Ramon syndrome

Summary

Ramon syndrome (MONDO:0009954) is a disease with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 1
• Phenotypes (HPO): 17

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		8	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

17 HPO clinical features (Orphanet curated; top 17 by frequency):

HPO ID	Term	Frequency
HP:0000169	Gingival fibromatosis	Very frequent (80-99%)
HP:0000189	Narrow palate	Very frequent (80-99%)
HP:0000293	Full cheeks	Very frequent (80-99%)
HP:0001249	Intellectual disability	Very frequent (80-99%)
HP:0001250	Seizure	Very frequent (80-99%)
HP:0001508	Failure to thrive	Very frequent (80-99%)
HP:0002797	Osteolysis	Very frequent (80-99%)
HP:0000684	Delayed eruption of teeth	Frequent (30-79%)
HP:0002230	Generalized hirsutism	Frequent (30-79%)
HP:0007703	Abnormality of retinal pigmentation	Frequent (30-79%)
HP:0000405	Conductive hearing impairment	Occasional (5-29%)
HP:0000407	Sensorineural hearing impairment	Occasional (5-29%)
HP:0000593	Abnormal anterior chamber morphology	Occasional (5-29%)
HP:0000682	Abnormality of dental enamel	Occasional (5-29%)
HP:0000819	Diabetes mellitus	Occasional (5-29%)
HP:0000962	Hyperkeratosis	Occasional (5-29%)
HP:0100585	Telangiectasia of the skin	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	Ramon syndrome
Mondo ID	MONDO:0009954
MeSH	C535285
OMIM	266270
Orphanet	3019
DOID	DOID:0070650
ICD-11	122538435
UMLS	C0796133
MedGen	208669
GARD	0007523
Is cancer (heuristic)	no

Also known as: cherubism-gingival fibromatosis-intellectual disability syndrome · gingival fibromatosis combined with cherubism · Ramon syndrome

Data availability: 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by body system or component › musculoskeletal system disorder › Ramon syndrome

Related subtypes (21): autoimmune disorder of musculoskeletal system, musculoskeletal system benign neoplasm, musculoskeletal system cancer, Klippel-Feil syndrome, enthesopathy, muscle tissue disorder, fasciitis, skeletal system disorder, synovial chondromatosis, auriculoosteodysplasia, hypertrophic osteoarthropathy, primary, autosomal dominant, Upington disease, osteoporosis-oculocutaneous hypopigmentation syndrome, short stature, Brussels type, wormian bone-multiple fractures-dentinogenesis imperfecta-skeletal dysplasia, CINCA syndrome, chondrodysplasia with joint dislocations, gPAPP type, ligament disorder, synovium disorder, disease of the tendon, Short stature, Dauber-Argente type

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: 5 · Orphanet: 2 · 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
ELMO2	Supportive	Autosomal recessive	Ramon syndrome	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ELMO2	Orphanet:140436	Familial intraosseous vascular malformation
ELMO2	Orphanet:3019	Ramon 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
ELMO2	HGNC:17233	ENSG00000062598	Q96JJ3	Engulfment and cell motility protein 2	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ELMO2	Engulfment and cell motility protein 2	Involved in cytoskeletal rearrangements required for phagocytosis of apoptotic cells and cell motility.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 0 · 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
Scaffold/PPI	1	17.3×	0.058

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ELMO2	Scaffold/PPI	no		PH_domain, ELMO_dom, ARM-like

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
cerebellar cortex	1
cerebellar hemisphere	1
right hemisphere of cerebellum	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ELMO2	289	ubiquitous	marker	cerebellar hemisphere, cerebellar cortex, right hemisphere of cerebellum

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ELMO2	1,168

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ELMO2	Q96JJ3	2

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
PTK6 Regulates RHO GTPases, RAS GTPase and MAP kinases	1	815.7×	0.006	ELMO2
FCGR3A-mediated phagocytosis	1	187.2×	0.007	ELMO2
Regulation of actin dynamics for phagocytic cup formation	1	184.2×	0.007	ELMO2
RHOG GTPase cycle	1	148.3×	0.007	ELMO2
VEGFA-VEGFR2 Pathway	1	139.3×	0.007	ELMO2

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
cell motility	1	401.2×	0.009	ELMO2
phagocytosis	1	240.7×	0.009	ELMO2
cell chemotaxis	1	185.2×	0.009	ELMO2
actin filament organization	1	118.7×	0.011	ELMO2
apoptotic process	1	28.7×	0.035	ELMO2

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ELMO2	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	ELMO2

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)
ELMO2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.