Craniopharyngioma

Summary

Craniopharyngioma (MONDO:0018907) is a disease with 6 cohort genes (1 GWAS associations across 1 studies) and 34 clinical trials. Top therapeutic interventions include phentermine, dabrafenib, and diazoxide.

At a glance

• Prevalence: 1-9 / 100 000 (Europe) [Orphanet-validated]
• Cohort genes: 6
• GWAS associations: 1
• ClinVar variants: 8
• Phenotypes (HPO): 46
• Clinical trials: 34

Clinical features

Epidemiology

Prevalence records

4 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	1-9 / 100 000	2	Europe	Validated
Annual incidence	1-9 / 1 000 000	0.19	United States	Validated
Annual incidence	1-9 / 1 000 000	0.17	Sweden	Validated
Annual incidence	1-9 / 100 000	1	Worldwide	Not yet validated

Signs & symptoms

Clinical features (HPO)

46 HPO clinical features (Orphanet curated; top 46 by frequency):

HPO ID	Term	Frequency
HP:0012286	Abnormal hypothalamus morphology	Obligate (100%)
HP:0002514	Cerebral calcification	Very frequent (80-99%)
HP:0010576	Intracranial cystic lesion	Very frequent (80-99%)
HP:0011750	Neoplasm of the anterior pituitary	Very frequent (80-99%)
HP:0012505	Enlarged pituitary gland	Very frequent (80-99%)
HP:0040075	Hypopituitarism	Very frequent (80-99%)
HP:0000044	Hypogonadotropic hypogonadism	Frequent (30-79%)
HP:0000135	Hypogonadism	Frequent (30-79%)
HP:0000863	Central diabetes insipidus	Frequent (30-79%)
HP:0000870	Increased circulating prolactin concentration	Frequent (30-79%)
HP:0001085	Papilledema	Frequent (30-79%)
HP:0001262	Excessive daytime somnolence	Frequent (30-79%)
HP:0001513	Obesity	Frequent (30-79%)
HP:0002017	Nausea and vomiting	Frequent (30-79%)
HP:0002315	Headache	Frequent (30-79%)
HP:0002360	Sleep abnormality	Frequent (30-79%)
HP:0007924	Slow decrease in visual acuity	Frequent (30-79%)
HP:0007987	Progressive visual field defects	Frequent (30-79%)
HP:0008245	Pituitary hypothyroidism	Frequent (30-79%)
HP:0011734	Central adrenal insufficiency	Frequent (30-79%)
HP:0030521	Bitemporal hemianopia	Frequent (30-79%)
HP:0030588	Abnormal visual field test	Frequent (30-79%)
HP:0000238	Hydrocephalus	Occasional (5-29%)
HP:0000365	Hearing impairment	Occasional (5-29%)
HP:0000648	Optic atrophy	Occasional (5-29%)
HP:0000823	Delayed puberty	Occasional (5-29%)
HP:0001510	Growth delay	Occasional (5-29%)
HP:0002516	Increased intracranial pressure	Occasional (5-29%)
HP:0002591	Polyphagia	Occasional (5-29%)
HP:0002637	Cerebral ischemia	Occasional (5-29%)
HP:0002659	Increased susceptibility to fractures	Occasional (5-29%)
HP:0003508	Proportionate short stature	Occasional (5-29%)
HP:0005978	Type II diabetes mellitus	Occasional (5-29%)
HP:0010535	Sleep apnea	Occasional (5-29%)
HP:0000708	Atypical behavior	Very rare (<1-4%)
HP:0001117	Sudden loss of visual acuity	Very rare (<1-4%)
HP:0001249	Intellectual disability	Very rare (<1-4%)
HP:0001250	Seizure	Very rare (<1-4%)
HP:0001259	Coma	Very rare (<1-4%)
HP:0001263	Global developmental delay	Very rare (<1-4%)
HP:0001658	Myocardial infarction	Very rare (<1-4%)
HP:0002321	Vertigo	Very rare (<1-4%)
HP:0002719	Recurrent infections	Very rare (<1-4%)
HP:0008897	Postnatal growth retardation	Very rare (<1-4%)
HP:0010939	Abnormal nasal bone morphology	Very rare (<1-4%)
HP:0430000	Abnormality of the frontal bone	Very rare (<1-4%)

