Cherubism

Summary

Cherubism (MONDO:0007315) is a disease caused by SH3BP2 (GenCC Strong), with 4 cohort genes and 2 clinical trials.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: SH3BP2 (GenCC Strong)
• Cohort genes: 4
• ClinVar variants: 783
• Phenotypes (HPO): 15
• Clinical trials: 2

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		300	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

15 HPO clinical features (Orphanet curated; top 15 by frequency):

HPO ID	Term	Frequency
HP:0000277	Abnormality of the mandible	Very frequent (80-99%)
HP:0000293	Full cheeks	Very frequent (80-99%)
HP:0012062	Bone cyst	Very frequent (80-99%)
HP:0012802	Broad jaw	Very frequent (80-99%)
HP:0000164	Abnormality of the dentition	Frequent (30-79%)
HP:0000677	Oligodontia	Frequent (30-79%)
HP:0006482	Abnormal dental morphology	Frequent (30-79%)
HP:0000505	Visual impairment	Occasional (5-29%)
HP:0000520	Proptosis	Occasional (5-29%)
HP:0000529	Progressive visual loss	Occasional (5-29%)
HP:0000648	Optic atrophy	Occasional (5-29%)
HP:0001608	Abnormality of the voice	Occasional (5-29%)
HP:0002781	Upper airway obstruction	Occasional (5-29%)
HP:0002870	Obstructive sleep apnea	Occasional (5-29%)
HP:0008872	Feeding difficulties in infancy	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	cherubism
Mondo ID	MONDO:0007315
MeSH	D002636
OMIM	118400
Orphanet	184
DOID	DOID:1856
ICD-11	1729261719
NCIT	C84630
SNOMED CT	76098004
UMLS	C0008029
MedGen	40219
GARD	0006036
MedDRA	10070535
Is cancer (heuristic)	no

Also known as: cherubism · CRBM · familial fibrous dysplasia of the jaws · familial multilocular cystic disease of the jaws

Data availability: 783 ClinVar variants · 4 GenCC gene-disease records · 1 cell line.

Disease family

An umbrella term covering 1 Mondo subtype.

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › autosomal genetic disease › autosomal dominant disease › cherubism

