Camurati-Engelmann disease type 1

Summary

Camurati-Engelmann disease type 1 (MONDO:0700385) is a disease caused by TGFB1 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: TGFB1 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 2

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Camurati-Engelmann disease type 1
Mondo ID	MONDO:0700385
OMIM	131300
DOID	DOID:0061229
Is cancer (heuristic)	no

Data availability: 2 ClinVar variants · 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › Camurati-Engelmann disease › Camurati-Engelmann disease type 1

Related subtypes (1): Camurati-Engelmann disease type 2

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 pathogenic/likely pathogenic, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
12529	NM_000660.7(TGFB1):c.653G>A (p.Arg218His)	TGFB1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
12531	NM_000660.7(TGFB1):c.652C>T (p.Arg218Cys)	TGFB1	Pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 11 · Orphanet: 3 · 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
TGFB1	Definitive	Autosomal dominant	Camurati-Engelmann disease	11

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TGFB1	Orphanet:1328	Camurati-Engelmann disease
TGFB1	Orphanet:565788	Infantile inflammatory bowel disease with neurological involvement
TGFB1	Orphanet:586	Cystic fibrosis

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
TGFB1	HGNC:11766	ENSG00000105329	P01137	Transforming growth factor beta-1 proprotein	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TGFB1	Transforming growth factor beta-1 proprotein	Transforming growth factor beta-1 proprotein: Precursor of the Latency-associated peptide (LAP) and Transforming growth factor beta-1 (TGF-beta-1) chains, which constitute the regulatory and active subunit of TGF-beta-1, respectively.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

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
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TGFB1	Other/Unknown	no		TGF-b_propeptide, TGF-b_C, TGFb1

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
granulocyte	1
leukocyte	1
monocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TGFB1	204	ubiquitous	marker	granulocyte, monocyte, leukocyte

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TGFB1	7,596

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TGFB1	P01137	20

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 52. 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
Influenza Virus Induced Apoptosis	1	5710.0×	0.003	TGFB1
TGFBR2 MSI Frameshift Mutants in Cancer	1	5710.0×	0.003	TGFB1
Loss of Function of TGFBR2 in Cancer	1	3806.7×	0.003	TGFB1
TGFBR2 Kinase Domain Mutants in Cancer	1	3806.7×	0.003	TGFB1
TGFBR1 LBD Mutants in Cancer	1	2855.0×	0.003	TGFB1
Loss of Function of TGFBR1 in Cancer	1	2284.0×	0.003	TGFB1
Loss of Function of SMAD2/3 in Cancer	1	1903.3×	0.003	TGFB1
Signaling by TGF-beta Receptor Complex in Cancer	1	1903.3×	0.003	TGFB1
SMAD2/3 Phosphorylation Motif Mutants in Cancer	1	1903.3×	0.003	TGFB1
TGFBR1 KD Mutants in Cancer	1	1903.3×	0.003	TGFB1
RUNX3 regulates CDKN1A transcription	1	1631.4×	0.003	TGFB1
TGFBR3 regulates TGF-beta signaling	1	1427.5×	0.003	TGFB1
RUNX3 regulates p14-ARF	1	1142.0×	0.004	TGFB1
TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition)	1	671.8×	0.006	TGFB1
Syndecan interactions	1	423.0×	0.008	TGFB1
Downregulation of TGF-beta receptor signaling	1	407.9×	0.008	TGFB1
Signaling by TGFBR3	1	368.4×	0.008	TGFB1
Elastic fibre formation	1	335.9×	0.008	TGFB1
TGF-beta receptor signaling activates SMADs	1	326.3×	0.008	TGFB1
Molecules associated with elastic fibres	1	308.6×	0.008	TGFB1
Transcriptional regulation by RUNX3	1	271.9×	0.009	TGFB1
Regulation of RUNX3 expression and activity	1	233.1×	0.010	TGFB1
Signaling by TGF-beta Receptor Complex	1	200.3×	0.011	TGFB1
Influenza Infection	1	175.7×	0.012	TGFB1
Response to elevated platelet cytosolic Ca2+	1	163.1×	0.012	TGFB1
Adipogenesis	1	156.4×	0.012	TGFB1
Non-integrin membrane-ECM interactions	1	154.3×	0.012	TGFB1
ECM proteoglycans	1	150.3×	0.012	TGFB1
Transcriptional regulation of white adipocyte differentiation	1	129.8×	0.014	TGFB1
Deubiquitination	1	124.1×	0.014	TGFB1

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
columnar/cuboidal epithelial cell maturation	1	16852.0×	0.002	TGFB1
adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains	1	16852.0×	0.002	TGFB1
positive regulation of microglia differentiation	1	16852.0×	0.002	TGFB1
regulation of interleukin-23 production	1	16852.0×	0.002	TGFB1
branch elongation involved in mammary gland duct branching	1	16852.0×	0.002	TGFB1
embryonic liver development	1	8426.0×	0.002	TGFB1
positive regulation of primary miRNA processing	1	8426.0×	0.002	TGFB1
negative regulation of natural killer cell mediated cytotoxicity directed against tumor cell target	1	5617.3×	0.002	TGFB1
regulation of blood vessel remodeling	1	5617.3×	0.002	TGFB1
frontal suture morphogenesis	1	5617.3×	0.002	TGFB1
regulation of enamel mineralization	1	5617.3×	0.002	TGFB1
tolerance induction to self antigen	1	4213.0×	0.002	TGFB1
positive regulation of exit from mitosis	1	4213.0×	0.002	TGFB1
response to laminar fluid shear stress	1	4213.0×	0.002	TGFB1
negative regulation of skeletal muscle tissue development	1	4213.0×	0.002	TGFB1
regulation of cartilage development	1	4213.0×	0.002	TGFB1
Langerhans cell differentiation	1	4213.0×	0.002	TGFB1
negative regulation of hyaluronan biosynthetic process	1	4213.0×	0.002	TGFB1
positive regulation of vasculature development	1	4213.0×	0.002	TGFB1
myofibroblast differentiation	1	3370.4×	0.002	TGFB1
regulation of protein import into nucleus	1	3370.4×	0.002	TGFB1
positive regulation of odontogenesis	1	3370.4×	0.002	TGFB1
negative regulation of release of sequestered calcium ion into cytosol	1	3370.4×	0.002	TGFB1
bronchiole development	1	3370.4×	0.002	TGFB1
regulation of branching involved in mammary gland duct morphogenesis	1	3370.4×	0.002	TGFB1
positive regulation of mononuclear cell migration	1	3370.4×	0.002	TGFB1
cellular response to acetaldehyde	1	3370.4×	0.002	TGFB1
connective tissue replacement involved in inflammatory response wound healing	1	2808.7×	0.002	TGFB1
negative regulation of extracellular matrix disassembly	1	2808.7×	0.002	TGFB1
regulation of striated muscle tissue development	1	2808.7×	0.002	TGFB1

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · 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).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TGFB1	1	2

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
VACTOSERTIB	2	TGFB1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
TGFB1	9	Binding:9

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

1 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)
VACTOSERTIB	2	TGFB1

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	1	TGFB1
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.