16q24.3 microdeletion syndrome

Summary

16q24.3 microdeletion syndrome (MONDO:0016838) is a disease with 8 cohort genes.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 8
• ClinVar variants: 12
• Phenotypes (HPO): 47

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		27	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

47 HPO clinical features (Orphanet curated; top 47 by frequency):

HPO ID	Term	Frequency
HP:0000348	High forehead	Very frequent (80-99%)
HP:0000411	Protruding ear	Very frequent (80-99%)
HP:0000717	Autism	Very frequent (80-99%)
HP:0000154	Wide mouth	Frequent (30-79%)
HP:0000218	High palate	Frequent (30-79%)
HP:0000307	Pointed chin	Frequent (30-79%)
HP:0000319	Smooth philtrum	Frequent (30-79%)
HP:0000343	Long philtrum	Frequent (30-79%)
HP:0000347	Micrognathia	Frequent (30-79%)
HP:0000609	Optic nerve hypoplasia	Frequent (30-79%)
HP:0001250	Seizure	Frequent (30-79%)
HP:0002007	Frontal bossing	Frequent (30-79%)
HP:0002079	Hypoplasia of the corpus callosum	Frequent (30-79%)
HP:0002119	Ventriculomegaly	Frequent (30-79%)
HP:0002342	Intellectual disability, moderate	Frequent (30-79%)
HP:0007165	Periventricular heterotopia	Frequent (30-79%)
HP:0030048	Colpocephaly	Frequent (30-79%)
HP:0000028	Cryptorchidism	Occasional (5-29%)
HP:0000276	Long face	Occasional (5-29%)
HP:0000325	Triangular face	Occasional (5-29%)
HP:0000365	Hearing impairment	Occasional (5-29%)
HP:0000384	Preauricular skin tag	Occasional (5-29%)
HP:0000389	Chronic otitis media	Occasional (5-29%)
HP:0000463	Anteverted nares	Occasional (5-29%)
HP:0000483	Astigmatism	Occasional (5-29%)
HP:0000486	Strabismus	Occasional (5-29%)
HP:0000505	Visual impairment	Occasional (5-29%)
HP:0000545	Myopia	Occasional (5-29%)
HP:0000582	Upslanted palpebral fissure	Occasional (5-29%)
HP:0000639	Nystagmus	Occasional (5-29%)
HP:0000750	Delayed speech and language development	Occasional (5-29%)
HP:0001385	Hip dysplasia	Occasional (5-29%)
HP:0001629	Ventricular septal defect	Occasional (5-29%)
HP:0001644	Dilated cardiomyopathy	Occasional (5-29%)
HP:0001653	Mitral regurgitation	Occasional (5-29%)
HP:0001873	Thrombocytopenia	Occasional (5-29%)
HP:0002015	Dysphagia	Occasional (5-29%)
HP:0002553	Highly arched eyebrow	Occasional (5-29%)
HP:0002650	Scoliosis	Occasional (5-29%)
HP:0002808	Kyphosis	Occasional (5-29%)
HP:0004422	Biparietal narrowing	Occasional (5-29%)
HP:0005518	Increased mean corpuscular volume	Occasional (5-29%)
HP:0006315	Single median maxillary incisor	Occasional (5-29%)
HP:0009623	Proximal placement of thumb	Occasional (5-29%)
HP:0010720	Abnormal hair pattern	Occasional (5-29%)
HP:0011968	Feeding difficulties	Occasional (5-29%)
HP:0012471	Thick vermilion border	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	16q24.3 microdeletion syndrome
Mondo ID	MONDO:0016838
Orphanet	261250
SNOMED CT	719580004
UMLS	C4304594
MedGen	930263
GARD	0010935
Is cancer (heuristic)	no

Also known as: chromosome 16q24.3 microdeletion syndrome · Del(16)(q24.3) · monosomy 16q24.3

Data availability: 12 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 16 › partial deletion of the long arm of chromosome 16 › 16q24.3 microdeletion syndrome

