Curry-Jones syndrome

Summary

Curry-Jones syndrome (MONDO:0011134) is a disease caused by SMO (GenCC Definitive), with 2 cohort genes.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: SMO (GenCC Definitive)
• Cohort genes: 2
• ClinVar variants: 8
• Phenotypes (HPO): 19

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		9	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

19 HPO clinical features (Orphanet curated; top 19 by frequency):

HPO ID	Term	Frequency
HP:0000316	Hypertelorism	Very frequent (80-99%)
HP:0001053	Hypopigmented skin patches	Very frequent (80-99%)
HP:0006101	Finger syndactyly	Very frequent (80-99%)
HP:0000324	Facial asymmetry	Frequent (30-79%)
HP:0000568	Microphthalmia	Frequent (30-79%)
HP:0001249	Intellectual disability	Frequent (30-79%)
HP:0001274	Agenesis of corpus callosum	Frequent (30-79%)
HP:0001363	Craniosynostosis	Frequent (30-79%)
HP:0001770	Toe syndactyly	Frequent (30-79%)
HP:0001829	Foot polydactyly	Frequent (30-79%)
HP:0002119	Ventriculomegaly	Frequent (30-79%)
HP:0002230	Generalized hirsutism	Frequent (30-79%)
HP:0008065	Aplasia/Hypoplasia of the skin	Frequent (30-79%)
HP:0009602	Abnormality of thumb phalanx	Frequent (30-79%)
HP:0011304	Broad thumb	Frequent (30-79%)
HP:0000588	Optic disc coloboma	Occasional (5-29%)
HP:0000612	Iris coloboma	Occasional (5-29%)
HP:0001177	Preaxial hand polydactyly	Occasional (5-29%)
HP:0002566	Intestinal malrotation	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	Curry-Jones syndrome
Mondo ID	MONDO:0011134
MeSH	C536735
OMIM	601707
Orphanet	1553
SNOMED CT	720819006
UMLS	C0795915
MedGen	167083
GARD	0005584
Is cancer (heuristic)	no

Also known as: corpus callosum agenesis polysyndactyly · corpus callosum agenesis-polysyndactyly syndrome · CRJS · curry Jones syndrome · curry-Jones syndrome · Curry-Jones syndrome, somatic mosaic

Data availability: 8 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › syndromic craniosynostosis › Curry-Jones syndrome

Related subtypes (39): Crouzon syndrome, Beare-Stevenson cutis gyrata syndrome, Shprintzen-Goldberg syndrome, acrocephalopolydactyly, Antley-Bixler syndrome, C syndrome, cranioectodermal dysplasia, cardiocranial syndrome, Pfeiffer type, craniosynostosis-fibular aplasia syndrome, Baller-Gerold syndrome, craniotelencephalic dysplasia, Summitt syndrome, X-linked intellectual disability-plagiocephaly syndrome, Lowry-MacLean syndrome, pseudoaminopterin syndrome, craniosynostosis 4, holoprosencephaly-craniosynostosis syndrome, Hunter-McAlpine craniosynostosis, craniomicromelic syndrome, Muenke syndrome, craniosynostosis-anal anomalies-porokeratosis syndrome, craniosynostosis 2, cloverleaf skull-multiple congenital anomalies syndrome, craniosynostosis-intracranial calcifications syndrome, Crouzon syndrome-acanthosis nigricans syndrome, craniosynostosis and dental anomalies, lethal occipital encephalocele-skeletal dysplasia syndrome, TCF12-related craniosynostosis, autosomal dominant intellectual disability-craniofacial anomalies-cardiac defects syndrome, cloverleaf skull-asphyxiating thoracic dysplasia syndrome, craniosynostosis, Philadelphia type, craniosynostosis-cataract syndrome, familial scaphocephaly syndrome, craniosynostosis-hydrocephalus-Arnold-Chiari malformation type I-radioulnar synostosis syndrome, osteosclerosis-developmental delay-craniosynostosis syndrome, craniosynostosis, Herrmann-Opitz type, trigonocephaly-broad thumbs syndrome, acrocephalosyndactyly, Weiss-Kruszka 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

8 retrieved; paginated sample, class counts are floors:

4 uncertain significance, 2 conflicting classifications of pathogenicity, 1 pathogenic, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
245609	NM_005631.5(SMO):c.1234C>T (p.Leu412Phe)	SMO	Pathogenic	criteria provided, single submitter
135263	NM_005631.5(SMO):c.2177G>A (p.Arg726Gln)	SMO	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2672182	NM_005631.5(SMO):c.537G>A (p.Thr179=)	SMO	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2672101	NM_005631.5(SMO):c.1102C>G (p.Pro368Ala)	SMO	Uncertain significance	criteria provided, single submitter
2672133	NM_005631.5(SMO):c.771G>A (p.Arg257=)	SMO	Uncertain significance	criteria provided, single submitter
3892521	NM_005631.5(SMO):c.869G>A (p.Arg290His)	SMO	Uncertain significance	criteria provided, single submitter
4526448	NM_005631.5(SMO):c.1235T>C (p.Leu412Pro)	SMO	Uncertain significance	no assertion criteria provided
736286	NM_005631.5(SMO):c.621C>T (p.Tyr207=)	SMO	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 18 · 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
SMO	Definitive	Autosomal dominant	Curry-Jones syndrome	9
SMOX	Definitive	Autosomal dominant	Curry-Jones syndrome	9

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SMO	Orphanet:1553	Curry-Jones syndrome
SMO	Orphanet:2495	Meningioma
SMO	Orphanet:388	Hirschsprung disease

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SMO	HGNC:11119	ENSG00000128602	Q99835	Protein smoothened	gencc,clinvar
SMOX	HGNC:15862	ENSG00000088826	Q9NWM0	Spermine oxidase	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SMO	Protein smoothened	G protein-coupled receptor which associates with the patched protein (PTCH) to transduce hedgehog protein signaling.
SMOX	Spermine oxidase	Flavoenzyme which catalyzes the oxidation of spermine to spermidine.