Identifiers

Disease identifiers

Field	Value
Canonical name	craniopharyngioma
Mondo ID	MONDO:0018907
EFO	EFO:1000209
MeSH	D003397
Orphanet	54595
DOID	DOID:3840
NCIT	C2964
SNOMED CT	189179009
UMLS	C0010276
MedGen	41339
GARD	0010486
MedDRA	10011318
NORD	1996
Anatomy (UBERON)	UBERON:0003689
Is cancer (heuristic)	no

Also known as: Adamantinomatous tumor · Adamantinomatous tumour · craniopharyngeal duct tumor · craniopharyngeal duct tumour · craniopharyngioma (morphologic abnormality) · craniopharyngioma (WHO grade I) · craniopharyngioma, benign · Dysodontogenic epithelial tumor · Dysodontogenic epithelial tumour · neoplasm of Rathke’s pouch · Rathke pouch neoplasm · Rathke pouch tumor · Rathke pouch tumour · Rathke’s pouch neoplasm · Rathke’s pouch tumor · Rathke’s pouch tumour · tumor of Rathke’s pouch · tumour of Rathke’s pouch

Data availability: 8 ClinVar variants · 1 GWAS association (1 study) · 1 cell line.

Disease family

An umbrella term covering 2 Mondo subtypes.

Classification path: disease › human disease › disease by etiologic mechanism › cancer or benign tumor › neoplastic disease or syndrome › neoplasm › benign neoplasm › nervous system benign neoplasm › central nervous system organ benign neoplasm › craniopharyngioma

Related subtypes (12): central nervous system chondroma, central nervous system hemangioma, central nervous system leiomyoma, central nervous system lipoma, benign neoplasm of brain, benign neoplasm of spinal cord, benign neoplasm of meninges, benign neoplasm of peripheral nervous system, myxoid glioneuronal tumor, diffuse leptomeningeal glioneuronal tumor, multinodular and vacuolating neuronal tumor, polymorphous low grade neuroepithelial tumor of the young

Subtypes (2): adamantinous craniopharyngioma, papillary craniopharyngioma

Genetics & variants

GWAS landscape

1 GWAS associations across 1 studies. Top hits map to 0 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs147220408	2e-07	RP9P - RPL7AP78	?

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90651924	Liu TY	2025	490	234,488	Diversity and longitudinal records: Genetic architecture of disease associations and polygenic risk in the Taiwanese Han population.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

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

MAF distribution

Bucket	Variants
common (>=0.05)	0
low_freq (0.01-0.05)	0
rare (<0.01)	0
unknown	1

Functional consequences

Consequence	Count
intergenic_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs147220408	7	32947772	GTATC>G		intergenic_variant	RP9P - RPL7AP78	2e-07	Tier 4: intronic/intergenic

ClinVar germline variants

8 retrieved; paginated sample, class counts are floors:

6 conflicting classifications of pathogenicity, 1 pathogenic/likely pathogenic, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
88913	NM_000038.6(APC):c.3183_3187del (p.Lys1061_Gln1062insTer)	APC	Pathogenic	criteria provided, multiple submitters, no conflicts
620626	NM_000400.4(ERCC2):c.1361TCA[2] (p.Ile456del)	ERCC2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
216367	NM_000264.5(PTCH1):c.113G>A (p.Gly38Glu)	LOC130002133	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
457720	NM_001042492.3(NF1):c.4836G>A (p.Arg1612=)	NF1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
620601	NM_000264.5(PTCH1):c.203G>A (p.Gly68Glu)	PTCH1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
241089	NM_016169.4(SUFU):c.839G>A (p.Arg280Gln)	SUFU	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
411263	NM_000368.5(TSC1):c.1355G>C (p.Gly452Ala)	TSC1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
64790	NM_000368.5(TSC1):c.1231C>A (p.Leu411Ile)	TSC1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 38 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TSC1	Orphanet:210159	Adult hepatocellular carcinoma
TSC1	Orphanet:269008	Isolated focal cortical dysplasia type IIb
TSC1	Orphanet:538	Lymphangioleiomyomatosis
TSC1	Orphanet:805	Tuberous sclerosis complex
SUFU	Orphanet:2495	Meningioma
SUFU	Orphanet:251858	Medulloblastoma with extensive nodularity
SUFU	Orphanet:251863	Desmoplastic/nodular medulloblastoma
SUFU	Orphanet:263662	Familial multiple meningioma
SUFU	Orphanet:280200	Microform holoprosencephaly
SUFU	Orphanet:377	Gorlin syndrome
SUFU	Orphanet:475	Isolated Joubert syndrome
ERCC2	Orphanet:1466	COFS syndrome
ERCC2	Orphanet:220295	Xeroderma pigmentosum-Cockayne syndrome complex
ERCC2	Orphanet:33364	Trichothiodystrophy
ERCC2	Orphanet:910	Xeroderma pigmentosum
APC	Orphanet:220460	Attenuated familial adenomatous polyposis
APC	Orphanet:261584	5q22 microdeletion syndrome
APC	Orphanet:314022	Gastric adenocarcinoma and proximal polyposis of the stomach
APC	Orphanet:3258	Cenani-Lenz syndrome
APC	Orphanet:873	Desmoid tumor
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
PTCH1	Orphanet:220386	Semilobar holoprosencephaly
PTCH1	Orphanet:2353	Schilbach-Rott syndrome
PTCH1	Orphanet:280195	Septopreoptic holoprosencephaly
PTCH1	Orphanet:280200	Microform holoprosencephaly
PTCH1	Orphanet:377	Gorlin syndrome
PTCH1	Orphanet:77301	Monosomy 9q22.3 syndrome
PTCH1	Orphanet:93924	Lobar holoprosencephaly
PTCH1	Orphanet:93925	Alobar holoprosencephaly
PTCH1	Orphanet:93926	Midline interhemispheric variant of holoprosencephaly

