-linked	Xq25 microduplication syndrome	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
STAG2	Orphanet:220386	Semilobar holoprosencephaly
STAG2	Orphanet:521258	Xq25 microduplication syndrome
STAG2	Orphanet:93925	Alobar holoprosencephaly

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
STAG2	HGNC:11355	ENSG00000101972	Q8N3U4	Cohesin subunit SA-2	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
STAG2	Cohesin subunit SA-2	Component of cohesin complex, a complex required for the cohesion of sister chromatids after DNA replication.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · 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
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
STAG2	Other/Unknown	no		STAG, ARM-type_fold, SCD

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
calcaneal tendon	1
mucosa of paranasal sinus	1
sural nerve	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
STAG2	299	ubiquitous	marker	mucosa of paranasal sinus, calcaneal tendon, sural nerve

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
STAG2	2,945

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
STAG2	Q8N3U4	9

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 24. 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
Mitotic Telophase/Cytokinesis	1	1427.5×	0.008	STAG2
Cohesin Loading onto Chromatin	1	1142.0×	0.008	STAG2
Establishment of Sister Chromatid Cohesion	1	1038.2×	0.008	STAG2
Meiosis	1	285.5×	0.017	STAG2
Reproduction	1	190.3×	0.017	STAG2
S Phase	1	181.3×	0.017	STAG2
SUMO E3 ligases SUMOylate target proteins	1	178.4×	0.017	STAG2
SUMOylation	1	163.1×	0.017	STAG2
SUMOylation of DNA damage response and repair proteins	1	146.4×	0.017	STAG2
Meiotic synapsis	1	141.0×	0.017	STAG2
ESR-mediated signaling	1	128.3×	0.017	STAG2
Signaling by Nuclear Receptors	1	102.0×	0.018	STAG2
Mitotic Metaphase and Anaphase	1	96.8×	0.018	STAG2
Mitotic Anaphase	1	96.8×	0.018	STAG2
Resolution of Sister Chromatid Cohesion	1	86.5×	0.018	STAG2
Estrogen-dependent gene expression	1	75.6×	0.020	STAG2
Mitotic Prometaphase	1	69.2×	0.020	STAG2
M Phase	1	66.0×	0.020	STAG2
Separation of Sister Chromatids	1	60.7×	0.021	STAG2
Cell Cycle, Mitotic	1	48.2×	0.025	STAG2
Cell Cycle	1	36.0×	0.032	STAG2
Post-translational protein modification	1	19.2×	0.057	STAG2
Metabolism of proteins	1	12.4×	0.084	STAG2
Signal Transduction	1	10.2×	0.098	STAG2

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
establishment of mitotic sister chromatid cohesion	1	2407.4×	0.002	STAG2
sister chromatid cohesion	1	766.0×	0.003	STAG2
mitotic spindle assembly	1	343.9×	0.005	STAG2
meiotic cell cycle	1	244.2×	0.005	STAG2
cell division	1	46.2×	0.022	STAG2

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
STAG2	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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	STAG2

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)
STAG2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.