Neuroblastoma

Summary

Neuroblastoma (MONDO:0005072) is a disease (an umbrella term covering 7 Mondo subtypes) with 66 cohort genes (119 GWAS associations across 13 studies) and 582 clinical trials. The dominant Reactome pathway is Glucuronidation (5 cohort genes). Molecularly, ALK R1275Q confers sensitivity to Crizotinib in Neuroblastoma (CIViC Level B); 23 further subtype–drug associations are mapped below. Top therapeutic interventions include irinotecan hydrochloride, isotretinoin, and dinutuximab.

At a glance

• Prevalence: 1-5 / 10 000 (Europe) [Orphanet-validated]
• Umbrella term: 7 Mondo subtypes
• Cohort genes: 66
• GWAS associations: 119
• ClinVar variants: 221
• Phenotypes (HPO): 34
• Clinical trials: 582
• Precision-medicine evidence (CIViC): 24 subtype–drug associations

Clinical features

Epidemiology

Prevalence records

5 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	1-5 / 10 000	11	Europe	Validated
Prevalence at birth	1-9 / 100 000	2.5	United States	Validated
Prevalence at birth	1-5 / 10 000	14	Germany	Validated
Annual incidence	1-9 / 100 000	1.26	Worldwide	Not yet validated
Prevalence at birth	1-9 / 100 000	5.8	Europe	Not yet validated

Signs & symptoms

Clinical features (HPO)

34 HPO clinical features (Orphanet curated; top 34 by frequency):

HPO ID	Term	Frequency
HP:0003006	Neuroblastoma	Very frequent (80-99%)
HP:0004375	Neoplasm of the nervous system	Very frequent (80-99%)
HP:0011976	Elevated urinary catecholamines	Very frequent (80-99%)
HP:0001824	Weight loss	Frequent (30-79%)
HP:0001873	Thrombocytopenia	Frequent (30-79%)
HP:0001903	Anemia	Frequent (30-79%)
HP:0001945	Fever	Frequent (30-79%)
HP:0002028	Chronic diarrhea	Frequent (30-79%)
HP:0002716	Lymphadenopathy	Frequent (30-79%)
HP:0003270	Abdominal distention	Frequent (30-79%)
HP:0003334	Elevated circulating catecholamine level	Frequent (30-79%)
HP:0012378	Fatigue	Frequent (30-79%)
HP:0031500	Abdominal mass	Frequent (30-79%)
HP:0000520	Proptosis	Occasional (5-29%)
HP:0000737	Irritability	Occasional (5-29%)
HP:0001017	Anemic pallor	Occasional (5-29%)
HP:0001482	Subcutaneous nodule	Occasional (5-29%)
HP:0001892	Abnormal bleeding	Occasional (5-29%)
HP:0001928	Abnormality of coagulation	Occasional (5-29%)
HP:0002098	Respiratory distress	Occasional (5-29%)
HP:0002176	Spinal cord compression	Occasional (5-29%)
HP:0002277	Horner syndrome	Occasional (5-29%)
HP:0002653	Bone pain	Occasional (5-29%)
HP:0002756	Pathologic fracture	Occasional (5-29%)
HP:0003281	Increased circulating ferritin concentration	Occasional (5-29%)
HP:0011977	Elevated urinary homovanillic acid	Occasional (5-29%)
HP:0011978	Elevated urinary vanillylmandelic acid	Occasional (5-29%)
HP:0025435	Increased circulating lactate dehydrogenase concentration	Occasional (5-29%)
HP:0031955	Antalgic gait	Occasional (5-29%)
HP:0000822	Hypertension	Very rare (<1-4%)
HP:0001251	Ataxia	Very rare (<1-4%)
HP:0001336	Myoclonus	Very rare (<1-4%)
HP:0010543	Opsoclonus	Very rare (<1-4%)
HP:0025553	Periorbital ecchymosis with tarsal plate sparing	Very rare (<1-4%)

Identifiers

Disease identifiers

Field	Value
Canonical name	neuroblastoma
Mondo ID	MONDO:0005072
EFO	EFO:0000621
MeSH	D009447
Orphanet	635
DOID	DOID:769
NCIT	C3270
SNOMED CT	432328008
UMLS	C0027819
MedGen	18012
GARD	0007185
MedDRA	10029260
Is cancer (heuristic)	no

Also known as: NB · neural Crest tumor, malignant · neuroblastoma · neuroblastoma (Schwannian Stroma-poor) · neuroblastoma, malignant

Data availability: 221 ClinVar variants · 119 GWAS associations (13 studies) · 673 cell lines · 28 intOGen driver records.

Disease family

An umbrella term covering 7 Mondo subtypes.

Classification path: disease › human disease › disease by etiologic mechanism › cancer or benign tumor › neoplastic disease or syndrome › neoplasm › embryonal neoplasm › primitive neuroectodermal tumor › neuroblastic tumor › neuroblastoma

Related subtypes (2): ganglioneuroma, ganglioneuroblastoma

Subtypes (7): retroperitoneal neuroblastoma, mediastinum neuroblastoma, extracranial neuroblastoma, differentiating neuroblastoma, cerebral neuroblastoma, dopaminergic neuroblastoma, retinal neuroblastoma

Genetics & variants

GWAS landscape

119 GWAS associations across 13 studies. Top hits map to 41 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs76015112	8e-23	RPTN	?	0.3
rs148828689	4e-18	MRPS18B	?	7.8
rs6435862	9e-18	BARD1	G	1.68
rs117249618	3e-17	LRRC45	?	7.8
rs4712653	8e-17	CASC15	C	1.4
rs117674897	2e-16	KANSL1L	?	6.1
rs2168101	3e-16	LMO1	C	1.42
rs110419	5e-16	LMO1	A	1.34
rs114591848	5e-16	ARHGEF40	?	7
rs9295536	8e-16	CASC15	A	1.36
rs4712656	8e-16	NBAT1, CASC15	C	1.37
rs6939340	9e-15	NBAT1, CASC15	G	1.37
rs77226427	1e-14	IL15RA	?	3.7
rs7587476	4e-14	BARD1	T	1.37
rs17487792	6e-14	BARD1	T	2.01
rs2886644	6e-14	L1TD1	?	3.5
rs57677160	7e-14	ANO7	?	6
rs4925229	8e-14	LAMA5	?	3.9
rs72990858	1e-13	NPM1P10 - HACE1	G	1.69
rs62621389	2e-13	OR7G2	?	5.3
rs3768716	5e-13	BARD1	C	1.39
rs3796727	1e-12	GPR78, CPZ	A	1.3
rs9745545	1e-12	SPIRE2	C	1.13
rs10737958	7e-12	PARP8	?	2
rs6441201	1e-11	RSRC1	A	1.23
rs4336470	3e-11	HACE1	C	1.26
rs58430496	3e-11	SNHG31	T	1.36
rs32396	5e-11	PARP8	?	2
rs77538589	1e-10	SALL4	?	3.3
rs10895322	3e-10	MMP20	G	2.76

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST010152	Avitabile M	2019	2,101	27,405	Neural crest-derived tumor neuroblastoma and melanoma share 1p13.2 as susceptibility locus that shows a long-range interaction with the SLC16A1 gene.
GCST004510	McDaniel LD	2017	2,101	4,202	Common variants upstream of MLF1 at 3q25 and within CPZ at 4p16 associated with neuroblastoma.
GCST001660	Diskin SJ	2012	2,101	4,202	Common variation at 6q16 within HACE1 and LIN28B influences susceptibility to neuroblastoma.
GCST000901	Wang K	2010	1,627	3,254	Integrative genomics identifies LMO1 as a neuroblastoma oncogene.
GCST000188	Maris JM	2008	1,032	2,043	Chromosome 6p22 locus associated with clinically aggressive neuroblastoma.
GCST90094905	Testori A	2022	629	2,990	Genetic analysis in African American children supports ancestry specific neuroblastoma susceptibility.
GCST000384	Capasso M	2009	397	2,043	Common variations in BARD1 influence susceptibility to high-risk neuroblastoma.
GCST011053	Bae JS	2020	296	1,000	Genome-Wide Association Study for the Identification of Novel Genetic Variants Associated with the Risk of Neuroblastoma in Korean Children.
GCST004885	Chang X	2017	260	5,109	Common variants in MMP20 at 11q22.2 predispose to 11q deletion and neuroblastoma risk.
GCST90094906	Testori A	2022	254	2,990	Genetic analysis in African American children supports ancestry specific neuroblastoma susceptibility.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	11
Tier 2: splice/UTR	0
Tier 3: regulatory	1
Tier 4: intronic/intergenic	38

MAF distribution

Bucket	Variants
common (>=0.05)	40
low_freq (0.01-0.05)	2
rare (<0.01)	0
unknown	8

