Boomerang dysplasia

Summary

Boomerang dysplasia (MONDO:0007208) is a disease caused by FLNB (GenCC Strong), with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: FLNB (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 45
• Phenotypes (HPO): 21

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		10	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

21 HPO clinical features (Orphanet curated; top 21 by frequency):

HPO ID	Term	Frequency
HP:0000774	Narrow chest	Very frequent (80-99%)
HP:0000824	Decreased response to growth hormone stimulation test	Very frequent (80-99%)
HP:0002983	Micromelia	Very frequent (80-99%)
HP:0002992	Abnormality of tibia morphology	Very frequent (80-99%)
HP:0006492	Aplasia/Hypoplasia of the fibula	Very frequent (80-99%)
HP:0008890	Severe short-limb dwarfism	Very frequent (80-99%)
HP:0011849	Abnormal bone ossification	Very frequent (80-99%)
HP:0100569	Abnormally ossified vertebrae	Very frequent (80-99%)
HP:0100856	Poorly ossified vertebrae	Very frequent (80-99%)
HP:0031095	Abnormal humerus morphology	Frequent (30-79%)
HP:0000028	Cryptorchidism	Frequent (30-79%)
HP:0001539	Omphalocele	Frequent (30-79%)
HP:0001561	Polyhydramnios	Frequent (30-79%)
HP:0001789	Hydrops fetalis	Frequent (30-79%)
HP:0002818	Abnormal morphology of the radius	Frequent (30-79%)
HP:0002823	Abnormality of femur morphology	Frequent (30-79%)
HP:0005916	Abnormal metacarpal morphology	Frequent (30-79%)
HP:0006101	Finger syndactyly	Frequent (30-79%)
HP:0006703	Aplasia/Hypoplasia of the lungs	Frequent (30-79%)
HP:0010318	Aplasia/Hypoplasia of the abdominal wall musculature	Frequent (30-79%)
HP:0040071	Abnormal morphology of ulna	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	Boomerang dysplasia
Mondo ID	MONDO:0007208
MeSH	C536573
OMIM	112310
Orphanet	1263
DOID	DOID:0050680
ICD-11	423736259
SNOMED CT	254054000
UMLS	C0432201
MedGen	96579
GARD	0000933
Is cancer (heuristic)	no

Also known as: Boomerang dysplasia · Boomerang-like skeletal dysplasia · dwarfism with short, bowed, rigid limbs and characteristic facies

Data availability: 45 ClinVar variants · 1 GenCC gene-disease record.

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 › Boomerang dysplasia

Related subtypes (49): atelosteogenesis, midface dysplasia, Kashin-Beck disease, achondroplasia, 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, cleidocranial dysplasia 2, 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

45 retrieved; paginated sample, class counts are floors:

17 uncertain significance, 16 conflicting classifications of pathogenicity, 5 benign/likely benign, 3 likely benign, 3 pathogenic, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
38961	NM_001457.4(FLNB):c.502G>A (p.Gly168Ser)	FLNB	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
6403	NM_001457.4(FLNB):c.512T>G (p.Leu171Arg)	FLNB	Pathogenic	no assertion criteria provided
6404	NM_001457.4(FLNB):c.703T>C (p.Ser235Pro)	FLNB	Pathogenic	no assertion criteria provided
6406	NM_001457.4(FLNB):c.5071G>A (p.Gly1691Ser)	FLNB	Pathogenic	criteria provided, multiple submitters, no conflicts
1047487	NM_001457.4(FLNB):c.1693G>A (p.Gly565Arg)	FLNB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1306802	NM_001457.4(FLNB):c.3325G>A (p.Val1109Ile)	FLNB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1356262	NM_001457.4(FLNB):c.1887C>G (p.Asp629Glu)	FLNB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1417463	NM_001457.4(FLNB):c.7036C>T (p.Arg2346Cys)	FLNB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
194935	NM_001457.4(FLNB):c.2773G>T (p.Gly925Cys)	FLNB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
252548	NM_001457.4(FLNB):c.808A>G (p.Met270Val)	FLNB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2906029	NM_001457.4(FLNB):c.4313G>A (p.Arg1438His)	FLNB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2963035	NM_001457.4(FLNB):c.4813C>T (p.Arg1605Cys)	FLNB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
346334	NM_001457.4(FLNB):c.3583G>A (p.Val1195Met)	FLNB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
346348	NM_001457.4(FLNB):c.5134G>A (p.Val1712Met)	FLNB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
346353	NM_001457.4(FLNB):c.5917G>A (p.Glu1973Lys)	FLNB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
346359	NM_001457.4(FLNB):c.6755A>T (p.Tyr2252Phe)	FLNB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
372367	NM_001457.4(FLNB):c.1588G>T (p.Gly530Trp)	FLNB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3892281	NM_001457.4(FLNB):c.6073G>A (p.Val2025Met)	FLNB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
449027	NM_001457.4(FLNB):c.4730C>T (p.Ala1577Val)	FLNB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
899585	NM_001457.4(FLNB):c.4826C>T (p.Thr1609Ile)	FLNB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1328287	NM_001457.4(FLNB):c.2996G>A (p.Arg999Gln)	FLNB	Uncertain significance	criteria provided, multiple submitters, no conflicts
1372524	NM_001457.4(FLNB):c.6866G>A (p.Arg2289His)	FLNB	Uncertain significance	criteria provided, multiple submitters, no conflicts
1426840	NM_001457.4(FLNB):c.4589A>G (p.Tyr1530Cys)	FLNB	Uncertain significance	criteria provided, multiple submitters, no conflicts
1480598	NM_001457.4(FLNB):c.3724+4G>C	FLNB	Uncertain significance	criteria provided, multiple submitters, no conflicts
1488755	NM_001457.4(FLNB):c.3299T>G (p.Leu1100Arg)	FLNB	Uncertain significance	criteria provided, single submitter
1903856	NM_001457.4(FLNB):c.2383G>A (p.Val795Met)	FLNB	Uncertain significance	criteria provided, multiple submitters, no conflicts
1990088	NM_001457.4(FLNB):c.3064G>A (p.Gly1022Arg)	FLNB	Uncertain significance	criteria provided, multiple submitters, no conflicts
2734540	NM_001457.4(FLNB):c.2195A>G (p.Tyr732Cys)	FLNB	Uncertain significance	criteria provided, multiple submitters, no conflicts
289425	NM_001457.4(FLNB):c.4391G>C (p.Gly1464Ala)	FLNB	Uncertain significance	criteria provided, multiple submitters, no conflicts
3382019	NM_001457.4(FLNB):c.1652A>T (p.Lys551Ile)	FLNB	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 13 · Orphanet: 5 · 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
FLNB	Strong	Autosomal dominant	Boomerang dysplasia	13

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
FLNB	Orphanet:1190	Atelosteogenesis type I
FLNB	Orphanet:1263	Boomerang dysplasia
FLNB	Orphanet:3275	Spondylocarpotarsal synostosis
FLNB	Orphanet:503	Larsen syndrome
FLNB	Orphanet:56305	Atelosteogenesis type III

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
FLNB	HGNC:3755	ENSG00000136068	O75369	Filamin-B	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
FLNB	Filamin-B	Connects cell membrane constituents to the actin cytoskeleton.

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
Antibody/Immunoglobulin	1	29.2×	0.034

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
FLNB	Antibody/Immunoglobulin	yes		Filamin/ABP280_rpt, Actinin_actin-bd_CS, CH_dom

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
mucosa of transverse colon	1
tibial nerve	1
transverse colon	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
FLNB	290	ubiquitous	marker	mucosa of transverse colon, tibial nerve, transverse colon

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
FLNB	2,927

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
FLNB	O75369	23

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. 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
ISG15 antiviral mechanism	1	150.3×	0.007	FLNB

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
keratinocyte development	1	1532.0×	0.003	FLNB
epithelial cell morphogenesis	1	936.2×	0.003	FLNB
skeletal muscle tissue development	1	290.6×	0.007	FLNB
cellular response to type II interferon	1	208.1×	0.007	FLNB
actin cytoskeleton organization	1	79.1×	0.015	FLNB
signal transduction	1	16.1×	0.062	FLNB

Therapeutics

Drug target analysis

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

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
FLNB	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
FLNB	2	Binding:2

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

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)
FLNB	2	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.