Related subtypes (2): chromosome 16q22 deletion syndrome, 16q24.1 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

12 retrieved; paginated sample, class counts are floors:

12 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
267483	Single allele	CPNE7	Pathogenic	no assertion criteria provided
267484	Single allele	LOC101927817	Pathogenic	no assertion criteria provided
267479	Single allele	MVD	Pathogenic	no assertion criteria provided
267481	Single allele	RNF166	Pathogenic	no assertion criteria provided
267474	Single allele	SLC22A31	Pathogenic	no assertion criteria provided
267478	Single allele	SLC22A31	Pathogenic	no assertion criteria provided
267480	Single allele	SLC22A31	Pathogenic	no assertion criteria provided
267477	Single allele	TRAPPC2L	Pathogenic	no assertion criteria provided
267485	Single allele	TRAPPC2L	Pathogenic	no assertion criteria provided
267482	Single allele	ZC3H18	Pathogenic	no assertion criteria provided
267475	Single allele	ZCCHC14	Pathogenic	no assertion criteria provided
267476	Single allele	ZFPM1	Pathogenic	no assertion criteria 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
MVD	Orphanet:79152	Disseminated superficial actinic porokeratosis

Cohort genes → proteins

8 cohort genes, 8 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	8

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
ZFPM1	HGNC:19762	ENSG00000179588	Q8IX07	Zinc finger protein ZFPM1	clinvar
CPNE7	HGNC:2320	ENSG00000178773	Q9UBL6	Copine-7	clinvar
ZCCHC14	HGNC:24134	ENSG00000140948	Q8WYQ9	Zinc finger CCHC domain-containing protein 14	clinvar
ZC3H18	HGNC:25091	ENSG00000158545	Q86VM9	Zinc finger CCCH domain-containing protein 18	clinvar
SLC22A31	HGNC:27091	ENSG00000259803	A6NKX4	Putative solute carrier family 22 member 31	clinvar
RNF166	HGNC:28856	ENSG00000158717	Q96A37	E3 ubiquitin-protein ligase RNF166	clinvar
TRAPPC2L	HGNC:30887	ENSG00000167515	Q9UL33	Trafficking protein particle complex subunit 2-like protein	clinvar
MVD	HGNC:7529	ENSG00000167508	P53602	Diphosphomevalonate decarboxylase	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ZFPM1	Zinc finger protein ZFPM1	Transcription regulator that plays an essential role in erythroid and megakaryocytic cell differentiation.
CPNE7	Copine-7	Calcium-dependent phospholipid-binding protein that may play a role in calcium-mediated intracellular processes.
SLC22A31	Putative solute carrier family 22 member 31	Organic anion transporter that mediates the uptake of ions.
RNF166	E3 ubiquitin-protein ligase RNF166	E3 ubiquitin-protein ligase that promotes the ubiquitination of different substrates.
TRAPPC2L	Trafficking protein particle complex subunit 2-like protein	Plays a role in vesicular transport from endoplasmic reticulum to Golgi.
MVD	Diphosphomevalonate decarboxylase	Catalyzes the ATP dependent decarboxylation of (R)-5-diphosphomevalonate to form isopentenyl diphosphate (IPP).

Protein-family classification

Druggable: 2 · Difficult: 4 · Unknown: 2 · Druggable fraction: 0.25

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
Transcription factor	4	4.1×	0.040
Transporter	1	9.7×	0.197
Kinase	1	3.5×	0.340
Other/Unknown	2	0.5×	0.984

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ZFPM1	Transcription factor	no		Znf_C2H2_type, Znf_CCHC_FOG, Znf_C2H2_sf
CPNE7	Other/Unknown	no		C2_dom, VWF_A, Copine_C
ZCCHC14	Transcription factor	no		SAM, Znf_CCHC, SAM/pointed_sf
ZC3H18	Transcription factor	no		Znf_CCCH, Znf_CCCH_sf, Znf-CCCH_4
SLC22A31	Transporter	yes		MFS_sugar_transport-like, MFS_dom, MFS_trans_sf
RNF166	Transcription factor	no		Znf_RING, Di19_Zn-bd, Znf_RING/FYVE/PHD
TRAPPC2L	Other/Unknown	no		Sedlin, Longin-like_dom_sf, TRAPPC2L
MVD	Kinase	yes	4.1.1.33	Mev_decarb, Ribsml_uS5_D2-typ_fold_subgr, Ribosomal_Su5_D2-typ_SF

Expression context

Cohort genes with no expression data: 0.