Functional consequences

Consequence	Count
intron_variant	34
missense_variant	10
non_coding_transcript_exon_variant	2
stop_gained	1
intergenic_variant	1
unknown	1
regulatory_region_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs76015112	1	152156618	A>G,T	0.05	missense_variant	RPTN	8e-23	Tier 1: coding
rs148828689	6	30625751	C>G,T		missense_variant	MRPS18B	4e-18	Tier 1: coding
rs6435862	2	214807822	G>A,C,T	0.29	intron_variant	BARD1	9e-18	Tier 4: intronic/intergenic
rs117249618	17	82029625	G>A,T		missense_variant	LRRC45	3e-17	Tier 1: coding
rs4712653	6	22125735	T>A,C,G	0.46	intron_variant	CASC15	8e-17	Tier 4: intronic/intergenic
rs117674897	2	210023010	T>C		missense_variant	KANSL1L	2e-16	Tier 1: coding
rs2168101	11	8233861	C>A	0.24	intron_variant	LMO1	3e-16	Tier 4: intronic/intergenic
rs110419	11	8231306	A>G,T	0.49	intron_variant	LMO1	5e-16	Tier 4: intronic/intergenic
rs114591848	14	21082053	G>A		missense_variant	ARHGEF40	5e-16	Tier 1: coding
rs9295536	6	22131700	C>A,G	0.43	intron_variant	CASC15	8e-16	Tier 4: intronic/intergenic
rs4712656	6	22136033	G>A,C,T	0.447	non_coding_transcript_exon_variant	NBAT1, CASC15	8e-16	Tier 4: intronic/intergenic
rs6939340	6	22139775	A>G	0.5	intron_variant	NBAT1, CASC15	9e-15	Tier 4: intronic/intergenic
rs77226427	10	5960555	G>A,T		stop_gained	IL15RA	1e-14	Tier 1: coding
rs7587476	2	214789163	T>A,C	0.246	intron_variant	BARD1	4e-14	Tier 4: intronic/intergenic
rs17487792	2	214778776	C>G,T	0.05	intron_variant	BARD1	6e-14	Tier 4: intronic/intergenic
rs2886644	1	62210612	C>G,T	0.05	missense_variant	L1TD1	6e-14	Tier 1: coding
rs57677160	2	241209595	C>A,T	0.05	missense_variant	ANO7	7e-14	Tier 1: coding
rs4925229	20	62346587	T>C	0.05	missense_variant	LAMA5	8e-14	Tier 1: coding
rs72990858	6	104699909	G>A	0.092	intergenic_variant	NPM1P10 - HACE1	1e-13	Tier 4: intronic/intergenic
rs62621389	19	9102975	C>T	0.05	missense_variant	OR7G2	2e-13	Tier 1: coding
rs3768716	2	214771070	T>A,C,G	0.23	intron_variant	BARD1	5e-13	Tier 4: intronic/intergenic
rs3796727	4	8611299	G>A,C	0.3	intron_variant	GPR78, CPZ	1e-12	Tier 4: intronic/intergenic
rs9745545	16	89846049	A>C,G,T	0.328	intron_variant	SPIRE2	1e-12	Tier 4: intronic/intergenic
rs10737958	5	50727540	C>A,G	0.05	intron_variant	PARP8	7e-12	Tier 4: intronic/intergenic
rs6441201	3	158460535	G>A,C	0.47	intron_variant	RSRC1	1e-11	Tier 4: intronic/intergenic
rs4336470	6	104732910	C>T	0.35	intron_variant	HACE1	3e-11	Tier 4: intronic/intergenic
rs58430496	2	214834723	C>T	0.247	intron_variant	SNHG31	3e-11	Tier 4: intronic/intergenic
rs32396	5	50810605	G>A,C	0.05	intron_variant	PARP8	5e-11	Tier 4: intronic/intergenic
rs77538589	20	51792134	C>T		missense_variant	SALL4	1e-10	Tier 1: coding
rs10895322	11	102599525	A>G	0.057	intron_variant	MMP20	3e-10	Tier 4: intronic/intergenic

ClinVar germline variants

221 retrieved; paginated sample, class counts are floors:

89 uncertain significance, 45 benign, 42 conflicting classifications of pathogenicity, 18 likely benign, 17 benign/likely benign, 7 other, 2 pathogenic, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
545115	NM_004304.5(ALK):c.3512T>C (p.Ile1171Thr)	ALK	Pathogenic	no assertion criteria provided
545114	NM_000135.4(FANCA):c.4261-2A>C	FANCA	Pathogenic	criteria provided, multiple submitters, no conflicts
590848	NM_003072.5(SMARCA4):c.535C>T (p.Gln179Ter)	SMARCA4	Likely pathogenic	criteria provided, single submitter
38194	NM_000059.4(BRCA2):c.8918G>A (p.Arg2973His)	BRCA2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
438754	NM_000059.4(BRCA2):c.1075G>A (p.Glu359Lys)	BRCA2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
545113	NM_000135.4(FANCA):c.2728C>T (p.Leu910Phe)	FANCA	Conflicting classifications of pathogenicity	no assertion criteria provided
155750	NM_001365951.3(KIF1B):c.4211T>C (p.Val1404Ala)	KIF1B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
196788	NM_001365951.3(KIF1B):c.3645G>A (p.Pro1215=)	KIF1B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
291464	NM_001365951.3(KIF1B):c.107-8T>A	KIF1B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
291465	NM_001365951.3(KIF1B):c.146C>A (p.Ser49Tyr)	KIF1B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
291469	NM_001365951.3(KIF1B):c.364-15A>G	KIF1B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
291470	NM_001365951.3(KIF1B):c.364-10A>G	KIF1B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
291472	NM_001365951.3(KIF1B):c.721-15A>G	KIF1B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
291520	NM_001365951.3(KIF1B):c.1341A>G (p.Ser447=)	KIF1B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
291521	NM_001365951.3(KIF1B):c.1360T>C (p.Leu454=)	KIF1B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
291552	NM_001365951.3(KIF1B):c.1955C>T (p.Thr652Ile)	KIF1B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
291564	NM_001365951.3(KIF1B):c.2985C>T (p.Ile995=)	KIF1B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
291565	NM_001365951.3(KIF1B):c.3129+11G>T	KIF1B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
291569	NM_001365951.3(KIF1B):c.3423-15A>T	KIF1B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
291570	NM_001365951.3(KIF1B):c.3456G>A (p.Thr1152=)	KIF1B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
291572	NM_001365951.3(KIF1B):c.3654A>G (p.Arg1218=)	KIF1B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
291578	NM_001365951.3(KIF1B):c.4155G>T (p.Leu1385Phe)	KIF1B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
291579	NM_001365951.3(KIF1B):c.4179T>C (p.His1393=)	KIF1B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
291581	NM_001365951.3(KIF1B):c.4683C>T (p.Ser1561=)	KIF1B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
291582	NM_001365951.3(KIF1B):c.4820G>A (p.Cys1607Tyr)	KIF1B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
291584	NM_001365951.3(KIF1B):c.5238C>T (p.Asn1746=)	KIF1B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
291601	NM_001365951.3(KIF1B):c.*839C>T	KIF1B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
291620	NM_001365951.3(KIF1B):c.*2268C>T	KIF1B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
291645	NM_001365951.3(KIF1B):c.*3639T>C	KIF1B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
4660	NM_001365951.3(KIF1B):c.2618C>T (p.Thr873Ile)	KIF1B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 153 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 3

Dual-evidence genes (GWAS + Mendelian — highest-confidence targets)

Gene	HGNC	Evidence routes
HACE1	HACE1	GWAS, Orphanet
LIN28B	LIN28B	GWAS, Orphanet
LMO1	LMO1	GWAS, Orphanet

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ALK	Orphanet:146	Differentiated thyroid carcinoma
ALK	Orphanet:178342	Inflammatory myofibroblastic tumor
ALK	Orphanet:251877	Ganglioneuroblastoma
ALK	Orphanet:251992	Ganglioneuroma
ALK	Orphanet:300895	ALK-positive anaplastic large cell lymphoma
ALK	Orphanet:364043	ALK-positive large B-cell lymphoma
ALK	Orphanet:626	Large/giant congenital melanocytic nevus
ALK	Orphanet:635	Neuroblastoma
MYCN	Orphanet:357027	Hereditary retinoblastoma
MYCN	Orphanet:357034	Non-hereditary retinoblastoma
MYCN	Orphanet:391641	Feingold syndrome type 1
MYCN	Orphanet:635	Neuroblastoma
CASP8	Orphanet:210159	Adult hepatocellular carcinoma
CASP8	Orphanet:275517	Autoimmune lymphoproliferative syndrome-recurrent viral infections due to CASP8 deficiency
EZH2	Orphanet:3447	Weaver syndrome
NF1	Orphanet:139474	17q11.2 microduplication syndrome
NF1	Orphanet:29072	Hereditary pheochromocytoma-paraganglioma
NF1	Orphanet:293199	Pleomorphic rhabdomyosarcoma
NF1	Orphanet:363700	Neurofibromatosis type 1 due to NF1 mutation or intragenic deletion
NF1	Orphanet:638	Neurofibromatosis-Noonan syndrome
NF1	Orphanet:86834	Juvenile myelomonocytic leukemia
NF1	Orphanet:97685	17q11 microdeletion syndrome
NF1	Orphanet:99756	Alveolar rhabdomyosarcoma
NF1	Orphanet:99757	Embryonal rhabdomyosarcoma
NRAS	Orphanet:146	Differentiated thyroid carcinoma
NRAS	Orphanet:2612	Linear nevus sebaceus syndrome
NRAS	Orphanet:268114	RAS-associated autoimmune leukoproliferative disease
NRAS	Orphanet:389	Langerhans cell histiocytosis
NRAS	Orphanet:626	Large/giant congenital melanocytic nevus
NRAS	Orphanet:648	Noonan syndrome
NRAS	Orphanet:86834	Juvenile myelomonocytic leukemia
NTRK1	Orphanet:146	Differentiated thyroid carcinoma
NTRK1	Orphanet:642	Hereditary sensory and autonomic neuropathy type 4
NTRK1	Orphanet:64752	Hereditary sensory and autonomic neuropathy type 5
NTRK1	Orphanet:99361	Isolated familial medullary thyroid carcinoma
SDHC	Orphanet:139411	Carney triad
SDHC	Orphanet:201	Cowden syndrome
SDHC	Orphanet:29072	Hereditary pheochromocytoma-paraganglioma
SDHC	Orphanet:44890	Gastrointestinal stromal tumor
SDHC	Orphanet:97286	Carney-Stratakis syndrome
BRCA2	Orphanet:1331	Familial prostate cancer
BRCA2	Orphanet:1333	Familial pancreatic carcinoma
BRCA2	Orphanet:145	Hereditary breast and/or ovarian cancer syndrome
BRCA2	Orphanet:178	Chordoma
BRCA2	Orphanet:227535	Hereditary breast cancer
BRCA2	Orphanet:319462	Inherited cancer-predisposing syndrome due to biallelic BRCA2 mutations
BRCA2	Orphanet:440437	Familial colorectal cancer Type X
BRCA2	Orphanet:654	Nephroblastoma
BRCA2	Orphanet:667662	Breast implant-associated anaplastic large cell lymphoma
BRCA2	Orphanet:694963	Inflammatory breast cancer

