Toriello-Carey syndrome

Summary

Toriello-Carey syndrome (MONDO:0009021) is a disease with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 1
• Phenotypes (HPO): 46

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		59	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

46 HPO clinical features (Orphanet curated; top 46 by frequency):

HPO ID	Term	Frequency
HP:0000347	Micrognathia	Very frequent (80-99%)
HP:0000377	Abnormal pinna morphology	Very frequent (80-99%)
HP:0000506	Telecanthus	Very frequent (80-99%)
HP:0001249	Intellectual disability	Very frequent (80-99%)
HP:0001273	Abnormal corpus callosum morphology	Very frequent (80-99%)
HP:0003196	Short nose	Very frequent (80-99%)
HP:0012745	Short palpebral fissure	Very frequent (80-99%)
HP:0000028	Cryptorchidism	Frequent (30-79%)
HP:0000174	Abnormal palate morphology	Frequent (30-79%)
HP:0000175	Cleft palate	Frequent (30-79%)
HP:0000260	Wide anterior fontanel	Frequent (30-79%)
HP:0000293	Full cheeks	Frequent (30-79%)
HP:0000365	Hearing impairment	Frequent (30-79%)
HP:0000470	Short neck	Frequent (30-79%)
HP:0001252	Hypotonia	Frequent (30-79%)
HP:0001274	Agenesis of corpus callosum	Frequent (30-79%)
HP:0001545	Anteriorly placed anus	Frequent (30-79%)
HP:0001671	Abnormal cardiac septum morphology	Frequent (30-79%)
HP:0002251	Aganglionic megacolon	Frequent (30-79%)
HP:0004322	Short stature	Frequent (30-79%)
HP:0000218	High palate	Occasional (5-29%)
HP:0000252	Microcephaly	Occasional (5-29%)
HP:0000369	Low-set ears	Occasional (5-29%)
HP:0000391	Thickened helices	Occasional (5-29%)
HP:0000774	Narrow chest	Occasional (5-29%)
HP:0001156	Brachydactyly	Occasional (5-29%)
HP:0001250	Seizure	Occasional (5-29%)
HP:0001338	Partial agenesis of the corpus callosum	Occasional (5-29%)
HP:0001511	Intrauterine growth retardation	Occasional (5-29%)
HP:0001600	Abnormality of the larynx	Occasional (5-29%)
HP:0001638	Cardiomyopathy	Occasional (5-29%)
HP:0001642	Pulmonic stenosis	Occasional (5-29%)
HP:0001643	Patent ductus arteriosus	Occasional (5-29%)
HP:0002059	Cerebral atrophy	Occasional (5-29%)
HP:0002079	Hypoplasia of the corpus callosum	Occasional (5-29%)
HP:0002119	Ventriculomegaly	Occasional (5-29%)
HP:0002643	Neonatal respiratory distress	Occasional (5-29%)
HP:0007360	Aplasia/Hypoplasia of the cerebellum	Occasional (5-29%)
HP:0008872	Feeding difficulties in infancy	Occasional (5-29%)
HP:0008897	Postnatal growth retardation	Occasional (5-29%)
HP:0030084	Clinodactyly	Occasional (5-29%)
HP:0045075	Sparse eyebrow	Occasional (5-29%)
HP:0001305	Dandy-Walker malformation	Very rare (<1-4%)
HP:0001636	Tetralogy of Fallot	Very rare (<1-4%)
HP:0001680	Coarctation of aorta	Very rare (<1-4%)
HP:0009892	Anotia	Very rare (<1-4%)

Identifiers

Disease identifiers

Field	Value
Canonical name	Toriello-Carey syndrome
Mondo ID	MONDO:0009021
MeSH	C563127
OMIM	217980
Orphanet	3338
ICD-11	147297969
SNOMED CT	722477003
UMLS	C0796184
MedGen	163225
GARD	0005225
Is cancer (heuristic)	no

Also known as: agenesis of corpus callosum with facial anomalies and Robin sequence · corpus callosum agenesis facial anomalies Robin sequence · corpus callosum agenesis-blepharophimosis-Robin sequence syndrome · Toriello-Carey syndrome

Data availability: 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by developmental or physiological process › disorder of development or morphogenesis › developmental defect during embryogenesis › multiple congenital anomalies/dysmorphic syndrome › multiple congenital anomalies/dysmorphic syndrome-variable intellectual disability syndrome › Toriello-Carey syndrome

