Chromosome 15q11.2 deletion syndrome

Summary

Chromosome 15q11.2 deletion syndrome (MONDO:0014294) is a disease with 3 cohort genes.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 3
• ClinVar variants: 19
• Phenotypes (HPO): 31

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		200	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

31 HPO clinical features (Orphanet curated; top 31 by frequency):

HPO ID	Term	Frequency
HP:0000174	Abnormal palate morphology	Frequent (30-79%)
HP:0000377	Abnormal pinna morphology	Frequent (30-79%)
HP:0000708	Atypical behavior	Frequent (30-79%)
HP:0000750	Delayed speech and language development	Frequent (30-79%)
HP:0001249	Intellectual disability	Frequent (30-79%)
HP:0001263	Global developmental delay	Frequent (30-79%)
HP:0001270	Motor delay	Frequent (30-79%)
HP:0001999	Abnormal facial shape	Frequent (30-79%)
HP:0002354	Memory impairment	Frequent (30-79%)
HP:0006891	Thick cerebral cortex	Frequent (30-79%)
HP:0007018	Attention deficit hyperactivity disorder	Frequent (30-79%)
HP:0010522	Dyslexia	Frequent (30-79%)
HP:0410263	Brain imaging abnormality	Frequent (30-79%)
HP:0000252	Microcephaly	Occasional (5-29%)
HP:0000337	Broad forehead	Occasional (5-29%)
HP:0000717	Autism	Occasional (5-29%)
HP:0000729	Autistic behavior	Occasional (5-29%)
HP:0000736	Short attention span	Occasional (5-29%)
HP:0001250	Seizure	Occasional (5-29%)
HP:0001251	Ataxia	Occasional (5-29%)
HP:0001627	Abnormal heart morphology	Occasional (5-29%)
HP:0002172	Postural instability	Occasional (5-29%)
HP:0002370	Poor coordination	Occasional (5-29%)
HP:0100716	Self-injurious behavior	Occasional (5-29%)
HP:0100753	Schizophrenia	Occasional (5-29%)
HP:0001629	Ventricular septal defect	Very rare (<1-4%)
HP:0001631	Atrial septal defect	Very rare (<1-4%)
HP:0001636	Tetralogy of Fallot	Very rare (<1-4%)
HP:0001680	Coarctation of aorta	Very rare (<1-4%)
HP:0002198	Dilated fourth ventricle	Very rare (<1-4%)
HP:0005160	Total anomalous pulmonary venous return	Very rare (<1-4%)

Identifiers

Disease identifiers

Field	Value
Canonical name	chromosome 15q11.2 deletion syndrome
Mondo ID	MONDO:0014294
OMIM	615656
Orphanet	261183
DOID	DOID:0060393
UMLS	C3180937
MedGen	467404
GARD	0010525
Is cancer (heuristic)	no

Also known as: 15q11.2 BP1-BP2 microdeletion syndrome · 15q11.2 microdeletion · 15q11.2 microdeletion syndrome · chromosome 15q11.2 deletion · chromosome 15q11.2 deletion syndrome · chromosome 15q11.2 microdeletion · Del(15)(q11.2) · monosomy 15q11.2

Data availability: 19 ClinVar variants.

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 the long arm of chromosome 15 › chromosome 15q11.2 deletion syndrome

Related subtypes (8): deafness-infertility syndrome, chromosome 15q13.3 microdeletion syndrome, chromosome 15q26-qter deletion syndrome, chromosome 15q24 deletion syndrome, chromosome 15q25 deletion syndrome, 15q14 microdeletion syndrome, Prader-Willi syndrome due to paternal 15q11q13 deletion, Angelman syndrome due to maternal 15q11q13 deletion

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

19 retrieved; paginated sample, class counts are floors:

11 pathogenic, 4 uncertain significance, 3 not provided, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1330198	GRCh37/hg19 15q11.2(chr15:22743127-23246000)x1	CYFIP1	Pathogenic	criteria provided, single submitter
2506528	GRCh37/hg19 15q11.2(chr15:22833525-23412276)	CYFIP1	Pathogenic	criteria provided, single submitter
2574676	GRCh37/hg19 15q11.2(chr15:22770421-23282799)	CYFIP1	Pathogenic	no assertion criteria provided
2574691	GRCh37/hg19 15q11.2(chr15:22770421-23195725)	CYFIP1	Pathogenic	no assertion criteria provided
2580327	GRCh37/hg19 15q11.2(chr15:22744149-23246340)x1	CYFIP1	Pathogenic	criteria provided, single submitter
3235914	GRCh38/hg38 15q11.2(chr15:22583760-23123885)	CYFIP1	Pathogenic	criteria provided, single submitter
3235943	GRCh38/hg38 15q11.2(chr15:22600363-23120182)	CYFIP1	Pathogenic	criteria provided, single submitter
3338424	Single allele	CYFIP1	Pathogenic	criteria provided, single submitter
3359215	Single allele	CYFIP1	Pathogenic	no assertion criteria provided
666449	GRCh37/hg19 15q11.2(chr15:22765628-23217514)x1	CYFIP1	Pathogenic	criteria provided, single submitter
2498204	NC_000015.10:g.22698177_(23120963_23380983)del	GOLGA8S	Pathogenic	criteria provided, single submitter
983494	NC_000017.11:g.2688360_2784321del	CLUH	Likely pathogenic	criteria provided, single submitter
1330174	GRCh37/hg19 15q11.2(chr15:22744149-23407579)x3	CYFIP1	Uncertain significance	criteria provided, single submitter
2499630	GRCh38/hg38 15q11.2(chr15:22781888-23030923)	CYFIP1	Uncertain significance	criteria provided, single submitter
2499631	GRCh38/hg38 15q11.2(chr15:22787668-23051531)	CYFIP1	Uncertain significance	criteria provided, single submitter
2499632	GRCh38/hg38 15q11.2(chr15:22787849-23051049)	CYFIP1	Uncertain significance	criteria provided, single submitter
2502281	GRCh37/hg19 15q11.2(chr15:22770421-23282799)x1	CYFIP1	not provided	no classification provided
3906221	GRCh37/hg19 15q11.2(chr15:22770421-23282799)x1	CYFIP1	not provided	no classification provided
3906222	GRCh37/hg19 15q11.2(chr15:22832519-23090897)x1	CYFIP1	not provided	no classification provided

