Chromosome 15q26-qter deletion syndrome

Summary

Chromosome 15q26-qter deletion syndrome (MONDO:0012964) is a disease with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 1
• ClinVar variants: 2
• Phenotypes (HPO): 59

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		30	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

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

HPO ID	Term	Frequency
HP:0001511	Intrauterine growth retardation	Very frequent (80-99%)
HP:0001518	Small for gestational age	Very frequent (80-99%)
HP:0000028	Cryptorchidism	Frequent (30-79%)
HP:0000047	Hypospadias	Frequent (30-79%)
HP:0000054	Micropenis	Frequent (30-79%)
HP:0000164	Abnormality of the dentition	Frequent (30-79%)
HP:0000175	Cleft palate	Frequent (30-79%)
HP:0000219	Thin upper lip vermilion	Frequent (30-79%)
HP:0000252	Microcephaly	Frequent (30-79%)
HP:0000280	Coarse facial features	Frequent (30-79%)
HP:0000316	Hypertelorism	Frequent (30-79%)
HP:0000322	Short philtrum	Frequent (30-79%)
HP:0000325	Triangular face	Frequent (30-79%)
HP:0000347	Micrognathia	Frequent (30-79%)
HP:0000365	Hearing impairment	Frequent (30-79%)
HP:0000369	Low-set ears	Frequent (30-79%)
HP:0000455	Broad nasal tip	Frequent (30-79%)
HP:0000486	Strabismus	Frequent (30-79%)
HP:0000581	Blepharophimosis	Frequent (30-79%)
HP:0000582	Upslanted palpebral fissure	Frequent (30-79%)
HP:0000729	Autistic behavior	Frequent (30-79%)
HP:0000750	Delayed speech and language development	Frequent (30-79%)
HP:0000776	Congenital diaphragmatic hernia	Frequent (30-79%)
HP:0001250	Seizure	Frequent (30-79%)
HP:0001263	Global developmental delay	Frequent (30-79%)
HP:0001508	Failure to thrive	Frequent (30-79%)
HP:0001510	Growth delay	Frequent (30-79%)
HP:0001647	Bicuspid aortic valve	Frequent (30-79%)
HP:0001680	Coarctation of aorta	Frequent (30-79%)
HP:0001718	Mitral stenosis	Frequent (30-79%)
HP:0001762	Talipes equinovarus	Frequent (30-79%)
HP:0001792	Small nail	Frequent (30-79%)
HP:0002089	Pulmonary hypoplasia	Frequent (30-79%)
HP:0002761	Generalized joint laxity	Frequent (30-79%)
HP:0002827	Hip dislocation	Frequent (30-79%)
HP:0002857	Genu valgum	Frequent (30-79%)
HP:0004322	Short stature	Frequent (30-79%)
HP:0005469	Flat occiput	Frequent (30-79%)
HP:0005709	2-3 toe cutaneous syndactyly	Frequent (30-79%)
HP:0007018	Attention deficit hyperactivity disorder	Frequent (30-79%)
HP:0008897	Postnatal growth retardation	Frequent (30-79%)
HP:0009381	Short finger	Frequent (30-79%)
HP:0009882	Short distal phalanx of finger	Frequent (30-79%)
HP:0010297	Bifid tongue	Frequent (30-79%)
HP:0012303	Abnormal aortic arch morphology	Frequent (30-79%)
HP:0030353	Decreased serum insulin-like growth factor 1	Frequent (30-79%)
HP:0030918	Low 1-minute APGAR score	Frequent (30-79%)
HP:0040019	Finger clinodactyly	Frequent (30-79%)
HP:0200055	Small hand	Frequent (30-79%)
HP:0000003	Multicystic kidney dysplasia	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	chromosome 15q26-qter deletion syndrome
Mondo ID	MONDO:0012964
MeSH	C567232
OMIM	612626
Orphanet	1596
DOID	DOID:0060397
SNOMED CT	766050000
UMLS	C2675463
MedGen	390804
GARD	0016572
Is cancer (heuristic)	no

Also known as: 15q26 deletion syndrome · chromosome 15q26-qter deletion syndrome · chromosome 15q26-qter deletion syndrome, isolated cases · distal monosomy 15q · distal monosomy type 15q · Drayer syndrome · monosomy 15q26 · telomeric 15q deletion syndrome

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 › chromosome 15q26-qter deletion syndrome

Related subtypes (8): deafness-infertility syndrome, chromosome 15q13.3 microdeletion syndrome, chromosome 15q24 deletion syndrome, chromosome 15q25 deletion syndrome, chromosome 15q11.2 deletion syndrome, 15q14 microdeletion 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 likely pathogenic, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
805881	GRCh37/hg19 15q26.2-26.3(chr15:96878099-102397836)x1	ADAMTS17	Pathogenic	criteria provided, single submitter
1077189	Single allele	ADAMTS17	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ADAMTS17	Orphanet:3449	Weill-Marchesani syndrome
ADAMTS17	Orphanet:363992	Ichthyosis-short stature-brachydactyly-microspherophakia syndrome

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
ADAMTS17	HGNC:17109	ENSG00000140470	Q8TE56	A disintegrin and metalloproteinase with thrombospondin motifs 17	clinvar

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)
ADAMTS17	Protease	yes		TSP1_rpt, Peptidase_M12B, Peptidase_M12B_N

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
primordial germ cell in gonad	1
right lobe of liver	1
thymus	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ADAMTS17	177	broad	marker	thymus, primordial germ cell in gonad, right lobe of liver

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ADAMTS17	817

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ADAMTS17	Q8TE56	70.06

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 9. 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
Defective B3GALTL causes PpS	1	308.6×	0.014	ADAMTS17
O-glycosylation of TSR domain-containing proteins	1	300.5×	0.014	ADAMTS17
Diseases associated with O-glycosylation of proteins	1	215.5×	0.014	ADAMTS17
O-linked glycosylation	1	144.6×	0.014	ADAMTS17
Diseases of glycosylation	1	131.3×	0.014	ADAMTS17
Diseases of metabolism	1	80.4×	0.019	ADAMTS17
Post-translational protein modification	1	19.2×	0.067	ADAMTS17
Disease	1	13.1×	0.081	ADAMTS17
Metabolism of proteins	1	12.4×	0.081	ADAMTS17

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
extracellular matrix organization	1	122.1×	0.016	ADAMTS17
proteolysis	1	34.2×	0.029	ADAMTS17

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
ADAMTS17	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	0
D	Druggable family + AlphaFold only, no drug	1	ADAMTS17
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)
ADAMTS17	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.