Related subtypes (68): acromegaloid facial appearance syndrome, Hypoglossia-hypodactyly syndrome, Brachymorphism-onychodysplasia-dysphalangism syndrome, campomelic dysplasia, cerebrocostomandibular syndrome, autosomal dominant popliteal pterygium syndrome, Pallister-Hall syndrome, autosomal dominant primary microcephaly, microgastria-limb reduction defect syndrome, Mobius syndrome, oculodentodigital dysplasia, Char syndrome, Prader-Willi syndrome, Silver-Russell syndrome, ulnar-mammary syndrome, short stature-wormian bones-dextrocardia syndrome, ablepharon macrostomia syndrome, Goodman syndrome, anophthalmia/microphthalmia-esophageal atresia syndrome, microphthalmia with limb anomalies, Antley-Bixler syndrome, campomelia, Cumming type, CHARGE syndrome, Donnai-Barrow syndrome, lethal faciocardiomelic dysplasia, hypertrichotic osteochondrodysplasia Cantu type, hypomandibular faciocranial dysostosis, isotretinoin-like syndrome, split hand-foot malformation 3, oculotrichoanal syndrome, Hennekam-Beemer syndrome, Mietens syndrome, Schinzel-Giedion syndrome, SHORT syndrome, moyamoya angiopathy-short stature-facial dysmorphism-hypergonadotropic hypogonadism syndrome, occipital horn syndrome, hydrocephalus-costovertebral dysplasia-Sprengel anomaly syndrome, Potocki-Shaffer syndrome, Marshall-Smith syndrome, PHACE syndrome, Noonan syndrome-like disorder with loose anagen hair, branchiogenic deafness syndrome, combined immunodeficiency with faciooculoskeletal anomalies, chromosome 1p32-p31 deletion syndrome, Malan overgrowth syndrome, dysmorphism-conductive hearing loss-heart defect syndrome, TELO2-related intellectual disability-neurodevelopmental disorder, short stature-heart defect-craniofacial anomalies syndrome, arachnodactyly-intellectual disability-dysmorphism syndrome, polyvalvular heart disease syndrome, Kallmann syndrome-heart disease syndrome, Meier-Gorlin syndrome, symptomatic form of Coffin-Lowry syndrome in female carriers, Prader-Willi-like syndrome, contractures-developmental delay-Pierre Robin syndrome, 22q11.2 deletion syndrome, Noonan syndrome, Carpenter syndrome, Bosley-Salih-Alorainy syndrome, Sotos syndrome, Robinow syndrome, King-Denborough syndrome, Weiss-Kruszka syndrome, retinitis pigmentosa-hearing loss-premature aging-short stature-facial dysmorphism syndrome, omphalocele-diaphragmatic hernia-cardiovascular anomalies-radial ray defect syndrome, 4q25 proximal deletion syndrome, restrictive dermopathy 1, mosaic SMO 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

No tiered GWAS variants or ClinVar records for this disease.

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 7 · Orphanet: 3 · 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
DDX3X	Supportive	Autosomal recessive	Toriello-Carey syndrome	7

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
DDX3X	Orphanet:3338	Toriello-Carey syndrome
DDX3X	Orphanet:457260	X-linked intellectual disability-hypotonia-movement disorder syndrome
DDX3X	Orphanet:99861	Precursor T-cell acute lymphoblastic leukemia

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
DDX3X	HGNC:2745	ENSG00000215301	O00571	ATP-dependent RNA helicase DDX3X	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
DDX3X	ATP-dependent RNA helicase DDX3X	Multifunctional ATP-dependent RNA helicase.

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
Enzyme (other)	1	12.0×	0.083

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
DDX3X	Enzyme (other)	yes	3.6.4.13	RNA-helicase_DEAD-box_CS, Helicase_C-like, DEAD/DEAH_box_helicase_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
choroid plexus epithelium	1
oocyte	1
sperm	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
DDX3X	294	ubiquitous	marker	choroid plexus epithelium, oocyte, sperm

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
DDX3X	6,454

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
DDX3X	O00571	17

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. 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
Dengue virus activates/modulates innate and adaptive immune responses	1	335.9×	0.006	DDX3X
Neutrophil degranulation	1	23.1×	0.043	DDX3X

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
positive regulation of toll-like receptor 8 signaling pathway	1	5617.3×	0.003	DDX3X
positive regulation of translation in response to endoplasmic reticulum stress	1	4213.0×	0.003	DDX3X
positive regulation of toll-like receptor 7 signaling pathway	1	3370.4×	0.003	DDX3X
positive regulation of chemokine (C-C motif) ligand 5 production	1	2808.7×	0.003	DDX3X
cytosolic ribosome assembly	1	2407.4×	0.003	DDX3X
cellular response to arsenic-containing substance	1	2106.5×	0.003	DDX3X
positive regulation of protein K63-linked ubiquitination	1	2106.5×	0.003	DDX3X
protein localization to cytoplasmic stress granule	1	2106.5×	0.003	DDX3X
cellular response to osmotic stress	1	1203.7×	0.004	DDX3X
positive regulation of mitochondrial translation	1	1123.5×	0.004	DDX3X
cytoplasmic pattern recognition receptor signaling pathway	1	887.0×	0.004	DDX3X
gamete generation	1	887.0×	0.004	DDX3X
positive regulation of translational initiation	1	842.6×	0.004	DDX3X
negative regulation of intrinsic apoptotic signaling pathway	1	766.0×	0.004	DDX3X
positive regulation of interferon-alpha production	1	648.1×	0.004	DDX3X
stress granule assembly	1	601.9×	0.004	DDX3X
positive regulation of viral genome replication	1	581.1×	0.004	DDX3X
positive regulation of NLRP3 inflammasome complex assembly	1	581.1×	0.004	DDX3X
negative regulation of extrinsic apoptotic signaling pathway via death domain receptors	1	581.1×	0.004	DDX3X
negative regulation of non-canonical NF-kappaB signal transduction	1	510.7×	0.005	DDX3X
negative regulation of protein-containing complex assembly	1	455.5×	0.005	DDX3X
positive regulation of type I interferon production	1	421.3×	0.005	DDX3X
extrinsic apoptotic signaling pathway via death domain receptors	1	401.2×	0.005	DDX3X
positive regulation of G1/S transition of mitotic cell cycle	1	401.2×	0.005	DDX3X
positive regulation of interferon-beta production	1	391.9×	0.005	DDX3X
translational initiation	1	358.6×	0.005	DDX3X
intrinsic apoptotic signaling pathway	1	358.6×	0.005	DDX3X
lipid homeostasis	1	337.0×	0.005	DDX3X
positive regulation of non-canonical NF-kappaB signal transduction	1	255.3×	0.006	DDX3X
positive regulation of translation	1	227.7×	0.007	DDX3X

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
DDX3X	IMATINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
DDX3X	1	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
IMATINIB	4	DDX3X

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
DDX3X	32	Binding:31, ADMET:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
DDX3X	3.6.4.13	RNA helicase

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)
IMATINIB	4	DDX3X

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	DDX3X
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.