Cohort genes → proteins

66 cohort genes, 65 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	44
civic_only	5
multi_evidence	17

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
ALK	HGNC:427	ENSG00000171094	Q9UM73	ALK tyrosine kinase receptor	clinvar,civic_evidence
MYCN	HGNC:7559	ENSG00000134323	P04198	N-myc proto-oncogene protein	clinvar,civic_evidence
CASP8	HGNC:1509	ENSG00000064012	Q14790	Caspase-8	civic_evidence
EZH2	HGNC:3527	ENSG00000106462	Q15910	Histone-lysine N-methyltransferase EZH2	civic_evidence
NF1	HGNC:7765	ENSG00000196712	P21359	Neurofibromin	civic_evidence
NRAS	HGNC:7989	ENSG00000213281	P01111	GTPase NRas	civic_evidence
NTRK1	HGNC:8031	ENSG00000198400	P04629	High affinity nerve growth factor receptor	civic_evidence
SDHC	HGNC:10682	ENSG00000143252	Q99643	Succinate dehydrogenase cytochrome b560 subunit, mitochondrial	clinvar
BRCA2	HGNC:1101	ENSG00000139618	P51587	Breast cancer type 2 susceptibility protein	clinvar
SLK	HGNC:11088	ENSG00000065613	Q9H2G2	STE20-like serine/threonine-protein kinase	gwas
SMARCA4	HGNC:11100	ENSG00000127616	P51532	SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 4	clinvar
TP53	HGNC:11998	ENSG00000141510	P04637	Cellular tumor antigen p53	gwas
TSC1	HGNC:12362	ENSG00000165699	Q92574	Hamartin	clinvar
TSC2	HGNC:12363	ENSG00000103197	P49815	Tuberin	clinvar
UGT1A10	HGNC:12531	ENSG00000242515	Q9HAW8	UDP-glucuronosyltransferase 1A10	gwas
UGT1A6	HGNC:12538	ENSG00000167165	P19224	UDP-glucuronosyltransferase 1A6	gwas
UGT1A7	HGNC:12539	ENSG00000244122	Q9HAW7	UDP-glucuronosyltransferase 1A7	gwas
UGT1A8	HGNC:12540	ENSG00000242366	Q9HAW9	UDP-glucuronosyltransferase 1A8	gwas
UGT1A9	HGNC:12541	ENSG00000241119	O60656	UDP-glucuronosyltransferase 1A9	gwas
NEUROG2	HGNC:13805	ENSG00000178403	Q9H2A3	Neurogenin-2	gwas
MRPS18B	HGNC:14516	ENSG00000204568	Q9Y676	Small ribosomal subunit protein mS40	gwas
PINK1	HGNC:14581	ENSG00000158828	Q9BXM7	Serine/threonine-protein kinase PINK1, mitochondrial	clinvar
SALL4	HGNC:15924	ENSG00000101115	Q9UJQ4	Sal-like protein 4	gwas
KIF1B	HGNC:16636	ENSG00000054523	O60333	Kinesin-like protein KIF1B	clinvar
XPO4	HGNC:17796	ENSG00000132953	Q9C0E2	Exportin-4	gwas
CHODL	HGNC:17807	ENSG00000154645	Q9H9P2	Chondrolectin	gwas
PHF6	HGNC:18145	ENSG00000156531	Q8IWS0	PHD finger protein 6	clinvar
HSD17B12	HGNC:18646	ENSG00000149084	Q53GQ0	Very-long-chain 3-oxoacyl-CoA reductase	gwas
NOL6	HGNC:19910	ENSG00000165271	Q9H6R4	Nucleolar protein 6	gwas
HACE1	HGNC:21033	ENSG00000085382	Q8IYU2	E3 ubiquitin-protein ligase HACE1	gwas
CPZ	HGNC:2333	ENSG00000109625	Q66K79	Carboxypeptidase Z	gwas
RSRC1	HGNC:24152	ENSG00000174891	Q96IZ7	Serine/Arginine-related protein 53	gwas
DLGAP4	HGNC:24476	ENSG00000080845	Q9Y2H0	Disks large-associated protein 4	gwas
ARHGAP24	HGNC:25361	ENSG00000138639	Q8N264	Rho GTPase-activating protein 24	gwas
ARHGEF40	HGNC:25516	ENSG00000165801	Q8TER5	Rho guanine nucleotide exchange factor 40	gwas
L1TD1	HGNC:25595	ENSG00000240563	Q5T7N2	LINE-1 type transposase domain-containing protein 1	gwas
STN1	HGNC:26200	ENSG00000107960	Q9H668	CST complex subunit STN1	gwas
KANSL1L	HGNC:26310	ENSG00000144445	A0AUZ9	KAT8 regulatory NSL complex subunit 1-like protein	gwas
RPTN	HGNC:26809	ENSG00000215853	Q6XPR3	Repetin	gwas
EEF1AKMT1	HGNC:27351	ENSG00000150456	Q8WVE0	EEF1A lysine methyltransferase 1	gwas
CASC15	HGNC:28245	ENSG00000272168		cancer susceptibility 15	gwas
LRRC45	HGNC:28302	ENSG00000169683	Q96CN5	Leucine-rich repeat-containing protein 45	gwas
MAGI3	HGNC:29647	ENSG00000081026	Q5TCQ9	Membrane-associated guanylate kinase, WW and PDZ domain-containing protein 3	gwas
SPIRE2	HGNC:30623	ENSG00000204991	Q8WWL2	Protein spire homolog 2	gwas
ANO7	HGNC:31677	ENSG00000146205	Q6IWH7	Anoctamin-7	gwas
LIN28B	HGNC:32207	ENSG00000187772	Q6ZN17	Protein lin-28 homolog B	gwas
ACSL1	HGNC:3569	ENSG00000151726	P33121	Long-chain-fatty-acid–CoA ligase 1	gwas
FANCA	HGNC:3582	ENSG00000187741	O15360	Fanconi anemia group A protein	clinvar
FGFR3	HGNC:3690	ENSG00000068078	P22607	Fibroblast growth factor receptor 3	clinvar
SMLR1	HGNC:44670	ENSG00000256162	H3BR10	Small leucine-rich protein 1	gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ALK	ALK tyrosine kinase receptor	Neuronal receptor tyrosine kinase that is essentially and transiently expressed in specific regions of the central and peripheral nervous systems and plays an important role in the genesis and differentiation of the nervous system.
MYCN	N-myc proto-oncogene protein	Positively regulates the transcription of MYCNOS in neuroblastoma cells.
CASP8	Caspase-8	Thiol protease that plays a key role in programmed cell death by acting as a molecular switch for apoptosis, necroptosis and pyroptosis, and is required to prevent tissue damage during embryonic development and adulthood.
EZH2	Histone-lysine N-methyltransferase EZH2	Catalytic subunit of the PRC2/EED-EZH2 complex, a Polycomb group (PcG) complex that methylates ‘Lys-9’ (H3K9me) and ‘Lys-27’ (H3K27me) of histone H3, leading to transcriptional repression of the affected target gene.
NF1	Neurofibromin	Stimulates the GTPase activity of Ras.
NRAS	GTPase NRas	Ras proteins bind GDP/GTP and possess intrinsic GTPase activity.
NTRK1	High affinity nerve growth factor receptor	Receptor tyrosine kinase involved in the development and the maturation of the central and peripheral nervous systems through regulation of proliferation, differentiation and survival of sympathetic and nervous neurons.
SDHC	Succinate dehydrogenase cytochrome b560 subunit, mitochondrial	Membrane-anchoring subunit of succinate dehydrogenase (SDH) that is involved in complex II of the mitochondrial electron transport chain and is responsible for transferring electrons from succinate to ubiquinone (coenzyme Q).
BRCA2	Breast cancer type 2 susceptibility protein	Involved in double-strand break repair and/or homologous recombination.
SLK	STE20-like serine/threonine-protein kinase	Mediates apoptosis and actin stress fiber dissolution.
SMARCA4	SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 4	ATPase involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology).
TP53	Cellular tumor antigen p53	Multifunctional transcription factor that induces cell cycle arrest, DNA repair or apoptosis upon binding to its target DNA sequence.
TSC1	Hamartin	Non-catalytic component of the TSC-TBC complex, a multiprotein complex that acts as a negative regulator of the canonical mTORC1 complex, an evolutionarily conserved central nutrient sensor that stimulates anabolic reactions and macromolec…
TSC2	Tuberin	Catalytic component of the TSC-TBC complex, a multiprotein complex that acts as a negative regulator of the canonical mTORC1 complex, an evolutionarily conserved central nutrient sensor that stimulates anabolic reactions and macromolecule…
UGT1A10	UDP-glucuronosyltransferase 1A10	UDP-glucuronosyltransferase (UGT) that catalyzes phase II biotransformation reactions in which lipophilic substrates are conjugated with glucuronic acid to increase the metabolite’s water solubility, thereby facilitating excretion into eit…
UGT1A6	UDP-glucuronosyltransferase 1A6	UDP-glucuronosyltransferase (UGT) that catalyzes phase II biotransformation reactions in which lipophilic substrates are conjugated with glucuronic acid to facilitate their inactivation and excretion from the body.
UGT1A7	UDP-glucuronosyltransferase 1A7	UDP-glucuronosyltransferase (UGT) that catalyzes phase II biotransformation reactions in which lipophilic substrates are conjugated with glucuronic acid to increase the metabolite’s water solubility, thereby facilitating excretion into eit…
UGT1A8	UDP-glucuronosyltransferase 1A8	UDP-glucuronosyltransferase (UGT) that catalyzes phase II biotransformation reactions in which lipophilic substrates are conjugated with glucuronic acid to increase the metabolite’s water solubility, thereby facilitating excretion into eit…
UGT1A9	UDP-glucuronosyltransferase 1A9	UDP-glucuronosyltransferase (UGT) that catalyzes phase II biotransformation reactions in which lipophilic substrates are conjugated with glucuronic acid to increase the metabolite’s water solubility, thereby facilitating excretion into eit…
NEUROG2	Neurogenin-2	Transcriptional regulator.
PINK1	Serine/threonine-protein kinase PINK1, mitochondrial	Serine/threonine-protein kinase which acts as a sensor of mitochondrial damage and protects against mitochondrial dysfunction during cellular stress.
SALL4	Sal-like protein 4	Transcription factor with a key role in the maintenance and self-renewal of embryonic and hematopoietic stem cells.
KIF1B	Kinesin-like protein KIF1B	Has a plus-end-directed microtubule motor activity and functions as a motor for transport of vesicles and organelles along microtubules.
XPO4	Exportin-4	Mediates the nuclear export of proteins (cargos), such as EIF5A, SMAD3 and isoform M2 of PKM (PKM2).
CHODL	Chondrolectin	May play a role in the development of the nervous system such as in neurite outgrowth and elongation.
PHF6	PHD finger protein 6	Transcriptional regulator that associates with ribosomal RNA promoters and suppresses ribosomal RNA (rRNA) transcription.
HSD17B12	Very-long-chain 3-oxoacyl-CoA reductase	Catalyzes the second of the four reactions of the long-chain fatty acids elongation cycle.
NOL6	Nucleolar protein 6	Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit.
HACE1	E3 ubiquitin-protein ligase HACE1	E3 ubiquitin-protein ligase involved in Golgi membrane fusion and regulation of small GTPases.
CPZ	Carboxypeptidase Z	Specifically cleaves substrates and peptides with C-terminal basic amino acids, especially those containing C-terminal Arg residues.
RSRC1	Serine/Arginine-related protein 53	Has a role in alternative splicing and transcription regulation.
DLGAP4	Disks large-associated protein 4	May play a role in the molecular organization of synapses and neuronal cell signaling.
ARHGAP24	Rho GTPase-activating protein 24	Rho GTPase-activating protein involved in cell polarity, cell morphology and cytoskeletal organization.
ARHGEF40	Rho guanine nucleotide exchange factor 40	Acts as a guanine nucleotide exchange factor (GEF) for RHOA and RHOC.
STN1	CST complex subunit STN1	Component of the CST complex proposed to act as a specialized replication factor promoting DNA replication under conditions of replication stress or natural replication barriers such as the telomere duplex.
RPTN	Repetin	Involved in the cornified cell envelope formation.
EEF1AKMT1	EEF1A lysine methyltransferase 1	Protein N-lysine methyltransferase that selectively catalyzes the trimethylation of EEF1A at ‘Lys-79’.
LRRC45	Leucine-rich repeat-containing protein 45	Component of the proteinaceous fiber-like linker between two centrioles, required for centrosome cohesion.
MAGI3	Membrane-associated guanylate kinase, WW and PDZ domain-containing protein 3	Acts as a scaffolding protein at cell-cell junctions, thereby regulating various cellular and signaling processes.
SPIRE2	Protein spire homolog 2	Acts as an actin nucleation factor, remains associated with the slow-growing pointed end of the new filament.
ANO7	Anoctamin-7	Has calcium-dependent phospholipid scramblase activity; scrambles phosphatidylserine, phosphatidylcholine and galactosylceramide.
LIN28B	Protein lin-28 homolog B	Suppressor of microRNA (miRNA) biogenesis, including that of let-7 and possibly of miR107, miR-143 and miR-200c.
ACSL1	Long-chain-fatty-acid–CoA ligase 1	Catalyzes the conversion of long-chain fatty acids to their active form acyl-CoAs for both synthesis of cellular lipids, and degradation via beta-oxidation.
FANCA	Fanconi anemia group A protein	DNA repair protein that may operate in a postreplication repair or a cell cycle checkpoint function.
FGFR3	Fibroblast growth factor receptor 3	Tyrosine-protein kinase that acts as a cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of cell proliferation, differentiation and apoptosis.
HLA-DQA1	HLA class II histocompatibility antigen, DQ alpha 1 chain	Binds peptides derived from antigens that access the endocytic route of antigen presenting cells (APC) and presents them on the cell surface for recognition by the CD4 T-cells.
HLA-DRB1	HLA class II histocompatibility antigen, DRB1 beta chain	A beta chain of antigen-presenting major histocompatibility complex class II (MHCII) molecule.
ANXA9	Annexin A9	Plays a role in epidermal differentiation.
IL15RA	Interleukin-15 receptor subunit alpha	High-affinity receptor for interleukin-15.
AQP3	Aquaporin-3	Aquaglyceroporins form homotetrameric transmembrane channels, with each monomer independently mediating glycerol and water transport across the plasma membrane along their osmotic gradient.

