Idiopathic hypereosinophilic syndrome

Summary

Idiopathic hypereosinophilic syndrome (MONDO:0011895) is a disease with 1 cohort gene.

At a glance

• Prevalence: Unknown (Europe) [Orphanet-validated]
• Cohort genes: 1
• ClinVar variants: 170
• Phenotypes (HPO): 78

Clinical features

Signs & symptoms

Clinical features (HPO)

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

HPO ID	Term	Frequency
HP:0001880	Eosinophilia	Very frequent (80-99%)
HP:0000980	Pallor	Frequent (30-79%)
HP:0001903	Anemia	Frequent (30-79%)
HP:0001945	Fever	Frequent (30-79%)
HP:0001974	Leukocytosis	Frequent (30-79%)
HP:0002098	Respiratory distress	Frequent (30-79%)
HP:0002863	Myelodysplasia	Frequent (30-79%)
HP:0003270	Abdominal distention	Frequent (30-79%)
HP:0031323	Myocardial eosinophilic infiltration	Frequent (30-79%)
HP:0100724	Hypercoagulability	Frequent (30-79%)
HP:0000622	Blurred vision	Occasional (5-29%)
HP:0000708	Atypical behavior	Occasional (5-29%)
HP:0000726	Dementia	Occasional (5-29%)
HP:0000964	Eczematoid dermatitis	Occasional (5-29%)
HP:0000965	Cutis marmorata	Occasional (5-29%)
HP:0000989	Pruritus	Occasional (5-29%)
HP:0001019	Erythroderma	Occasional (5-29%)
HP:0001025	Urticaria	Occasional (5-29%)
HP:0001217	Clubbing	Occasional (5-29%)
HP:0001250	Seizure	Occasional (5-29%)
HP:0001289	Confusion	Occasional (5-29%)
HP:0001298	Encephalopathy	Occasional (5-29%)
HP:0001324	Muscle weakness	Occasional (5-29%)
HP:0001347	Hyperreflexia	Occasional (5-29%)
HP:0001369	Arthritis	Occasional (5-29%)
HP:0001386	Joint swelling	Occasional (5-29%)
HP:0001433	Hepatosplenomegaly	Occasional (5-29%)
HP:0001508	Failure to thrive	Occasional (5-29%)
HP:0001635	Congestive heart failure	Occasional (5-29%)
HP:0001644	Dilated cardiomyopathy	Occasional (5-29%)
HP:0001727	Thromboembolic stroke	Occasional (5-29%)
HP:0001733	Pancreatitis	Occasional (5-29%)
HP:0001744	Splenomegaly	Occasional (5-29%)
HP:0001785	Ankle swelling	Occasional (5-29%)
HP:0001873	Thrombocytopenia	Occasional (5-29%)
HP:0001894	Thrombocytosis	Occasional (5-29%)
HP:0002013	Vomiting	Occasional (5-29%)
HP:0002015	Dysphagia	Occasional (5-29%)
HP:0002024	Malabsorption	Occasional (5-29%)
HP:0002027	Abdominal pain	Occasional (5-29%)
HP:0002028	Chronic diarrhea	Occasional (5-29%)
HP:0002094	Dyspnea	Occasional (5-29%)
HP:0002099	Asthma	Occasional (5-29%)
HP:0002113	Pulmonary infiltrates	Occasional (5-29%)
HP:0002170	Intracranial hemorrhage	Occasional (5-29%)
HP:0002202	Pleural effusion	Occasional (5-29%)
HP:0002204	Pulmonary embolism	Occasional (5-29%)
HP:0002206	Pulmonary fibrosis	Occasional (5-29%)
HP:0002326	Transient ischemic attack	Occasional (5-29%)
HP:0002354	Memory impairment	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	idiopathic hypereosinophilic syndrome
Mondo ID	MONDO:0011895
OMIM	607685
Orphanet	3260
ICD-10-CM	D72.110
ICD-11	703101846
SNOMED CT	423294001
UMLS	C0206141
MedGen	61525
GARD	0016625
Is cancer (heuristic)	no

Also known as: HES · hypereosinophilic syndrome, idiopathic · hypereosinophilic syndrome, idiopathic, resistant to imatinib, isolated cases, somatic mutation

Data availability: 170 ClinVar variants.

