SAPHO syndrome

disease

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Also known as acquired hyperostosis syndromePPHSPustulo-psoriatic hyperostotic Spondyloarthritissynovitis acne pustulosis hyperostosis osteitissynovitis, acne, Pustlosis, hyperostosis, and osteomyelitissynovitis, acne, pustulosis, hyperostosis, and osteitis syndromesynovitis-acne-pustulosis-hyperostosis-osteitis syndrome

Summary

SAPHO syndrome (MONDO:0019266) is a disease with 10 cohort genes (24 GWAS associations across 1 studies) and 6 clinical trials. Top therapeutic interventions include pamidronic acid, etanercept, and fapi ga-68.

At a glance

Prevalence: Unknown (Worldwide) [Orphanet-validated]
Cohort genes: 10
GWAS associations: 24
Phenotypes (HPO): 30
Clinical trials: 6

Clinical features

Signs & symptoms

Clinical features (HPO)

30 HPO clinical features (Orphanet curated; top 30 by frequency):

HPO ID	Term	Frequency
HP:0000765	Abnormal thorax morphology	Very frequent (80-99%)
HP:0002653	Bone pain	Very frequent (80-99%)
HP:0002797	Osteolysis	Very frequent (80-99%)
HP:0002829	Arthralgia	Very frequent (80-99%)
HP:0005464	Craniofacial osteosclerosis	Very frequent (80-99%)
HP:0010622	Neoplasm of the skeletal system	Very frequent (80-99%)
HP:0100686	Enthesitis	Very frequent (80-99%)
HP:0100769	Synovitis	Very frequent (80-99%)
HP:0200039	Pustule	Very frequent (80-99%)
HP:0100749	Chest pain	Very frequent (80-99%)
HP:0100774	Hyperostosis	Very frequent (80-99%)
HP:0000925	Abnormality of the vertebral column	Frequent (30-79%)
HP:0000969	Edema	Frequent (30-79%)
HP:0001061	Acne	Frequent (30-79%)
HP:0001369	Arthritis	Frequent (30-79%)
HP:0002754	Osteomyelitis	Frequent (30-79%)
HP:0003765	Psoriasiform dermatitis	Frequent (30-79%)
HP:0100781	Abnormality of the sacroiliac joint	Frequent (30-79%)
HP:0100847	Palmoplantar pustulosis	Frequent (30-79%)
HP:0000988	Skin rash	Occasional (5-29%)
HP:0001581	Recurrent skin infections	Occasional (5-29%)
HP:0002024	Malabsorption	Occasional (5-29%)
HP:0002027	Abdominal pain	Occasional (5-29%)
HP:0002028	Chronic diarrhea	Occasional (5-29%)
HP:0002037	Inflammation of the large intestine	Occasional (5-29%)
HP:0002570	Steatorrhea	Occasional (5-29%)
HP:0002757	Recurrent fractures	Occasional (5-29%)
HP:0004936	Venous thrombosis	Occasional (5-29%)
HP:0006824	Cranial nerve paralysis	Occasional (5-29%)
HP:0002633	Vasculitis	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	SAPHO syndrome
Mondo ID	MONDO:0019266
EFO	EFO:1001164
MeSH	D020083
Orphanet	793
DOID	DOID:13677
ICD-11	1901494067
NCIT	C119049
SNOMED CT	60684003
UMLS	C0263859
MedGen	120490
GARD	0007606
MedDRA	10051316
Is cancer (heuristic)	no

Also known as: acquired hyperostosis syndrome · PPHS · Pustulo-psoriatic hyperostotic Spondyloarthritis · synovitis acne pustulosis hyperostosis osteitis · synovitis, acne, Pustlosis, hyperostosis, and osteomyelitis · synovitis, acne, pustulosis, hyperostosis, and osteitis syndrome · synovitis-acne-pustulosis-hyperostosis-osteitis syndrome

Data availability: 24 GWAS associations (1 study).

