Hereditary progressive mucinous histiocytosis

Summary

Hereditary progressive mucinous histiocytosis (MONDO:0007725) is a disease with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 1
• Phenotypes (HPO): 6

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		18	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

6 HPO clinical features (Orphanet curated; top 6 by frequency):

HPO ID	Term	Frequency
HP:0025475	Erythematous macule	Very frequent (80-99%)
HP:0030350	Erythematous papule	Very frequent (80-99%)
HP:0040138	Mucinous histiocytosis	Very frequent (80-99%)
HP:0000989	Pruritus	Occasional (5-29%)
HP:0002716	Lymphadenopathy	Excluded (0%)
HP:0031871	Abnormal Langerhans cell morphology	Excluded (0%)

Identifiers

Disease identifiers

Field	Value
Canonical name	hereditary progressive mucinous histiocytosis
Mondo ID	MONDO:0007725
MeSH	C564186
OMIM	142630
Orphanet	158025
ICD-11	284196883
UMLS	C1840586
MedGen	326771
GARD	0016989
Is cancer (heuristic)	no

Data availability: 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by body system or component › immune system disorder › lymphoid system disorder › lymphatic system disorder › histiocytosis › non-Langerhans cell histiocytosis › hereditary progressive mucinous histiocytosis

Related subtypes (14): Niemann-Pick disease, sinus histiocytosis with massive lymphadenopathy, sea-blue histiocyte syndrome, multicentric reticulohistiocytosis, generalized eruptive histiocytosis, benign cephalic histiocytosis, juvenile xanthogranuloma, xanthoma disseminatum, papular xanthoma, necrobiotic xanthogranuloma, indeterminate dendritic cell tumor, progressive nodular histiocytosis, Erdheim-Chester disease, xanthogranuloma

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

No tiered GWAS variants or ClinVar records for this disease.

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 17 · Orphanet: 7 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
PDGFRB	Limited	Autosomal dominant	hereditary progressive mucinous histiocytosis	17

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PDGFRB	Orphanet:168950	Myeloid/lymphoid neoplasm associated with PDGFRB rearrangement
PDGFRB	Orphanet:1980	Bilateral striopallidodentate calcinosis
PDGFRB	Orphanet:2591	Infantile myofibromatosis
PDGFRB	Orphanet:314950	Primary hypereosinophilic syndrome
PDGFRB	Orphanet:363665	Acroosteolysis-keloid-like lesions-premature aging syndrome
PDGFRB	Orphanet:477831	Kosaki overgrowth syndrome
PDGFRB	Orphanet:86830	Chronic myeloproliferative disease, unclassifiable

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
PDGFRB	HGNC:8804	ENSG00000113721	P09619	Platelet-derived growth factor receptor beta	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PDGFRB	Platelet-derived growth factor receptor beta	Tyrosine-protein kinase that acts as a cell-surface receptor for homodimeric PDGFB and PDGFD and for heterodimers formed by PDGFA and PDGFB, and plays an essential role in the regulation of embryonic development, cell proliferation, surviv…

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)
PDGFRB	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
endocervix	1
right coronary artery	1
stromal cell of endometrium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PDGFRB	270	ubiquitous	marker	stromal cell of endometrium, right coronary artery, endocervix

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PDGFRB	5,111

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PDGFRB	P09619	8

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 6. 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
Downstream signal transduction	1	380.7×	0.012	PDGFRB
Signaling by PDGF	1	253.8×	0.012	PDGFRB
Constitutive Signaling by Aberrant PI3K in Cancer	1	126.9×	0.015	PDGFRB
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	1	96.8×	0.015	PDGFRB
PIP3 activates AKT signaling	1	66.8×	0.016	PDGFRB
RAF/MAP kinase cascade	1	61.1×	0.016	PDGFRB

