Chromosome 2p16.1-p15 deletion syndrome

Summary

Chromosome 2p16.1-p15 deletion syndrome (MONDO:0012916) is a disease with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 1
• ClinVar variants: 1
• Phenotypes (HPO): 77

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		11	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

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

HPO ID	Term	Frequency
HP:0000431	Wide nasal bridge	Very frequent (80-99%)
HP:0000494	Downslanted palpebral fissures	Very frequent (80-99%)
HP:0000506	Telecanthus	Very frequent (80-99%)
HP:0000508	Ptosis	Very frequent (80-99%)
HP:0000581	Blepharophimosis	Very frequent (80-99%)
HP:0000609	Optic nerve hypoplasia	Very frequent (80-99%)
HP:0000648	Optic atrophy	Very frequent (80-99%)
HP:0000750	Delayed speech and language development	Very frequent (80-99%)
HP:0001263	Global developmental delay	Very frequent (80-99%)
HP:0002342	Intellectual disability, moderate	Very frequent (80-99%)
HP:0000160	Narrow mouth	Very frequent (80-99%)
HP:0000218	High palate	Very frequent (80-99%)
HP:0000232	Everted lower lip vermilion	Very frequent (80-99%)
HP:0000252	Microcephaly	Very frequent (80-99%)
HP:0000286	Epicanthus	Very frequent (80-99%)
HP:0000319	Smooth philtrum	Very frequent (80-99%)
HP:0000343	Long philtrum	Very frequent (80-99%)
HP:0000426	Prominent nasal bridge	Very frequent (80-99%)
HP:0000126	Hydronephrosis	Frequent (30-79%)
HP:0000248	Brachycephaly	Frequent (30-79%)
HP:0000278	Retrognathia	Frequent (30-79%)
HP:0000340	Sloping forehead	Frequent (30-79%)
HP:0000341	Narrow forehead	Frequent (30-79%)
HP:0000369	Low-set ears	Frequent (30-79%)
HP:0000411	Protruding ear	Frequent (30-79%)
HP:0000486	Strabismus	Frequent (30-79%)
HP:0000505	Visual impairment	Frequent (30-79%)
HP:0000527	Long eyelashes	Frequent (30-79%)
HP:0000717	Autism	Frequent (30-79%)
HP:0000729	Autistic behavior	Frequent (30-79%)
HP:0001182	Tapered finger	Frequent (30-79%)
HP:0001252	Hypotonia	Frequent (30-79%)
HP:0001290	Generalized hypotonia	Frequent (30-79%)
HP:0001508	Failure to thrive	Frequent (30-79%)
HP:0001510	Growth delay	Frequent (30-79%)
HP:0001511	Intrauterine growth retardation	Frequent (30-79%)
HP:0001840	Metatarsus adductus	Frequent (30-79%)
HP:0002061	Lower limb spasticity	Frequent (30-79%)
HP:0002205	Recurrent respiratory infections	Frequent (30-79%)
HP:0005274	Prominent nasal tip	Frequent (30-79%)
HP:0006610	Wide intermamillary distance	Frequent (30-79%)
HP:0007018	Attention deficit hyperactivity disorder	Frequent (30-79%)
HP:0100490	Camptodactyly of finger	Frequent (30-79%)
HP:0000003	Multicystic kidney dysplasia	Occasional (5-29%)
HP:0000023	Inguinal hernia	Occasional (5-29%)
HP:0000098	Tall stature	Occasional (5-29%)
HP:0000135	Hypogonadism	Occasional (5-29%)
HP:0000348	High forehead	Occasional (5-29%)
HP:0000365	Hearing impairment	Occasional (5-29%)
HP:0000767	Pectus excavatum	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	chromosome 2p16.1-p15 deletion syndrome
Mondo ID	MONDO:0012916
MeSH	C567289
OMIM	612513
Orphanet	261349
DOID	DOID:0060415
SNOMED CT	719651000
UMLS	C2675875
MedGen	390902
GARD	0013391
Is cancer (heuristic)	no

Also known as: 2p15-p16.1 microdeletion syndrome · 2p15p16.1 microdeletion syndrome · chromosome 2p16.1-p15 deletion syndrome · chromosome 2p16.1-p15 deletion syndrome, isolated cases · Del(2)(p15p16.1) · monosomy 2p15-p16.1 · monosomy 2p15p16.1

Data availability: 1 ClinVar variant.

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 short arm of chromosome 2 › chromosome 2p16.1-p15 deletion syndrome

Related subtypes (5): hypotonia-cystinuria syndrome, chromosome 2p12-p11.2 deletion syndrome, chromosome 2p16.3 deletion syndrome, 2p21 microdeletion syndrome, 2p13.2 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

1 retrieved; paginated sample, class counts are floors:

1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
984375	NM_014709.4(USP34):c.8048-1053_8840+1025del	USP34	Pathogenic	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

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

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
USP34	HGNC:20066	ENSG00000115464	Q70CQ2	Ubiquitin carboxyl-terminal hydrolase 34	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
USP34	Ubiquitin carboxyl-terminal hydrolase 34	Ubiquitin hydrolase that can remove conjugated ubiquitin from AXIN1 and AXIN2, thereby acting as a regulator of Wnt signaling pathway.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
Protease	1	36.6×	0.027

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
USP34	Protease	yes		Peptidase_C19_UCH, ARM-type_fold, USP_CS

Expression context

Cohort genes with no expression data: 0.

1 cohort gene 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)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
cardia of stomach	1
nipple	1
renal medulla	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
USP34	292	ubiquitous	marker	renal medulla, nipple, cardia of stomach

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
USP34	2,181

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
USP34	Q70CQ2	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. Enrichment computed across 1 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
TCF dependent signaling in response to WNT	1	117.7×	0.017	USP34
Ub-specific processing proteases	1	53.1×	0.019	USP34

GO biological processes 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.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
protein K48-linked deubiquitination	1	648.1×	0.009	USP34
protein deubiquitination	1	177.4×	0.012	USP34
positive regulation of canonical Wnt signaling pathway	1	154.6×	0.012	USP34
regulation of protein stability	1	125.8×	0.012	USP34
Wnt signaling pathway	1	99.7×	0.012	USP34
proteolysis	1	34.2×	0.029	USP34

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 1 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
USP34	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; 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	1	USP34
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
USP34	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.