8 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)	8
unknown	0

Top tissues across cohort

Tissue	Cohort genes
cerebellar hemisphere	3
right hemisphere of cerebellum	3
cerebellar cortex	2
ileal mucosa	1
nasal cavity epithelium	1
pancreatic ductal cell	1
gluteal muscle	1
lateral nuclear group of thalamus	1
triceps brachii	1
adult organism	1
endometrium epithelium	1
secondary oocyte	1
sural nerve	1
granulocyte	1
leukocyte	1
monocyte	1
right adrenal gland	1
right adrenal gland cortex	1
right testis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ZFPM1	208	ubiquitous	marker	pancreatic ductal cell, ileal mucosa, nasal cavity epithelium
CPNE7	182	ubiquitous	marker	lateral nuclear group of thalamus, triceps brachii, gluteal muscle
ZCCHC14	295	ubiquitous	marker	secondary oocyte, adult organism, endometrium epithelium
ZC3H18	243	ubiquitous	marker	sural nerve, right hemisphere of cerebellum, cerebellar hemisphere
SLC22A31	155	broad	marker	cerebellar hemisphere, cerebellar cortex, right hemisphere of cerebellum
RNF166	210	ubiquitous	marker	granulocyte, monocyte, leukocyte
TRAPPC2L	285	ubiquitous	marker	right adrenal gland cortex, right adrenal gland, right testis
MVD	189	ubiquitous	marker	right hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex

Protein interactions among cohort

Intra-cohort edges: 2.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ZC3H18	4,341
ZCCHC14	2,437
TRAPPC2L	1,387
ZFPM1	1,283
MVD	1,189
RNF166	995
CPNE7	769
SLC22A31	426

Intra-cohort edges

A	B	Sources
CPNE7	SLC22A31	string_interaction
SLC22A31	TRAPPC2L	string_interaction

Structural data

PDB: 3 · AlphaFold-only: 5 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ZFPM1	Q8IX07	1
ZC3H18	Q86VM9	1
MVD	P53602	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
TRAPPC2L	Q9UL33	92.21
RNF166	Q96A37	84.93
CPNE7	Q9UBL6	78.41
SLC22A31	A6NKX4	78.02
ZCCHC14	Q8WYQ9	50.94

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 19. Enrichment computed across 8 evidence-associated genes (5 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 5 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Synthesis of dolichyl-phosphate	1	326.3×	0.041	MVD
Cholesterol biosynthesis	1	228.4×	0.041	MVD
Lanosterol biosynthesis	1	152.3×	0.041	MVD
Glycerophospholipid biosynthesis	1	67.2×	0.045	CPNE7
Regulation of cholesterol biosynthesis by SREBP (SREBF)	1	63.4×	0.045	MVD
Nuclear RNA decay	1	61.7×	0.045	ZC3H18
Synthesis of substrates in N-glycan biosythesis	1	58.6×	0.045	MVD
Activation of gene expression by SREBF (SREBP)	1	51.9×	0.045	MVD
Biosynthesis of the N-glycan precursor (dolichol lipid-linked oligosaccharide, LLO) and transfer to a nascent protein	1	41.5×	0.050	MVD
COPII-mediated vesicle transport	1	32.6×	0.058	TRAPPC2L
Metabolism of steroids	1	27.5×	0.060	MVD
RAB GEFs exchange GTP for GDP on RABs	1	24.8×	0.060	TRAPPC2L
RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function	1	24.0×	0.060	ZFPM1
Factors involved in megakaryocyte development and platelet production	1	13.3×	0.099	ZFPM1
Asparagine N-linked glycosylation	1	12.0×	0.102	MVD
Metabolism of lipids	1	6.3×	0.177	MVD
Post-translational protein modification	1	3.8×	0.262	MVD
Metabolism of proteins	1	2.5×	0.362	MVD
Metabolism	1	2.3×	0.362	MVD