Disease family

An umbrella term covering 1 Mondo subtype.

Classification path: disease › human disease › disease by body system or component › musculoskeletal system disorder › muscle tissue disorder › cardiomyopathy › idiopathic cardiomyopathy › idiopathic hypereosinophilic syndrome

Related subtypes (1): idiopathic giant cell myocarditis

Subtypes (1): idiopathic acute eosinophilic pneumonia

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

170 retrieved; paginated sample, class counts are floors:

68 uncertain significance, 57 conflicting classifications of pathogenicity, 23 benign/likely benign, 22 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
135014	NM_006206.6(PDGFRA):c.2306A>T (p.Lys769Met)	PDGFRA	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
135020	NM_006206.6(PDGFRA):c.2936G>A (p.Arg979His)	PDGFRA	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
135026	NM_006206.6(PDGFRA):c.853A>G (p.Ser285Gly)	PDGFRA	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1593747	NM_006206.6(PDGFRA):c.932-13C>A	PDGFRA	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
218679	NM_006206.6(PDGFRA):c.1135T>G (p.Leu379Val)	PDGFRA	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
240309	NM_006206.6(PDGFRA):c.1450G>A (p.Val484Met)	PDGFRA	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
240314	NM_006206.6(PDGFRA):c.1673G>A (p.Arg558His)	PDGFRA	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
240317	NM_006206.6(PDGFRA):c.17C>T (p.Pro6Leu)	PDGFRA	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
240319	NM_006206.6(PDGFRA):c.1891C>T (p.Pro631Ser)	PDGFRA	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
240334	NM_006206.6(PDGFRA):c.2742G>C (p.Arg914=)	PDGFRA	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
240335	NM_006206.6(PDGFRA):c.276G>A (p.Ala92=)	PDGFRA	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
240337	NM_006206.6(PDGFRA):c.2942G>A (p.Arg981His)	PDGFRA	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
240352	NM_006206.6(PDGFRA):c.517G>A (p.Asp173Asn)	PDGFRA	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
240362	NM_006206.6(PDGFRA):c.801A>G (p.Pro267=)	PDGFRA	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
348894	NM_006206.6(PDGFRA):c.219T>C (p.Asn73=)	PDGFRA	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
348896	NM_006206.6(PDGFRA):c.827C>T (p.Thr276Met)	PDGFRA	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
348898	NM_006206.6(PDGFRA):c.954A>G (p.Lys318=)	PDGFRA	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
348900	NM_006206.6(PDGFRA):c.1122-6T>A	PDGFRA	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
348902	NM_006206.6(PDGFRA):c.1471G>A (p.Ala491Thr)	PDGFRA	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
348903	NM_006206.6(PDGFRA):c.1821G>C (p.Val607=)	PDGFRA	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
348904	NM_006206.6(PDGFRA):c.2003-7C>T	PDGFRA	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
348908	NM_006206.6(PDGFRA):c.3191A>G (p.Asp1064Gly)	PDGFRA	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
348910	NM_006206.6(PDGFRA):c.*39C>T	PDGFRA	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
348917	NM_006206.6(PDGFRA):c.*505A>G	PDGFRA	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
348942	NM_006206.6(PDGFRA):c.*2336T>C	PDGFRA	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
348953	NM_006206.6(PDGFRA):c.*2970G>T	PDGFRA	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
39617	NM_006206.6(PDGFRA):c.1631T>C (p.Val544Ala)	PDGFRA	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
407381	NM_006206.6(PDGFRA):c.838G>T (p.Ala280Ser)	PDGFRA	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
407398	NM_006206.6(PDGFRA):c.2965A>G (p.Ile989Val)	PDGFRA	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
407410	NM_006206.6(PDGFRA):c.1274A>G (p.His425Arg)	PDGFRA	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 6 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PDGFRA	Orphanet:168940	Chronic eosinophilic leukemia
PDGFRA	Orphanet:168947	Myeloid/lymphoid neoplasm associated with PDGFRA rearrangement
PDGFRA	Orphanet:199306	Cleft lip/palate
PDGFRA	Orphanet:314950	Primary hypereosinophilic syndrome
PDGFRA	Orphanet:44890	Gastrointestinal stromal tumor
PDGFRA	Orphanet:585877	B-lymphoblastic leukemia/lymphoma with recurrent genetic abnormality