Related subtypes (191): autosomal dominant polycystic liver disease, cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy, type 1, tuberous sclerosis, Treacher-Collins syndrome, hereditary breast ovarian cancer syndrome, autosomal dominant polycystic kidney disease, Lynch syndrome, branchio-oto-renal syndrome, autosomal dominant Aarskog syndrome, acroosteolysis dominant type, ADULT syndrome, autosomal dominant Alport syndrome, amelogenesis imperfecta type 1B, Townes-Brocks syndrome, nevoid basal cell carcinoma syndrome, blepharophimosis, ptosis, and epicanthus inversus syndrome, autosomal dominant brachyolmia, branchiooculofacial syndrome, pheochromocytoma/paraganglioma syndrome 4, cataract-aberrant oral frenula-growth delay syndrome, autosomal dominant chondrodysplasia punctata, autosomal dominant popliteal pterygium syndrome, blepharocheilodontic syndrome, cochleosaccular degeneration-cataract syndrome, renal coloboma syndrome, Beare-Stevenson cutis gyrata syndrome, autosomal dominant vibratory urticaria, neurohypophyseal diabetes insipidus, autosomal dominant Kenny-Caffey syndrome, Rapp-Hodgkin syndrome, Ehlers-Danlos syndrome, classic type, autosomal dominant Ehlers-Danlos syndrome, vascular type, multiple endocrine neoplasia type 1, Coffin-Siris syndrome 1, isolated congenital adermatoglyphia, Flynn-Aird syndrome, Frasier syndrome, hand-foot-genital syndrome, Holt-Oram syndrome, hyperkeratosis-hyperpigmentation syndrome, autosomal dominant ichthyosis vulgaris, hyper-IgE recurrent infection syndrome 1, autosomal dominant, autosomal dominant keratitis, autosomal dominant keratitis-ichthyosis-hearing loss syndrome, LADD syndrome, trichorhinophalangeal syndrome type II, Noonan syndrome with multiple lentigines, microcephaly with or without chorioretinopathy, lymphedema, or intellectual disability, Marfan syndrome, melanoma, cutaneous malignant, susceptibility to, 2, autosomal dominant primary microcephaly, autosomal dominant progressive external ophthalmoplegia, monilethrix, Muir-Torre syndrome, autosomal dominant myoglobinuria, autosomal dominant centronuclear myopathy, nail-patella syndrome, multiple endocrine neoplasia type 2B, autosomal dominant omodysplasia, pheochromocytoma/paraganglioma syndrome 1, Pelger-Huet anomaly, multiple endocrine neoplasia type 2A, piebaldism, autosomal dominant medullary cystic kidney disease with or without hyperuricemia, generalized juvenile polyposis/juvenile polyposis coli, juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome, Peutz-Jeghers syndrome, contractures, pterygia, and spondylocarpotarsal fusion syndrome 1A, autosomal dominant distal renal tubular acidosis, retinoschisis, autosomal dominant, autosomal dominant Robinow syndrome, scapuloperoneal spinal muscular atrophy, autosomal dominant, autosomal dominant sideroblastic anemia, spondyloepiphyseal dysplasia tarda, autosomal dominant, proximal symphalangism, calcaneonavicular coalition, thanatophoric dysplasia type 1, trichorhinophalangeal syndrome type I, Muckle-Wells syndrome, autosomal dominant hypophosphatemic rickets, von Hippel-Lindau disease, Denys-Drash syndrome, autosomal dominant severe congenital neutropenia, Costello syndrome, EEC syndrome, multiple cutaneous and mucosal venous malformations, diffuse nonepidermolytic palmoplantar keratoderma, Timothy syndrome, pheochromocytoma/paraganglioma syndrome 2, spondyloepimetaphyseal dysplasia with multiple dislocations, Brooke-Spiegler syndrome, macrocephaly-autism syndrome, pheochromocytoma/paraganglioma syndrome 3, Duane-radial ray syndrome, PCWH syndrome, heart-hand syndrome, Slovenian type, congenital stationary night blindness autosomal dominant 3, mandibulofacial dysostosis-microcephaly syndrome, multiple endocrine neoplasia type 4, juvenile cataract-microcornea-renal glucosuria syndrome, Crouzon syndrome-acanthosis nigricans syndrome, Birk-Barel syndrome, thrombophilia due to protein S deficiency, autosomal dominant, dyskeratosis congenita, autosomal