CIC-rearranged sarcoma

Summary

CIC-rearranged sarcoma (MONDO:0956989) is a cancer with 17 cohort genes (2 CIViC-evidence somatic drivers; 19 ClinVar predisposition records) and 3 clinical trials. Top therapeutic interventions include regorafenib, fludeoxyglucose f 18, and ifosfamide.

At a glance

• Classification: Cancer
• Cohort genes: 17
• ClinVar variants: 19
• Clinical trials: 3

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	CIC-rearranged sarcoma
Mondo ID	MONDO:0956989
DOID	DOID:0081250
NCIT	C120224
UMLS	C3899764
MedGen	859358
Is cancer (heuristic)	yes

Data availability: 19 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › cancer or benign tumor › neoplastic disease or syndrome › neoplasm › cancer › sarcoma › small cell sarcoma › EWSR1-negative small round cell tumor › CIC-rearranged sarcoma

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

19 retrieved; paginated sample, class counts are floors:

17 not provided, 1 benign, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
805966	NM_001393392.1(AKR1C2):c.666T>C (p.His222=)	AKR1C2	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
255466	NM_000173.7(GP1BA):c.1311_1349del (p.415_427SEPAPSPTTPEPT[2])	GP1BA	Benign	criteria provided, multiple submitters, no conflicts
805970	NM_001393982.1(ANKRD36C):c.1633+1G>A	ANKRD36C	not provided	no classification provided
805963	NM_005190.4(CCNC):c.346+77dup	CCNC	not provided	no classification provided
805974	NM_001892.6(CSNK1A1):c.*1105_*1108del	CSNK1A1	not provided	no classification provided
805979	NM_152450.3(FAM81A):c.651-3dup	FAM81A	not provided	no classification provided
805973	NM_004477.3(FRG1):c.317+1G>T	FRG1	not provided	no classification provided
805962	NM_003870.4(IQGAP1):c.650-14_650-13insA	IQGAP1	not provided	no classification provided
805977	NM_000670.5(ADH4):c.51dup (p.Ala18fs)	LOC100507053	not provided	no classification provided
805972	NM_002139.4(RBMX):c.866-2_866-1insTATGAGAGTTAT	LOC126863330	not provided	no classification provided
805967	NM_001079935.2(OR7E24):c.32dup (p.Leu12fs)	OR7E24	not provided	no classification provided
805971	NM_002568.4(PABPC1):c.*2-1_*2insCCACTGGTGTTCCAACTGTTTAAA	PABPC1	not provided	no classification provided
805964	NM_016131.5(RAB10):c.189-1G>T	RAB10	not provided	no classification provided
805975	NM_021239.3(RBM25):c.-16+6264dup	RBM25	not provided	no classification provided
805969	NM_002139.4(RBMX):c.-1del	RBMX	not provided	no classification provided
805965	NM_025235.4(TNKS2):c.1865dup (p.Asn622fs)	TNKS2	not provided	no classification provided
805978	NM_177987.3(TUBB8):c.843C>G (p.Tyr281Ter)	TUBB8	not provided	no classification provided
805968	NM_001009899.4(USF3):c.3047dup (p.Asn1016fs)	USF3	not provided	no classification provided
805976	NM_007153.3(ZNF208):c.3843G>C (p.Ter1281Tyr)	ZNF208	not provided	no classification provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 10 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
ZNF208	Act	ESCA
PABPC1	Act	BCC,DLBCLNOS,HCC,LUSC,PCM,UTUC,WDTC

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TUBB8	Orphanet:488191	Female infertility due to oocyte meiotic arrest
USF3	Orphanet:201	Cowden syndrome
AKR1C2	Orphanet:443087	46,XY difference of sex development due to testicular 17,20-desmolase deficiency
FRG1	Orphanet:269	Facioscapulohumeral dystrophy
GP1BA	Orphanet:140957	Autosomal dominant macrothrombocytopenia
GP1BA	Orphanet:274	Bernard-Soulier syndrome
GP1BA	Orphanet:52530	Pseudo-von Willebrand disease
GP1BA	Orphanet:853	Fetal and neonatal alloimmune thrombocytopenia
RBMX	Orphanet:3078	Severe X-linked intellectual disability, Gustavson type
RBMX	Orphanet:85286	X-linked intellectual disability, Shashi type

