Chromosome 9p deletion syndrome

Summary

Chromosome 9p deletion syndrome (MONDO:0008013) is a disease with 6 cohort genes and 1 clinical trial.

At a glance

• Cohort genes: 6
• ClinVar variants: 10
• Phenotypes (HPO): 58
• Clinical trials: 1

Clinical features

Signs & symptoms

Clinical features (HPO)

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

HPO ID	Term	Frequency
HP:0000218	High palate	Very frequent (80-99%)
HP:0000243	Trigonocephaly	Very frequent (80-99%)
HP:0000248	Brachycephaly	Very frequent (80-99%)
HP:0000272	Malar flattening	Very frequent (80-99%)
HP:0000316	Hypertelorism	Very frequent (80-99%)
HP:0000343	Long philtrum	Very frequent (80-99%)
HP:0000347	Micrognathia	Very frequent (80-99%)
HP:0000369	Low-set ears	Very frequent (80-99%)
HP:0000463	Anteverted nares	Very frequent (80-99%)
HP:0000465	Webbed neck	Very frequent (80-99%)
HP:0000470	Short neck	Very frequent (80-99%)
HP:0000581	Blepharophimosis	Very frequent (80-99%)
HP:0001249	Intellectual disability	Very frequent (80-99%)
HP:0001263	Global developmental delay	Very frequent (80-99%)
HP:0001816	Thin nail	Very frequent (80-99%)
HP:0002162	Low posterior hairline	Very frequent (80-99%)
HP:0005280	Depressed nasal bridge	Very frequent (80-99%)
HP:0006610	Wide intermamillary distance	Very frequent (80-99%)
HP:0007477	Abnormal dermatoglyphics	Very frequent (80-99%)
HP:0008551	Microtia	Very frequent (80-99%)
HP:0009623	Proximal placement of thumb	Very frequent (80-99%)
HP:0009738	Abnormality of the antihelix	Very frequent (80-99%)
HP:0009892	Anotia	Very frequent (80-99%)
HP:0000028	Cryptorchidism	Frequent (30-79%)
HP:0000047	Hypospadias	Frequent (30-79%)
HP:0000062	Ambiguous genitalia	Frequent (30-79%)
HP:0000160	Narrow mouth	Frequent (30-79%)
HP:0000164	Abnormality of the dentition	Frequent (30-79%)
HP:0000252	Microcephaly	Frequent (30-79%)
HP:0000286	Epicanthus	Frequent (30-79%)
HP:0000486	Strabismus	Frequent (30-79%)
HP:0000574	Thick eyebrow	Frequent (30-79%)
HP:0000582	Upslanted palpebral fissure	Frequent (30-79%)
HP:0000639	Nystagmus	Frequent (30-79%)
HP:0000664	Synophrys	Frequent (30-79%)
HP:0001250	Seizure	Frequent (30-79%)
HP:0001252	Hypotonia	Frequent (30-79%)
HP:0001276	Hypertonia	Frequent (30-79%)
HP:0001376	Limitation of joint mobility	Frequent (30-79%)
HP:0001850	Abnormality of the tarsal bones	Frequent (30-79%)
HP:0002553	Highly arched eyebrow	Frequent (30-79%)
HP:0002650	Scoliosis	Frequent (30-79%)
HP:0003196	Short nose	Frequent (30-79%)
HP:0000074	Ureteropelvic junction obstruction	Occasional (5-29%)
HP:0000175	Cleft palate	Occasional (5-29%)
HP:0000413	Atresia of the external auditory canal	Occasional (5-29%)
HP:0000453	Choanal atresia	Occasional (5-29%)
HP:0000494	Downslanted palpebral fissures	Occasional (5-29%)
HP:0000568	Microphthalmia	Occasional (5-29%)
HP:0000772	Abnormal rib morphology	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	chromosome 9p deletion syndrome
Mondo ID	MONDO:0008013
MeSH	C538024
OMIM	158170
Orphanet	261112
DOID	DOID:0060732
SNOMED CT	62599000
UMLS	C0795830
MedGen	167073
GARD	0003773
Is cancer (heuristic)	no

Also known as: 9p deletion · 9p deletion syndrome · 9p monosomy · 9p- syndrome · Alfi syndrome · chromosome 9p deletion · deletion 9p · monosomy 9p · monosomy 9p syndrome · monosomy type 9p · partial deletion of chromosome 9p · partial deletion of the short arm of chromosome 9 · partial deletion of the short arm of chromosome type 9 · partial monosomy 9p · partial monosomy of chromosome 9p · partial monosomy of the short arm of chromosome 9

Data availability: 10 ClinVar variants.

Disease family

An umbrella term covering 2 Mondo subtypes.

