Cleidocranial dysplasia 2

Summary

Cleidocranial dysplasia 2 (MONDO:0859307) is a disease caused by CBFB (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: CBFB (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 5

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	cleidocranial dysplasia 2
Mondo ID	MONDO:0859307
OMIM	620099
UMLS	C5774243
MedGen	1824016
Is cancer (heuristic)	no

Data availability: 5 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › musculoskeletal system disorder › skeletal system disorder › bone disorder › bone development disease › osteochondrodysplasia › cleidocranial dysplasia 2

Related subtypes (49): atelosteogenesis, midface dysplasia, Kashin-Beck disease, achondroplasia, Boomerang dysplasia, campomelic dysplasia, cleidocranial dysplasia 1, Leri-Weill dyschondrosteosis, hypochondroplasia, metaphyseal chondrodysplasia, Jansen type, Schmid metaphyseal chondrodysplasia, Kniest dysplasia, pseudoachondroplasia, ulna metaphyseal dysplasia syndrome, acheiropody, microcephalic osteodysplastic primordial dwarfism type I, microcephalic osteodysplastic primordial dwarfism type II, bone dysplasia, lethal Holmgren type, cleidocranial dysplasia, recessive form, diastrophic dysplasia, hypertrichotic osteochondrodysplasia Cantu type, lethal Kniest-like dysplasia, metaphyseal chondrodysplasia, Kaitila type, metaphyseal chondrodysplasia, Spahr type, metaphyseal chondrodysplasia-retinitis pigmentosa syndrome, pycnodysostosis, pyknoachondrogenesis, Pyle disease, schneckenbecken dysplasia, mesomelia-synostoses syndrome, lethal chondrodysplasia, Seller type, acrocapitofemoral dysplasia, brachyolmia, Desbuquois dysplasia, fibrochondrogenesis, multiple epiphyseal dysplasia, spondyloepiphyseal dysplasia, thanatophoric dysplasia, Blount disease, osteogenesis imperfecta, achondrogenesis, acromesomelic dysplasia, neonatal osteosclerotic dysplasia, Akaba Hayasaka syndrome, Fairbank disease, mesomelic dysplasia, spondyloepimetaphyseal dysplasia, arterial tortuosity-bone fragility syndrome, linkeropathy

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

5 retrieved; paginated sample, class counts are floors:

3 uncertain significance, 2 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1712242	NM_022845.3(CBFB):c.78+1G>T	CBFB	Pathogenic	no assertion criteria provided
1712243	NM_022845.3(CBFB):c.283-1039_400-7568del	CBFB	Pathogenic	no assertion criteria provided
1712245	NM_022845.3(CBFB):c.247C>T (p.Arg83Ter)	CBFB	Uncertain significance	criteria provided, single submitter
1712246	NM_022845.3(CBFB):c.283-2A>G	CBFB	Uncertain significance	criteria provided, single submitter
930504	NM_022845.3(CBFB):c.295_296dup (p.Pro100fs)	CBFB	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · Orphanet: 1 · 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
CBFB	Strong	Autosomal dominant	cleidocranial dysplasia 2	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CBFB	Orphanet:98829	Acute myeloid leukemia with abnormal bone marrow eosinophils inv(16)(p13q22) or t(16;16)(p13;q22)

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
CBFB	HGNC:1539	ENSG00000067955	Q13951	Core-binding factor subunit beta	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CBFB	Core-binding factor subunit beta	Forms the heterodimeric complex core-binding factor (CBF) with RUNX family proteins (RUNX1, RUNX2, and RUNX3).

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)
CBFB	Other/Unknown	no		CBF_beta, CBF_bsu_sf

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
secondary oocyte	1
sural nerve	1
tibia	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CBFB	298	ubiquitous	marker	secondary oocyte, sural nerve, tibia

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CBFB	1,717

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CBFB	Q13951	20

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 25. 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
RUNX3 regulates RUNX1-mediated transcription	1	3806.7×	0.001	CBFB
RUNX1 regulates expression of components of tight junctions	1	2284.0×	0.001	CBFB
RUNX1 regulates transcription of genes involved in interleukin signaling	1	2284.0×	0.001	CBFB
RUNX2 regulates chondrocyte maturation	1	2284.0×	0.001	CBFB
RUNX2 regulates genes involved in differentiation of myeloid cells	1	2284.0×	0.001	CBFB
RUNX1 regulates estrogen receptor mediated transcription	1	1903.3×	0.001	CBFB
RUNX1 regulates transcription of genes involved in BCR signaling	1	1903.3×	0.001	CBFB
RUNX1 regulates transcription of genes involved in WNT signaling	1	1903.3×	0.001	CBFB
RUNX3 Regulates Immune Response and Cell Migration	1	1903.3×	0.001	CBFB
RUNX1 regulates transcription of genes involved in differentiation of myeloid cells	1	1427.5×	0.002	CBFB
RUNX2 regulates genes involved in cell migration	1	1427.5×	0.002	CBFB
RUNX1 and FOXP3 control the development of regulatory T lymphocytes (Tregs)	1	1142.0×	0.002	CBFB
RUNX1 regulates transcription of genes involved in differentiation of keratinocytes	1	1142.0×	0.002	CBFB
RUNX3 regulates p14-ARF	1	1142.0×	0.002	CBFB
RUNX2 regulates bone development	1	815.7×	0.002	CBFB
Regulation of RUNX1 Expression and Activity	1	671.8×	0.002	CBFB
RUNX2 regulates osteoblast differentiation	1	456.8×	0.003	CBFB
RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known	1	300.5×	0.005	CBFB
Transcriptional regulation by RUNX2	1	253.8×	0.005	CBFB
Regulation of RUNX3 expression and activity	1	233.1×	0.005	CBFB
Regulation of RUNX2 expression and activity	1	181.3×	0.007	CBFB
Transcriptional regulation of granulopoiesis	1	125.5×	0.009	CBFB
RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function	1	120.2×	0.009	CBFB
RUNX1 regulates transcription of genes involved in differentiation of HSCs	1	95.2×	0.011	CBFB
Estrogen-dependent gene expression	1	75.6×	0.013	CBFB

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 CD4-positive, alpha-beta T cell differentiation	1	4213.0×	0.001	CBFB
positive regulation of CD8-positive, alpha-beta T cell differentiation	1	3370.4×	0.001	CBFB
lymphocyte differentiation	1	2808.7×	0.001	CBFB
definitive hemopoiesis	1	936.2×	0.003	CBFB
myeloid cell differentiation	1	648.1×	0.004	CBFB
cell maturation	1	443.5×	0.005	CBFB
osteoblast differentiation	1	121.2×	0.013	CBFB
protein polyubiquitination	1	115.4×	0.013	CBFB
transcription by RNA polymerase II	1	70.5×	0.019	CBFB
negative regulation of transcription by RNA polymerase II	1	17.7×	0.068	CBFB
positive regulation of transcription by RNA polymerase II	1	14.9×	0.073	CBFB
regulation of transcription by RNA polymerase II	1	11.7×	0.086	CBFB

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
CBFB	APOMORPHINE HYDROCHLORIDE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CBFB	2	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
APOMORPHINE HYDROCHLORIDE	4	CBFB
MOLIBRESIB	2	CBFB

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
CBFB	15	Binding:12, Functional:3

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

2 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)
APOMORPHINE HYDROCHLORIDE	4	CBFB
MOLIBRESIB	2	CBFB

Druggability pyramid

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

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