chromosome 17q11.2 deletion syndrome, 1.4Mb

Summary

chromosome 17q11.2 deletion syndrome, 1.4Mb (MONDO:0013357) is a disease with 4 cohort genes.

At a glance

• Prevalence: Unknown (Worldwide) [Orphanet-validated]
• Cohort genes: 4
• ClinVar variants: 10
• Phenotypes (HPO): 94

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		170	Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

94 HPO clinical features (Orphanet curated; top 50 by frequency):

HPO ID	Term	Frequency
HP:0012760	Reduced social responsiveness	Very frequent (80-99%)
HP:0000736	Short attention span	Very frequent (80-99%)
HP:0001480	Freckling	Very frequent (80-99%)
HP:0007565	Multiple cafe-au-lait spots	Very frequent (80-99%)
HP:0000271	Abnormality of the face	Frequent (30-79%)
HP:0000529	Progressive visual loss	Frequent (30-79%)
HP:0000708	Atypical behavior	Frequent (30-79%)
HP:0000822	Hypertension	Frequent (30-79%)
HP:0001072	Thickened skin	Frequent (30-79%)
HP:0001328	Specific learning disability	Frequent (30-79%)
HP:0001627	Abnormal heart morphology	Frequent (30-79%)
HP:0001999	Abnormal facial shape	Frequent (30-79%)
HP:0002076	Migraine	Frequent (30-79%)
HP:0002315	Headache	Frequent (30-79%)
HP:0002354	Memory impairment	Frequent (30-79%)
HP:0002360	Sleep abnormality	Frequent (30-79%)
HP:0002463	Language impairment	Frequent (30-79%)
HP:0004562	Beaking of vertebral bodies T12-L3	Frequent (30-79%)
HP:0009732	Plexiform neurofibroma	Frequent (30-79%)
HP:0009737	Lisch nodules	Frequent (30-79%)
HP:0011442	Abnormality of central motor function	Frequent (30-79%)
HP:0025105	Nevus anemicus	Frequent (30-79%)
HP:0100585	Telangiectasia of the skin	Frequent (30-79%)
HP:0200034	Papule	Frequent (30-79%)
HP:0410263	Brain imaging abnormality	Frequent (30-79%)
HP:0000337	Broad forehead	Occasional (5-29%)
HP:0000486	Strabismus	Occasional (5-29%)
HP:0000490	Deeply set eye	Occasional (5-29%)
HP:0000501	Glaucoma	Occasional (5-29%)
HP:0000520	Proptosis	Occasional (5-29%)
HP:0000610	Abnormal choroid morphology	Occasional (5-29%)
HP:0000618	Blindness	Occasional (5-29%)
HP:0000729	Autistic behavior	Occasional (5-29%)
HP:0000823	Delayed puberty	Occasional (5-29%)
HP:0000925	Abnormality of the vertebral column	Occasional (5-29%)
HP:0000935	Thickened cortex of long bones	Occasional (5-29%)
HP:0000938	Osteopenia	Occasional (5-29%)
HP:0000939	Osteoporosis	Occasional (5-29%)
HP:0001034	Hypermelanotic macule	Occasional (5-29%)
HP:0001176	Large hands	Occasional (5-29%)
HP:0001249	Intellectual disability	Occasional (5-29%)
HP:0001250	Seizure	Occasional (5-29%)
HP:0001263	Global developmental delay	Occasional (5-29%)
HP:0001271	Polyneuropathy	Occasional (5-29%)
HP:0001297	Stroke	Occasional (5-29%)
HP:0001511	Intrauterine growth retardation	Occasional (5-29%)
HP:0001639	Hypertrophic cardiomyopathy	Occasional (5-29%)
HP:0001642	Pulmonic stenosis	Occasional (5-29%)
HP:0001680	Coarctation of aorta	Occasional (5-29%)
HP:0001833	Long foot	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	chromosome 17q11.2 deletion syndrome, 1.4Mb
Mondo ID	MONDO:0013357
MeSH	C563524
OMIM	613675
Orphanet	97685, 137634
DOID	DOID:0060403
SNOMED CT	722122000
UMLS	C5401456
MedGen	1726802
GARD	0005408
Is cancer (heuristic)	no

Also known as: 17q11 microdeletion syndrome · chromosome 17q11.2 deletion syndrome · chromosome 17q11.2 deletion syndrome, 1.4-MB · Del(17)(q11) · macrocephaly, macrosomia, and facial dysmorphism syndrome · MMFD · monosomy 17q11 · neurofibromatosis 1 microdeletion syndrome · neurofibromatosis type 1 microdeletion syndrome · NF1 microdeletion syndrome · overgrowth-macrocephaly-facial dysmorphism syndrome · RNF135-related overgrowth syndrome · Van Asperen syndrome

Data availability: 10 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 17 › partial deletion of the long arm of chromosome 17 › chromosome 17q11.2 deletion syndrome, 1.4Mb