Protein-family classification

Druggable: 27 · Difficult: 14 · Unknown: 25 · Druggable fraction: 0.41

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
Kinase	10	4.2×	0.001
Enzyme (other)	11	2.0×	0.089
Complement	1	4.1×	0.616
Transcription factor	10	1.2×	0.616
Protease	2	1.1×	0.812
Scaffold/PPI	4	1.1×	0.812
Antibody/Immunoglobulin	2	0.9×	0.856
Other/Unknown	25	0.7×	0.999
GPCR	1	0.4×	0.999

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ALK	Kinase	yes	2.7.10.1	Prot_kinase_dom, MAM_dom, Ser-Thr/Tyr_kinase_cat_dom
MYCN	Transcription factor	no		Tscrpt_reg_Myc, bHLH_dom, Tscrpt_reg_Myc_N
CASP8	Enzyme (other)	yes	3.4.22.61	Pept_C14_p20, DED_dom, Pept_C14_p10
EZH2	Enzyme (other)	yes	2.1.1.356	SANT/Myb, SET_dom, EZH1/EZH2_N
NF1	Other/Unknown	no		CRAL-TRIO_dom, RasGAP_dom, Rho_GTPase_activation_prot
NRAS	Other/Unknown	no		Small_GTPase, Small_GTP-bd, Small_GTPase_Ras-type
NTRK1	Kinase	yes	2.7.10.1	Cys-rich_flank_reg_C, Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom
SDHC	Enzyme (other)	yes	1.3.5.1	SuccDH_FuR_B_TM-su, Succ_DH_cytb556, Succ_DH_cyt_bsu_CS
BRCA2	Other/Unknown	no		BRCA2_repeat, NA-bd_OB-fold, BRCA2_OB_1
SLK	Kinase	yes		Prot_kinase_dom, UVR_dom, Ser/Thr_kinase_AS
SMARCA4	Other/Unknown	no		SNF2_N, Bromodomain, Helicase_C-like
TP53	Transcription factor	no		p53_tumour_suppressor, p53-like_TF_DNA-bd_sf, p53_tetrameristn
TSC1	Other/Unknown	no		Hamartin
TSC2	Other/Unknown	no		Rap/Ran_GAP_dom, Tuberin, ARM-like
UGT1A10	Enzyme (other)	yes	2.4.1.17	UDP_glucos_trans, UDP_glycos_trans_CS, UDP-glycosyltransferase
UGT1A6	Enzyme (other)	yes	2.4.1.17	UDP_glucos_trans, UDP_glycos_trans_CS, UDP-glycosyltransferase
UGT1A7	Enzyme (other)	yes	2.4.1.17	UDP_glucos_trans, UDP_glycos_trans_CS, UDP-glycosyltransferase
UGT1A8	Enzyme (other)	yes	2.4.1.17	UDP_glucos_trans, UDP_glycos_trans_CS, UDP-glycosyltransferase
UGT1A9	Enzyme (other)	yes	2.4.1.17	UDP_glucos_trans, UDP_glycos_trans_CS, UDP-glycosyltransferase
NEUROG2	Transcription factor	no		bHLH_dom, Ngn-2_bHLH, HLH_DNA-bd_sf
MRPS18B	Other/Unknown	no		Ribosomal_bS18, Ribosomal_bS18_sf, MRPS18B
PINK1	Kinase	yes		Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf
SALL4	Transcription factor	no		Znf_C2H2_type, Znf_C2H2_sf, Sal_C2H2-zinc-finger
KIF1B	Scaffold/PPI	no		FHA_dom, Kinesin_motor_dom, PH_domain
XPO4	Other/Unknown	no		ARM-like, XPO1_C_dom, ARM-type_fold
CHODL	Other/Unknown	no		C-type_lectin-like, C-type_lectin-like/link_sf, CTDL_fold
PHF6	Transcription factor	no		Znf_PHD, Znf_RING/FYVE/PHD, EPHD
HSD17B12	Enzyme (other)	yes	1.1.1.62	SDR_fam, Sc_DH/Rdtase_CS, NAD(P)-bd_dom_sf
NOL6	Other/Unknown	no		NOL6/Upt22, Nrap_D1, Nrap_D2
HACE1	Scaffold/PPI	no		HECT_dom, Ankyrin_rpt, Hect_E3_ubiquitin_ligase
CPZ	Protease	yes		Peptidase_M14, CarboxyPept-like_regulatory, Frizzled_dom
RSRC1	Transcription factor	no		SRRP53
DLGAP4	Other/Unknown	no		SAPAP
ARHGAP24	Scaffold/PPI	no		RhoGAP_dom, PH_domain, Rho_GTPase_activation_prot
ARHGEF40	Scaffold/PPI	no		DH_dom, PH_domain, PH-like_dom_sf
L1TD1	Other/Unknown	no		Transposase_22, L1_dsRBD, L1_C
STN1	Other/Unknown	no		NA-bd_OB_tRNA, NA-bd_OB-fold, Stn1
KANSL1L	Other/Unknown	no		NSL1, PEHE_dom
RPTN	Other/Unknown	no		S100/CaBP7/8-like_CS, EF_hand_dom, EF-hand-dom_pair
EEF1AKMT1	Enzyme (other)	yes	2.1.1.244	DNA_methylase_N6_adenine_CS, Efm5/EEF1AKMT1, SAM-dependent_MTases_sf
CASC15	Other/Unknown	no
LRRC45	Other/Unknown	no		Leu-rich_rpt, LRR_dom_sf, Centro_Cilium_Assembly
MAGI3	Kinase	yes		WW_dom, PDZ, Guanylate_kin-like_dom
SPIRE2	Transcription factor	no		Znf_FYVE_PHD, KIND_dom, Spire
ANO7	Other/Unknown	no		Anoctamin, Anoct_dimer, Anoctamin_TM
LIN28B	Transcription factor	no		Znf_CCHC, CSP_DNA-bd, CSD
ACSL1	Enzyme (other)	yes	6.2.1.3	AMP-dep_synth/lig_dom, AMP-binding_CS, ANL_N_sf
FANCA	Other/Unknown	no		FANCA, Fanconi_A_N, Fanconi_A_C
FGFR3	Kinase	yes	2.7.10.1	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Ig_sub2
SMLR1	Other/Unknown	no

Expression context

Cohort genes with no expression data: 0.