Genes & proteins

Mendelian disease overlap and somatic drivers

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

Cohort genes → proteins

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
CYFIP1	HGNC:13759	ENSG00000273749	Q7L576	Cytoplasmic FMR1-interacting protein 1	clinvar
CLUH	HGNC:29094	ENSG00000132361	O75153	Clustered mitochondria protein homolog	clinvar
GOLGA8S	HGNC:44409	ENSG00000261739	H3BPF8	Golgin subfamily A member 8S	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CYFIP1	Cytoplasmic FMR1-interacting protein 1	Component of the CYFIP1-EIF4E-FMR1 complex which binds to the mRNA cap and mediates translational repression.
CLUH	Clustered mitochondria protein homolog	mRNA-binding protein involved in proper cytoplasmic distribution of mitochondria.

Protein-family classification

Druggable: 0 · Difficult: 0 · 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
Other/Unknown	3	1.8×	0.174

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CYFIP1	Other/Unknown	no		Cytoplasmic_FMR1-int, CYRIA/CYRIB_Rac1-bd
CLUH	Other/Unknown	no		TPR-like_helical_dom_sf, GSKIP_dom_sf, CLU_dom
GOLGA8S	Other/Unknown	no		GOLGA, GOLGA_C, GOLGA_cons_dom

Expression context

Cohort genes with no expression data: 0.

3 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)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
epithelium of esophagus	1
esophagus squamous epithelium	1
germinal epithelium of ovary	1
apex of heart	1
gingival epithelium	1
right lobe of liver	1
left testis	1
right testis	1
testis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CYFIP1	295	ubiquitous	marker	esophagus squamous epithelium, germinal epithelium of ovary, epithelium of esophagus
CLUH	283	ubiquitous	marker	gingival epithelium, apex of heart, right lobe of liver
GOLGA8S	120		marker	left testis, testis, right testis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CYFIP1	2,156
CLUH	1,875
GOLGA8S	160

Structural data

PDB: 1 · AlphaFold-only: 2 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CYFIP1	Q7L576	5

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
CLUH	O75153	83.11
GOLGA8S	H3BPF8	69.74

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 9. Enrichment computed across 3 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
RHO GTPases Activate WASPs and WAVEs	1	317.2×	0.011	CYFIP1
FCGR3A-mediated phagocytosis	1	187.2×	0.011	CYFIP1
Regulation of actin dynamics for phagocytic cup formation	1	184.2×	0.011	CYFIP1
RHOG GTPase cycle	1	148.3×	0.011	CYFIP1
VEGFA-VEGFR2 Pathway	1	139.3×	0.011	CYFIP1
RAC2 GTPase cycle	1	126.9×	0.011	CYFIP1
RAC3 GTPase cycle	1	119.0×	0.011	CYFIP1
RAC1 GTPase cycle	1	61.1×	0.018	CYFIP1
Neutrophil degranulation	1	23.1×	0.043	CYFIP1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
regulation of translation at postsynapse, modulating synaptic transmission	1	1872.4×	0.005	CYFIP1
positive regulation of neurotrophin TRK receptor signaling pathway	1	1123.5×	0.005	CYFIP1
intracellular distribution of mitochondria	1	802.5×	0.005	CLUH
regulation of modification of postsynaptic actin cytoskeleton	1	802.5×	0.005	CYFIP1
positive regulation of Arp2/3 complex-mediated actin nucleation	1	702.2×	0.005	CYFIP1
dendrite extension	1	561.7×	0.006	CYFIP1
ruffle organization	1	432.1×	0.006	CYFIP1
positive regulation of lamellipodium assembly	1	200.6×	0.010	CYFIP1
regulation of actin filament polymerization	1	193.7×	0.010	CYFIP1
Rac protein signal transduction	1	187.2×	0.010	CYFIP1
axon extension	1	165.2×	0.010	CYFIP1
lamellipodium assembly	1	147.8×	0.011	CYFIP1
cognition	1	95.2×	0.015	CYFIP1
regulation of translation	1	73.0×	0.019	CYFIP1
cell morphogenesis	1	52.5×	0.023	CYFIP1
mitochondrion organization	1	50.6×	0.023	CLUH
Golgi organization	1	44.6×	0.025	GOLGA8S
regulation of cell shape	1	41.0×	0.026	CYFIP1
axon guidance	1	30.2×	0.033	CYFIP1

Therapeutics

Drug target analysis

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

Druggability breadth: 2 of 3 evidence-associated genes (67%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CYFIP1	0	0
CLUH	0	0
GOLGA8S	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
CYFIP1	7	Binding:7
CLUH	1	Binding:1

Pharmacogenomics

Cohort genes with a PharmGKB record: 3; 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	3	CYFIP1, CLUH, GOLGA8S

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
CYFIP1	7	—
CLUH	1	—
GOLGA8S	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.