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 9 › chromosome 9p deletion syndrome

Related subtypes (2): partial monosomy of the long arm of chromosome 9, 9q21.13 microdeletion syndrome

Subtypes (2): distal monosomy 9p, 9p13 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:

9 pathogenic, 1 not provided

ClinVar	Variant (HGVS)	Gene	Classification	Review
1703681	GRCh37/hg19 9p24.1-22.1(chr9:4992582-19322101)	ADAMTSL1	Pathogenic	no assertion criteria provided
1703680	GRCh37/hg19 9p24.3-23(chr9:203861-12570076)	AK3	Pathogenic	no assertion criteria provided
1703682	GRCh37/hg19 9p24.3-24.1(chr9:203861-7959823)	AK3	Pathogenic	no assertion criteria provided
981212	GRCh37/hg19 9p24.3-22.2(chr9:204193-18073357)x1	AK3	Pathogenic	no assertion criteria provided
981213	GRCh37/hg19 9p23-22.2(chr9:13638428-17121764)x1	BNC2	Pathogenic	no assertion criteria provided
3896738	NC_000009.11:g.(?134929)(8733886_?)del	CDC37L1	Pathogenic	criteria provided, single submitter
1703678	GRCh37/hg19 9p24.3-23(chr9:203861-12127088)	DOCK8-AS1	Pathogenic	no assertion criteria provided
1684649	Single allele	LOC121331318	Pathogenic	criteria provided, single submitter
917492	NC_000009.12:g.1_190938del	LOC130001433	Pathogenic	criteria provided, single submitter
4074308	GRCh37/hg19 9p24.3-24.1(chr9:203861-4713062)x1	AK3	not provided	no classification provided

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
ADAMTSL1	Orphanet:521445	Microcephaly-facial dysmorphism-ocular anomalies-multiple congenital anomalies syndrome
BNC2	Orphanet:93110	Posterior urethral valve

Cohort genes → proteins

6 cohort genes, 6 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	6

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
ADAMTSL1	HGNC:14632	ENSG00000178031	Q8N6G6	ADAMTS-like protein 1	clinvar
CDC37L1	HGNC:17179	ENSG00000106993	Q7L3B6	Hsp90 co-chaperone Cdc37-like 1	clinvar
AK3	HGNC:17376	ENSG00000147853	Q9UIJ7	GTP:AMP phosphotransferase AK3, mitochondrial	clinvar
DOCK8-AS1	HGNC:26436	ENSG00000183784	Q5T8R8	Uncharacterized protein DOCK8-AS1	clinvar
BNC2	HGNC:30988	ENSG00000173068	Q6ZN30	Zinc finger protein basonuclin-2	clinvar
AK4	HGNC:363	ENSG00000162433	P27144	Adenylate kinase 4, mitochondrial	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CDC37L1	Hsp90 co-chaperone Cdc37-like 1	Co-chaperone that binds to numerous proteins and promotes their interaction with Hsp70 and Hsp90.
AK3	GTP:AMP phosphotransferase AK3, mitochondrial	Mitochondrial adenylate kinase with a specific GTP:AMP phosphotransferase activity.
BNC2	Zinc finger protein basonuclin-2	Probable transcription factor specific for skin keratinocytes.
AK4	Adenylate kinase 4, mitochondrial	Broad-specificity mitochondrial nucleoside phosphate kinase involved in cellular nucleotide homeostasis by catalyzing nucleoside-phosphate interconversions.

Protein-family classification

Druggable: 3 · Difficult: 1 · Unknown: 2 · Druggable fraction: 0.5

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	2	9.2×	0.071
Antibody/Immunoglobulin	1	4.9×	0.377
Transcription factor	1	1.4×	0.719
Other/Unknown	2	0.6×	0.936

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ADAMTSL1	Antibody/Immunoglobulin	yes		TSP1_rpt, Ig_sub2, Ig_sub
CDC37L1	Other/Unknown	no		Cdc37, Cdc37_Hsp90-bd, Cdc37_Hsp90-bd_sf
AK3	Kinase	yes	2.7.4.10	Adenylat/UMP-CMP_kin, Adenyl_kin_sub, Adenylate_kinase_lid-dom
DOCK8-AS1	Other/Unknown	no		DUF5555
BNC2	Transcription factor	no		Znf_C2H2_type, Disconnected-like
AK4	Kinase	yes	2.7.4.10	Adenylat/UMP-CMP_kin, Adenyl_kin_sub, Adenylate_kinase_lid-dom

Expression context

Cohort genes with no expression data: 0.

