Mandibulofacial dysostosis

Summary

Mandibulofacial dysostosis (MONDO:0015483) is a disease (an umbrella term covering 6 Mondo subtypes) with 1 cohort gene.

At a glance

• Umbrella term: 6 Mondo subtypes
• Cohort genes: 1
• ClinVar variants: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	mandibulofacial dysostosis
Mondo ID	MONDO:0015483
MeSH	D008342
Orphanet	155899
ICD-10-CM	Q75.4
ICD-11	470731247
GARD	0019980
MedDRA	10051456
Is cancer (heuristic)	no

Also known as: bilateral and symmetric oto-mandibular dysplasia

Data availability: 1 ClinVar variant.

Disease family

An umbrella term covering 6 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 › mandibulofacial dysostosis

Related subtypes (107): trigonocephaly, spondylocostal dysostosis, synostosis, Adams-Oliver syndrome, adactylia, unilateral, ADULT syndrome, ankyloblepharon-ectodermal defects-cleft lip/palate syndrome, Cooks syndrome, brachydactyly-arterial hypertension syndrome, fibular aplasia-ectrodactyly syndrome, brachytelephalangy-dysmorphism-Kallmann syndrome, congenital pseudoarthrosis of clavicle, external auditory canal atresia-vertical talus-hypertelorism syndrome, femoral-facial syndrome, hand-foot-genital syndrome, oculoauriculovertebral spectrum with radial defects, IVIC syndrome, nail-patella syndrome, patella aplasia/hypoplasia, pelvis-shoulder dysplasia, phocomelia-ectrodactyly-deafness-sinus arrhythmia syndrome, postaxial tetramelic oligodactyly, Currarino triad, radio-renal syndrome, splenogonadal fusion-limb defects-micrognathia syndrome, Karsch-Neugebauer syndrome, tetramelic monodactyly, tibia, hypoplasia or aplasia of, with polydactyly, humerus trochlea aplasia, Aphalangy-hemivertebrae-urogenital-intestinal dysgenesis syndrome, camptodactyly syndrome, Guadalajara type 2, camptodactyly with fibrous tissue hyperplasia and skeletal dysplasia, split hand-foot malformation 1 with sensorineural hearing loss, EEM syndrome, lethal faciocardiomelic dysplasia, femur-fibula-ulna complex, Gollop-Wolfgang complex, acromesomelic dysplasia 2B, Fuhrmann syndrome, absence deformity of leg-cataract syndrome, intellectual disability-spasticity-ectrodactyly syndrome, fibular aplasia, tibial campomelia, and oligosyndactyly syndrome, otoonychoperoneal syndrome, pelviscapular dysplasia, rapadilino syndrome, EEC syndrome, spondylocostal dysostosis-anal and genitourinary malformations syndrome, tetraamelia-multiple malformations syndrome, thrombocytopenia-absent radius syndrome, phocomelia, Schinzel type, ulna hypoplasia-intellectual disability syndrome, absent radius-anogenital anomalies syndrome, ulnar hypoplasia-split foot syndrome, aphalangy-syndactyly-microcephaly syndrome, absent tibia-polydactyly-arachnoid cyst syndrome, autosomal recessive amelia, pelvic dysplasia-arthrogryposis of lower limbs syndrome, camptodactyly, myopia, and fibrosis of the medial rectus muscle of eye, radio-ulnar synostosis-amegakaryocytic thrombocytopenia syndrome, genitopatellar syndrome, Duane-radial ray syndrome, intellectual disability-brachydactyly-Pierre Robin syndrome, camptodactyly syndrome, Guadalajara type 3, mammary-digital-nail syndrome, postaxial polydactyly-anterior pituitary anomalies-facial dysmorphism syndrome, split-foot malformation-mesoaxial polydactyly syndrome, amniotic band syndrome, radial deficiency-tibial hypoplasia syndrome, oromandibular-limb anomalies syndrome, congenital pseudoarthrosis of the limbs, oculomaxillofacial dysostosis, shoulder and thorax deformity-congenital heart disease syndrome, femoral agenesis/hypoplasia, progressive non-infectious anterior vertebral fusion, hemimelia, heart-hand syndrome, split hand-foot malformation, Melhem-Fahl syndrome, limb transversal defect-cardiac anomaly syndrome, frontonasal dysplasia, imperforate oropharynx-costo vetebral anomalies syndrome, non-syndromic amelia, congenital absence of upper arm and forearm with hand present, congenital absence of thigh and lower leg with foot present, congenital absence of both forearm and hand, congenital absence of both lower leg and foot, acheiria, apodia, split hand, split foot, hyperphalangy, Prata-Liberal-Goncalves syndrome, syngnathia multiple anomalies, hereditary thrombocytosis with transverse limb defect, thalidomide embryopathy, tibial aplasia-ectrodactyly syndrome, bipartite talus, acrofacial dysostosis, adactyly of foot, neurodevelopmental disorder-craniofacial dysmorphism-cardiac defect-hip dysplasia syndrome, Rubinstein-Taybi syndrome, ischio-vertebral syndrome, congenital progressive bone marrow failure-B-cell immunodeficiency-skeletal dysplasia syndrome, omphalocele-diaphragmatic hernia-cardiovascular anomalies-radial ray defect syndrome, preaxial digit brachydactyly-webbed fingers, proximal femoral focal deficiency, dysostosis multiplex, Ain-Naz type

Subtypes (6): Treacher-Collins syndrome, otofaciocervical syndrome, X-linked mandibulofacial dysostosis, mandibulofacial dysostosis-macroblepharon-macrostomia syndrome, mandibulofacial dysostosis with alopecia, acrodysostosis

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

1 retrieved; paginated sample, class counts are floors:

1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
2687899	NM_004247.4(EFTUD2):c.1421del (p.Leu474fs)	EFTUD2	Pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
EFTUD2	Orphanet:79113	Mandibulofacial dysostosis-microcephaly syndrome

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
EFTUD2	HGNC:30858	ENSG00000108883	Q15029	116 kDa U5 small nuclear ribonucleoprotein component	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
EFTUD2	116 kDa U5 small nuclear ribonucleoprotein component	Required for pre-mRNA splicing as component of the spliceosome, including pre-catalytic, catalytic and post-catalytic spliceosomal complexes.

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)
EFTUD2	Other/Unknown	no		EFG_V-like, T_Tr_GTP-bd_dom, EFTu-like_2

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
bone marrow cell	1
tibialis anterior	1
ventricular zone	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
EFTUD2	253	ubiquitous	marker	bone marrow cell, tibialis anterior, ventricular zone

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
EFTUD2	8,471

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
EFTUD2	Q15029	68

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. 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
mRNA Splicing - Minor Pathway	1	223.9×	0.013	EFTUD2
mRNA Splicing - Major Pathway	1	54.6×	0.022	EFTUD2
Dengue Virus-Host Interactions	1	45.7×	0.022	EFTUD2

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
response to cocaine	1	581.1×	0.005	EFTUD2
cellular response to xenobiotic stimulus	1	240.7×	0.006	EFTUD2
mRNA splicing, via spliceosome	1	91.6×	0.011	EFTUD2

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
EFTUD2	1	2

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
MOLIBRESIB	2	EFTUD2

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
EFTUD2	8	Binding:8

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	EFTUD2

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	EFTUD2
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.