62 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	1
moderate (6-20)	0
broad (>20)	65
unknown	0

Top tissues across cohort

Tissue	Cohort genes
male germ line stem cell (sensu Vertebrata) in testis	7
ventricular zone	7
ganglionic eminence	6
secondary oocyte	5
right hemisphere of cerebellum	5
lower esophagus mucosa	5
calcaneal tendon	4
tendon of biceps brachii	4
mucosa of transverse colon	4
liver	4
right lobe of liver	4
primordial germ cell in gonad	4
oocyte	4
left testis	4
right testis	4
cortical plate	3
gingival epithelium	3
endothelial cell	3
rectum	3
gastrocnemius	3

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ALK	181	broad	marker	sperm, male germ cell, male germ line stem cell (sensu Vertebrata) in testis
MYCN	223	broad	yes	ventricular zone, cortical plate, embryo
CASP8	252	ubiquitous	marker	monocyte, mononuclear cell, leukocyte
EZH2	216	ubiquitous	marker	ganglionic eminence, ventricular zone, embryo
NF1	283	ubiquitous	marker	colonic epithelium, calcaneal tendon, adrenal tissue
NRAS	278	ubiquitous	marker	gingival epithelium, epithelium of nasopharynx, secondary oocyte
NTRK1	160	broad	marker	dorsal root ganglion, apex of heart, male germ line stem cell (sensu Vertebrata) in testis
SDHC	134	ubiquitous	marker	islet of Langerhans, right adrenal gland cortex, right adrenal gland
BRCA2	184	ubiquitous	marker	male germ line stem cell (sensu Vertebrata) in testis, secondary oocyte, ventricular zone
SLK	293	ubiquitous	marker	esophagus squamous epithelium, endothelial cell, amniotic fluid
SMARCA4	295	ubiquitous	marker	ganglionic eminence, cortical plate, cervix squamous epithelium
TP53	223	ubiquitous	marker	ventricular zone, ganglionic eminence, tendon of biceps brachii
TSC1	297	ubiquitous	marker	substantia nigra pars compacta, gluteal muscle, lateral globus pallidus
TSC2	282	ubiquitous	marker	right hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex
UGT1A10	60	tissue_specific	marker	mucosa of transverse colon, duodenum, rectum
UGT1A6	88	broad	marker	liver, right lobe of liver, adult mammalian kidney
UGT1A7	68	tissue_specific	marker	lower esophagus mucosa, esophagus mucosa, male germ line stem cell (sensu Vertebrata) in testis
UGT1A8	44	tissue_specific	marker	mucosa of transverse colon, rectum, gall bladder
UGT1A9	45	tissue_specific	marker	adult mammalian kidney, right lobe of liver, liver
NEUROG2	43	tissue_specific	marker	ganglionic eminence, ventricular zone, primordial germ cell in gonad
MRPS18B	140	ubiquitous	marker	gastrocnemius, muscle of leg, skeletal muscle organ
PINK1	295	ubiquitous	marker	tendon of biceps brachii, gastrocnemius, gluteal muscle
SALL4	150	broad	marker	secondary oocyte, oocyte, male germ line stem cell (sensu Vertebrata) in testis
KIF1B	287	ubiquitous	marker	skeletal muscle tissue of rectus abdominis, biceps brachii, medial globus pallidus
XPO4	226	ubiquitous	marker	skeletal muscle tissue of rectus abdominis, biceps brachii, skeletal muscle tissue of biceps brachii
CHODL	185	broad	marker	calcaneal tendon, right testis, left testis
PHF6	254	ubiquitous	marker	corpus epididymis, oocyte, endothelial cell
HSD17B12	295	ubiquitous	marker	endothelial cell, pigmented layer of retina, retina
NOL6	278	ubiquitous	marker	tongue squamous epithelium, lower esophagus mucosa, apex of heart
HACE1	244	ubiquitous	yes	secondary oocyte, oocyte, Brodmann (1909) area 23

Protein interactions among cohort

Intra-cohort edges: 38.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TP53	22,736
EZH2	9,646
NTRK1	9,181
SMARCA4	8,138
NRAS	7,598
MYCN	7,345
MET	5,823
NF1	5,540
TSC1	5,445
SDHC	5,278

Intra-cohort edges

A	B	Sources
ALK	NRAS	string_interaction
ANO7	OR7G2	string_interaction
ARHGEF40	NTRK1	biogrid_interaction
ARHGEF40	OR7G2	string_interaction
BARD1	BRCA2	string_interaction
BRCA2	MLF1	biogrid_interaction
BRCA2	TP53	string_interaction
DLGAP4	MAGI3	intact
DLGAP4	NRAS	intact
EZH2	FGFR3	intact
EZH2	MYCN	string_interaction
EZH2	SALL4	biogrid_interaction
FANCA	MEN1	biogrid_interaction
FGFR3	HSD17B12	intact
HACE1	MLF1	string_interaction
HSD17B12	LMO1	string_interaction
KANSL1L	OR7G2	string_interaction
KIF1B	NF1	string_interaction
KIF1B	SDHC	string_interaction
L1TD1	OR7G2	string_interaction
LRRC45	OR7G2	string_interaction
MAP2K4	MAP2K7	biogrid_interaction
MAP2K7	NRAS	biogrid_interaction
MEN1	TP53	intact
MLF1	OR7G2	string_interaction
MLF1	RSRC1	string_interaction
MRPS18B	OR7G2	string_interaction
MYCN	TP53	string_interaction
NF1	NRAS	string_interaction
NF1	TP53	string_interaction
NRAS	TP53	string_interaction
NTRK1	NTRK2	string_interaction
OR7G2	RPTN	string_interaction
TSC1	TSC2	biogrid_interaction, intact, string_interaction
UGT1A10	UGT1A7	biogrid_interaction, intact
UGT1A10	UGT1A9	biogrid_interaction, intact
UGT1A7	UGT1A8	biogrid_interaction, intact
UGT1A7	UGT1A9	biogrid_interaction, intact

Structural data

PDB: 41 · AlphaFold-only: 24 · No structure: 1

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TP53	P04637	313
MET	P08581	130
HLA-DRB1	P01911	108
ALK	Q9UM73	79
MRPS18B	Q9Y676	76
MEN1	O00255	69
NTRK1	P04629	65
EZH2	Q15910	38
MAP2K7	O14733	37
CASP8	Q14790	36
NRAS	P01111	35
SMARCA4	P51532	31
HLA-DQA1	P01909	28
NF1	P21359	26
FGFR3	P22607	15
BRCA2	P51587	14
SALL4	Q9UJQ4	13
BARD1	Q99728	11
NTRK2	Q16620	9
STN1	Q9H668	8
SLK	Q9H2G2	7
PINK1	Q9BXM7	6
FANCA	O15360	6
TSC1	Q92574	5
HACE1	Q8IYU2	4
IL15RA	Q13261	4
MAP2K4	P45985	4
NOL6	Q9H6R4	3
AQP3	Q92482	3
MLF1	P58340	3

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
HSD17B12	Q53GQ0	94.55
UGT1A9	O60656	92.26
UGT1A10	Q9HAW8	92.11
UGT1A7	Q9HAW7	91.76
UGT1A8	Q9HAW9	91.56
UGT1A6	P19224	91.50
ANXA9	O76027	90.51
ACSL1	P33121	90.16
XPO4	Q9C0E2	88.96
LMO1	P25800	88.15
EEF1AKMT1	Q8WVE0	86.57
OR7G2	Q8NG99	85.65
CPZ	Q66K79	85.33
LRRC45	Q96CN5	83.38
ANO7	Q6IWH7	78.56
CHODL	Q9H9P2	76.83
ARHGAP24	Q8N264	66.68
SMLR1	H3BR10	65.89
NEUROG2	Q9H2A3	64.98
ARHGEF40	Q8TER5	64.28
RSRC1	Q96IZ7	58.46
KANSL1L	A0AUZ9	50.48
DLGAP4	Q9Y2H0	50.01
RPTN	Q6XPR3	42.63