Cohort genes → proteins

6 cohort genes, 6 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	6

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
TSC1	HGNC:12362	ENSG00000165699	Q92574	Hamartin	clinvar
SUFU	HGNC:16466	ENSG00000107882	Q9UMX1	Suppressor of fused homolog	clinvar
ERCC2	HGNC:3434	ENSG00000104884	P18074	General transcription and DNA repair factor IIH helicase subunit XPD	clinvar
APC	HGNC:583	ENSG00000134982	P25054	Adenomatous polyposis coli protein	clinvar
NF1	HGNC:7765	ENSG00000196712	P21359	Neurofibromin	clinvar
PTCH1	HGNC:9585	ENSG00000185920	Q13635	Protein patched homolog 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
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…
SUFU	Suppressor of fused homolog	Negative regulator in the hedgehog/smoothened signaling pathway.
ERCC2	General transcription and DNA repair factor IIH helicase subunit XPD	ATP-dependent 5’-3’ DNA helicase.
APC	Adenomatous polyposis coli protein	Tumor suppressor.
NF1	Neurofibromin	Stimulates the GTPase activity of Ras.
PTCH1	Protein patched homolog 1	Acts as a receptor for sonic hedgehog (SHH), indian hedgehog (IHH) and desert hedgehog (DHH).

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 5 · Druggable fraction: 0.17

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
Other/Unknown	5	1.5×	0.348
Enzyme (other)	1	2.0×	0.407

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TSC1	Other/Unknown	no		Hamartin
SUFU	Other/Unknown	no		Suppressor_of_fused, Suppressor_of_fused_euk, SUFU-like_domain
ERCC2	Enzyme (other)	yes	3.6.4.12	RAD3/XPD, DNA/RNA_helicase_DEAH_CS, Helicase-like_DEXD_c2
APC	Other/Unknown	no		Armadillo, APC_rpt, SAMP
NF1	Other/Unknown	no		CRAL-TRIO_dom, RasGAP_dom, Rho_GTPase_activation_prot
PTCH1	Other/Unknown	no		SSD, TM_rcpt_patched, HMGCR/SNAP/NPC1-like_SSD

Expression context

Cohort genes with no expression data: 0.

5 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)	6
unknown	0

Top tissues across cohort

Tissue	Cohort genes
substantia nigra pars compacta	2
gluteal muscle	1
lateral globus pallidus	1
kidney epithelium	1
upper arm skin	1
vena cava	1
left adrenal gland	1
right adrenal gland	1
stromal cell of endometrium	1
medial globus pallidus	1
substantia nigra pars reticulata	1
adrenal tissue	1
calcaneal tendon	1
colonic epithelium	1
dorsal root ganglion	1
tibia	1
trigeminal ganglion	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TSC1	297	ubiquitous	marker	substantia nigra pars compacta, gluteal muscle, lateral globus pallidus
SUFU	226	ubiquitous	yes	upper arm skin, kidney epithelium, vena cava
ERCC2	184	ubiquitous	marker	stromal cell of endometrium, right adrenal gland, left adrenal gland
APC	297	ubiquitous	marker	substantia nigra pars compacta, substantia nigra pars reticulata, medial globus pallidus
NF1	283	ubiquitous	marker	colonic epithelium, calcaneal tendon, adrenal tissue
PTCH1	275	ubiquitous	marker	tibia, dorsal root ganglion, trigeminal ganglion