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
cell migration involved in coronary angiogenesis	1	16852.0×	8e-04	PDGFRB
metanephric glomerular mesangial cell proliferation involved in metanephros development	1	16852.0×	8e-04	PDGFRB
cell migration involved in vasculogenesis	1	8426.0×	8e-04	PDGFRB
smooth muscle cell chemotaxis	1	8426.0×	8e-04	PDGFRB
positive regulation of metanephric mesenchymal cell migration by platelet-derived growth factor receptor-beta signaling pathway	1	5617.3×	8e-04	PDGFRB
positive regulation of cell proliferation by VEGF-activated platelet derived growth factor receptor signaling pathway	1	5617.3×	8e-04	PDGFRB
metanephric glomerular capillary formation	1	5617.3×	8e-04	PDGFRB
smooth muscle adaptation	1	4213.0×	1e-03	PDGFRB
platelet-derived growth factor receptor-beta signaling pathway	1	3370.4×	0.001	PDGFRB
retina vasculature development in camera-type eye	1	1685.2×	0.002	PDGFRB
cardiac myofibril assembly	1	1296.3×	0.002	PDGFRB
positive regulation of DNA biosynthetic process	1	1123.5×	0.002	PDGFRB
positive regulation of smooth muscle cell migration	1	991.3×	0.002	PDGFRB
positive regulation of calcium ion import	1	936.2×	0.002	PDGFRB
aorta morphogenesis	1	887.0×	0.002	PDGFRB
positive regulation of chemotaxis	1	842.6×	0.002	PDGFRB
positive regulation of MAP kinase activity	1	648.1×	0.003	PDGFRB
platelet-derived growth factor receptor signaling pathway	1	561.7×	0.003	PDGFRB
positive regulation of mitotic nuclear division	1	543.6×	0.003	PDGFRB
positive regulation of reactive oxygen species metabolic process	1	510.7×	0.003	PDGFRB
peptidyl-tyrosine phosphorylation	1	421.3×	0.004	PDGFRB
positive regulation of calcium-mediated signaling	1	421.3×	0.004	PDGFRB
positive regulation of smooth muscle cell proliferation	1	330.4×	0.004	PDGFRB
cell chemotaxis	1	185.2×	0.007	PDGFRB
cell surface receptor protein tyrosine kinase signaling pathway	1	173.7×	0.008	PDGFRB
regulation of actin cytoskeleton organization	1	157.5×	0.008	PDGFRB
protein autophosphorylation	1	145.3×	0.008	PDGFRB
positive regulation of ERK1 and ERK2 cascade	1	85.1×	0.014	PDGFRB
positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	1	78.4×	0.015	PDGFRB
angiogenesis	1	62.4×	0.017	PDGFRB

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
PDGFRB	PONATINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
PDGFRB	102	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
PONATINIB	4	PDGFRB
FEDRATINIB	4	PDGFRB
TIVOZANIB	4	PDGFRB
LENVATINIB	4	PDGFRB
AXITINIB	4	PDGFRB
SORAFENIB	4	PDGFRB
SUNITINIB MALATE	4	PDGFRB
REGORAFENIB	4	PDGFRB
PACRITINIB	4	PDGFRB
VANDETANIB	4	PDGFRB
NILOTINIB	4	PDGFRB
BOSUTINIB	4	PDGFRB
NINTEDANIB ESYLATE	4	PDGFRB
GILTERITINIB	4	PDGFRB
TOVORAFENIB	4	PDGFRB
PEXIDARTINIB	4	PDGFRB
PAZOPANIB	4	PDGFRB
NINTEDANIB	4	PDGFRB
SUNITINIB	4	PDGFRB
DASATINIB	4	PDGFRB
ERLOTINIB	4	PDGFRB
LAPATINIB	4	PDGFRB
QUIZARTINIB	4	PDGFRB
MIDOSTAURIN	4	PDGFRB
IMATINIB	4	PDGFRB
VATALANIB	3	PDGFRB
FAMITINIB	3	PDGFRB
MASITINIB	3	PDGFRB
CRENOLANIB	3	PDGFRB
SARACATINIB	3	PDGFRB

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
PDGFRB	1,237	Binding:1213, Functional:16, ADMET:8

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
PDGFRB	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
PDGFRB	1,237

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	PDGFRB
FEDRATINIB	4	PDGFRB
TIVOZANIB	4	PDGFRB
LENVATINIB	4	PDGFRB
AXITINIB	4	PDGFRB
SORAFENIB	4	PDGFRB
SUNITINIB MALATE	4	PDGFRB
REGORAFENIB	4	PDGFRB
PACRITINIB	4	PDGFRB
VANDETANIB	4	PDGFRB
NILOTINIB	4	PDGFRB
BOSUTINIB	4	PDGFRB
NINTEDANIB ESYLATE	4	PDGFRB
GILTERITINIB	4	PDGFRB
TOVORAFENIB	4	PDGFRB
PEXIDARTINIB	4	PDGFRB
PAZOPANIB	4	PDGFRB
NINTEDANIB	4	PDGFRB
SUNITINIB	4	PDGFRB
DASATINIB	4	PDGFRB
ERLOTINIB	4	PDGFRB
LAPATINIB	4	PDGFRB
QUIZARTINIB	4	PDGFRB
MIDOSTAURIN	4	PDGFRB
IMATINIB	4	PDGFRB
VATALANIB	3	PDGFRB
FAMITINIB	3	PDGFRB
MASITINIB	3	PDGFRB
CRENOLANIB	3	PDGFRB
SARACATINIB	3	PDGFRB

Druggability pyramid

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

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