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 7 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
T-helper cell lineage commitment	1	2407.4×	0.006	ZFPM1
negative regulation of mast cell differentiation	1	2407.4×	0.006	ZFPM1
tricuspid valve formation	1	1203.7×	0.006	ZFPM1
mitral valve formation	1	802.5×	0.006	ZFPM1
regulation of definitive erythrocyte differentiation	1	802.5×	0.006	ZFPM1
isopentenyl diphosphate biosynthetic process, mevalonate pathway	1	802.5×	0.006	MVD
regulation of chemokine production	1	802.5×	0.006	ZFPM1
definitive erythrocyte differentiation	1	802.5×	0.006	ZFPM1
RNA destabilization	1	601.9×	0.007	ZC3H18
primitive erythrocyte differentiation	1	601.9×	0.007	ZFPM1
negative regulation of interleukin-4 production	1	343.9×	0.011	ZFPM1
glycerophospholipid biosynthetic process	1	267.5×	0.013	CPNE7
isoprenoid biosynthetic process	1	240.7×	0.013	MVD
vesicle coat assembly	1	218.9×	0.013	TRAPPC2L
cardiac muscle tissue morphogenesis	1	200.6×	0.013	ZFPM1
atrial septum morphogenesis	1	185.2×	0.013	ZFPM1
atrioventricular valve morphogenesis	1	172.0×	0.013	ZFPM1
megakaryocyte differentiation	1	172.0×	0.013	ZFPM1
granulocyte differentiation	1	172.0×	0.013	ZFPM1
embryonic hemopoiesis	1	141.6×	0.014	ZFPM1
obsolete vesicle tethering	1	141.6×	0.014	TRAPPC2L
platelet formation	1	100.3×	0.017	ZFPM1
megakaryocyte development	1	100.3×	0.017	ZFPM1
COPII vesicle coat assembly	1	100.3×	0.017	TRAPPC2L
ventricular septum morphogenesis	1	61.7×	0.026	ZFPM1
cholesterol biosynthetic process	1	60.2×	0.026	MVD
outflow tract morphogenesis	1	43.8×	0.034	ZFPM1
erythrocyte differentiation	1	38.2×	0.038	ZFPM1
positive regulation of type II interferon production	1	32.1×	0.043	ZFPM1
cellular response to calcium ion	1	28.7×	0.047	CPNE7

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 1 · Undrugged: 7

Druggability breadth: 2 of 8 evidence-associated genes (25%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ZC3H18	1	2
ZFPM1	0	0
CPNE7	0	0
ZCCHC14	0	0
SLC22A31	0	0
RNF166	0	0
TRAPPC2L	0	0
MVD	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
MOLIBRESIB	2	ZC3H18

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
ZC3H18	8	Binding:8
MVD	3	Binding:3

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
MVD	4.1.1.33	diphosphomevalonate decarboxylase

Pharmacogenomics

Cohort genes with a PharmGKB record: 8; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

1 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)
MOLIBRESIB	2	ZC3H18

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	1	ZC3H18
C	Druggable family + PDB, no drug	1	MVD
D	Druggable family + AlphaFold only, no drug	1	SLC22A31
E	Difficult family or no structure, no drug	5	ZFPM1, CPNE7, ZCCHC14, RNF166, TRAPPC2L

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
ZFPM1	0	—
CPNE7	0	—
ZCCHC14	0	—
SLC22A31	0	—
RNF166	0	—
TRAPPC2L	0	—
MVD	3	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.