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
NF1	5,540
TSC1	5,445
PTCH1	3,368
APC	2,903
ERCC2	2,746
SUFU	2,188

Intra-cohort edges

A	B	Sources
PTCH1	SUFU	string_interaction

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ERCC2	P18074	51
APC	P25054	31
NF1	P21359	26
PTCH1	Q13635	16
SUFU	Q9UMX1	10
TSC1	Q92574	5

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 82. Enrichment computed across 6 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
APC truncation mutants are not K63 polyubiquitinated	1	1903.3×	0.016	APC
Hedgehog ‘off’ state	2	59.5×	0.016	SUFU, PTCH1
Hedgehog ‘on’ state	2	52.9×	0.016	SUFU, PTCH1
Inhibition of TSC complex formation by AKT (PKB)	1	380.7×	0.031	TSC1
GLI proteins bind promoters of Hh responsive genes to promote transcription	1	271.9×	0.031	PTCH1
RAS signaling downstream of NF1 loss-of-function variants	1	271.9×	0.031	NF1
Ligand-receptor interactions	1	237.9×	0.031	PTCH1
Signaling by AXIN mutants	1	173.0×	0.031	APC
Signaling by CTNNB1 phospho-site mutants	1	173.0×	0.031	APC
Signaling by APC mutants	1	173.0×	0.031	APC
Signaling by AMER1 mutants	1	173.0×	0.031	APC
APC truncation mutants have impaired AXIN binding	1	135.9×	0.031	APC
AXIN missense mutants destabilize the destruction complex	1	135.9×	0.031	APC
Truncations of AMER1 destabilize the destruction complex	1	135.9×	0.031	APC
Cytosolic iron-sulfur cluster assembly	1	126.9×	0.031	ERCC2
Signaling by GSK3beta mutants	1	126.9×	0.031	APC
CTNNB1 S33 mutants aren’t phosphorylated	1	126.9×	0.031	APC
CTNNB1 S37 mutants aren’t phosphorylated	1	126.9×	0.031	APC
CTNNB1 S45 mutants aren’t phosphorylated	1	126.9×	0.031	APC
CTNNB1 T41 mutants aren’t phosphorylated	1	126.9×	0.031	APC
Diseases of signal transduction by growth factor receptors and second messengers	2	18.9×	0.031	APC, NF1
Beta-catenin phosphorylation cascade	1	112.0×	0.033	APC
Activation of SMO	1	105.7×	0.034	PTCH1
Signaling by WNT in cancer	1	100.2×	0.034	APC
Apoptotic cleavage of cellular proteins	1	79.3×	0.040	APC
Apoptotic execution phase	1	79.3×	0.040	APC
RNA Pol II CTD phosphorylation and interaction with CE during HIV infection	1	68.0×	0.040	ERCC2
RNA Pol II CTD phosphorylation and interaction with CE	1	68.0×	0.040	ERCC2
Energy dependent regulation of mTOR by LKB1-AMPK	1	65.6×	0.040	TSC1
mRNA Capping	1	63.4×	0.040	ERCC2

GO biological processes 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.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
hair follicle maturation	2	702.2×	4e-04	ERCC2, NF1
neural tube closure	3	93.6×	4e-04	TSC1, SUFU, PTCH1
regulation of cell-matrix adhesion	2	432.1×	7e-04	TSC1, NF1
smooth muscle tissue development	2	351.1×	8e-04	NF1, PTCH1
negative regulation of protein import into nucleus	2	312.1×	8e-04	SUFU, NF1
negative regulation of stem cell proliferation	2	280.9×	8e-04	NF1, PTCH1
dorsal/ventral neural tube patterning	2	267.5×	8e-04	SUFU, PTCH1
spinal cord development	2	170.2×	0.002	ERCC2, NF1
embryonic organ development	2	160.5×	0.002	ERCC2, PTCH1
negative regulation of smoothened signaling pathway	2	151.8×	0.002	SUFU, PTCH1
stem cell proliferation	2	104.0×	0.003	NF1, PTCH1
negative regulation of osteoblast differentiation	2	98.5×	0.003	SUFU, PTCH1
positive regulation of mast cell apoptotic process	1	2808.7×	0.005	NF1
regulation of glial cell differentiation	1	2808.7×	0.005	NF1
observational learning	1	2808.7×	0.005	NF1
positive regulation of cellular response to drug	1	2808.7×	0.005	SUFU
cerebral cortex development	2	68.5×	0.005	TSC1, NF1
response to chlorate	1	1404.3×	0.007	PTCH1
smoothened signaling pathway involved in ventral spinal cord interneuron specification	1	1404.3×	0.007	SUFU
smoothened signaling pathway involved in spinal cord motor neuron cell fate specification	1	1404.3×	0.007	SUFU
neural plate axis specification	1	1404.3×	0.007	PTCH1
positive regulation of mitotic recombination	1	1404.3×	0.007	ERCC2
gamma-aminobutyric acid secretion, neurotransmission	1	1404.3×	0.007	NF1
cell proliferation involved in metanephros development	1	1404.3×	0.007	PTCH1
maintenance of protein localization in organelle	1	1404.3×	0.007	SUFU
spermatid development	2	48.4×	0.007	SUFU, PTCH1
Schwann cell proliferation	1	936.2×	0.007	NF1
forebrain astrocyte development	1	936.2×	0.007	NF1
Schwann cell migration	1	936.2×	0.007	NF1
memory T cell differentiation	1	936.2×	0.007	TSC1