Cohort genes → proteins

17 cohort genes, 17 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	17

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
ZNF208	HGNC:12999	ENSG00000160321	O43345	Zinc finger protein 208	clinvar
TNKS2	HGNC:15677	ENSG00000107854	Q9H2K2	Poly [ADP-ribose] polymerase tankyrase-2	clinvar
CCNC	HGNC:1581	ENSG00000112237	P24863	Cyclin-C	clinvar
TUBB8	HGNC:20773	ENSG00000261456	Q3ZCM7	Tubulin beta-8 chain	clinvar
RBM25	HGNC:23244	ENSG00000119707	P49756	RNA-binding protein 25	clinvar
CSNK1A1	HGNC:2451	ENSG00000113712	P48729	Casein kinase I isoform alpha	clinvar
FAM81A	HGNC:28379	ENSG00000157470	Q8TBF8	Protein FAM81A	clinvar
USF3	HGNC:30494	ENSG00000176542	Q68DE3	Basic helix-loop-helix domain-containing protein USF3	clinvar
ANKRD36C	HGNC:32946	ENSG00000174501	Q5JPF3	Ankyrin repeat domain-containing protein 36C	clinvar
AKR1C2	HGNC:385	ENSG00000151632	P52895	Aldo-keto reductase family 1 member C2	clinvar
FRG1	HGNC:3954	ENSG00000109536	Q14331	Protein FRG1	clinvar
GP1BA	HGNC:4439	ENSG00000185245	P07359	Platelet glycoprotein Ib alpha chain	clinvar
IQGAP1	HGNC:6110	ENSG00000140575	P46940	Ras GTPase-activating-like protein IQGAP1	clinvar
OR7E24	HGNC:8396	ENSG00000237521	Q6IFN5	Olfactory receptor 7E24	clinvar
PABPC1	HGNC:8554	ENSG00000070756	P11940	Polyadenylate-binding protein 1	clinvar
RAB10	HGNC:9759	ENSG00000084733	P61026	Ras-related protein Rab-10	clinvar
RBMX	HGNC:9910	ENSG00000147274	P38159	RNA-binding motif protein, X chromosome	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ZNF208	Zinc finger protein 208	May be involved in transcriptional regulation.
TNKS2	Poly [ADP-ribose] polymerase tankyrase-2	Poly-ADP-ribosyltransferase involved in various processes such as Wnt signaling pathway, telomere length and vesicle trafficking.
CCNC	Cyclin-C	Component of the Mediator complex, a coactivator involved in regulated gene transcription of nearly all RNA polymerase II-dependent genes.
TUBB8	Tubulin beta-8 chain	Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers.
RBM25	RNA-binding protein 25	RNA-binding protein that acts as a regulator of alternative pre-mRNA splicing.
CSNK1A1	Casein kinase I isoform alpha	Casein kinases are operationally defined by their preferential utilization of acidic proteins such as caseins as substrates.
FAM81A	Protein FAM81A	Facilitates the interaction and assembly of proteins within the postsynaptic density by promoting the condensation of postsynaptic proteins via liquid-liquid phase separation.
USF3	Basic helix-loop-helix domain-containing protein USF3	Involved in the negative regulation of epithelial-mesenchymal transition, the process by which epithelial cells lose their polarity and adhesion properties to become mesenchymal cells with enhanced migration and invasive properties.
AKR1C2	Aldo-keto reductase family 1 member C2	Cytosolic aldo-keto reductase that catalyzes NADPH-dependent reduction of ketosteroids to hydroxysteroids.
FRG1	Protein FRG1	Binds to mRNA in a sequence-independent manner.
GP1BA	Platelet glycoprotein Ib alpha chain	GP-Ib, a surface membrane protein of platelets, participates in the formation of platelet plugs by binding to the A1 domain of vWF, which is already bound to the subendothelium.
IQGAP1	Ras GTPase-activating-like protein IQGAP1	Plays a crucial role in regulating the dynamics and assembly of the actin cytoskeleton.
OR7E24	Olfactory receptor 7E24	Odorant receptor.
PABPC1	Polyadenylate-binding protein 1	Binds the poly(A) tail of mRNA, including that of its own transcript, and regulates processes of mRNA metabolism such as pre-mRNA splicing and mRNA stability.
RAB10	Ras-related protein Rab-10	The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes.
RBMX	RNA-binding motif protein, X chromosome	RNA-binding protein that plays several role in the regulation of pre- and post-transcriptional processes.