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
PDGFRA	HGNC:8803	ENSG00000134853	P16234	Platelet-derived growth factor receptor alpha	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PDGFRA	Platelet-derived growth factor receptor alpha	Tyrosine-protein kinase that acts as a cell-surface receptor for PDGFA, PDGFB and PDGFC and plays an essential role in the regulation of embryonic development, cell proliferation, survival and chemotaxis.

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
Kinase	1	27.7×	0.036

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
PDGFRA	Kinase	yes	2.7.10.1	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Tyr_kinase_rcpt_3_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
decidua	1
synovial joint	1
tibia	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PDGFRA	289	ubiquitous	marker	tibia, decidua, synovial joint

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PDGFRA	5,186

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PDGFRA	P16234	15

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 13. 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
Imatinib-resistant PDGFR mutants	1	11420.0×	2e-04	PDGFRA
Sunitinib-resistant PDGFR mutants	1	11420.0×	2e-04	PDGFRA
Regorafenib-resistant PDGFR mutants	1	11420.0×	2e-04	PDGFRA
Sorafenib-resistant PDGFR mutants	1	11420.0×	2e-04	PDGFRA
PDGFR mutants bind TKIs	1	11420.0×	2e-04	PDGFRA
Signaling by PDGFRA transmembrane, juxtamembrane and kinase domain mutants	1	878.5×	0.002	PDGFRA
Signaling by PDGFRA extracellular domain mutants	1	878.5×	0.002	PDGFRA
Downstream signal transduction	1	380.7×	0.004	PDGFRA
Signaling by PDGF	1	253.8×	0.006	PDGFRA
Constitutive Signaling by Aberrant PI3K in Cancer	1	126.9×	0.010	PDGFRA
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	1	96.8×	0.012	PDGFRA
PIP3 activates AKT signaling	1	66.8×	0.016	PDGFRA
RAF/MAP kinase cascade	1	61.1×	0.016	PDGFRA

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
platelet-derived growth factor receptor-alpha signaling pathway	1	8426.0×	0.003	PDGFRA
positive regulation of cell proliferation by VEGF-activated platelet derived growth factor receptor signaling pathway	1	5617.3×	0.003	PDGFRA
metanephric glomerular capillary formation	1	5617.3×	0.003	PDGFRA
regulation of mesenchymal stem cell differentiation	1	4213.0×	0.003	PDGFRA
luteinization	1	1872.4×	0.003	PDGFRA
negative regulation of platelet activation	1	1872.4×	0.003	PDGFRA
cell activation	1	1685.2×	0.003	PDGFRA
retina vasculature development in camera-type eye	1	1685.2×	0.003	PDGFRA
cardiac myofibril assembly	1	1296.3×	0.004	PDGFRA
Leydig cell differentiation	1	1203.7×	0.004	PDGFRA
embryonic digestive tract morphogenesis	1	936.2×	0.004	PDGFRA
male genitalia development	1	887.0×	0.004	PDGFRA
white fat cell differentiation	1	842.6×	0.004	PDGFRA
positive regulation of chemotaxis	1	842.6×	0.004	PDGFRA
signal transduction involved in regulation of gene expression	1	702.2×	0.004	PDGFRA
adrenal gland development	1	674.1×	0.004	PDGFRA
estrogen metabolic process	1	624.1×	0.004	PDGFRA
embryonic cranial skeleton morphogenesis	1	581.1×	0.004	PDGFRA
platelet-derived growth factor receptor signaling pathway	1	561.7×	0.004	PDGFRA
face morphogenesis	1	495.6×	0.004	PDGFRA
peptidyl-tyrosine phosphorylation	1	421.3×	0.005	PDGFRA
positive regulation of calcium-mediated signaling	1	421.3×	0.005	PDGFRA
cellular response to reactive oxygen species	1	411.0×	0.005	PDGFRA
embryonic skeletal system morphogenesis	1	391.9×	0.005	PDGFRA
platelet aggregation	1	337.0×	0.005	PDGFRA
cellular response to amino acid stimulus	1	306.4×	0.005	PDGFRA
odontogenesis of dentin-containing tooth	1	300.9×	0.005	PDGFRA
positive regulation of fibroblast proliferation	1	295.6×	0.005	PDGFRA
roof of mouth development	1	247.8×	0.006	PDGFRA
hematopoietic progenitor cell differentiation	1	237.3×	0.006	PDGFRA