dominant 2, dyskeratosis congenita, autosomal dominant 3, colorectal cancer, hereditary nonpolyposis, type 6, colorectal cancer, hereditary nonpolyposis, type 7, brain small vessel disease 2A, autosomal dominant, intellectual disability, autosomal dominant 14, intellectual disability, autosomal dominant 15, intellectual disability, autosomal dominant 16, hypopigmentation-punctate palmoplantar keratoderma syndrome, intellectual disability-facial dysmorphism syndrome due to SETD5 haploinsufficiency, postaxial polydactyly-anterior pituitary anomalies-facial dysmorphism syndrome, intellectual developmental disorder with microcephaly and with or without ocular malformations or hypogonadotropic hypogonadism, intellectual disability, autosomal dominant 29, intellectual disability, autosomal dominant 30, Houge-Janssens syndrome 2, severe achondroplasia-developmental delay-acanthosis nigricans syndrome, dyskeratosis congenita, autosomal dominant 6, epidermolysis bullosa simplex 6, generalized, with scarring and hair loss, autosomal dominant complex spastic paraplegia, early-onset autosomal dominant Alzheimer disease, muscular dystrophy, limb-girdle, autosomal dominant, Feingold syndrome, Carney complex, neuronopathy, distal hereditary motor, autosomal dominant, autosomal dominant coarctation of aorta, autosomal dominant spondylocostal dysostosis, autosomal dominant hypohidrotic ectodermal dysplasia, Cowden disease, autosomal dominant distal myopathy, autosomal dominant rhegmatogenous retinal detachment, palmoplantar keratoderma-spastic paralysis syndrome, Alagille syndrome due to a JAG1 point mutation, PTEN hamartoma tumor syndrome, gastric adenocarcinoma and proximal polyposis of the stomach, autosomal dominant proximal renal tubular acidosis, autosomal dominant spastic ataxia, Waardenburg syndrome, hereditary retinoblastoma, autosomal dominant hypocalcemia, Li-Fraumeni syndrome, Loeys-Dietz syndrome, hereditary hemorrhagic telangiectasia, hereditary inclusion body myopathy-joint contractures-ophthalmoplegia syndrome, microcephalic osteodysplastic dysplasia, Saul-Wilson type, autosomal dominant intermediate Charcot-Marie-Tooth disease, autosomal dominant cutis laxa, autosomal dominant nonsyndromic hearing loss, autosomal dominant optic atrophy, autosomal dominant Emery-Dreifuss muscular dystrophy, autosomal dominant cerebellar ataxia, autosomal dominant osteopetrosis, autosomal dominant epidermolytic ichthyosis, ventricular arrhythmias due to cardiac ryanodine receptor calcium release deficiency syndrome, distal arthrogryposis type 2B1, neurofibromatosis, autosomal dominant cataract, arthrogryposis, distal, type 2B2, arthrogryposis, distal, type 2B3, Charcot-Marie-Tooth disease, demyelinating, type 1G, Delpire-McNeill syndrome, LAMA5-related multisystemic syndrome, autosomal dominant oculocutaneous albinism, Charcot-Marie-tooth disease, axonal, type 2DD, Pilarowski-Bjornsson syndrome, intellectual disability, autosomal dominant, fatty acyl-CoA reductase 1 upregulation, GUCY2D-related dominant retinopathy, RPE65-related dominant retinopathy, autosomal dominant titinopathy, NOG-related symphalangism spectrum disorder, ALPL-related autosomal dominant hypophosphatasia, MYH10-related neurodevelopmental disorder with congenital anomalies, spastic paraplegia 30A, autosomal dominant, TMEM127-related tumor predisposition, MAX-related tumor predisposition, BMPR1A-related juvenile polyposis syndrome, RP1-related dominant retinopathy, Birt-Hogg-Dube syndrome, inclusion body myopathy and brain white matter abnormalities, KINSSHIP syndrome, autosomal dominant nebulin-related myopathy, IMPG1-related dominant retinopathy, PROM1-related dominant retinopathy, PURA-related severe neonatal hypotonia-seizures-encephalopathy syndrome, ALG8-related autosomal dominant polycystic kidney and/or liver disease, NOTCH1-related AOS spectrum disorder, FLNB-associated autosomal dominant filamin related bone disorder, familial antiphospholipid syndrome