Protein-family classification

Druggable: 3 · Difficult: 5 · Unknown: 9 · Druggable fraction: 0.18

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	3	3.0×	0.429
Kinase	1	1.6×	0.773
GPCR	1	1.4×	0.773
Transcription factor	2	1.0×	0.773
Other/Unknown	9	0.9×	0.773
Enzyme (other)	1	0.7×	0.773

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ZNF208	Transcription factor	no		KRAB, Znf_C2H2_type, KRAB_dom_sf
TNKS2	Scaffold/PPI	no		SAM, Ankyrin_rpt, Poly(ADP-ribose)pol_cat_dom
CCNC	Other/Unknown	no		Cyclin_N, Cyclin-like_dom, Cyclin_C_2
TUBB8	Other/Unknown	no		Tubulin, Beta_tubulin, Tubulin_FtsZ_GTPase
RBM25	Other/Unknown	no		RRM_dom, PWI_dom, Nucleotide-bd_a/b_plait_sf
CSNK1A1	Kinase	yes	2.7.11.1	Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf
FAM81A	Other/Unknown	no		FAM81
USF3	Transcription factor	no		bHLH_dom, HLH_DNA-bd_sf, USF3_bHLH
ANKRD36C	Scaffold/PPI	no		Ankyrin_rpt, Ankyrin_rpt-contain_sf, CC144C-like_CC_dom
AKR1C2	Enzyme (other)	yes	1.1.1.213	Aldo/ket_reductase_CS, AKR, NADP_OxRdtase_dom
FRG1	Other/Unknown	no		Actin-crosslinking, FRG1
GP1BA	Other/Unknown	no		LRRNT, Cys-rich_flank_reg_C, Leu-rich_rpt
IQGAP1	Scaffold/PPI	no		IQ_motif_EF-hand-BS, IQGAP_helical, WW_dom
OR7E24	GPCR	yes		GPCR_Rhodpsn, Olfact_rcpt, GPCR_Rhodpsn_7TM
PABPC1	Other/Unknown	no		RRM_dom, PABP_HYD_C, RRM_euk-type
RAB10	Other/Unknown	no		Small_GTPase, Small_GTP-bd, P-loop_NTPase
RBMX	Other/Unknown	no		RRM_dom, RRM_euk-type, RBM1CTR

Expression context

Cohort genes with no expression data: 0.

16 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)	1
broad (>20)	16
unknown	0

Top tissues across cohort

Tissue	Cohort genes
cortical plate	4
calcaneal tendon	3
male germ line stem cell (sensu Vertebrata) in testis	2
primordial germ cell in gonad	2
secondary oocyte	2
parotid gland	2
sural nerve	2
ganglionic eminence	2
monocyte	2
buccal mucosa cell	1
skeletal muscle tissue of biceps brachii	1
skeletal muscle tissue of rectus abdominis	1
corpus epididymis	1
oral cavity	1
medial globus pallidus	1
tendon of biceps brachii	1
adrenal tissue	1
stromal cell of endometrium	1
Brodmann (1909) area 9	1
prefrontal cortex	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ZNF208	178	broad	marker	buccal mucosa cell, primordial germ cell in gonad, male germ line stem cell (sensu Vertebrata) in testis
TNKS2	285	ubiquitous	marker	skeletal muscle tissue of rectus abdominis, skeletal muscle tissue of biceps brachii, secondary oocyte
CCNC	294	ubiquitous	marker	parotid gland, oral cavity, corpus epididymis
TUBB8	107		marker	primordial germ cell in gonad, male germ line stem cell (sensu Vertebrata) in testis, cortical plate
RBM25	295	ubiquitous	marker	tendon of biceps brachii, sural nerve, medial globus pallidus
CSNK1A1	294	ubiquitous	marker	stromal cell of endometrium, cortical plate, adrenal tissue
FAM81A	168	ubiquitous	marker	cortical plate, Brodmann (1909) area 9, prefrontal cortex
USF3	254	ubiquitous	yes	kidney epithelium, deltoid, tibialis anterior
ANKRD36C	134	broad	marker	corpus callosum, calcaneal tendon, sural nerve
AKR1C2	159	ubiquitous	marker	islet of Langerhans, right lobe of liver, olfactory segment of nasal mucosa
FRG1	146	ubiquitous	marker	calcaneal tendon, ganglionic eminence, embryo
GP1BA	186	tissue_specific	marker	monocyte, mononuclear cell, leukocyte
IQGAP1	299	ubiquitous	marker	calcaneal tendon, colonic epithelium, monocyte
OR7E24	16		marker	oocyte, secondary oocyte, frontal pole
PABPC1	288	ubiquitous	marker	parotid gland, pylorus, esophagus squamous epithelium
RAB10	264	ubiquitous	marker	epithelial cell of pancreas, ileal mucosa, pancreatic ductal cell
RBMX	255	ubiquitous	marker	ventricular zone, ganglionic eminence, cortical plate