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): Cobimetinib, Dabrafenib, Dextrose, Methionine, Nivolumab, PEGINTERFERON ALFA-2B, Tovorafenib, Trametinib, Vemurafenib.

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 5

Druggability breadth: 4 of 6 evidence-associated genes (67%) 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
ERCC2	SUNITINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ERCC2	16	4
TSC1	0	0
SUFU	0	0
APC	0	0
NF1	0	0
PTCH1	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
SUNITINIB	4	ERCC2
DINACICLIB	3	ERCC2
DEFACTINIB	3	ERCC2
ALVOCIDIB	3	ERCC2
SELICICLIB	2	ERCC2
ZOTIRACICLIB	2	ERCC2
DANUSERTIB	2	ERCC2
MILCICLIB	2	ERCC2
PF-00562271	1	ERCC2
PHA-793887	1	ERCC2
KW-2449	1	ERCC2
BMS-387032	1	ERCC2
PF-03758309	1	ERCC2
TAK-901	1	ERCC2
RGB-286638	1	ERCC2
XL-228	1	ERCC2

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
APC	24	Binding:24
PTCH1	4	Binding:4
ERCC2	3	Binding:3
SUFU	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
ERCC2	3.6.4.12	DNA helicase

Pharmacogenomics

Cohort genes with a PharmGKB record: 6; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

16 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)
SUNITINIB	4	ERCC2
DINACICLIB	3	ERCC2
DEFACTINIB	3	ERCC2
ALVOCIDIB	3	ERCC2
SELICICLIB	2	ERCC2
ZOTIRACICLIB	2	ERCC2
DANUSERTIB	2	ERCC2
MILCICLIB	2	ERCC2
PF-00562271	1	ERCC2
PHA-793887	1	ERCC2
KW-2449	1	ERCC2
BMS-387032	1	ERCC2
PF-03758309	1	ERCC2
TAK-901	1	ERCC2
RGB-286638	1	ERCC2
XL-228	1	ERCC2

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	ERCC2
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	5	TSC1, SUFU, APC, NF1, PTCH1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
TSC1	0	—
SUFU	1	—
APC	24	—
NF1	0	—
PTCH1	4	—

