atelosteogenesis type I

Summary

atelosteogenesis type I (MONDO:0007167) is a disease caused by FLNB (GenCC Definitive), with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: FLNB (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 62
• Phenotypes (HPO): 32

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

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

Signs & symptoms

Clinical features (HPO)

32 HPO clinical features (Orphanet curated; top 32 by frequency):

HPO ID	Term	Frequency
HP:0000774	Narrow chest	Frequent (30-79%)
HP:0001156	Brachydactyly	Frequent (30-79%)
HP:0001762	Talipes equinovarus	Frequent (30-79%)
HP:0002089	Pulmonary hypoplasia	Frequent (30-79%)
HP:0002991	Abnormal fibula morphology	Frequent (30-79%)
HP:0003097	Short femur	Frequent (30-79%)
HP:0003417	Coronal cleft vertebrae	Frequent (30-79%)
HP:0004599	Absent or minimally ossified vertebral bodies	Frequent (30-79%)
HP:0005257	Thoracic hypoplasia	Frequent (30-79%)
HP:0008905	Rhizomelia	Frequent (30-79%)
HP:0009107	Abnormal ossification involving the femoral head and neck	Frequent (30-79%)
HP:0009826	Limb undergrowth	Frequent (30-79%)
HP:0011800	Midface retrusion	Frequent (30-79%)
HP:0000175	Cleft palate	Occasional (5-29%)
HP:0000316	Hypertelorism	Occasional (5-29%)
HP:0000347	Micrognathia	Occasional (5-29%)
HP:0000369	Low-set ears	Occasional (5-29%)
HP:0000506	Telecanthus	Occasional (5-29%)
HP:0000520	Proptosis	Occasional (5-29%)
HP:0000926	Platyspondyly	Occasional (5-29%)
HP:0001373	Joint dislocation	Occasional (5-29%)
HP:0001561	Polyhydramnios	Occasional (5-29%)
HP:0001602	Laryngeal stenosis	Occasional (5-29%)
HP:0002280	Enlarged cisterna magna	Occasional (5-29%)
HP:0002650	Scoliosis	Occasional (5-29%)
HP:0003026	Short long bone	Occasional (5-29%)
HP:0004785	Malrotation of colon	Occasional (5-29%)
HP:0004894	Laryngotracheal stenosis	Occasional (5-29%)
HP:0005562	Multiple renal cysts	Occasional (5-29%)
HP:0007973	Retinal dysplasia	Occasional (5-29%)
HP:0008857	Neonatal short-trunk short stature	Occasional (5-29%)
HP:0030992	Abnormal pancreatic duct morphology	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	atelosteogenesis type I
Mondo ID	MONDO:0007167
MeSH	C535396
OMIM	108720
Orphanet	1190
ICD-11	449799342
SNOMED CT	725141006
UMLS	C0265283
MedGen	82701
GARD	0009287
Is cancer (heuristic)	no

Also known as: AO1 · AOI · atelosteogenesis type 1 · atelosteogenesis, type I · giant cell chondrodysplasia · spondylo-humero-femoral dysplasia

Data availability: 62 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 › atelosteogenesis › atelosteogenesis type I

Related subtypes (2): atelosteogenesis type III, atelosteogenesis type II

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

62 retrieved; paginated sample, class counts are floors:

23 uncertain significance, 18 conflicting classifications of pathogenicity, 6 not provided, 5 pathogenic, 5 benign/likely benign, 3 likely benign, 1 likely pathogenic, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
126375	NM_001457.4(FLNB):c.517G>A (p.Ala173Thr)	FLNB	Pathogenic	no assertion criteria provided
1685823	NM_001457.4(FLNB):c.4807C>T (p.Pro1603Ser)	FLNB	Pathogenic	criteria provided, single submitter
38961	NM_001457.4(FLNB):c.502G>A (p.Gly168Ser)	FLNB	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
6400	NM_001457.4(FLNB):c.518C>T (p.Ala173Val)	FLNB	Pathogenic	criteria provided, single submitter
6401	NM_001457.4(FLNB):c.604A>G (p.Met202Val)	FLNB	Pathogenic	no assertion criteria provided
6406	NM_001457.4(FLNB):c.5071G>A (p.Gly1691Ser)	FLNB	Pathogenic	criteria provided, multiple submitters, no conflicts
3236011	NM_001457.4(FLNB):c.641TCA[1] (p.Ile215del)	FLNB	Likely pathogenic	criteria provided, single submitter
1030455	NM_001457.4(FLNB):c.3616A>G (p.Met1206Val)	FLNB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1030457	NM_001457.4(FLNB):c.906+3A>G	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
1333671	NM_001457.4(FLNB):c.4805C>A (p.Ser1602Tyr)	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
1030456	NM_001457.4(FLNB):c.4585T>C (p.Ser1529Pro)	FLNB	Uncertain significance	criteria provided, single submitter
1031983	NM_001457.4(FLNB):c.5524T>C (p.Phe1842Leu)	FLNB	Uncertain significance	criteria provided, single submitter
1031984	NM_001457.4(FLNB):c.6643A>G (p.Ser2215Gly)	FLNB	Uncertain significance	criteria provided, single submitter
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

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	Definitive	Autosomal dominant	atelosteogenesis type I	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.