Protein interactions among cohort

Intra-cohort edges: 2.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PABPC1	5,523
TUBB8	4,732
RBMX	4,460
IQGAP1	4,386
CCNC	3,374
RBM25	3,240
CSNK1A1	3,015
RAB10	2,901
TNKS2	2,722
GP1BA	1,703

Intra-cohort edges

A	B	Sources
ANKRD36C	FRG1	string_interaction
OR7E24	USF3	string_interaction

Structural data

PDB: 11 · AlphaFold-only: 6 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TNKS2	Q9H2K2	197
CCNC	P24863	36
PABPC1	P11940	30
GP1BA	P07359	22
AKR1C2	P52895	16
CSNK1A1	P48729	5
IQGAP1	P46940	5
RAB10	P61026	4
FRG1	Q14331	3
RBMX	P38159	2
RBM25	P49756	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
TUBB8	Q3ZCM7	91.99
OR7E24	Q6IFN5	84.78
FAM81A	Q8TBF8	82.30
ZNF208	O43345	70.22
ANKRD36C	Q5JPF3	52.44
USF3	Q68DE3	36.98

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 206. Enrichment computed across 17 evidence-associated genes (13 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 13 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
XAV939 stabilizes AXIN	1	439.2×	0.113	TNKS2
Defective F9 activation	1	146.4×	0.113	GP1BA
Enhanced binding of GP1BA variant to VWF multimer:collagen	1	125.5×	0.113	GP1BA
Defective binding of VWF variant to GPIb:IX:V	1	125.5×	0.113	GP1BA
FXIIa, PKa-dependent activation of coagulation pathway	1	87.8×	0.113	GP1BA
Signaling by AXIN mutants	1	79.9×	0.113	CSNK1A1
Signaling by CTNNB1 phospho-site mutants	1	79.9×	0.113	CSNK1A1
Signaling by APC mutants	1	79.9×	0.113	CSNK1A1
Signaling by AMER1 mutants	1	79.9×	0.113	CSNK1A1
GP1b-IX-V activation signalling	1	73.2×	0.113	GP1BA
Z-decay: degradation of maternal mRNAs by zygotically expressed factors	1	73.2×	0.113	PABPC1
Synthesis of bile acids and bile salts via 24-hydroxycholesterol	1	67.6×	0.113	AKR1C2
APC truncation mutants have impaired AXIN binding	1	62.8×	0.113	CSNK1A1
AXIN missense mutants destabilize the destruction complex	1	62.8×	0.113	CSNK1A1
Truncations of AMER1 destabilize the destruction complex	1	62.8×	0.113	CSNK1A1
Synthesis of bile acids and bile salts via 27-hydroxycholesterol	1	58.6×	0.113	AKR1C2
Signaling by GSK3beta mutants	1	58.6×	0.113	CSNK1A1
CTNNB1 S33 mutants aren’t phosphorylated	1	58.6×	0.113	CSNK1A1
CTNNB1 S37 mutants aren’t phosphorylated	1	58.6×	0.113	CSNK1A1
CTNNB1 S45 mutants aren’t phosphorylated	1	58.6×	0.113	CSNK1A1
CTNNB1 T41 mutants aren’t phosphorylated	1	58.6×	0.113	CSNK1A1
Maturation of nucleoprotein	1	58.6×	0.113	CSNK1A1
RHO GTPases activate IQGAPs	2	53.2×	0.113	TUBB8, IQGAP1
Translocation of SLC2A4 (GLUT4) to the plasma membrane	2	23.7×	0.113	TUBB8, RAB10
TCF dependent signaling in response to WNT	2	18.1×	0.113	TNKS2, CSNK1A1
mRNA Polyadenylation	2	13.5×	0.113	RBM25, RBMX
Diseases of signal transduction by growth factor receptors and second messengers	3	13.1×	0.113	CCNC, CSNK1A1, IQGAP1
RHO GTPase Effectors	2	10.5×	0.113	TUBB8, IQGAP1
Viral Infection Pathways	3	7.1×	0.113	CCNC, TUBB8, CSNK1A1
Infectious disease	3	5.7×	0.113	CCNC, TUBB8, CSNK1A1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 15 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
establishment of protein localization to endoplasmic reticulum membrane	1	374.5×	0.039	RAB10
protein localization to basolateral plasma membrane	1	374.5×	0.039	RAB10
mitotic actomyosin contractile ring assembly actin filament organization	1	374.5×	0.039	IQGAP1
negative regulation of motile cilium assembly	1	374.5×	0.039	RAB10
negative regulation of dephosphorylation	1	280.9×	0.039	IQGAP1
G0 to G1 transition	1	280.9×	0.039	CCNC
establishment of neuroblast polarity	1	280.9×	0.039	RAB10
cellular response to jasmonic acid stimulus	1	280.9×	0.039	AKR1C2
positive regulation of telomere capping	1	224.7×	0.039	TNKS2
polarized epithelial cell differentiation	1	187.2×	0.039	RAB10
cellular response to prostaglandin D stimulus	1	160.5×	0.039	AKR1C2
blood coagulation, intrinsic pathway	1	140.4×	0.039	GP1BA
cellular response to nutrient	1	140.4×	0.039	CSNK1A1
protein poly-ADP-ribosylation	1	140.4×	0.039	TNKS2
caveola assembly	1	140.4×	0.039	IQGAP1
spindle assembly involved in female meiosis	1	124.8×	0.039	TUBB8
regulation of blood coagulation	1	124.8×	0.039	GP1BA
establishment of protein localization to membrane	1	124.8×	0.039	RAB10
negative regulation of nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay	1	124.8×	0.039	PABPC1
negative regulation of nuclear-transcribed mRNA catabolic process, nonsense-mediated decay	1	124.8×	0.039	PABPC1
progesterone metabolic process	1	112.3×	0.039	AKR1C2
daunorubicin metabolic process	1	102.1×	0.039	AKR1C2
protein localization to chromosome, telomeric region	1	102.1×	0.039	TNKS2
protein auto-ADP-ribosylation	1	102.1×	0.039	TNKS2
podocyte development	1	102.1×	0.039	IQGAP1
regulation of alternative mRNA splicing, via spliceosome	2	32.6×	0.039	RBM25, RBMX
mRNA splicing, via spliceosome	3	18.3×	0.039	FRG1, PABPC1, RBMX
Wnt signaling pathway	2	13.3×	0.039	TNKS2, CSNK1A1
CRD-mediated mRNA stabilization	1	93.6×	0.039	PABPC1
negative regulation of telomere maintenance via telomere lengthening	1	93.6×	0.039	TNKS2