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › autoinflammatory syndrome › SAPHO syndrome

Genetics & variants

GWAS landscape

24 GWAS associations across 1 studies. Top hits map to 10 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs4505038	8e-13	PEX16	?	7.25
rs4897770	2e-11	TCERG1L - LINC01164	?	0.09
rs12442139	1e-10	LOXL1 - STOML1	?	0.16
rs13062589	4e-10	TVP23CP3 - KLHL6	?	0.17
rs2243861	4e-09	IQCA1L	?	0.06
rs2850133	9e-09	LINC01671 - PDE9A	?	0.2
rs10927436	1e-08	KAZN	?	0.13
rs9567768	2e-08	HTR2A - GNG5P5	?	0.22
rs8007562	6e-08	DEGS2 - YY1-DT	?	4.36
rs78395560	7e-08	CACNG4	?	4.11
rs28461568	8e-08	PIP5K1B - PRKACG	?	0.09
chr5: 177549334	1e-07		?	0.11
chr20: 3776368	1e-07		?	0.06
rs118184987	1e-07	NUDT16-DT	?	10.2
rs2280792	2e-07	PAPLN, PAPLN-AS1	?	0.23
rs4937861	2e-07	IGSF9B - LINC02730	?	0.1
rs10401843	2e-07	FBXO17	?	0.22
rs7508251	2e-07	SPMAP2 - C2CD4C	?	0.23
rs1809265	3e-07	DYSF - RPS20P10	?	0.21
chr1: 227462940	3e-07		?	0.08
rs574637	4e-07	CLIP2	?	0.12
rs6847701	5e-07	PTGES3P3 - LINC02275	?	0.27
rs2279486	5e-07	APBA2	?	3.6
rs1461616	6e-07	LINC02027 - GBE1	?	0.15

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST012256	Cai R	2021	49	0	Genome-Wide Association Identifies Risk Pathways for SAPHO Syndrome.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	1
Tier 2: splice/UTR	0
Tier 3: regulatory	1
Tier 4: intronic/intergenic	22

MAF distribution

Bucket	Variants
common (>=0.05)	21
low_freq (0.01-0.05)	0
rare (<0.01)	0
unknown	3

Functional consequences

Consequence	Count
intron_variant	9
intergenic_variant	9
unknown	3
TF_binding_site_variant	1
missense_variant	1
synonymous_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs4505038	11	45913146	T>C,G	0.05	intron_variant	PEX16	8e-13	Tier 4: intronic/intergenic
rs4897770	10	131747080	T>A,C	0.05	intron_variant	TCERG1L - LINC01164	2e-11	Tier 4: intronic/intergenic
rs12442139	15	73953145	C>A,G,T	0.05	intergenic_variant	LOXL1 - STOML1	1e-10	Tier 4: intronic/intergenic
rs13062589	3	183478017	C>G,T	0.05	intergenic_variant	TVP23CP3 - KLHL6	4e-10	Tier 4: intronic/intergenic
rs2243861	7	151192688	T>C	0.05	intron_variant	IQCA1L	4e-09	Tier 4: intronic/intergenic
rs2850133	21	42621255	C>T	0.05	TF_binding_site_variant	LINC01671 - PDE9A	9e-09	Tier 3: regulatory
rs10927436	1	14436734	A>C	0.05	intron_variant	KAZN	1e-08	Tier 4: intronic/intergenic
rs9567768	13	47012077	C>A,T	0.05	intron_variant	HTR2A - GNG5P5	2e-08	Tier 4: intronic/intergenic
rs8007562	14	100187511	A>G,T	0.05	intergenic_variant	DEGS2 - YY1-DT	6e-08	Tier 4: intronic/intergenic
rs78395560	17	66999339	A>C,G	0.05	intron_variant	CACNG4	7e-08	Tier 4: intronic/intergenic
rs28461568	9	69011592	T>A,G	0.05	intergenic_variant	PIP5K1B - PRKACG	8e-08	Tier 4: intronic/intergenic
chr5: 177549334							1e-07	Tier 4: intronic/intergenic
chr20: 3776368							1e-07	Tier 4: intronic/intergenic
rs118184987	3	131376632	G>A	0.05	intergenic_variant	NUDT16-DT	1e-07	Tier 4: intronic/intergenic
rs2280792	14	73244686	A>G,T	0.05	missense_variant	PAPLN, PAPLN-AS1	2e-07	Tier 1: coding
rs4937861	11	133994384	A>G	0.05	intergenic_variant	IGSF9B - LINC02730	2e-07	Tier 4: intronic/intergenic
rs10401843	19	38958873	G>A,C	0.05	intron_variant	FBXO17	2e-07	Tier 4: intronic/intergenic
rs7508251	19	401714	A>G	0.05	intergenic_variant	SPMAP2 - C2CD4C	2e-07	Tier 4: intronic/intergenic
rs1809265	2	71786487	C>A,T	0.05	intergenic_variant	DYSF - RPS20P10	3e-07	Tier 4: intronic/intergenic
chr1: 227462940							3e-07	Tier 4: intronic/intergenic
rs574637	7	74338369	C>G,T	0.05	intron_variant	CLIP2	4e-07	Tier 4: intronic/intergenic
rs6847701	4	169860168	G>A	0.05	intron_variant	PTGES3P3 - LINC02275	5e-07	Tier 4: intronic/intergenic
rs2279486	15	29107922	C>T	0.05	synonymous_variant	APBA2	5e-07	Tier 4: intronic/intergenic
rs1461616	3	81371045	C>A,T	0.05	intergenic_variant	LINC02027 - GBE1	6e-07	Tier 4: intronic/intergenic