6 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)	6
unknown	0

Top tissues across cohort

Tissue	Cohort genes
sural nerve	2
lower esophagus	1
lower esophagus muscularis layer	1
gastrocnemius	1
muscle of leg	1
tibialis anterior	1
cardiac muscle of right atrium	1
left ventricle myocardium	1
upper arm skin	1
adult mammalian kidney	1
cortex of kidney	1
kidney	1
germinal epithelium of ovary	1
parietal pleura	1
adult organism	1
heart right ventricle	1
renal medulla	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ADAMTSL1	182	ubiquitous	marker	lower esophagus muscularis layer, lower esophagus, sural nerve
CDC37L1	278	ubiquitous	marker	gastrocnemius, muscle of leg, tibialis anterior
AK3	256	ubiquitous	marker	cardiac muscle of right atrium, left ventricle myocardium, upper arm skin
DOCK8-AS1	138	tissue_specific	marker	adult mammalian kidney, kidney, cortex of kidney
BNC2	229	ubiquitous	marker	germinal epithelium of ovary, sural nerve, parietal pleura
AK4	272	ubiquitous	marker	adult organism, renal medulla, heart right ventricle

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
AK4	3,474
AK3	3,306
CDC37L1	1,247
BNC2	1,104
ADAMTSL1	855
DOCK8-AS1	0

Structural data

PDB: 2 · AlphaFold-only: 4 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
AK3	Q9UIJ7	4
AK4	P27144	3

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
CDC37L1	Q7L3B6	72.63
ADAMTSL1	Q8N6G6	71.26
BNC2	Q6ZN30	54.10
DOCK8-AS1	Q5T8R8	47.31

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 17. Enrichment computed across 6 evidence-associated genes (4 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 4 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Interconversion of nucleotide di- and triphosphates	1	89.2×	0.045	AK4
Defective B3GALTL causes PpS	1	77.2×	0.045	ADAMTSL1
Metabolism of nucleotides	1	75.1×	0.045	AK4
O-glycosylation of TSR domain-containing proteins	1	75.1×	0.045	ADAMTSL1
Hemostasis	2	18.0×	0.045	CDC37L1, AK3
Diseases associated with O-glycosylation of proteins	1	53.9×	0.052	ADAMTSL1
Response to elevated platelet cytosolic Ca2+	1	40.8×	0.057	CDC37L1
O-linked glycosylation	1	36.1×	0.057	ADAMTSL1
Diseases of glycosylation	1	32.8×	0.057	ADAMTSL1
Platelet activation, signaling and aggregation	1	26.4×	0.063	CDC37L1
Platelet degranulation	1	22.0×	0.069	CDC37L1
Diseases of metabolism	1	20.1×	0.069	ADAMTSL1
Factors involved in megakaryocyte development and platelet production	1	16.6×	0.077	AK3
Post-translational protein modification	1	4.8×	0.234	ADAMTSL1
Disease	1	3.3×	0.302	ADAMTSL1
Metabolism of proteins	1	3.1×	0.302	ADAMTSL1
Metabolism	1	2.9×	0.302	AK4

GO biological processes 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.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
ADP biosynthetic process	2	963.0×	2e-05	AK3, AK4
nucleoside triphosphate biosynthetic process	2	842.6×	2e-05	AK3, AK4
AMP metabolic process	2	749.0×	2e-05	AK3, AK4
GTP metabolic process	2	449.4×	4e-05	AK3, AK4
ribonucleoside diphosphate biosynthetic process	1	1685.2×	0.002	AK4
ITP metabolic process	1	1685.2×	0.002	AK3
UTP metabolic process	1	1685.2×	0.002	AK3
mesenchyme development	1	481.5×	0.005	BNC2
tongue development	1	421.3×	0.005	BNC2
endochondral bone growth	1	337.0×	0.005	BNC2
nucleobase-containing small molecule interconversion	1	337.0×	0.005	AK4
regulation of oxidative phosphorylation	1	240.7×	0.007	AK4
ATP metabolic process	1	93.6×	0.016	AK4
roof of mouth development	1	49.6×	0.029	BNC2
blood coagulation	1	34.8×	0.038	AK3
extracellular matrix organization	1	24.4×	0.048	ADAMTSL1
cellular response to hypoxia	1	24.2×	0.048	AK4
protein folding	1	20.7×	0.053	CDC37L1
protein stabilization	1	13.4×	0.076	CDC37L1
regulation of DNA-templated transcription	1	6.3×	0.149	BNC2

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 6

Druggability breadth: 1 of 6 evidence-associated genes (17%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ADAMTSL1	0	0
CDC37L1	0	0
AK3	0	0
DOCK8-AS1	0	0
BNC2	0	0
AK4	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 2.

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

Symbol	Assays	Type breakdown
AK4	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
AK3	2.7.4.10	nucleoside-triphosphate-adenylate kinase
AK4	2.7.4.10, 2.7.4.3	nucleoside-triphosphate-adenylate kinase, adenylate kinase

Pharmacogenomics

Cohort genes with a PharmGKB record: 5; 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	2	AK3, AK4
D	Druggable family + AlphaFold only, no drug	1	ADAMTSL1
E	Difficult family or no structure, no drug	3	CDC37L1, DOCK8-AS1, BNC2

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
ADAMTSL1	0	—
CDC37L1	0	—
AK3	0	—
DOCK8-AS1	0	—
BNC2	0	—
AK4	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 1.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT04586400	Not specified	RECRUITING	Chromosome 9 P Minus Syndrome