Subtypes (1): Al Gazali Khidr Prem Chandran 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

600 retrieved; paginated sample, class counts are floors:

265 uncertain significance, 198 likely benign, 100 benign, 20 conflicting classifications of pathogenicity, 15 benign/likely benign, 1 likely pathogenic, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
372503	NM_001122681.2(SH3BP2):c.1258G>A (p.Gly420Arg)	SH3BP2	Pathogenic	criteria provided, multiple submitters, no conflicts
1526420	NM_001122681.2(SH3BP2):c.1259G>C (p.Gly420Ala)	SH3BP2	Likely pathogenic	no assertion criteria provided
1025635	NM_001122681.2(SH3BP2):c.1507G>A (p.Glu503Lys)	SH3BP2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1084498	NM_001122681.2(SH3BP2):c.644C>G (p.Pro215Arg)	SH3BP2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1132791	NM_001122681.2(SH3BP2):c.1294C>T (p.Arg432Trp)	SH3BP2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1364255	NM_001122681.2(SH3BP2):c.560A>G (p.Asp187Gly)	SH3BP2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1370004	NM_001122681.2(SH3BP2):c.32C>T (p.Pro11Leu)	SH3BP2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2061547	NM_001122681.2(SH3BP2):c.694G>A (p.Gly232Ser)	SH3BP2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2164742	NM_001122681.2(SH3BP2):c.172G>A (p.Val58Ile)	SH3BP2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
280675	NM_001122681.2(SH3BP2):c.1252C>T (p.Pro418Ser)	SH3BP2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3440960	NM_001122681.2(SH3BP2):c.1375G>A (p.Val459Ile)	SH3BP2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
348572	NM_001122681.2(SH3BP2):c.440C>T (p.Ser147Leu)	SH3BP2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
348575	NM_001122681.2(SH3BP2):c.472C>T (p.Arg158Trp)	SH3BP2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
348577	NM_001122681.2(SH3BP2):c.517+5G>A	SH3BP2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
348580	NM_001122681.2(SH3BP2):c.585G>A (p.Glu195=)	SH3BP2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
348581	NM_001122681.2(SH3BP2):c.656A>T (p.Asp219Val)	SH3BP2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
348582	NM_001122681.2(SH3BP2):c.937G>A (p.Gly313Arg)	SH3BP2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
348584	NM_001122681.2(SH3BP2):c.1141G>A (p.Val381Met)	SH3BP2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
348587	NM_001122681.2(SH3BP2):c.1280_1282del (p.Ser427del)	SH3BP2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
348590	NM_001122681.2(SH3BP2):c.1367C>T (p.Ser456Leu)	SH3BP2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
348593	NM_001122681.2(SH3BP2):c.1514C>G (p.Ser505Cys)	SH3BP2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3795340	NM_001122681.2(SH3BP2):c.531C>A (p.Asp177Glu)	SH3BP2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2424606	NC_000004.11:g.(?493125)(3495228_?)dup	ADD1	Uncertain significance	criteria provided, single submitter
1421534	NC_000004.11:g.(?493125)(3495228_?)del	CRIPAK	Uncertain significance	criteria provided, single submitter
1001039	NM_001122681.2(SH3BP2):c.1192C>T (p.Arg398Trp)	SH3BP2	Uncertain significance	criteria provided, single submitter
1004411	NM_001122681.2(SH3BP2):c.586+5G>T	SH3BP2	Uncertain significance	criteria provided, single submitter
1005548	NM_001122681.2(SH3BP2):c.914C>T (p.Pro305Leu)	SH3BP2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1005732	NM_001122681.2(SH3BP2):c.1007C>T (p.Ser336Phe)	SH3BP2	Uncertain significance	criteria provided, single submitter
1016332	NM_001122681.2(SH3BP2):c.1675G>T (p.Gly559Trp)	SH3BP2	Uncertain significance	criteria provided, single submitter
1018085	NM_001122681.2(SH3BP2):c.506C>T (p.Thr169Met)	SH3BP2	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · 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
SH3BP2	Strong	Autosomal dominant	cherubism	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SH3BP2	Orphanet:184	Cherubism
RIT1	Orphanet:648	Noonan syndrome

Cohort genes → proteins

4 cohort genes, 4 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	4

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SH3BP2	HGNC:10825	ENSG00000087266	P78314	SH3 domain-binding protein 2	gencc,clinvar
RIT1	HGNC:10023	ENSG00000143622	Q92963	GTP-binding protein Rit1	clinvar
MXD4	HGNC:13906	ENSG00000123933	Q14582	Max dimerization protein 4	clinvar
ADD1	HGNC:243	ENSG00000087274	P35611	Alpha-adducin	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SH3BP2	SH3 domain-binding protein 2	Binds differentially to the SH3 domains of certain proteins of signal transduction pathways.
RIT1	GTP-binding protein Rit1	Plays a crucial role in coupling NGF stimulation to the activation of both EPHB2 and MAPK14 signaling pathways and in NGF-dependent neuronal differentiation.
MXD4	Max dimerization protein 4	Transcriptional repressor.
ADD1	Alpha-adducin	Membrane-cytoskeleton-associated protein that promotes the assembly of the spectrin-actin network.