Therapeutics

Drug target analysis

Approved (phase 4): 6 · Phase ≥3: 7 · Phased (≥1): 10 · Undrugged: 7

Druggability breadth: 12 of 17 evidence-associated genes (71%) 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
TNKS2	NIRAPARIB
CCNC	SORAFENIB
TUBB8	COLCHICINE
CSNK1A1	PYRVINIUM
AKR1C2	DIAZEPAM
PABPC1	OXCARBAZEPINE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CSNK1A1	29	4
TUBB8	21	4
TNKS2	12	4
AKR1C2	11	4
PABPC1	6	4
CCNC	4	4
RBM25	1	2
FRG1	1	2
IQGAP1	1	2
RAB10	1	3

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
NIRAPARIB	4	TNKS2
RUCAPARIB	4	TNKS2
OLAPARIB	4	TNKS2
SUNITINIB	4	CSNK1A1, TNKS2
MIDOSTAURIN	4	TNKS2
SORAFENIB	4	CCNC, CSNK1A1
COLCHICINE	4	TUBB8
VINBLASTINE	4	TUBB8
LEVOFLOXACIN ANHYDROUS	4	TUBB8
DOCETAXEL	4	TUBB8
NOSCAPINE	4	TUBB8
VINBLASTINE SULFATE	4	TUBB8
PACLITAXEL	4	TUBB8
LEVOFLOXACIN	4	TUBB8
VINORELBINE	4	TUBB8
TIRBANIBULIN	4	TUBB8
PODOFILOX	4	TUBB8
VINCRISTINE	4	TUBB8
DOCETAXEL ANHYDROUS	4	TUBB8
PYRVINIUM	4	CSNK1A1
RUXOLITINIB	4	CSNK1A1
BOSUTINIB	4	CSNK1A1
ENCORAFENIB	4	CSNK1A1
QUIZARTINIB	4	CSNK1A1
DIAZEPAM	4	AKR1C2
NAPROXEN	4	AKR1C2
DEXIBUPROFEN	4	AKR1C2
BERBERINE	4	AKR1C2
MECLOFENAMIC ACID	4	AKR1C2
FLURBIPROFEN	4	AKR1C2

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 2.