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 5 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CLIP2	Orphanet:904	Williams syndrome
PEX16	Orphanet:44	Neonatal adrenoleukodystrophy
PEX16	Orphanet:642954	Autosomal recessive ataxia due to PEX16 deficiency
PEX16	Orphanet:772	Infantile Refsum disease
PEX16	Orphanet:912	Zellweger syndrome

Cohort genes → proteins

10 cohort genes, 10 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	10

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
CACNG4	HGNC:1408	ENSG00000075461	Q9UBN1	Voltage-dependent calcium channel gamma-4 subunit	gwas
CDC25B	HGNC:1726	ENSG00000101224	P30305	M-phase inducer phosphatase 2	gwas
CDC42BPA	HGNC:1737	ENSG00000143776	Q5VT25	Serine/threonine-protein kinase MRCK alpha	gwas
FBXO17	HGNC:18754	ENSG00000269190	Q96EF6	F-box only protein 17	gwas
PAPLN	HGNC:19262	ENSG00000100767	O95428	Papilin	gwas
DRC11L	HGNC:22831	ENSG00000278685	A6NCM1	Dynein regulatory complex subunit like-11	gwas
CLIP2	HGNC:2586	ENSG00000106665	Q9UDT6	CAP-Gly domain-containing linker protein 2	gwas
N4BP3	HGNC:29852	ENSG00000145911	O15049	NEDD4-binding protein 3	gwas
APBA2	HGNC:579	ENSG00000034053	Q99767	Amyloid-beta A4 precursor protein-binding family A member 2	gwas
PEX16	HGNC:8857	ENSG00000121680	Q9Y5Y5	Peroxisomal membrane protein PEX16	gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CACNG4	Voltage-dependent calcium channel gamma-4 subunit	Regulates the activity of L-type calcium channels that contain CACNA1C as pore-forming subunit.
CDC25B	M-phase inducer phosphatase 2	Tyrosine protein phosphatase which functions as a dosage-dependent inducer of mitotic progression.
CDC42BPA	Serine/threonine-protein kinase MRCK alpha	Serine/threonine-protein kinase which is an important downstream effector of CDC42 and plays a role in the regulation of cytoskeleton reorganization and cell migration.
FBXO17	F-box only protein 17	Substrate-recognition component of the SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex.
CLIP2	CAP-Gly domain-containing linker protein 2	Seems to link microtubules to dendritic lamellar body (DLB), a membranous organelle predominantly present in bulbous dendritic appendages of neurons linked by dendrodendritic gap junctions.
N4BP3	NEDD4-binding protein 3	Plays a positive role in the antiviral innate immune signaling pathway.
APBA2	Amyloid-beta A4 precursor protein-binding family A member 2	Putative function in synaptic vesicle exocytosis by binding to STXBP1, an essential component of the synaptic vesicle exocytotic machinery.
PEX16	Peroxisomal membrane protein PEX16	Required for peroxisome membrane biogenesis.

