15q14 microdeletion syndrome

Summary

15q14 microdeletion syndrome (MONDO:0014822) is a disease with 3 cohort genes.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 3
• ClinVar variants: 2
• Phenotypes (HPO): 28

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		9	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

28 HPO clinical features (Orphanet curated; top 28 by frequency):

HPO ID	Term	Frequency
HP:0000175	Cleft palate	Very frequent (80-99%)
HP:0001249	Intellectual disability	Very frequent (80-99%)
HP:0001263	Global developmental delay	Very frequent (80-99%)
HP:0004322	Short stature	Very frequent (80-99%)
HP:0000750	Delayed speech and language development	Very frequent (80-99%)
HP:0000252	Microcephaly	Frequent (30-79%)
HP:0000307	Pointed chin	Frequent (30-79%)
HP:0000319	Smooth philtrum	Frequent (30-79%)
HP:0000322	Short philtrum	Frequent (30-79%)
HP:0000341	Narrow forehead	Frequent (30-79%)
HP:0000490	Deeply set eye	Frequent (30-79%)
HP:0004422	Biparietal narrowing	Frequent (30-79%)
HP:0000023	Inguinal hernia	Occasional (5-29%)
HP:0000164	Abnormality of the dentition	Occasional (5-29%)
HP:0000276	Long face	Occasional (5-29%)
HP:0000343	Long philtrum	Occasional (5-29%)
HP:0000369	Low-set ears	Occasional (5-29%)
HP:0000426	Prominent nasal bridge	Occasional (5-29%)
HP:0000444	Convex nasal ridge	Occasional (5-29%)
HP:0000717	Autism	Occasional (5-29%)
HP:0001061	Acne	Occasional (5-29%)
HP:0001250	Seizure	Occasional (5-29%)
HP:0001601	Laryngomalacia	Occasional (5-29%)
HP:0001631	Atrial septal defect	Occasional (5-29%)
HP:0002650	Scoliosis	Occasional (5-29%)
HP:0002721	Immunodeficiency	Occasional (5-29%)
HP:0002808	Kyphosis	Occasional (5-29%)
HP:0001629	Ventricular septal defect	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	15q14 microdeletion syndrome
Mondo ID	MONDO:0014822
OMIM	616898
Orphanet	261190
SNOMED CT	719575008
UMLS	C4305230
MedGen	930899
GARD	0017242
Is cancer (heuristic)	no

Also known as: Del(15)(q14) · monosomy 15q14

Data availability: 2 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 › 15q14 microdeletion 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, chromosome 15q11.2 deletion 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

2 retrieved; paginated sample, class counts are floors:

1 pathogenic, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
1341971	GRCh37/hg19 15q14(chr15:33809650-40027263)x1	ACTC1	Pathogenic	criteria provided, single submitter
2622505	NM_002039.4(GAB1):c.110G>A (p.Arg37His)	GAB1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

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

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ACTC1	Orphanet:154	Familial isolated dilated cardiomyopathy
ACTC1	Orphanet:54260	Left ventricular noncompaction
ACTC1	Orphanet:99103	Atrial septal defect, ostium secundum type

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
ACTC1	HGNC:143	ENSG00000159251	P68032	Actin, alpha cardiac muscle 1	clinvar
PIGU	HGNC:15791	ENSG00000101464	Q9H490	GPI-anchor transamidase component PIGU	clinvar
GAB1	HGNC:4066	ENSG00000109458	Q13480	GRB2-associated-binding protein 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ACTC1	Actin, alpha cardiac muscle 1	Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells.
PIGU	GPI-anchor transamidase component PIGU	Component of the glycosylphosphatidylinositol-anchor (GPI-anchor) transamidase (GPI-T) complex that catalyzes the formation of the linkage between a proprotein and a GPI-anchor and participates in GPI anchored protein biosynthesis.
GAB1	GRB2-associated-binding protein 1	Adapter protein that plays a role in intracellular signaling cascades triggered by activated receptor-type kinases.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 2 · 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	5.8×	0.327
Other/Unknown	2	1.2×	0.587

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ACTC1	Other/Unknown	no		Actin, Actin_CS, Actin/actin-like_CS
PIGU	Other/Unknown	no		PIG-U
GAB1	Scaffold/PPI	no		PH_domain, PH-like_dom_sf, Gab1-4-like

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
heart right ventricle	1
left ventricle myocardium	1
myocardium	1
ganglionic eminence	1
mucosa of transverse colon	1
ventricular zone	1
colonic epithelium	1
oocyte	1
secondary oocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ACTC1	224	broad	marker	left ventricle myocardium, heart right ventricle, myocardium
PIGU	240	ubiquitous	marker	mucosa of transverse colon, ganglionic eminence, ventricular zone
GAB1	278	ubiquitous	marker	secondary oocyte, oocyte, colonic epithelium

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
GAB1	1,982
ACTC1	996
PIGU	720

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ACTC1	P68032	16
GAB1	Q13480	5
PIGU	Q9H490	4

