2q24 microdeletion syndrome

Summary

2q24 microdeletion syndrome (MONDO:0015566) is a disease with 3 cohort genes.

At a glance

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

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		23	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:0000470	Short neck	Very frequent (80-99%)
HP:0000494	Downslanted palpebral fissures	Very frequent (80-99%)
HP:0000525	Abnormality iris morphology	Very frequent (80-99%)
HP:0000708	Atypical behavior	Very frequent (80-99%)
HP:0001188	Hand clenching	Very frequent (80-99%)
HP:0001249	Intellectual disability	Very frequent (80-99%)
HP:0001250	Seizure	Very frequent (80-99%)
HP:0001263	Global developmental delay	Very frequent (80-99%)
HP:0001319	Neonatal hypotonia	Very frequent (80-99%)
HP:0001508	Failure to thrive	Very frequent (80-99%)
HP:0001510	Growth delay	Very frequent (80-99%)
HP:0001518	Small for gestational age	Very frequent (80-99%)
HP:0001770	Toe syndactyly	Very frequent (80-99%)
HP:0010078	Bullet-shaped distal phalanx of the hallux	Very frequent (80-99%)
HP:0011344	Severe global developmental delay	Very frequent (80-99%)
HP:0100490	Camptodactyly of finger	Very frequent (80-99%)
HP:0100807	Long fingers	Very frequent (80-99%)
HP:0000358	Posteriorly rotated ears	Very frequent (80-99%)
HP:0000190	Abnormal oral frenulum morphology	Frequent (30-79%)
HP:0000274	Small face	Frequent (30-79%)
HP:0000316	Hypertelorism	Frequent (30-79%)
HP:0000322	Short philtrum	Frequent (30-79%)
HP:0000518	Cataract	Frequent (30-79%)
HP:0000568	Microphthalmia	Frequent (30-79%)
HP:0000589	Coloboma	Frequent (30-79%)
HP:0000729	Autistic behavior	Frequent (30-79%)
HP:0002871	Central apnea	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	2q24 microdeletion syndrome
Mondo ID	MONDO:0015566
MeSH	C538316
Orphanet	1617
SNOMED CT	719658006
UMLS	C2931816
MedGen	419168
GARD	0003746
Is cancer (heuristic)	no

Also known as: 2q24 deletion · chromosome 2q24 microdeletion syndrome · Del(2)(q24) · deletion 2q24 · monosomy 2q24

Data availability: 3 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 chromosome 2 › partial deletion of the long arm of chromosome 2 › 2q24 microdeletion syndrome

Related subtypes (8): 2q37 microdeletion syndrome, chromosome 2q32-q33 deletion syndrome, chromosome 2q31.2 deletion 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

3 retrieved; paginated sample, class counts are floors:

2 pathogenic, 1 not provided

ClinVar	Variant (HGVS)	Gene	Classification	Review
981210	GRCh37/hg19 2q24.2-31.3(chr2:163078055-182119617)x1	B3GALT1	Pathogenic	no assertion criteria provided
1339653	GRCh37/hg19 2q24.2-31.1(chr2:160347642-174075851)x1	DCAF17	Pathogenic	criteria provided, single submitter
3906191	GRCh37/hg19 2q24.1-24.2(chr2:156006517-162061520)x1	ACVR1	not provided	no classification provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ACVR1	Orphanet:337	Fibrodysplasia ossificans progressiva

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
ACVR1	HGNC:171	ENSG00000115170	Q04771	Activin receptor type-1	clinvar
DCAF17	HGNC:25784	ENSG00000115827	Q5H9S7	DDB1- and CUL4-associated factor 17	clinvar
B3GALT1	HGNC:916	ENSG00000172318	Q9Y5Z6	Beta-1,3-galactosyltransferase 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ACVR1	Activin receptor type-1	Bone morphogenetic protein (BMP) type I receptor that is involved in a wide variety of biological processes, including bone, heart, cartilage, nervous, and reproductive system development and regulation.
DCAF17	DDB1- and CUL4-associated factor 17	May function as a substrate receptor for CUL4-DDB1 E3 ubiquitin-protein ligase complex.
B3GALT1	Beta-1,3-galactosyltransferase 1	Beta-1,3-galactosyltransferase that transfers galactose from UDP-alpha-D-galactose to substrates with a terminal beta-N-acetylglucosamine (beta-GlcNAc) residue.