Protein-family classification

Druggable: 0 · Difficult: 2 · Unknown: 2 · 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	4.3×	0.605
Transcription factor	1	2.1×	0.605
Other/Unknown	2	0.9×	0.769

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SH3BP2	Scaffold/PPI	no		SH2, PH_domain, PH-like_dom_sf
RIT1	Other/Unknown	no		Small_GTPase, Small_GTP-bd, Small_GTPase_Ras-type
MXD4	Transcription factor	no		bHLH_dom, HLH_DNA-bd_sf
ADD1	Other/Unknown	no		Aldolase_II/adducin_N, Aldolase_II/adducin_N_sf, Aldolase-II_Adducin_sf

Expression context

Cohort genes with no expression data: 0.

4 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)	4
unknown	0

Top tissues across cohort

Tissue	Cohort genes
monocyte	2
right hemisphere of cerebellum	2
granulocyte	1
sural nerve	1
leukocyte	1
mononuclear cell	1
cerebellar cortex	1
cerebellar hemisphere	1
nerve	1
tibial nerve	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SH3BP2	213	ubiquitous	marker	granulocyte, sural nerve, monocyte
RIT1	268	ubiquitous	marker	monocyte, mononuclear cell, leukocyte
MXD4	242	ubiquitous	marker	right hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex
ADD1	304	ubiquitous	marker	right hemisphere of cerebellum, nerve, tibial nerve

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
RIT1	3,298
ADD1	2,157
MXD4	810
SH3BP2	763

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
RIT1	Q92963	3
SH3BP2	P78314	2

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
MXD4	Q14582	73.22
ADD1	P35611	65.73

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 17. Enrichment computed across 4 evidence-associated genes (3 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 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Signalling to p38 via RIT and RIN	1	761.3×	0.018	RIT1
Caspase-mediated cleavage of cytoskeletal proteins	1	317.2×	0.018	ADD1
IRE1alpha activates chaperones	1	173.0×	0.018	ADD1
Apoptotic cleavage of cellular proteins	1	158.6×	0.018	ADD1
Apoptotic execution phase	1	158.6×	0.018	ADD1
Miscellaneous transport and binding events	1	146.4×	0.018	ADD1
Unfolded Protein Response (UPR)	1	119.0×	0.018	ADD1
Nuclear signaling by ERBB4	1	115.3×	0.018	MXD4
Signaling by ERBB4	1	90.6×	0.021	MXD4
XBP1(S) activates chaperone genes	1	71.8×	0.024	ADD1
Apoptosis	1	56.0×	0.027	ADD1
Programmed Cell Death	1	48.8×	0.029	ADD1
Signaling by Receptor Tyrosine Kinases	1	17.2×	0.074	MXD4
Cellular responses to stress	1	12.3×	0.096	ADD1
Cellular responses to stimuli	1	10.5×	0.105	ADD1
Transport of small molecules	1	8.4×	0.122	ADD1
Signal Transduction	1	3.4×	0.267	MXD4

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 4 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 adherens junction organization	1	2106.5×	0.005	ADD1
positive regulation of establishment of endothelial barrier	1	702.2×	0.007	ADD1
barbed-end actin filament capping	1	200.6×	0.017	ADD1
actin filament bundle assembly	1	113.9×	0.022	ADD1
Ras protein signal transduction	1	51.4×	0.031	RIT1
cellular response to calcium ion	1	50.1×	0.031	ADD1
signal transduction	2	8.0×	0.031	SH3BP2, RIT1
actin cytoskeleton organization	1	19.8×	0.062	ADD1
negative regulation of transcription by RNA polymerase II	1	4.4×	0.230	MXD4
regulation of transcription by RNA polymerase II	1	2.9×	0.302	MXD4

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 4 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
SH3BP2	0	0
RIT1	0	0
MXD4	0	0
ADD1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 4; 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	4	SH3BP2, RIT1, MXD4, ADD1

Undrugged target profiles

4 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
SH3BP2	0	—
RIT1	0	—
MXD4	0	—
ADD1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 2.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01630447	Not specified	RECRUITING	Genetic and Functional Analysis of Cherubism
NCT01916772	Not specified	COMPLETED	Natural History of Cherubism Observational Study