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 453. Enrichment computed across 66 evidence-associated genes (51 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 51 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Glucuronidation	5	74.6×	2e-06	UGT1A10, UGT1A6, UGT1A7, UGT1A8, UGT1A9
Aspirin ADME	4	24.9×	0.004	UGT1A6, UGT1A7, UGT1A8, UGT1A9
Inhibition of TSC complex formation by AKT (PKB)	2	89.6×	0.021	TSC1, TSC2
NGF-independant TRKA activation	2	89.6×	0.021	NTRK1, NTRK2
Paracetamol ADME	3	24.9×	0.021	UGT1A10, UGT1A6, UGT1A9
RAS signaling downstream of NF1 loss-of-function variants	2	64.0×	0.026	NF1, NRAS
FCERI mediated MAPK activation	3	20.4×	0.026	MAP2K4, MAP2K7, NRAS
Bacterial Infection Pathways	3	19.8×	0.026	MAP2K4, MAP2K7, MET
t(4;14) translocations of FGFR3	1	223.9×	0.037	FGFR3
Signaling by FGFR3 fusions in cancer	1	223.9×	0.037	FGFR3
Drug resistance of ALK mutants	1	223.9×	0.037	ALK
ASP-3026-resistant ALK mutants	1	223.9×	0.037	ALK
NVP-TAE684-resistant ALK mutants	1	223.9×	0.037	ALK
alectinib-resistant ALK mutants	1	223.9×	0.037	ALK
brigatinib-resistant ALK mutants	1	223.9×	0.037	ALK
ceritinib-resistant ALK mutants	1	223.9×	0.037	ALK
crizotinib-resistant ALK mutants	1	223.9×	0.037	ALK
lorlatinib-resistant ALK mutants	1	223.9×	0.037	ALK
Loss of function of TP53 in cancer due to loss of tetramerization ability	1	223.9×	0.037	TP53
Activated NTRK2 signals through RAS	2	44.8×	0.037	NRAS, NTRK2
MET activates RAS signaling	2	40.7×	0.037	MET, NRAS
Uptake and function of anthrax toxins	2	37.3×	0.037	MAP2K4, MAP2K7
Activated NTRK2 signals through FRS2 and FRS3	2	37.3×	0.037	NRAS, NTRK2
Defective homologous recombination repair (HRR) due to PALB2 loss of function	2	37.3×	0.037	BRCA2, BARD1
Uptake and actions of bacterial toxins	2	32.0×	0.037	MAP2K4, MAP2K7
Diseases of DNA Double-Strand Break Repair	2	32.0×	0.037	BRCA2, BARD1
Defective homologous recombination repair (HRR) due to BRCA2 loss of function	2	32.0×	0.037	BRCA2, BARD1
Signalling to RAS	2	26.3×	0.037	NRAS, NTRK1
Translocation of ZAP-70 to Immunological synapse	2	24.9×	0.037	HLA-DQA1, HLA-DRB1
Resolution of D-Loop Structures	2	24.9×	0.037	BRCA2, BARD1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 61 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
flavone metabolic process	4	1105.0×	0e+00	UGT1A10, UGT1A7, UGT1A8, UGT1A9
toxin catabolic process	2	552.5×	0e+00	UGT1A10, UGT1A7
negative regulation of fatty acid metabolic process	5	345.3×	0e+00	UGT1A10, UGT1A6, UGT1A7, UGT1A8, UGT1A9
liver development	6	21.8×	6e-05	UGT1A10, UGT1A7, UGT1A8, UGT1A9, MET, NF1
flavonoid metabolic process	3	103.6×	4e-04	UGT1A7, UGT1A8, UGT1A9
negative regulation of mitophagy	3	75.3×	9e-04	TP53, TSC2, PINK1
glucuronate metabolic process	2	276.3×	0.001	UGT1A10, UGT1A6
negative regulation of reactive oxygen species metabolic process	3	46.0×	0.003	MYCN, TP53, PINK1
retinoic acid metabolic process	3	39.5×	0.003	UGT1A7, UGT1A8, UGT1A9
cellular senescence	4	19.4×	0.003	BRCA2, TP53, MAP2K4, MAP2K7
MAPK cascade	5	12.6×	0.003	FGFR3, MAP2K4, MEN1, NF1, NRAS
xenobiotic metabolic process	5	12.2×	0.003	UGT1A10, UGT1A6, UGT1A7, UGT1A8, UGT1A9
negative regulation of Rac protein signal transduction	2	138.1×	0.004	ARHGAP24, NF1
mechanoreceptor differentiation	2	110.5×	0.007	NTRK1, NTRK2
response to gamma radiation	3	28.6×	0.007	BRCA2, TP53, MEN1
xenobiotic catabolic process	3	27.6×	0.008	UGT1A10, UGT1A7, ACSL1
coumarin metabolic process	2	92.1×	0.008	UGT1A7, UGT1A8
peptidyl-tyrosine autophosphorylation	2	61.4×	0.016	ALK, NTRK1
cellular response to ionizing radiation	3	20.2×	0.016	BRCA2, TP53, BARD1
cell surface receptor protein tyrosine kinase signaling pathway	4	11.4×	0.016	ALK, MET, NTRK1, NTRK2
transcription initiation-coupled chromatin remodeling	3	18.8×	0.018	SMARCA4, TP53, MEN1
negative regulation of astrocyte differentiation	2	50.2×	0.023	MYCN, NF1
protein autophosphorylation	4	9.5×	0.026	ALK, SLK, NTRK1, NTRK2
regulation of cell-matrix adhesion	2	42.5×	0.029	TSC1, NF1
negative regulation of neuroblast proliferation	2	39.5×	0.032	TP53, NF1
negative regulation of macroautophagy	2	36.8×	0.032	TSC1, PINK1
positive regulation of programmed cell death	2	36.8×	0.032	MYCN, NTRK1
regulation of DNA damage checkpoint	2	36.8×	0.032	BRCA2, BARD1
positive regulation of miRNA transcription	3	14.3×	0.032	MYCN, SMARCA4, TP53
positive regulation of GTPase activity	3	13.6×	0.033	EZH2, NF1, NTRK1

Therapeutics

Drugs indicated for this disease

3 approved, 22 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Dinutuximab	Approved (phase 4)
Dinutuximab Beta	Approved (phase 4)
Naxitamab	Approved (phase 4)
Aldesleukin	Phase 3 (in late-stage trials)
Busulfan	Phase 3 (in late-stage trials)
Carboplatin	Phase 3 (in late-stage trials)
Cisplatin	Phase 3 (in late-stage trials)
Dacarbazine	Phase 3 (in late-stage trials)
Doxorubicin	Phase 3 (in late-stage trials)
Etoposide	Phase 3 (in late-stage trials)
Etoposide Phosphate	Phase 3 (in late-stage trials)
Filgrastim	Phase 3 (in late-stage trials)
Human Immunoglobulin G	Phase 3 (in late-stage trials)
Ifosfamide	Phase 3 (in late-stage trials)
Irinotecan	Phase 3 (in late-stage trials)
Isotretinoin	Phase 3 (in late-stage trials)
Lorlatinib	Phase 3 (in late-stage trials)
Melphalan	Phase 3 (in late-stage trials)
Prednisone	Phase 3 (in late-stage trials)
Sargramostim	Phase 3 (in late-stage trials)
Temozolomide	Phase 3 (in late-stage trials)
Thiotepa	Phase 3 (in late-stage trials)
Topotecan	Phase 3 (in late-stage trials)
Vincristine	Phase 3 (in late-stage trials)
Vindesine	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): ANTI-GD2 MONOCLONAL ANTIBODY 3F8, ANTINEOPLASTON A10, Arsenic Trioxide, Becatecarin, Bevacizumab, Catequentinib, Ceritinib, Cyclosporine, Dasatinib Anhydrous, Dexrazoxane, Eflornithine, Endostatin, N-Terminal-Mggshhhhh, Fenretinide, Fludarabine, Fludarabine Phosphate, Gefitinib, Iobenguane, Levetiracetam, Methotrexate, Mycophenolate Mofetil, Ornithine, Racotumomab, Regramostim, Rivoceranib, Sintilimab, Sirolimus, Sorafenib, Spironolactone, Tacrolimus Anhydrous, Temsirolimus, Thalidomide, Tretinoin, Vorinostat.

Drug target analysis

Approved (phase 4): 16 · Phase ≥3: 17 · Phased (≥1): 20 · Undrugged: 46

Druggability breadth: 38 of 66 evidence-associated genes (58%) 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
ALK	CERITINIB
CASP8	PRIMAQUINE PHOSPHATE
EZH2	TAZEMETOSTAT
NTRK1	PONATINIB
SLK	AFATINIB
TP53	NITROFURANTOIN
UGT1A10	DICLOFENAC
UGT1A6	DICLOFENAC
UGT1A7	DICLOFENAC
UGT1A9	DICLOFENAC
FGFR3	PONATINIB
MAP2K4	FEDRATINIB
MAP2K7	NERATINIB
MEN1	LOPERAMIDE
MET	AFATINIB
NTRK2	FEDRATINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
MEN1	475	4
TP53	196	4
MET	95	4
SLK	81	4
NTRK1	66	4
FGFR3	64	4
ALK	61	4
NTRK2	50	4
MAP2K4	18	4
MAP2K7	7	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
CERITINIB	4	ALK, FGFR3, MET, NTRK1, NTRK2
BOSUTINIB	4	ALK, MAP2K4, MAP2K7, MET, NTRK1, NTRK2
CRIZOTINIB	4	ALK, FGFR3, MET, NTRK1, NTRK2, SLK
ALECTINIB	4	ALK
ENTRECTINIB	4	ALK, FGFR3, MET, NTRK1, NTRK2, SLK
LORLATINIB	4	ALK, NTRK1, NTRK2
GILTERITINIB	4	ALK, SLK
OSIMERTINIB	4	ALK
BRIGATINIB	4	ALK, FGFR3, MET
REPOTRECTINIB	4	ALK, NTRK1, NTRK2
FEDRATINIB	4	ALK, FGFR3, MAP2K4, MET, NTRK1, NTRK2
RUXOLITINIB	4	ALK, MAP2K4, NTRK1, NTRK2
INFIGRATINIB PHOSPHATE	4	ALK, FGFR3, MET, NTRK2
INFIGRATINIB	4	ALK, FGFR3, MET, NTRK2
PALBOCICLIB	4	ALK, MAP2K4, MET
VANDETANIB	4	ALK, FGFR3, MET, SLK
UPADACITINIB	4	ALK
PAZOPANIB	4	ALK, FGFR3, MAP2K4, MET, SLK
NINTEDANIB	4	ALK, FGFR3, MAP2K4, MET, NTRK1, NTRK2
SUNITINIB	4	ALK, FGFR3, MAP2K4, MEN1, MET, NTRK1
ERLOTINIB	4	ALK, MET, SLK
MIDOSTAURIN	4	ALK, FGFR3, MAP2K4, MET, NTRK1, NTRK2
PRIMAQUINE PHOSPHATE	4	CASP8
TAZEMETOSTAT	4	EZH2
PONATINIB	4	FGFR3, NTRK1
AXITINIB	4	FGFR3, MET, NTRK1, SLK
SORAFENIB	4	FGFR3, MEN1, MET, NTRK1, NTRK2, SLK
CABOZANTINIB	4	MET, NTRK1
ABEMACICLIB	4	NTRK1
LAROTRECTINIB	4	NTRK1, NTRK2

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 20.