Protein-family classification

Druggable: 3 · Difficult: 1 · Unknown: 6 · Druggable fraction: 0.3

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
Phosphatase	1	8.4×	0.513
Antibody/Immunoglobulin	1	2.9×	0.513
Kinase	1	2.8×	0.513
Scaffold/PPI	1	1.7×	0.526
Other/Unknown	6	1.1×	0.526

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CACNG4	Other/Unknown	no		PMP22/EMP/MP20/Claudin, VDCC_g4su, VDCC_gsu
CDC25B	Phosphatase	yes	3.1.3.48	MPI_Phosphatase, Rhodanese-like_dom, Rhodanese-like_dom_sf
CDC42BPA	Kinase	yes		CRIB_dom, Prot_kinase_dom, AGC-kinase_C
FBXO17	Other/Unknown	no		F-box_dom, F-box-assoc_dom, Galactose-bd-like_sf
PAPLN	Antibody/Immunoglobulin	yes		TSP1_rpt, Kunitz_BPTI, Ig_sub2
DRC11L	Other/Unknown	no		IQ_motif_EF-hand-BS, ATPase_AAA_core, P-loop_NTPase
CLIP2	Other/Unknown	no		CAP-Gly_domain, CAP-Gly_dom_sf
N4BP3	Other/Unknown	no		N4BP3
APBA2	Scaffold/PPI	no		PDZ, PTB/PI_dom, PH-like_dom_sf
PEX16	Other/Unknown	no		Pex16

Expression context

Cohort genes with no expression data: 0.

8 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)	10
unknown	0

Top tissues across cohort

Tissue	Cohort genes
cortical plate	2
ganglionic eminence	2
granulocyte	2
right hemisphere of cerebellum	2
right lobe of liver	2
ventricular zone	1
right lung	1
globus pallidus	1
medial globus pallidus	1
pylorus	1
adult mammalian kidney	1
metanephros cortex	1
decidua	1
tendon of biceps brachii	1
tibial nerve	1
left testis	1
male germ line stem cell (sensu Vertebrata) in testis	1
right testis	1
C1 segment of cervical spinal cord	1
endometrium epithelium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CACNG4	146	broad	marker	cortical plate, ventricular zone, ganglionic eminence
CDC25B	279	ubiquitous	marker	granulocyte, right lung, right hemisphere of cerebellum
CDC42BPA	291	ubiquitous	marker	medial globus pallidus, globus pallidus, pylorus
FBXO17	135	ubiquitous	marker	right lobe of liver, metanephros cortex, adult mammalian kidney
PAPLN	234	broad	marker	tibial nerve, tendon of biceps brachii, decidua
DRC11L	54		yes	male germ line stem cell (sensu Vertebrata) in testis, left testis, right testis
CLIP2	232	ubiquitous	marker	cortical plate, C1 segment of cervical spinal cord, ganglionic eminence
N4BP3	178	broad	yes	lower esophagus mucosa, esophagus mucosa, endometrium epithelium
APBA2	131	ubiquitous	marker	superior frontal gyrus, right hemisphere of cerebellum, cerebellum
PEX16	281	ubiquitous	marker	prefrontal cortex, granulocyte, right lobe of liver

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CDC42BPA	2,908
APBA2	2,193
CDC25B	2,036
DRC11L	1,326
PEX16	1,231
CLIP2	1,059
CACNG4	1,055
PAPLN	888
FBXO17	676
N4BP3	551

Structural data

PDB: 2 · AlphaFold-only: 8 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CDC25B	P30305	19
CLIP2	Q9UDT6	2

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
FBXO17	Q96EF6	90.35
PEX16	Q9Y5Y5	83.07
DRC11L	A6NCM1	81.58
CDC42BPA	Q5VT25	75.69
PAPLN	O95428	67.18
N4BP3	O15049	65.88
CACNG4	Q9UBN1	65.80
APBA2	Q99767	59.74