Protein-family classification

Druggable: 2 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.67

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
Kinase	1	9.2×	0.313
Enzyme (other)	1	4.0×	0.345
Other/Unknown	1	0.6×	0.914

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ACVR1	Kinase	yes	2.7.10.2	TGFB_receptor, Activin_recp, Prot_kinase_dom
DCAF17	Other/Unknown	no		DCAF17
B3GALT1	Enzyme (other)	yes	2.4.1.134	Glyco_trans_31, Nucleotide-diphossugar_trans

Expression context

Cohort genes with no expression data: 0.

2 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
cortical plate	2
male germ line stem cell (sensu Vertebrata) in testis	2
cartilage tissue	1
saphenous vein	1
synovial joint	1
adrenal tissue	1
hindlimb stylopod muscle	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ACVR1	293	ubiquitous	marker	cartilage tissue, synovial joint, saphenous vein
DCAF17	220	ubiquitous	yes	cortical plate, male germ line stem cell (sensu Vertebrata) in testis, adrenal tissue
B3GALT1	136	broad	marker	cortical plate, hindlimb stylopod muscle, male germ line stem cell (sensu Vertebrata) in testis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ACVR1	2,369
DCAF17	1,488
B3GALT1	641

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ACVR1	Q04771	85

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
B3GALT1	Q9Y5Z6	89.11
DCAF17	Q5H9S7	87.38

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 5. Enrichment computed across 3 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Blood group systems biosynthesis	1	571.0×	0.007	B3GALT1
Lewis blood group biosynthesis	1	335.9×	0.007	B3GALT1
Metabolism of carbohydrates and carbohydrate derivatives	1	60.1×	0.028	B3GALT1
Neddylation	1	23.7×	0.052	DCAF17
Metabolism	1	5.8×	0.165	B3GALT1

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
endocardial cushion cell fate commitment	1	5617.3×	0.006	ACVR1
positive regulation of determination of dorsal identity	1	2808.7×	0.006	ACVR1
glucosylceramide metabolic process	1	1872.4×	0.006	B3GALT1
positive regulation of cardiac epithelial to mesenchymal transition	1	1404.3×	0.006	ACVR1
endocardial cushion fusion	1	1123.5×	0.006	ACVR1
atrial septum primum morphogenesis	1	1123.5×	0.006	ACVR1
cardiac muscle cell fate commitment	1	1123.5×	0.006	ACVR1
embryonic heart tube morphogenesis	1	624.1×	0.009	ACVR1
acute inflammatory response	1	561.7×	0.009	ACVR1
mitral valve morphogenesis	1	561.7×	0.009	ACVR1
endocardial cushion formation	1	468.1×	0.009	ACVR1
negative regulation of activin receptor signaling pathway	1	468.1×	0.009	ACVR1
atrioventricular valve morphogenesis	1	401.2×	0.009	ACVR1
regulation of ossification	1	401.2×	0.009	ACVR1
gastrulation with mouth forming second	1	312.1×	0.010	ACVR1
activin receptor signaling pathway	1	295.6×	0.010	ACVR1
smooth muscle cell differentiation	1	295.6×	0.010	ACVR1
pharyngeal system development	1	267.5×	0.010	ACVR1
oligosaccharide biosynthetic process	1	216.1×	0.011	B3GALT1
positive regulation of intracellular signal transduction	1	216.1×	0.011	ACVR1
cellular response to BMP stimulus	1	187.2×	0.012	ACVR1
branching involved in blood vessel morphogenesis	1	175.5×	0.012	ACVR1
mesoderm formation	1	165.2×	0.012	ACVR1
acrosome assembly	1	151.8×	0.012	DCAF17
germ cell development	1	151.8×	0.012	ACVR1
ventricular septum morphogenesis	1	144.0×	0.012	ACVR1
dorsal/ventral pattern formation	1	140.4×	0.012	ACVR1
negative regulation of extrinsic apoptotic signaling pathway	1	140.4×	0.012	ACVR1
positive regulation of bone mineralization	1	130.6×	0.012	ACVR1
positive regulation of SMAD protein signal transduction	1	127.7×	0.012	ACVR1

