Otopalatodigital syndrome spectrum disorder

Summary

Otopalatodigital syndrome spectrum disorder (MONDO:0018233) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 2

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	otopalatodigital syndrome spectrum disorder
Mondo ID	MONDO:0018233
Orphanet	364541
DOID	DOID:0111782
UMLS	C2748918
MedGen	411701
GARD	0021570
Is cancer (heuristic)	no

Also known as: OPD spectrum disorder · OPSD

Data availability: 2 ClinVar variants.

Disease family

An umbrella term covering 3 Mondo subtypes.

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › skeletal dysplasia › filamin-related bone disorder › otopalatodigital syndrome spectrum disorder

Related subtypes (5): cardiospondylocarpofacial syndrome, Frank-Ter Haar syndrome, spondylocarpotarsal synostosis syndrome, terminal osseous dysplasia-pigmentary defects syndrome, FLNB-associated autosomal dominant filamin related bone disorder

Subtypes (3): Melnick-Needles syndrome, frontometaphyseal dysplasia, otopalatodigital syndrome

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:

2 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
11762	NM_001110556.2(FLNA):c.4904_4912del (p.Arg1635_Val1637del)	FLNA	Pathogenic	no assertion criteria provided
11768	NM_001110556.2(FLNA):c.5182G>T (p.Gly1728Cys)	FLNA	Pathogenic	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 11 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
FLNA	Orphanet:1826	Frontometaphyseal dysplasia
FLNA	Orphanet:2301	Congenital short bowel syndrome
FLNA	Orphanet:2484	Melnick-Needles syndrome
FLNA	Orphanet:482606	X-linked keloid scarring-reduced joint mobility-increased optic cup-to-disc ratio syndrome
FLNA	Orphanet:555877	FLNA-related X-linked myxomatous valvular dysplasia
FLNA	Orphanet:75497	X-linked Ehlers-Danlos syndrome
FLNA	Orphanet:88630	Terminal osseous dysplasia-pigmentary defects syndrome
FLNA	Orphanet:90650	Otopalatodigital syndrome type 1
FLNA	Orphanet:90652	Otopalatodigital syndrome type 2
FLNA	Orphanet:98892	Periventricular nodular heterotopia
FLNA	Orphanet:99811	Neuronal intestinal pseudoobstruction

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
FLNA	HGNC:3754	ENSG00000196924	P21333	Filamin-A	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
FLNA	Filamin-A	Promotes orthogonal branching of actin filaments and links actin filaments to membrane glycoproteins.

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)
FLNA	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
popliteal artery	1
right coronary artery	1
tibial artery	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
FLNA	285	ubiquitous	marker	right coronary artery, popliteal artery, tibial artery

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
FLNA	5,321

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
FLNA	P21333	26

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 5. 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
OAS antiviral response	1	1268.9×	0.002	FLNA
GP1b-IX-V activation signalling	1	951.7×	0.002	FLNA
Cell-extracellular matrix interactions	1	671.8×	0.002	FLNA
RHO GTPases activate PAKs	1	543.8×	0.002	FLNA
Platelet degranulation	1	87.8×	0.011	FLNA

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
regulation of membrane repolarization during atrial cardiac muscle cell action potential	1	16852.0×	0.001	FLNA
regulation of membrane repolarization during cardiac muscle cell action potential	1	16852.0×	0.001	FLNA
tubulin deacetylation	1	5617.3×	0.002	FLNA
formation of radial glial scaffolds	1	4213.0×	0.002	FLNA
adenylate cyclase-inhibiting dopamine receptor signaling pathway	1	3370.4×	0.002	FLNA
establishment of Sertoli cell barrier	1	3370.4×	0.002	FLNA
protein localization to bicellular tight junction	1	2808.7×	0.002	FLNA
negative regulation of transcription by RNA polymerase I	1	2407.4×	0.002	FLNA
blood coagulation, intrinsic pathway	1	2106.5×	0.002	FLNA
positive regulation of platelet activation	1	1296.3×	0.002	FLNA
positive regulation of integrin-mediated signaling pathway	1	1296.3×	0.002	FLNA
positive regulation of actin filament bundle assembly	1	1203.7×	0.002	FLNA
actin crosslink formation	1	1203.7×	0.002	FLNA
wound healing, spreading of cells	1	1123.5×	0.002	FLNA
positive regulation of potassium ion transmembrane transport	1	991.3×	0.002	FLNA
positive regulation of neuron migration	1	991.3×	0.002	FLNA
positive regulation of neural precursor cell proliferation	1	766.0×	0.003	FLNA
obsolete negative regulation of DNA-binding transcription factor activity	1	732.7×	0.003	FLNA
megakaryocyte development	1	702.2×	0.003	FLNA
receptor clustering	1	624.1×	0.003	FLNA
protein localization to cell surface	1	495.6×	0.004	FLNA
establishment of protein localization	1	432.1×	0.004	FLNA
positive regulation of protein import into nucleus	1	421.3×	0.004	FLNA
semaphorin-plexin signaling pathway	1	401.2×	0.004	FLNA
positive regulation of substrate adhesion-dependent cell spreading	1	374.5×	0.004	FLNA
negative regulation of protein catabolic process	1	366.4×	0.004	FLNA
release of sequestered calcium ion into cytosol	1	343.9×	0.004	FLNA
mitotic spindle assembly	1	343.9×	0.004	FLNA
platelet aggregation	1	337.0×	0.004	FLNA
mRNA transcription by RNA polymerase II	1	330.4×	0.004	FLNA

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
FLNA	1	2

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
MOLIBRESIB	2	FLNA

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
FLNA	7	Binding:7

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)
MOLIBRESIB	2	FLNA

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	FLNA
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.