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 40. Enrichment computed across 10 evidence-associated genes (6 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 6 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Presynaptic depolarization and calcium channel opening	1	158.6×	0.038	CACNG4
Neurodegenerative Diseases	1	146.4×	0.038	CDC25B
LGI-ADAM interactions	1	135.9×	0.038	CACNG4
Glutamate binding, activation of AMPA receptors and synaptic plasticity	1	126.9×	0.038	CACNG4
Phase 2 - plateau phase	1	126.9×	0.038	CACNG4
Defective Intrinsic Pathway for Apoptosis	1	126.9×	0.038	CDC25B
Diseases of programmed cell death	1	105.7×	0.038	CDC25B
Regulation of MITF-M-dependent genes involved in cell cycle and proliferation	1	95.2×	0.038	CDC25B
Trafficking of AMPA receptors	1	90.6×	0.038	CACNG4
Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer’s disease models	1	86.5×	0.038	CDC25B
Class I peroxisomal membrane protein import	1	86.5×	0.038	PEX16
Neuronal System	2	14.8×	0.038	CACNG4, APBA2
Phase 0 - rapid depolarisation	1	57.7×	0.053	CACNG4
Cyclin A/B1/B2 associated events during G2/M transition	1	51.4×	0.055	CDC25B
Protein-protein interactions at synapses	1	44.3×	0.056	APBA2
Cyclin A:Cdk2-associated events at S phase entry	1	44.3×	0.056	CDC25B
RHOJ GTPase cycle	1	33.4×	0.062	CDC42BPA
Neurexins and neuroligins	1	32.8×	0.062	APBA2
S Phase	1	30.2×	0.062	CDC25B
RHOQ GTPase cycle	1	30.2×	0.062	CDC42BPA
MITF-M-dependent gene expression	1	30.2×	0.062	CDC25B
Mitotic G2-G2/M phases	1	21.1×	0.081	CDC25B
G2/M Transition	1	21.1×	0.081	CDC25B
MITF-M-regulated melanocyte development	1	19.0×	0.086	CDC25B
Cardiac conduction	1	18.1×	0.086	CACNG4
Neurotransmitter receptors and postsynaptic signal transmission	1	16.7×	0.088	CACNG4
Developmental Biology	2	4.8×	0.088	CACNG4, CDC25B
Muscle contraction	1	12.9×	0.105	CACNG4
Transmission across Chemical Synapses	1	12.7×	0.105	CACNG4
CDC42 GTPase cycle	1	12.1×	0.107	CDC42BPA

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 10 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
ER-dependent peroxisome organization	1	1685.2×	0.012	PEX16
ER-dependent peroxisome localization	1	1685.2×	0.012	PEX16
peroxisome membrane biogenesis	1	561.7×	0.019	PEX16
positive regulation of G2/MI transition of meiotic cell cycle	1	561.7×	0.019	CDC25B
protein to membrane docking	1	337.0×	0.025	PEX16
protein import into peroxisome membrane	1	280.9×	0.025	PEX16
postsynaptic neurotransmitter receptor diffusion trapping	1	210.7×	0.025	CACNG4
female meiosis I	1	187.2×	0.025	CDC25B
protein targeting to peroxisome	1	168.5×	0.025	PEX16
regulation of AMPA receptor activity	1	168.5×	0.025	CACNG4
protein import into peroxisome matrix	1	140.4×	0.027	PEX16
microtubule severing	1	129.6×	0.027	DRC11L
glycoprotein catabolic process	1	105.3×	0.028	FBXO17
protein phosphorylation	2	13.6×	0.028	CDC25B, CDC42BPA
peroxisome organization	1	80.2×	0.035	PEX16
transmission of nerve impulse	1	64.8×	0.035	CACNG4
positive regulation of synaptic transmission, glutamatergic	1	62.4×	0.035	CACNG4
oocyte maturation	1	60.2×	0.035	CDC25B
positive regulation of G2/M transition of mitotic cell cycle	1	60.2×	0.035	CDC25B
response to cocaine	1	58.1×	0.035	CACNG4
actomyosin structure organization	1	56.2×	0.035	CDC42BPA
nervous system development	2	9.2×	0.036	N4BP3, APBA2
positive regulation of mitotic cell cycle	1	46.8×	0.038	CDC25B
presynaptic modulation of chemical synaptic transmission	1	45.5×	0.038	APBA2
positive regulation of cytokinesis	1	40.1×	0.041	CDC25B
SCF-dependent proteasomal ubiquitin-dependent protein catabolic process	1	37.5×	0.043	FBXO17
cytoplasmic microtubule organization	1	34.4×	0.045	CLIP2
G2/M transition of mitotic cell cycle	1	31.2×	0.047	CDC25B
ERAD pathway	1	18.1×	0.076	FBXO17
locomotory behavior	1	17.9×	0.076	APBA2

Therapeutics

Drugs indicated for this disease

No approved or late-stage (phase ≥3) drug is indicated for this disease; the following are in earlier-phase trials only.

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Etanercept.