Related subtypes (5): chromosome 17q23.1-q23.2 deletion syndrome, chromosome 17q12 deletion syndrome, distal monosomy 17q, Koolen-de Vries syndrome due to 17q21.31 microdeletion syndrome, 17q24.2 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

10 retrieved; paginated sample, class counts are floors:

6 pathogenic, 2 benign/likely benign, 1 uncertain significance, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
1703547	GRCh37/hg19 17q11.2(chr17:28993036-30412788)	ADAP2	Pathogenic	no assertion criteria provided
4820058	NC_000017.11:g.(30668200_30669500)_(32083800_32085200)del	ADAP2	Pathogenic	criteria provided, single submitter
666441	GRCh37/hg19 17q11.2(chr17:28941066-30326958)x1	ADAP2	Pathogenic	criteria provided, single submitter
3362875	Single allele	COPRS	Pathogenic	criteria provided, single submitter
141513	NM_001042492.3(NF1):c.2033dup (p.Ile679fs)	NF1	Pathogenic	criteria provided, multiple submitters, no conflicts
439967	NM_001042492.3(NF1):c.7970+1G>A	NF1	Pathogenic	criteria provided, multiple submitters, no conflicts
229064	NM_001042492.3(NF1):c.7439A>G (p.His2480Arg)	NF1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1032948	NM_032322.4(RNF135):c.575C>T (p.Thr192Ile)	RNF135	Uncertain significance	criteria provided, single submitter
141237	NM_001042492.3(NF1):c.340C>T (p.Leu114=)	NF1	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
184363	NM_001042492.3(NF1):c.1137C>T (p.Cys379=)	NF1	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 10 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
RNF135	Orphanet:137634	Overgrowth-macrocephaly-facial dysmorphism syndrome
NF1	Orphanet:139474	17q11.2 microduplication syndrome
NF1	Orphanet:29072	Hereditary pheochromocytoma-paraganglioma
NF1	Orphanet:293199	Pleomorphic rhabdomyosarcoma
NF1	Orphanet:363700	Neurofibromatosis type 1 due to NF1 mutation or intragenic deletion
NF1	Orphanet:638	Neurofibromatosis-Noonan syndrome
NF1	Orphanet:86834	Juvenile myelomonocytic leukemia
NF1	Orphanet:97685	17q11 microdeletion syndrome
NF1	Orphanet:99756	Alveolar rhabdomyosarcoma
NF1	Orphanet:99757	Embryonal rhabdomyosarcoma

Cohort genes → proteins

4 cohort genes, 4 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	4

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
ADAP2	HGNC:16487	ENSG00000184060	Q9NPF8	Arf-GAP with dual PH domain-containing protein 2	clinvar
RNF135	HGNC:21158	ENSG00000181481	Q8IUD6	E3 ubiquitin-protein ligase RNF135	clinvar
COPRS	HGNC:28848	ENSG00000172301	Q9NQ92	Coordinator of PRMT5 and differentiation stimulator	clinvar
NF1	HGNC:7765	ENSG00000196712	P21359	Neurofibromin	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ADAP2	Arf-GAP with dual PH domain-containing protein 2	GTPase-activating protein for the ADP ribosylation factor family (Potential).
RNF135	E3 ubiquitin-protein ligase RNF135	E2-dependent E3 ubiquitin-protein ligase that functions as a RIGI coreceptor in the sensing of viral RNAs in cell cytoplasm and the activation of the antiviral innate immune response.
COPRS	Coordinator of PRMT5 and differentiation stimulator	Histone-binding protein required for histone H4 methyltransferase activity of PRMT5.
NF1	Neurofibromin	Stimulates the GTPase activity of Ras.

Protein-family classification

Druggable: 0 · Difficult: 2 · 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	4.3×	0.605
Transcription factor	1	2.1×	0.605
Other/Unknown	2	0.9×	0.769

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ADAP2	Scaffold/PPI	no		ArfGAP_dom, PH_domain, PH-like_dom_sf
RNF135	Transcription factor	no		Znf_RING, B30.2/SPRY, SPRY_dom
COPRS	Other/Unknown	no		COPR5
NF1	Other/Unknown	no		CRAL-TRIO_dom, RasGAP_dom, Rho_GTPase_activation_prot

Expression context

Cohort genes with no expression data: 0.

4 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)	4
unknown	0

Top tissues across cohort

Tissue	Cohort genes
leukocyte	1
monocyte	1
mononuclear cell	1
layer of synovial tissue	1
pancreatic ductal cell	1
parietal pleura	1
adult organism	1
left testis	1
right testis	1
adrenal tissue	1
calcaneal tendon	1
colonic epithelium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ADAP2	253	ubiquitous	marker	monocyte, mononuclear cell, leukocyte
RNF135	253	ubiquitous	marker	pancreatic ductal cell, parietal pleura, layer of synovial tissue
COPRS	259	ubiquitous	marker	left testis, right testis, adult organism
NF1	283	ubiquitous	marker	colonic epithelium, calcaneal tendon, adrenal tissue

Protein interactions among cohort

Intra-cohort edges: 4.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
NF1	5,540
RNF135	1,083
ADAP2	1,058
COPRS	796