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

Symbol	Assays	Type breakdown
MET	2,015	Binding:2005, Functional:6, ADMET:4
ALK	1,815	Binding:1801, Functional:13, ADMET:1
NTRK1	1,194	Binding:1182, ADMET:7, Functional:5
FGFR3	975	Binding:948, Functional:18, ADMET:9
TP53	869	Binding:775, ADMET:83, Functional:10, Toxicity:1
EZH2	839	Binding:833, Functional:6
NTRK2	554	Binding:547, ADMET:5, Functional:2
SLK	280	Binding:279, Functional:1
MAP2K4	255	Binding:255
SMARCA4	230	Binding:207, ADMET:12, Functional:11
MAP2K7	217	Binding:217
UGT1A9	153	ADMET:149, Binding:4
CASP8	116	Binding:106, Functional:10
UGT1A10	101	ADMET:99, Binding:2
MEN1	93	Binding:86, Functional:7
UGT1A8	87	ADMET:86, Binding:1
UGT1A6	76	ADMET:71, Binding:5
UGT1A7	76	ADMET:74, Binding:2
LIN28B	27	Binding:27
PINK1	24	Binding:24
NRAS	18	Binding:18
HLA-DRB1	17	Binding:17
SALL4	12	Binding:12
HSD17B12	12	Binding:12
MYCN	11	Binding:11
PHF6	4	Binding:4
MAGI3	4	Binding:4
ACSL1	4	Binding:4
IL15RA	4	Binding:4
MMP20	4	Binding:4
AQP3	3	Binding:3
HLA-DQA1	2	Binding:2
TSC2	1	Binding:1
MRPS18B	1	Binding:1
KIF1B	1	Binding:1
XPO4	1	Binding:1
ANXA9	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
ALK	2.7.10.1	receptor protein-tyrosine kinase
CASP8	3.4.22.61	caspase-8
EZH2	2.1.1.356	[histone H3]-lysine27 N-trimethyltransferase
NTRK1	2.7.10.1	receptor protein-tyrosine kinase
SDHC	1.3.5.1	succinate dehydrogenase
UGT1A10	2.4.1.17	glucuronosyltransferase
UGT1A6	2.4.1.17	glucuronosyltransferase
UGT1A7	2.4.1.17	glucuronosyltransferase
UGT1A8	2.4.1.17	glucuronosyltransferase
UGT1A9	2.4.1.17	glucuronosyltransferase
HSD17B12	1.1.1.62	17beta-estradiol 17-dehydrogenase
EEF1AKMT1	2.1.1.244	protein N-terminal methyltransferase
ACSL1	6.2.1.3	long-chain-fatty-acid-CoA ligase
FGFR3	2.7.10.1	receptor protein-tyrosine kinase
MAP2K4	2.7.12.2	mitogen-activated protein kinase kinase
MAP2K7	2.7.12.2	mitogen-activated protein kinase kinase
MET	2.7.10.1	receptor protein-tyrosine kinase
MMP20	3.4.24.B6
NTRK2	2.7.10.1	receptor protein-tyrosine kinase
BARD1	2.3.2.27	RING-type E3 ubiquitin transferase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
ALK	1,815
CASP8	116
EZH2	839
NTRK1	1,194
SLK	280
SMARCA4	230
TP53	869
UGT1A10	101
UGT1A9	153
FGFR3	975
MAP2K4	255
MAP2K7	217
MET	2,015
NTRK2	554

Pharmacogenomics

Cohort genes with a PharmGKB record: 65; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

29 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)
CERITINIB	4	ALK, FGFR3, MET, NTRK1, NTRK2
BOSUTINIB	4	ALK, MAP2K4, MAP2K7, MET, NTRK1, NTRK2
CRIZOTINIB	4	ALK, FGFR3, MET, NTRK1, NTRK2, SLK
ALECTINIB	4	ALK
ENTRECTINIB	4	ALK, FGFR3, MET, NTRK1, NTRK2, SLK
GILTERITINIB	4	ALK, SLK
OSIMERTINIB	4	ALK
BRIGATINIB	4	ALK, FGFR3, MET
REPOTRECTINIB	4	ALK, NTRK1, NTRK2
FEDRATINIB	4	ALK, FGFR3, MAP2K4, MET, NTRK1, NTRK2
RUXOLITINIB	4	ALK, MAP2K4, NTRK1, NTRK2
INFIGRATINIB PHOSPHATE	4	ALK, FGFR3, MET, NTRK2
INFIGRATINIB	4	ALK, FGFR3, MET, NTRK2
PALBOCICLIB	4	ALK, MAP2K4, MET
VANDETANIB	4	ALK, FGFR3, MET, SLK
UPADACITINIB	4	ALK
PAZOPANIB	4	ALK, FGFR3, MAP2K4, MET, SLK
NINTEDANIB	4	ALK, FGFR3, MAP2K4, MET, NTRK1, NTRK2
SUNITINIB	4	ALK, FGFR3, MAP2K4, MEN1, MET, NTRK1
ERLOTINIB	4	ALK, MET, SLK
MIDOSTAURIN	4	ALK, FGFR3, MAP2K4, MET, NTRK1, NTRK2
PRIMAQUINE PHOSPHATE	4	CASP8
TAZEMETOSTAT	4	EZH2
PONATINIB	4	FGFR3, NTRK1
AXITINIB	4	FGFR3, MET, NTRK1, SLK
SORAFENIB	4	FGFR3, MEN1, MET, NTRK1, NTRK2, SLK
CABOZANTINIB	4	MET, NTRK1
ABEMACICLIB	4	NTRK1
LAROTRECTINIB	4	NTRK1, NTRK2

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	16	ALK, CASP8, EZH2, NTRK1, SLK, TP53, UGT1A10, UGT1A6, UGT1A7, UGT1A9 (+6 more)
B	Phased (≥1) drug, not yet approved	4	NRAS, SMARCA4, HSD17B12, MMP20
C	Druggable family + PDB, no drug	6	SDHC, PINK1, MAGI3, HLA-DQA1, HLA-DRB1, IL15RA
D	Druggable family + AlphaFold only, no drug	5	UGT1A8, CPZ, EEF1AKMT1, ACSL1, OR7G2
E	Difficult family or no structure, no drug	35	MYCN, NF1, BRCA2, TSC1, TSC2, NEUROG2, MRPS18B, SALL4, KIF1B, XPO4 (+25 more)

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
NF1	0	NRAS
MYCN	11	—
SDHC	0	—
BRCA2	0	—
TSC1	0	—
TSC2	1	—
UGT1A8	87	—
NEUROG2	0	—
MRPS18B	1	—
PINK1	24	—
SALL4	12	—
KIF1B	1	—
XPO4	1	—
CHODL	0	—
PHF6	4	—
NOL6	0	—
HACE1	0	—
CPZ	0	—
RSRC1	0	—
DLGAP4	0	—
ARHGAP24	0	—
ARHGEF40	0	—
L1TD1	0	—
STN1	0	—
KANSL1L	0	—
RPTN	0	—
EEF1AKMT1	0	—
CASC15	0	—
LRRC45	0	—
MAGI3	4	—

Clinical trials & evidence

Clinical trials

Clinical trials: 582.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE1	171
PHASE2	168
Not specified	131
PHASE1/PHASE2	60
PHASE3	32
EARLY_PHASE1	13
PHASE2/PHASE3	4
PHASE4	3