Protein-family classification

Druggable: 2 · 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
GPCR	1	12.0×	0.160
Enzyme (other)	1	6.0×	0.160

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SMO	GPCR	yes		Frizzled/Smoothened_7TM, Frizzled/SFRP, GPCR_2-like_7TM
SMOX	Enzyme (other)	yes	1.5.3.16	Amino_oxidase, FAD/NAD-bd_sf, Flavin_monoamine_oxidase

Expression context

Cohort genes with no expression data: 0.

2 cohort genes 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
left ovary	1
right ovary	1
ventricular zone	1
C1 segment of cervical spinal cord	1
amygdala	1
lower esophagus mucosa	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SMO	225	ubiquitous	marker	ventricular zone, left ovary, right ovary
SMOX	258	ubiquitous	marker	amygdala, lower esophagus mucosa, C1 segment of cervical spinal cord

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SMO	2,882
SMOX	717

Structural data

PDB: 2 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SMO	Q99835	15
SMOX	Q9NWM0	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 14. Enrichment computed across 2 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
PAOs oxidise polyamines to amines	1	1903.3×	0.005	SMOX
Interconversion of polyamines	1	1427.5×	0.005	SMOX
Activation of SMO	1	317.2×	0.014	SMO
BBSome-mediated cargo-targeting to cilium	1	248.3×	0.014	SMO
Cargo trafficking to the periciliary membrane	1	124.1×	0.020	SMO
Class B/2 (Secretin family receptors)	1	95.2×	0.020	SMO
Signaling by Hedgehog	1	92.1×	0.020	SMO
Hedgehog ‘off’ state	1	89.2×	0.020	SMO
Hedgehog ‘on’ state	1	79.3×	0.020	SMO
Cilium Assembly	1	54.4×	0.026	SMO
Organelle biogenesis and maintenance	1	33.0×	0.036	SMO
GPCR ligand binding	1	32.1×	0.036	SMO
Signaling by GPCR	1	20.0×	0.053	SMO
Signal Transduction	1	5.1×	0.187	SMO

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
ventral midline determination	1	8426.0×	0.003	SMO
mesenchymal to epithelial transition involved in metanephric renal vesicle formation	1	8426.0×	0.003	SMO
regulation of heart morphogenesis	1	8426.0×	0.003	SMO
negative regulation of hair follicle development	1	4213.0×	0.003	SMO
polyamine catabolic process	1	2808.7×	0.003	SMOX
spermine catabolic process	1	2808.7×	0.003	SMOX
pancreas morphogenesis	1	2808.7×	0.003	SMO
regulation of cerebellar granule cell precursor proliferation	1	2106.5×	0.003	SMO
contact inhibition	1	2106.5×	0.003	SMO
epithelial-mesenchymal cell signaling	1	2106.5×	0.003	SMO
response to inositol	1	2106.5×	0.003	SMO
regulation of somatic stem cell population maintenance	1	1685.2×	0.004	SMO
polyamine biosynthetic process	1	1404.3×	0.004	SMOX
cerebellar cortex morphogenesis	1	1404.3×	0.004	SMO
midgut development	1	1053.2×	0.004	SMO
spinal cord dorsal/ventral patterning	1	1053.2×	0.004	SMO
determination of left/right asymmetry in lateral mesoderm	1	936.2×	0.004	SMO
myoblast migration	1	936.2×	0.004	SMO
thalamus development	1	702.2×	0.005	SMO
positive regulation of organ growth	1	702.2×	0.005	SMO
forebrain morphogenesis	1	702.2×	0.005	SMO
type B pancreatic cell development	1	648.1×	0.005	SMO
atrial septum morphogenesis	1	648.1×	0.005	SMO
negative regulation of epithelial cell differentiation	1	601.9×	0.005	SMO
mammary gland epithelial cell differentiation	1	601.9×	0.005	SMO
left/right axis specification	1	601.9×	0.005	SMO
negative regulation of DNA binding	1	561.7×	0.005	SMO
somite development	1	561.7×	0.005	SMO
smooth muscle tissue development	1	526.6×	0.005	SMO
astrocyte activation	1	495.6×	0.005	SMO

Therapeutics

Drug target analysis

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

Druggability breadth: 2 of 2 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
SMO	INFIGRATINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SMO	11	4
SMOX	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
INFIGRATINIB	4	SMO
SONIDEGIB	4	SMO
SONIDEGIB PHOSPHATE	4	SMO
VISMODEGIB	4	SMO
LINIFANIB	3	SMO
PATIDEGIB	3	SMO
FORETINIB	2	SMO
CEP-32496	2	SMO
TALADEGIB	2	SMO
TAK-441	1	SMO
LEQ506	1	SMO

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
SMO	131	Binding:111, Functional:20
SMOX	18	Binding:15, ADMET:3

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
SMOX	1.5.3.16	spermine oxidase

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
SMO	131

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

11 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)
INFIGRATINIB	4	SMO
SONIDEGIB	4	SMO
SONIDEGIB PHOSPHATE	4	SMO
VISMODEGIB	4	SMO
LINIFANIB	3	SMO
PATIDEGIB	3	SMO
FORETINIB	2	SMO
CEP-32496	2	SMO
TALADEGIB	2	SMO
TAK-441	1	SMO
LEQ506	1	SMO

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	SMO
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	1	SMOX
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)
SMOX	18	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.