Intra-cohort edges

A	B	Sources
ADAP2	COPRS	string_interaction
ADAP2	NF1	string_interaction
ADAP2	RNF135	string_interaction
NF1	RNF135	string_interaction

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
NF1	P21359	26
RNF135	Q8IUD6	5

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ADAP2	Q9NPF8	92.49
COPRS	Q9NQ92	62.95

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 28. Enrichment computed across 4 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
RAS signaling downstream of NF1 loss-of-function variants	1	543.8×	0.037	NF1
NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10	1	292.8×	0.037	RNF135
TRAF3-dependent IRF activation pathway	1	253.8×	0.037	RNF135
TRAF6 mediated NF-kB activation	1	152.3×	0.037	RNF135
TRAF6 mediated IRF7 activation	1	126.9×	0.037	RNF135
Negative regulators of DDX58/IFIH1 signaling	1	108.8×	0.037	RNF135
Ovarian tumor domain proteases	1	92.8×	0.037	RNF135
DDX58/IFIH1-mediated induction of interferon-alpha/beta	1	84.6×	0.037	RNF135
Oncogenic MAPK signaling	1	82.8×	0.037	NF1
Regulation of RAS by GAPs	1	64.5×	0.042	NF1
Disease	2	8.7×	0.042	RNF135, NF1
RMTs methylate histone arginines	1	48.8×	0.047	COPRS
MAPK1/MAPK3 signaling	1	43.8×	0.047	NF1
Deubiquitination	1	41.4×	0.047	RNF135
SARS-CoV-2-host interactions	1	39.6×	0.047	RNF135
MAPK family signaling cascades	1	34.3×	0.051	NF1
SARS-CoV-2 activates/modulates innate and adaptive immune responses	1	29.7×	0.055	RNF135
SARS-CoV-2 Infection	1	26.8×	0.057	RNF135
RAF/MAP kinase cascade	1	20.4×	0.071	NF1
Diseases of signal transduction by growth factor receptors and second messengers	1	18.9×	0.071	NF1
SARS-CoV Infections	1	18.5×	0.071	RNF135
Viral Infection Pathways	1	10.3×	0.120	RNF135
Innate Immune System	1	8.5×	0.135	RNF135
Infectious disease	1	8.3×	0.135	RNF135
Post-translational protein modification	1	6.4×	0.166	RNF135
Immune System	1	4.3×	0.231	RNF135
Metabolism of proteins	1	4.1×	0.232	RNF135
Signal Transduction	1	3.4×	0.267	NF1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 4 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
positive regulation of mast cell apoptotic process	1	4213.0×	0.007	NF1
regulation of glial cell differentiation	1	4213.0×	0.007	NF1
observational learning	1	4213.0×	0.007	NF1
gamma-aminobutyric acid secretion, neurotransmission	1	2106.5×	0.007	NF1
Schwann cell proliferation	1	1404.3×	0.007	NF1
forebrain astrocyte development	1	1404.3×	0.007	NF1
Schwann cell migration	1	1404.3×	0.007	NF1
glutamate secretion, neurotransmission	1	1404.3×	0.007	NF1
negative regulation of mast cell proliferation	1	1404.3×	0.007	NF1
negative regulation of Schwann cell migration	1	1404.3×	0.007	NF1
vascular associated smooth muscle cell migration	1	1404.3×	0.007	NF1
mast cell apoptotic process	1	1053.2×	0.007	NF1
negative regulation of Rac protein signal transduction	1	1053.2×	0.007	NF1
myeloid leukocyte migration	1	1053.2×	0.007	NF1
heart development	2	39.4×	0.007	ADAP2, NF1
mast cell proliferation	1	842.6×	0.008	NF1
amygdala development	1	702.2×	0.008	NF1
regulation of blood vessel endothelial cell migration	1	702.2×	0.008	NF1
vascular associated smooth muscle cell proliferation	1	702.2×	0.008	NF1
negative regulation of Schwann cell proliferation	1	601.9×	0.008	NF1
free ubiquitin chain polymerization	1	601.9×	0.008	RNF135
RIG-I signaling pathway	1	601.9×	0.008	RNF135
negative regulation of neurotransmitter secretion	1	601.9×	0.008	NF1
hair follicle maturation	1	526.6×	0.009	NF1
negative regulation of leukocyte migration	1	421.3×	0.009	NF1
negative regulation of vascular associated smooth muscle cell migration	1	421.3×	0.009	NF1
regulation of bone resorption	1	383.0×	0.009	NF1
negative regulation of astrocyte differentiation	1	383.0×	0.009	NF1
regulation of long-term synaptic potentiation	1	383.0×	0.009	NF1
positive regulation of extrinsic apoptotic signaling pathway in absence of ligand	1	383.0×	0.009	NF1

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 4 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
ADAP2	0	0
RNF135	0	0
COPRS	0	0
NF1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 4; 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	4	ADAP2, RNF135, COPRS, NF1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
ADAP2	0	—
RNF135	0	—
COPRS	0	—
NF1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.