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 39. Enrichment computed across 3 evidence-associated genes (3 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 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
MET activates PTPN11	1	761.3×	0.012	GAB1
MET activates PI3K/AKT signaling	1	634.4×	0.012	GAB1
Activated NTRK2 signals through PI3K	1	543.8×	0.012	GAB1
Attachment of GPI anchor to uPAR	1	423.0×	0.012	PIGU
MET receptor recycling	1	380.7×	0.012	GAB1
MET activates RAP1 and RAC1	1	346.1×	0.012	GAB1
Signaling by FGFR4 in disease	1	317.2×	0.012	GAB1
Erythropoietin activates Phosphoinositide-3-kinase (PI3K)	1	317.2×	0.012	GAB1
Regulation of CDH1 Function	1	317.2×	0.012	ACTC1
Constitutive Signaling by EGFRvIII	1	237.9×	0.012	GAB1
PI3K events in ERBB2 signaling	1	223.9×	0.012	GAB1
Signaling by ERBB2 ECD mutants	1	223.9×	0.012	GAB1
GAB1 signalosome	1	211.5×	0.012	GAB1
PI-3K cascade:FGFR3	1	211.5×	0.012	GAB1
Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants	1	190.3×	0.012	GAB1
PI-3K cascade:FGFR4	1	190.3×	0.012	GAB1
PI-3K cascade:FGFR1	1	173.0×	0.012	GAB1
PI-3K cascade:FGFR2	1	165.5×	0.012	GAB1
Signaling by FGFR3 in disease	1	165.5×	0.012	GAB1
Signaling by ERBB2 KD Mutants	1	141.0×	0.014	GAB1
Striated Muscle Contraction	1	102.9×	0.017	ACTC1
Formation of the dystrophin-glycoprotein complex (DGC)	1	102.9×	0.017	ACTC1
Signaling by FGFR1 in disease	1	97.6×	0.017	GAB1
PI3K Cascade	1	90.6×	0.017	GAB1
Signaling by FGFR2 in disease	1	88.5×	0.017	GAB1
RET signaling	1	86.5×	0.017	GAB1
Activation of STAT3 by cadherin engagement	1	54.4×	0.026	ACTC1
Non-integrin membrane-ECM interactions	1	51.4×	0.026	ACTC1
RHOB GTPase cycle	1	51.4×	0.026	ACTC1
Constitutive Signaling by Aberrant PI3K in Cancer	1	42.3×	0.030	GAB1

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
actin-myosin filament sliding	1	2808.7×	0.007	ACTC1
cytoplasmic actin-based contraction involved in cell motility	1	1123.5×	0.007	ACTC1
mesenchyme migration	1	1123.5×	0.007	ACTC1
skeletal muscle thin filament assembly	1	936.2×	0.007	ACTC1
GPI anchored protein biosynthesis	1	936.2×	0.007	PIGU
attachment of GPI anchor to protein	1	702.2×	0.007	PIGU
endothelial cell chemotaxis	1	561.7×	0.007	GAB1
regulation of receptor signaling pathway via JAK-STAT	1	468.1×	0.007	PIGU
cardiac muscle tissue morphogenesis	1	468.1×	0.007	ACTC1
cardiac myofibril assembly	1	432.1×	0.007	ACTC1
vascular endothelial growth factor signaling pathway	1	351.1×	0.008	GAB1
actin filament-based movement	1	267.5×	0.009	ACTC1
heart contraction	1	255.3×	0.009	ACTC1
actomyosin structure organization	1	187.2×	0.012	ACTC1
GPI anchor biosynthetic process	1	165.2×	0.012	PIGU
cardiac muscle contraction	1	133.8×	0.014	ACTC1
positive regulation of blood vessel endothelial cell migration	1	130.6×	0.014	GAB1
vasodilation	1	122.1×	0.014	GAB1
epidermal growth factor receptor signaling pathway	1	82.6×	0.020	GAB1
insulin receptor signaling pathway	1	73.9×	0.020	GAB1
cellular response to mechanical stimulus	1	72.0×	0.020	GAB1
response to ethanol	1	48.9×	0.029	ACTC1
actin filament organization	1	39.6×	0.033	ACTC1
positive regulation of angiogenesis	1	38.5×	0.033	GAB1
positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	1	26.1×	0.047	GAB1
response to xenobiotic stimulus	1	23.0×	0.051	ACTC1
angiogenesis	1	20.8×	0.054	GAB1
positive regulation of gene expression	1	12.9×	0.082	ACTC1
intracellular signal transduction	1	12.7×	0.082	GAB1
negative regulation of apoptotic process	1	11.6×	0.087	ACTC1

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
ACTC1	0	0
PIGU	0	0
GAB1	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
ACTC1	6	Binding:6
GAB1	2	Binding:2

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	ACTC1, PIGU, GAB1

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)
ACTC1	6	—
PIGU	0	—
GAB1	2	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.