Drug target analysis

Approved (phase 4): 3 · Phase ≥3: 3 · Phased (≥1): 3 · Undrugged: 7

Druggability breadth: 4 of 10 evidence-associated genes (40%) 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
CACNG4	NIMODIPINE
CDC25B	MENADIONE
CDC42BPA	VANDETANIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CDC42BPA	13	4
CDC25B	4	4
CACNG4	2	4
FBXO17	0	0
PAPLN	0	0
DRC11L	0	0
CLIP2	0	0
N4BP3	0	0
APBA2	0	0
PEX16	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
NIMODIPINE	4	CACNG4
TACRINE	4	CACNG4
MENADIONE	4	CDC25B
VANDETANIB	4	CDC42BPA
DASATINIB	4	CDC42BPA
ALVOCIDIB	3	CDC42BPA
LESTAURTINIB	3	CDC42BPA
BUPARVAQUONE	2	CDC25B
SODIUM TUNGSTATE	2	CDC25B
DORAMAPIMOD	2	CDC42BPA
FORETINIB	2	CDC42BPA
SAR-407899 FREE BASE	2	CDC42BPA
CENISERTIB	2	CDC42BPA
LAUROGUADINE	2	CDC42BPA
DECERNOTINIB	2	CDC42BPA
UCN-01	2	CDC42BPA
PLUMBAGIN	1	CDC25B
PF-00562271	1	CDC42BPA
RGB-286638	1	CDC42BPA

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
CDC42BPA	216	Binding:215, Functional:1
CDC25B	166	Binding:166
CACNG4	13	Binding:13
PEX16	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
CDC25B	3.1.3.48	protein-tyrosine-phosphatase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
CDC25B	166
CDC42BPA	216

Pharmacogenomics

Cohort genes with a PharmGKB record: 10; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

19 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)
NIMODIPINE	4	CACNG4
TACRINE	4	CACNG4
MENADIONE	4	CDC25B
VANDETANIB	4	CDC42BPA
DASATINIB	4	CDC42BPA
ALVOCIDIB	3	CDC42BPA
LESTAURTINIB	3	CDC42BPA
BUPARVAQUONE	2	CDC25B
SODIUM TUNGSTATE	2	CDC25B
DORAMAPIMOD	2	CDC42BPA
FORETINIB	2	CDC42BPA
SAR-407899 FREE BASE	2	CDC42BPA
CENISERTIB	2	CDC42BPA
LAUROGUADINE	2	CDC42BPA
DECERNOTINIB	2	CDC42BPA
UCN-01	2	CDC42BPA
PLUMBAGIN	1	CDC25B
PF-00562271	1	CDC42BPA
RGB-286638	1	CDC42BPA

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	3	CACNG4, CDC25B, CDC42BPA
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	1	PAPLN
E	Difficult family or no structure, no drug	6	FBXO17, DRC11L, CLIP2, N4BP3, APBA2, PEX16

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
FBXO17	0	—
PAPLN	0	—
DRC11L	0	—
CLIP2	0	—
N4BP3	0	—
APBA2	0	—
PEX16	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 6.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	3
PHASE2/PHASE3	1
PHASE1	1
EARLY_PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT06011889	PHASE2/PHASE3	RECRUITING	Study of the Efficacy and Safety of Etanercept Treatment in Patients With SAPHO Syndrome
NCT02544659	PHASE1	COMPLETED	Efficacy of Bisphosphonates in Patients With Synovitis, Acne, Pustulosis, Hyperostosis, and Osteitis (SAPHO) Syndrome
NCT04596462	EARLY_PHASE1	UNKNOWN	Characterizing SAPHO With 68Ga-FAPI PET/CT
NCT07081880	Not specified	RECRUITING	Study of the Pathophysiological Mechanisms Involved in the SAPHO Syndrome: Genetic Component and Immune Response
NCT07086599	Not specified	RECRUITING	Typological Study of Sleep Pathologies During Psoriatic Rheumatism and SAPHO Syndrome: Prospective Study Within the Paris Saint-Joseph Hospital Group
NCT01688219	Not specified	COMPLETED	Immune Response in the SAPHO Syndrome

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
PAMIDRONIC ACID	4	4
ETANERCEPT	4	1
FAPI GA-68	2	1

Cohort genes: CACNG4, CDC25B, CDC42BPA, FBXO17, PAPLN, DRC11L, CLIP2, N4BP3, APBA2, PEX16
Drugs: Pamidronic Acid, Etanercept