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
PDGFRA	PONATINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
PDGFRA	77	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
PONATINIB	4	PDGFRA
FEDRATINIB	4	PDGFRA
TIVOZANIB	4	PDGFRA
LENVATINIB	4	PDGFRA
AXITINIB	4	PDGFRA
SORAFENIB	4	PDGFRA
IMATINIB MESYLATE	4	PDGFRA
INFIGRATINIB PHOSPHATE	4	PDGFRA
INFIGRATINIB	4	PDGFRA
REGORAFENIB	4	PDGFRA
CERITINIB	4	PDGFRA
VANDETANIB	4	PDGFRA
NILOTINIB	4	PDGFRA
BOSUTINIB	4	PDGFRA
NINTEDANIB ESYLATE	4	PDGFRA
PEXIDARTINIB	4	PDGFRA
AVAPRITINIB	4	PDGFRA
RIPRETINIB	4	PDGFRA
PAZOPANIB	4	PDGFRA
NINTEDANIB	4	PDGFRA
SUNITINIB	4	PDGFRA
DASATINIB	4	PDGFRA
ERLOTINIB	4	PDGFRA
QUIZARTINIB	4	PDGFRA
MIDOSTAURIN	4	PDGFRA
IMATINIB	4	PDGFRA
VATALANIB	3	PDGFRA
MASITINIB	3	PDGFRA
CRENOLANIB	3	PDGFRA
SARACATINIB	3	PDGFRA

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
PDGFRA	1,172	Binding:1160, Functional:8, ADMET:4

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
PDGFRA	2.7.10.1	receptor protein-tyrosine kinase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
PDGFRA	1,172

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

30 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)
PONATINIB	4	PDGFRA
FEDRATINIB	4	PDGFRA
TIVOZANIB	4	PDGFRA
LENVATINIB	4	PDGFRA
AXITINIB	4	PDGFRA
SORAFENIB	4	PDGFRA
IMATINIB MESYLATE	4	PDGFRA
INFIGRATINIB PHOSPHATE	4	PDGFRA
INFIGRATINIB	4	PDGFRA
REGORAFENIB	4	PDGFRA
CERITINIB	4	PDGFRA
VANDETANIB	4	PDGFRA
NILOTINIB	4	PDGFRA
BOSUTINIB	4	PDGFRA
NINTEDANIB ESYLATE	4	PDGFRA
PEXIDARTINIB	4	PDGFRA
AVAPRITINIB	4	PDGFRA
RIPRETINIB	4	PDGFRA
PAZOPANIB	4	PDGFRA
NINTEDANIB	4	PDGFRA
SUNITINIB	4	PDGFRA
DASATINIB	4	PDGFRA
ERLOTINIB	4	PDGFRA
QUIZARTINIB	4	PDGFRA
MIDOSTAURIN	4	PDGFRA
IMATINIB	4	PDGFRA
VATALANIB	3	PDGFRA
MASITINIB	3	PDGFRA
CRENOLANIB	3	PDGFRA
SARACATINIB	3	PDGFRA

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	PDGFRA
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.