Top trials by phase / activity

NCT	Phase	Status	Title
NCT06047535	PHASE4	NOT_YET_RECRUITING	Naxitamab and Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) Combined With Isotretinoin for Maintenance Treatment of Patients With High-Risk Neuroblastoma in First Complete Response.
NCT00336531	PHASE4	COMPLETED	Efficacy of Prophylactic Itraconazole in High-Dose Chemotherapy and Autologous Hematopoietic Stem Cell Transplantation
NCT02933333	PHASE4	UNKNOWN	G-CSF Alone or Combination With GM-CSF on Prevention and Treatment of Infection in Children With Malignant Tumor
NCT01704716	PHASE3	RECRUITING	High Risk Neuroblastoma Study 1.8 of SIOP-Europe (SIOPEN)
NCT02176967	PHASE3	ACTIVE_NOT_RECRUITING	Response and Biology-Based Risk Factor-Guided Therapy in Treating Younger Patients With Non-high Risk Neuroblastoma
NCT03126916	PHASE3	RECRUITING	Testing the Addition of 131I-MIBG or Lorlatinib to Intensive Therapy in People With High-Risk Neuroblastoma (NBL)
NCT04706910	PHASE3	RECRUITING	18F-DOPA II - PET Imaging Optimization
NCT04724369	PHASE3	ACTIVE_NOT_RECRUITING	Open-Label Study of 18F-mFBG for Imaging Neuroblastoma
NCT05770037	PHASE2/PHASE3	RECRUITING	DETERMINE Trial Treatment Arm 01: Alectinib in Adult, Paediatric and Teenage/Young Adult Patients With ALK Positive Cancers
NCT06071897	PHASE3	RECRUITING	Induction Chemoimmunotherapy for Patients With High-risk Neuroblastoma
NCT06172296	PHASE3	RECRUITING	Dinutuximab With Chemotherapy, Surgery and Stem Cell Transplantation for the Treatment of Children With Newly Diagnosed High Risk Neuroblastoma
NCT06988475	PHASE2/PHASE3	RECRUITING	DETERMINE Trial Treatment Arm 06: Capmatinib in Adult Patients With Cancers Harbouring MET Dysregulations
NCT07375563	PHASE3	RECRUITING	Chemoimmunotherapy Combined With Autologous NK Cell Therapy for Pediatric Patients With Refractory and Relapsed High-Risk Neuroblastoma and Ganglioneuroblastoma
NCT00002802	PHASE3	COMPLETED	Therapy Based on Stage of Disease and Risk Assessment in Treating Children With Neuroblastoma
NCT00003093	PHASE3	COMPLETED	Combination Chemotherapy in Treating Children With Neuroblastoma
NCT00003119	PHASE3	COMPLETED	Surgery in Treating Children With Neuroblastoma
NCT00004188	PHASE3	COMPLETED	Combination Chemotherapy and Peripheral Stem Cell Transplantation in Treating Patients With Neuroblastoma
NCT00025428	PHASE3	COMPLETED	Combination Chemotherapy Before Surgery in Treating Children With Localized Neuroblastoma
NCT00026312	PHASE3	COMPLETED	Isotretinoin With or Without Dinutuximab, Aldesleukin, and Sargramostim Following Stem Cell Transplant in Treating Patients With Neuroblastoma
NCT00030719	PHASE3	UNKNOWN	Combination Chemotherapy With or Without Filgrastim Before Surgery, High-Dose Chemotherapy, and Radiation Therapy Followed by Isotretinoin With or Without Monoclonal Antibody in Treating Patients With Neuroblastoma
NCT00033293	PHASE3	COMPLETED	Cyclophosphamide and Prednisone With or Without Immunoglobulin in Treating Abnormal Muscle Movement in Children With Neuroblastoma
NCT00126412	PHASE3	COMPLETED	Meta-Iodobenzylguanidine (123I mIBG) Scintigraphy in Patients Being Evaluated for Phaeochromocytoma or Neuroblastoma
NCT00276731	PHASE3	UNKNOWN	Combination Chemotherapy Followed By Surgery With or Without Radiation Therapy in Treating Young Patients With Stage II or Stage III Neuroblastoma
NCT00324324	PHASE3	TERMINATED	Moxifloxacin in Preventing Bacterial Infections in Patients Who Have Undergone Donor Stem Cell Transplant
NCT00365755	PHASE3	COMPLETED	Combination Chemotherapy in Treating Young Patients Who Are Undergoing Surgery and an Autologous Bone Marrow Transplant for Disseminated Neuroblastoma
NCT00410631	PHASE3	UNKNOWN	Observation, Combination Chemotherapy, Radiation Therapy, and/or Autologous Stem Cell Transplant in Treating Young Patients With Neuroblastoma
NCT00416676	PHASE3	UNKNOWN	Combination Chemotherapy and Surgery With or Without Radiation Therapy in Treating Patients With Stage 2 or Stage 3 Neuroblastoma
NCT00417053	PHASE3	UNKNOWN	Combination Chemotherapy in Treating Infants With Newly Diagnosed Neuroblastoma Who Are Undergoing Surgery With or Without Autologous Bone Marrow or Peripheral Stem Cell Transplant
NCT00499616	PHASE3	COMPLETED	Combination Chemotherapy and Surgery With or Without Isotretinoin in Treating Young Patients With Neuroblastoma
NCT00539500	PHASE2/PHASE3	TERMINATED	Autologous Stem Cell Rescue With CD133+ Selected Cells in High-Risk Neuroblastoma
NCT00567567	PHASE3	COMPLETED	Comparing Two Different Myeloablation Therapies in Treating Young Patients Who Are Undergoing a Stem Cell Transplant for High-Risk Neuroblastoma
NCT00716976	PHASE3	COMPLETED	Sodium Thiosulfate in Preventing Hearing Loss in Young Patients Receiving Cisplatin for Newly Diagnosed Germ Cell Tumor, Hepatoblastoma, Medulloblastoma, Neuroblastoma, Osteosarcoma, or Other Malignancy
NCT00782145	PHASE3	COMPLETED	A Web-Based Stem Cell Transplant Support System or Standard Care in Young Patients Undergoing Stem Cell Transplant and Their Families
NCT01373736	PHASE3	UNKNOWN	123I-MIBG Scintigraphy in Patients Being Evaluated for Neuroendocrine Tumors
NCT01868269	PHASE3	COMPLETED	Opsoclonus Myoclonus Syndrome/Dancing Eye Syndrome (OMS/DES) in Children With and Without Neuroblastoma (NBpos and NBneg)Opsoclonus Myoclonus Syndrome/Dancing Eye Syndrome (OMS/DES) in Children With and Without Neuroblastoma (NBpos and NBneg)
NCT01987596	PHASE3	TERMINATED	Study of Fixed vs. Flexible Filgrastim to Accelerate Bone Marrow Recovery After Chemotherapy in Children With Cancer
NCT03042416	PHASE3	COMPLETED	18F-DOPA PET Imaging: an Evaluation of Biodistribution and Safety
NCT03042429	PHASE3	COMPLETED	Combination Chemotherapy Followed by Stem Cell Transplant in High-risk Neuroblastoma Patients
NCT03275402	PHASE2/PHASE3	TERMINATED	131I-omburtamab Radioimmunotherapy for Neuroblastoma Central Nervous System/Leptomeningeal Metastases
NCT00107289	PHASE2	RECRUITING	Iodine I 131 Metaiodobenzylguanidine in Treating Patients With Recurrent, Progressive, or Refractory Neuroblastoma or Malignant Pheochromocytoma or Paraganglioma

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
IRINOTECAN HYDROCHLORIDE	4	35
ISOTRETINOIN	4	27
DINUTUXIMAB	4	22
IOBENGUANE I 131	4	18
TOPOTECAN	4	18
NAXITAMAB	4	14
2-MERCAPTOETHANESULFONIC ACID	4	12
MELPHALAN	4	11
EFLORNITHINE	4	10
THIOTEPA	4	10
ETOPOSIDE PHOSPHATE	4	9
DEXRAZOXANE	4	8
EDOTREOTIDE GALLIUM GA-68	4	8
SARGRAMOSTIM	4	7
CARBOPLATIN	4	6
BUSULFAN	4	5
DINUTUXIMAB BETA	4	5
ALDESLEUKIN	4	4
ETOPOSIDE	4	4
FILGRASTIM	4	4
VINCRISTINE SULFATE	4	4
VINDESINE	4	4
ARSENIC TRIOXIDE	4	3
DACARBAZINE	4	3
DOXORUBICIN HYDROCHLORIDE	4	3
LORLATINIB	4	3
TEMOZOLOMIDE	4	3
TIPIRACIL HYDROCHLORIDE	4	3
TRETINOIN	4	3
ALEMTUZUMAB	4	2

Precision-medicine subtype map (CIViC)

Drug × molecular subtype: 24 predictive associations from 29 curated evidence items; also 4 predisposing, 3 prognostic, 1 oncogenic.

Molecular subtype	Therapy	Effect	Level	CIViC
ALK R1275Q	Crizotinib	Sensitivity/Response	CIViC B	EID2342 +3
ALK F1174L	Crizotinib	Resistance	CIViC B	EID2345 +1
ALK F1174L	Crizotinib	Sensitivity/Response	CIViC C	EID1271 +1
ALK F1245V	Entrectinib	Sensitivity/Response	CIViC C	EID2987
ALK I1171T	Ceritinib	Sensitivity/Response	CIViC C	EID9404
ALK F1245C	Crizotinib	Resistance	CIViC C	EID1333
ALK Exon 4-11 Deletion	Brigatinib	Sensitivity/Response	CIViC D	EID1336
ALK F1174L	AZD3463	Sensitivity/Response	CIViC D	EID1327
ALK F1174L	Lorlatinib	Sensitivity/Response	CIViC D	EID1329
ALK F1174L	ALK Inhibitor TAE684	Sensitivity/Response	CIViC D	EID142
ALK F1174L	Alectinib	Sensitivity/Response	CIViC D	EID37
ALK F1245C	Lorlatinib	Sensitivity/Response	CIViC D	EID1330
ALK R1275Q	Lorlatinib	Sensitivity/Response	CIViC D	EID1331
CDK9 Overexpression	Dinaciclib	Sensitivity/Response	CIViC D	EID7012
EZH2 Overexpression	Tazemetostat + GSK126	Sensitivity/Response	CIViC D	EID9115
MYCN Amplification	JQ1	Sensitivity/Response	CIViC D	EID6017
MYCN Amplification	Birabresib	Sensitivity/Response	CIViC D	EID6018
MYCN Amplification	JQ1 + Panobinostat	Sensitivity/Response	CIViC D	EID6019
MYCN Amplification	GSK126 + JQEZ5	Sensitivity/Response	CIViC D	EID6020
MYCN Amplification	FACT Complex-targeting Curaxin CBL0137	Sensitivity/Response	CIViC D	EID744
MYCN Overexpression	Niraparib + Veliparib + Olaparib + Talazoparib	Sensitivity/Response	CIViC D	EID9006
NF1 Loss	Binimetinib	Sensitivity/Response	CIViC D	EID1956
NRAS Q61K	Everolimus + Binimetinib	Sensitivity/Response	CIViC D	EID1002
ALK R1275Q	ALK Inhibitor TAE684	Resistance	CIViC D	EID48