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 2

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

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
ACVR1	MOMELOTINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ACVR1	39	4
DCAF17	0	0
B3GALT1	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
MOMELOTINIB	4	ACVR1
FEDRATINIB	4	ACVR1
PACRITINIB	4	ACVR1
VANDETANIB	4	ACVR1
LORLATINIB	4	ACVR1
GILTERITINIB	4	ACVR1
NINTEDANIB	4	ACVR1
DASATINIB	4	ACVR1
CRIZOTINIB	4	ACVR1
DACTOLISIB	3	ACVR1
SARACATINIB	3	ACVR1
CANERTINIB	3	ACVR1
ALVOCIDIB	3	ACVR1
CEDIRANIB	3	ACVR1
DOVITINIB	3	ACVR1
LESTAURTINIB	3	ACVR1
TANDUTINIB	2	ACVR1
CENISERTIB	2	ACVR1
ILORASERTIB	2	ACVR1
OSI-632	2	ACVR1
RAVOXERTINIB	2	ACVR1
DANUSERTIB	2	ACVR1
R-406	2	ACVR1
AT-9283	2	ACVR1
ZILURGISERTIB	2	ACVR1
MILCICLIB	2	ACVR1
TOZASERTIB	2	ACVR1
AEE-788	2	ACVR1
KER-047	2	ACVR1
GSK-1070916	1	ACVR1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 2.

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

Symbol	Assays	Type breakdown
ACVR1	299	Binding:293, Functional:4, ADMET:2
B3GALT1	3	Binding:3

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
ACVR1	2.7.10.2	non-specific protein-tyrosine kinase
B3GALT1	2.4.1.134	galactosylxylosylprotein 3-beta-galactosyltransferase

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
ACVR1	299

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

30 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.

Compound	Max phase	Cohort target (bioactivity)
MOMELOTINIB	4	ACVR1
FEDRATINIB	4	ACVR1
PACRITINIB	4	ACVR1
VANDETANIB	4	ACVR1
LORLATINIB	4	ACVR1
GILTERITINIB	4	ACVR1
NINTEDANIB	4	ACVR1
DASATINIB	4	ACVR1
CRIZOTINIB	4	ACVR1
DACTOLISIB	3	ACVR1
SARACATINIB	3	ACVR1
CANERTINIB	3	ACVR1
ALVOCIDIB	3	ACVR1
CEDIRANIB	3	ACVR1
DOVITINIB	3	ACVR1
LESTAURTINIB	3	ACVR1
TANDUTINIB	2	ACVR1
CENISERTIB	2	ACVR1
ILORASERTIB	2	ACVR1
OSI-632	2	ACVR1
RAVOXERTINIB	2	ACVR1
DANUSERTIB	2	ACVR1
R-406	2	ACVR1
AT-9283	2	ACVR1
ZILURGISERTIB	2	ACVR1
MILCICLIB	2	ACVR1
TOZASERTIB	2	ACVR1
AEE-788	2	ACVR1
KER-047	2	ACVR1
GSK-1070916	1	ACVR1

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	ACVR1
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	1	B3GALT1
E	Difficult family or no structure, no drug	1	DCAF17

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
DCAF17	0	—
B3GALT1	3	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.