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

Symbol	Assays	Type breakdown
TUBB8	1,757	Binding:1717, Functional:34, ADMET:6
CSNK1A1	518	Binding:514, Functional:4
CCNC	226	Binding:226
TNKS2	225	Binding:222, Functional:3
AKR1C2	80	Binding:62, ADMET:18
PABPC1	12	Binding:8, Functional:4
IQGAP1	9	Binding:9
RBM25	8	Binding:8
FRG1	6	Binding:6
RBMX	6	Binding:6
RAB10	2	Binding:2

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
CSNK1A1	2.7.11.1	non-specific serine/threonine protein kinase
AKR1C2	1.1.1.213, 1.1.1.357, 1.1.1.50, 1.3.1.20	3alpha-hydroxysteroid 3-dehydrogenase (Re-specific), 3alpha-hydroxysteroid 3-dehydrogenase, 3alpha-hydroxysteroid 3-dehydrogenase (Si-specific), trans-1,2-dihydrobenzene-1,2-diol dehydrogenase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
TNKS2	225
CCNC	226
TUBB8	1,757
CSNK1A1	518

Pharmacogenomics

Cohort genes with a PharmGKB record: 17; with CPIC/DPWG dosing guidelines: 0.

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

Drug repurposing candidates

30 approved/phased drugs hit cohort targets but don’t yet appear in disease-level clinical trials. Target-inhibition rationale is strongest for cancer driver genes; a bioactivity hit is a screening signal, not a treatment claim.

Compound	Max phase	Cohort target (bioactivity)
NIRAPARIB	4	TNKS2
RUCAPARIB	4	TNKS2
OLAPARIB	4	TNKS2
SUNITINIB	4	CSNK1A1, TNKS2
MIDOSTAURIN	4	TNKS2
SORAFENIB	4	CCNC, CSNK1A1
COLCHICINE	4	TUBB8
VINBLASTINE	4	TUBB8
LEVOFLOXACIN ANHYDROUS	4	TUBB8
DOCETAXEL	4	TUBB8
NOSCAPINE	4	TUBB8
VINBLASTINE SULFATE	4	TUBB8
PACLITAXEL	4	TUBB8
LEVOFLOXACIN	4	TUBB8
VINORELBINE	4	TUBB8
TIRBANIBULIN	4	TUBB8
PODOFILOX	4	TUBB8
VINCRISTINE	4	TUBB8
DOCETAXEL ANHYDROUS	4	TUBB8
PYRVINIUM	4	CSNK1A1
RUXOLITINIB	4	CSNK1A1
BOSUTINIB	4	CSNK1A1
ENCORAFENIB	4	CSNK1A1
QUIZARTINIB	4	CSNK1A1
DIAZEPAM	4	AKR1C2
NAPROXEN	4	AKR1C2
DEXIBUPROFEN	4	AKR1C2
BERBERINE	4	AKR1C2
MECLOFENAMIC ACID	4	AKR1C2
FLURBIPROFEN	4	AKR1C2

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	6	TNKS2, CCNC, TUBB8, CSNK1A1, AKR1C2, PABPC1
B	Phased (≥1) drug, not yet approved	4	RBM25, FRG1, IQGAP1, RAB10
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	1	OR7E24
E	Difficult family or no structure, no drug	6	ZNF208, FAM81A, USF3, ANKRD36C, GP1BA, RBMX

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)
ZNF208	0	—
FAM81A	0	—
USF3	0	—
ANKRD36C	0	—
GP1BA	0	—
OR7E24	0	—
RBMX	6	—

Clinical trials & evidence

Clinical trials

Clinical trials: 3.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2/PHASE3	1
PHASE2	1
PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT06820957	PHASE2/PHASE3	ACTIVE_NOT_RECRUITING	Testing a New Combination of Anti-cancer Drugs in Patients Newly Diagnosed With Ewing Sarcoma Who Have Cancer That Has Spread to Other Parts of the Body
NCT02389244	PHASE2	ACTIVE_NOT_RECRUITING	A Phase II Study Evaluating Efficacy and Safety of Regorafenib in Patients With Metastatic Bone Sarcomas
NCT06414434	PHASE1	ACTIVE_NOT_RECRUITING	BTX-A51 in Patients With Liposarcoma or CIC-rearranged Sarcoma

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
REGORAFENIB	4	2
FLUDEOXYGLUCOSE F 18	4	1
IFOSFAMIDE	4	1
BTX-A51	1	1
CHEMBL541887	0	1