Trisomy 9p

Summary

Trisomy 9p (MONDO:0016526) 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): 27

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		150	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

27 HPO clinical features (Orphanet curated; top 27 by frequency):

HPO ID	Term	Frequency
HP:0000248	Brachycephaly	Very frequent (80-99%)
HP:0000252	Microcephaly	Very frequent (80-99%)
HP:0000400	Macrotia	Very frequent (80-99%)
HP:0000411	Protruding ear	Very frequent (80-99%)
HP:0000470	Short neck	Very frequent (80-99%)
HP:0000490	Deeply set eye	Very frequent (80-99%)
HP:0000615	Abnormal pupil morphology	Very frequent (80-99%)
HP:0001249	Intellectual disability	Very frequent (80-99%)
HP:0001263	Global developmental delay	Very frequent (80-99%)
HP:0001800	Hypoplastic toenails	Very frequent (80-99%)
HP:0001804	Hypoplastic fingernail	Very frequent (80-99%)
HP:0002714	Downturned corners of mouth	Very frequent (80-99%)
HP:0005105	Abnormal nasal morphology	Very frequent (80-99%)
HP:0006610	Wide intermamillary distance	Very frequent (80-99%)
HP:0007477	Abnormal dermatoglyphics	Very frequent (80-99%)
HP:0000316	Hypertelorism	Frequent (30-79%)
HP:0000494	Downslanted palpebral fissures	Frequent (30-79%)
HP:0000678	Dental crowding	Frequent (30-79%)
HP:0000960	Sacral dimple	Frequent (30-79%)
HP:0001156	Brachydactyly	Frequent (30-79%)
HP:0002650	Scoliosis	Frequent (30-79%)
HP:0002808	Kyphosis	Frequent (30-79%)
HP:0004209	Clinodactyly of the 5th finger	Frequent (30-79%)
HP:0007598	Bilateral single transverse palmar creases	Frequent (30-79%)
HP:0011079	Impacted tooth	Frequent (30-79%)
HP:0100798	Fingernail dysplasia	Frequent (30-79%)
HP:0100335	Non-midline cleft of the upper lip	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	trisomy 9p
Mondo ID	MONDO:0016526
Orphanet	236, 262767
ICD-11	1126301219
UMLS	C0265428
MedGen	120539
GARD	0020866
Is cancer (heuristic)	no

Also known as: 9p duplication · 9p trisomy · chromosome 9p duplication · Duplication 9p · Duplication of the short arm of chromosome 9 · partial duplication of chromosome 9p · partial duplication of the short arm of chromosome 9 · partial trisomy 9p · partial trisomy of chromosome 9p · partial trisomy of the short arm of chromosome 9 · partial trisomy of the short arm of chromosome type 9 · trisomy of the short arm of chromosome 9 · trisomy type 9p

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 duplication › partial trisomy/tetrasomy of chromosome 9 › syndrome caused by partial chromosomal duplication of the short arm of chromosome 9 › trisomy 9p

Related subtypes (1): tetrasomy 9p

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:

2 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
929260	46,XY,der(21)t(9;21)(p11;p12)		Pathogenic	no assertion criteria provided
4819211	Single allele	CD274	Pathogenic	criteria provided, single submitter

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
CD274	HGNC:17635	ENSG00000120217	Q9NZQ7	Programmed cell death 1 ligand 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CD274	Programmed cell death 1 ligand 1	Plays a critical role in induction and maintenance of immune tolerance to self.

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
Antibody/Immunoglobulin	1	29.2×	0.034

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CD274	Antibody/Immunoglobulin	yes		Ig_sub, Ig-like_dom, Ig_V-set

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
cartilage tissue	1
lower lobe of lung	1
placenta	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CD274	208	ubiquitous	marker	cartilage tissue, placenta, lower lobe of lung

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CD274	5,012

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CD274	Q9NZQ7	76

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 8. 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
Regulation of PD-L1(CD274) translation	1	1268.9×	0.004	CD274
STAT3 nuclear events downstream of ALK signaling	1	1038.2×	0.004	CD274
Co-inhibition by PD-1	1	519.1×	0.004	CD274
PD-L1(CD274) glycosylation and translocation to plasma membrane	1	519.1×	0.004	CD274
GSK3B-mediated proteasomal degradation of PD-L1(CD274)	1	237.9×	0.006	CD274
SPOP-mediated proteasomal degradation of PD-L1(CD274)	1	228.4×	0.006	CD274
AMPK-induced ERAD and lysosome mediated degradation of PD-L1(CD274)	1	193.6×	0.006	CD274
Regulation of PD-L1(CD274) transcription	1	108.8×	0.009	CD274

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
negative regulation of tumor necrosis factor superfamily cytokine production	1	16852.0×	6e-04	CD274
positive regulation of activated CD8-positive, alpha-beta T cell apoptotic process	1	16852.0×	6e-04	CD274
negative regulation of CD8-positive, alpha-beta T cell activation	1	4213.0×	0.002	CD274
negative regulation of T cell mediated immune response to tumor cell	1	2106.5×	0.002	CD274
TRIF-dependent toll-like receptor signaling pathway	1	1532.0×	0.002	CD274
negative regulation of CD4-positive, alpha-beta T cell proliferation	1	1404.3×	0.002	CD274
negative regulation of activated T cell proliferation	1	1053.2×	0.003	CD274
negative regulation of interleukin-10 production	1	732.7×	0.004	CD274
negative regulation of T cell activation	1	526.6×	0.004	CD274
positive regulation of interleukin-10 production	1	401.2×	0.004	CD274
negative regulation of type II interferon production	1	383.0×	0.004	CD274
T cell costimulation	1	374.5×	0.004	CD274
response to cytokine	1	374.5×	0.004	CD274
negative regulation of T cell receptor signaling pathway	1	366.4×	0.004	CD274
negative regulation of T cell proliferation	1	330.4×	0.004	CD274
positive regulation of T cell proliferation	1	259.3×	0.005	CD274
cellular response to lipopolysaccharide	1	98.0×	0.013	CD274
adaptive immune response	1	84.3×	0.014	CD274
cell surface receptor signaling pathway	1	64.1×	0.017	CD274
immune response	1	47.1×	0.022	CD274
signal transduction	1	16.1×	0.062	CD274

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
CD274	MOCLOBEMIDE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CD274	4	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
MOCLOBEMIDE	4	CD274
PYRVINIUM	4	CD274
RIFABUTIN	4	CD274
EVIXAPODLIN	1	CD274

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
CD274	525	Binding:520, Functional:5

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
CD274	525

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

4 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)
MOCLOBEMIDE	4	CD274
PYRVINIUM	4	CD274
RIFABUTIN	4	CD274
EVIXAPODLIN	1	CD274

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	CD274
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	0

Undrugged target profiles

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

Clinical trials & evidence

Clinical trials

Clinical trials: 0.