Clinical trials & evidence

Clinical trials

Clinical trials: 34.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	17
PHASE2	11
PHASE3	3
PHASE4	1
PHASE1/PHASE2	1
EARLY_PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT02190994	PHASE4	UNKNOWN	Effect of Perioperative Glucocorticoid Replacement on Prognosis of Surgical Patients With Sellar Lesions
NCT00306683	PHASE3	COMPLETED	Effect of Diazoxide on the Obesity Secondary to Hypothalamic-pituitary Lesions
NCT00517959	PHASE3	UNKNOWN	SCRT Versus Conventional RT in Children and Young Adults With Low Grade and Benign Brain Tumors
NCT02860923	PHASE3	COMPLETED	Efficacy and Safety of Exenatide in the Treatment of Hypothalamic Obesity After Craniopharyngioma Therapy
NCT00840047	PHASE2	ACTIVE_NOT_RECRUITING	Methionine PET/CT Studies In Patients With Cancer
NCT01419067	PHASE2	ACTIVE_NOT_RECRUITING	A Phase II Trial of Limited Surgery and Proton Therapy for Craniopharyngioma or Observation After Radical Resection
NCT02792582	PHASE2	ACTIVE_NOT_RECRUITING	A Phase II Trial of Intensity-Modulated Proton Therapy for Incompletely Resected Craniopharyngioma and Observation for Craniopharyngioma After Radical Resection
NCT05465174	PHASE2	RECRUITING	Tovorafenib for Treatment of Craniopharyngioma in Children and Young Adults
NCT05525273	PHASE2	RECRUITING	Treatment of BRAF ( B-Rapidly Accelerated Fibrosarcoma) Mutated Papillary Craniopharyngioma
NCT06299891	PHASE2	RECRUITING	Efficacy and Safety of Phentermine/Topiramate in Youth With Hypothalamic Obesity
NCT06970145	PHASE1/PHASE2	RECRUITING	Safety and Efficacy of Anlotinib in the Treatment of Recurrent Craniopharyngioma
NCT01484873	PHASE2	COMPLETED	Weight Loss Study for Patients With Obesity Due to Craniopharyngioma or Other Brain Tumor
NCT02063295	PHASE2	COMPLETED	An Efficacy, Safety, and Pharmacokinetics Study of Beloranib in Obese Subjects With Hypothalamic Injury
NCT02842723	PHASE2	COMPLETED	Management of Pediatric Craniopharyngioma by a Combination of Partial Surgical Resection, and Protontherapy (Craniopharyngioma)
NCT02849743	PHASE2	COMPLETED	Intranasal Oxytocin in Hypothalamic Obesity
NCT03194906	PHASE2	COMPLETED	Memantine for Prevention of Cognitive Late Effects in Pediatric Patients Receiving Cranial Radiation Therapy for Localized Brain Tumors
NCT06217848	EARLY_PHASE1	UNKNOWN	The Effect of GLP-1 Agonist in Patients With Hypothalamic Obesity: Prospective, Pilot Study
NCT04087902	Not specified	ACTIVE_NOT_RECRUITING	Long-Term Longitudinal QoL in Patients Undergoing EEA
NCT04648462	Not specified	RECRUITING	Proton Therapy Research Infrastructure- ProTRAIT- Neuro-oncology
NCT06801756	Not specified	RECRUITING	Craniopharyngioma and Pregnancies
NCT06874426	Not specified	RECRUITING	The Impact of Endoscopic Endonasal Skull Base Surgery on Olfaction
NCT07177482	Not specified	RECRUITING	ImmunoPET Targeting Trophoblast Cell-surface Antigen 2 (Trop-2) in Craniopharyngioma Patients
NCT07301554	Not specified	NOT_YET_RECRUITING	Food Preferences and Craniopharyngiomas
NCT07316101	Not specified	NOT_YET_RECRUITING	Clinical Trial of an Anti-Fog Drainage Device for Endoscopic Endonasal Sellar Region Tumor Surgery
NCT00949156	Not specified	UNKNOWN	Tumor Classification and Its Application in Surgical Treatment of Craniopharyngioma
NCT01206543	Not specified	COMPLETED	1.5T Intraoperative MR Imaging in Craniopharyngiomas
NCT01272622	Not specified	COMPLETED	Prospective Study of Children and Adolescents With Craniopharyngioma
NCT01881854	Not specified	COMPLETED	Sleep Wake and Melatonin Pattern in Craniopharyngioma
NCT02162732	Not specified	COMPLETED	Molecular-Guided Therapy for Childhood Cancer
NCT03330080	Not specified	COMPLETED	Examination of Sleep and Family Functioning in Pediatric Craniopharyngioma Patients
NCT03708913	Not specified	WITHDRAWN	Neuromodulation for Hypothalamic Obesity
NCT04158284	Not specified	UNKNOWN	Multicenter Registry for Patients With Childhood.Onset Craniopharyngioma, Xanthogranuloma, Cysts of Rathke’s Pouch, Meningioma, Pituitary Adenoma, Arachnoid Cysts
NCT04937335	Not specified	COMPLETED	Craniopharyngioma With Tumoral Hemorrhage
NCT07342686	Not specified	COMPLETED	Hypothalamic-Stratified Nursing Pathway for Pediatric Craniopharyngioma

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
PHENTERMINE	4	3
DABRAFENIB	4	1
DIAZOXIDE	4	1
HYDROCORTISONE	4	1
PREDNISONE	4	1
TOVORAFENIB	4	1
METHIONINE	3	1
CHEMBL15720	0	1
CHEMBL1234268	0	1
RACEMETHIONINE	-1	1