Isolated craniosynostosis

Summary

Isolated craniosynostosis (MONDO:0015337) is a disease with 1 cohort gene (2 GWAS associations across 1 studies).

At a glance

• Cohort genes: 1
• GWAS associations: 2

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	isolated craniosynostosis
Mondo ID	MONDO:0015337
Orphanet	139390
UMLS	C5848302
MedGen	1863457
Is cancer (heuristic)	no

Also known as: nonsyndromic craniosynostosis

Data availability: 2 GWAS associations (1 study) · 1 GenCC gene-disease record.

Disease family

An umbrella term covering 4 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › musculoskeletal system disorder › skeletal system disorder › bone disorder › bone development disease › dysostosis › synostosis › craniosynostosis › isolated craniosynostosis

Related subtypes (28): craniosynostosis, Adelaide type, craniosynostosis with ectopia lentis, craniosynostosis syndrome, autosomal recessive, craniosynostosis with ocular abnormalities and hallucal defects, syndromic craniosynostosis, craniosynostosis Fontaine type, craniosynostosis Maroteaux Fonfria type, craniosynostosis alopecia brain defect, craniosynostosis arthrogryposis cleft palate, craniosynostosis autosomal dominant, craniosynostosis cleft lip palate arthrogryposis, craniosynostosis contractures cleft, craniosynostosis exostoses nevus epibulbar dermoid, craniosynostosis intellectual disability heart defects, Hordnes Engebretsen Knudtson syndrome, Iida Kannari syndrome, mehta lewis patton syndrome, non-syndromic unicoronal craniosynostosis, non-syndromic unilambdoid craniosynostosis, non-syndromic unifrontosphenoidal craniosynostosis, non-syndromic unisquamosal craniosynostosis, non-syndromic multisutural craniosynostosis, non-syndromic non-specific multisutural craniosynostosis, non-syndromic bilambdoid craniosynostosis, non-syndromic unicoronal and sagittal craniosynostosis, non-syndromic metopic and sagittal craniosynostosis, non-syndromic bicoronal and metopic craniosynostosis, non-syndromic bicoronal and sagittal craniosynostosis

Subtypes (4): isolated cloverleaf skull syndrome, isolated trigonocephaly, isolated oxycephaly, non-syndromic unisutural craniosynostosis

Genetics & variants

GWAS landscape

2 GWAS associations across 1 studies. Top hits map to 1 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs6127972	1e-06	BMP7	T
rs1884302	2e-06	BMP2 - LINC01428	C

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST010297	Justice CM	2020	0	0	A genome-wide association study implicates the BMP7 locus as a risk factor for nonsyndromic metopic craniosynostosis.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	0
Tier 2: splice/UTR	0
Tier 3: regulatory	0
Tier 4: intronic/intergenic	2

MAF distribution

Bucket	Variants
common (>=0.05)	2
low_freq (0.01-0.05)	0
rare (<0.01)	0
unknown	0

Functional consequences

Consequence	Count
intron_variant	2

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs6127972	20	57222001	G>A,T	0.05	intron_variant	BMP7	1e-06	Tier 4: intronic/intergenic
rs1884302	20	7125642	T>C,G	0.05	intron_variant	BMP2 - LINC01428	2e-06	Tier 4: intronic/intergenic

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 0 · 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
BMP7	Limited	Autosomal dominant	isolated craniosynostosis	5

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
BMP7	HGNC:1074	ENSG00000101144	P18075	Bone morphogenetic protein 7	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
BMP7	Bone morphogenetic protein 7	Growth factor of the TGF-beta superfamily that plays important role in various biological processes, including embryogenesis, hematopoiesis, neurogenesis and skeletal morphogenesis.

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)
BMP7	Other/Unknown	no		TGF-b_propeptide, TGF-b_C, TGF-beta-like

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
endometrium epithelium	1
pigmented layer of retina	1
ventricular zone	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
BMP7	243	broad	marker	pigmented layer of retina, ventricular zone, endometrium epithelium

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
BMP7	3,134

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
BMP7	P18075	4

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 7. 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
Transcriptional regulation of brown and beige adipocyte differentiation	1	1142.0×	0.006	BMP7
Transcriptional regulation of brown and beige adipocyte differentiation by EBF2	1	380.7×	0.006	BMP7
Elastic fibre formation	1	335.9×	0.006	BMP7
Molecules associated with elastic fibres	1	308.6×	0.006	BMP7
Adipogenesis	1	156.4×	0.009	BMP7
Extracellular matrix organization	1	63.1×	0.018	BMP7
Developmental Biology	1	14.5×	0.069	BMP7

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 mesenchymal cell apoptotic process involved in nephron morphogenesis	1	16852.0×	0.001	BMP7
mesenchymal cell apoptotic process involved in nephron morphogenesis	1	16852.0×	0.001	BMP7
negative regulation of glomerular mesangial cell proliferation	1	8426.0×	0.001	BMP7
nephrogenic mesenchyme morphogenesis	1	8426.0×	0.001	BMP7
negative regulation of striated muscle cell apoptotic process	1	5617.3×	0.001	BMP7
neural fold elevation formation	1	5617.3×	0.001	BMP7
monocyte aggregation	1	5617.3×	0.001	BMP7
metanephric mesenchyme morphogenesis	1	5617.3×	0.001	BMP7
metanephric mesenchymal cell proliferation involved in metanephros development	1	5617.3×	0.001	BMP7
positive regulation of hyaluranon cable assembly	1	5617.3×	0.001	BMP7
positive regulation of cardiac neural crest cell migration involved in outflow tract morphogenesis	1	5617.3×	0.001	BMP7
negative regulation of prostatic bud formation	1	4213.0×	0.001	BMP7
allantois development	1	4213.0×	0.001	BMP7
regulation of branching involved in prostate gland morphogenesis	1	3370.4×	0.002	BMP7
regulation of removal of superoxide radicals	1	2808.7×	0.002	BMP7
negative regulation of mitotic nuclear division	1	2407.4×	0.002	BMP7
mesenchyme development	1	2407.4×	0.002	BMP7
pericardium morphogenesis	1	2106.5×	0.002	BMP7
ameloblast differentiation	1	2106.5×	0.002	BMP7
mesenchymal cell differentiation	1	2106.5×	0.002	BMP7
chorio-allantoic fusion	1	2106.5×	0.002	BMP7
positive regulation of epithelial cell differentiation	1	1872.4×	0.002	BMP7
heart trabecula morphogenesis	1	1872.4×	0.002	BMP7
mesonephros development	1	1532.0×	0.002	BMP7
embryonic skeletal joint morphogenesis	1	1532.0×	0.002	BMP7
endocardial cushion formation	1	1404.3×	0.002	BMP7
branching involved in salivary gland morphogenesis	1	1404.3×	0.002	BMP7
positive regulation of heterotypic cell-cell adhesion	1	1296.3×	0.002	BMP7
cardiac septum morphogenesis	1	1203.7×	0.002	BMP7
hindbrain development	1	1123.5×	0.002	BMP7

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
BMP7	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

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	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	BMP7

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
BMP7	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.