Nevoid basal cell carcinoma syndrome

Summary

Nevoid basal cell carcinoma syndrome (MONDO:0007187) is a cancer caused by variants in PTCH1 and SUFU, with 7 cohort genes (3 CIViC-evidence somatic drivers; 6,834 ClinVar predisposition records) and 22 clinical trials. Top therapeutic interventions include vismodegib, sonidegib, and aminolevulinic acid.

At a glance

• Classification: Cancer
• Prevalence: 1-9 / 100 000 (Worldwide) [Orphanet-validated]
• Causal genes: PTCH1 (GenCC Definitive), SUFU (GenCC Definitive)
• Cohort genes: 7
• ClinVar variants: 6,834
• Phenotypes (HPO): 45
• Clinical trials: 22

Clinical features

Epidemiology

Prevalence records

7 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	1-9 / 100 000	1.1	Worldwide	Validated
Point prevalence	1-9 / 100 000	2	Europe	Validated
Point prevalence	1-9 / 100 000	3.2	United Kingdom	Validated
Point prevalence	1-9 / 1 000 000	0.39	Italy	Validated
Point prevalence	1-9 / 1 000 000	0.61	Australia	Validated
Point prevalence	<1 / 1 000 000	0.007	Korea, Republic of	Validated
Prevalence at birth	1-9 / 100 000	5.3	United Kingdom	Validated

Signs & symptoms

Clinical features (HPO)

45 HPO clinical features (Orphanet curated; top 45 by frequency):

HPO ID	Term	Frequency
HP:0000995	Melanocytic nevus	Very frequent (80-99%)
HP:0002514	Cerebral calcification	Very frequent (80-99%)
HP:0002664	Neoplasm	Very frequent (80-99%)
HP:0010610	Palmar pits	Very frequent (80-99%)
HP:0010612	Plantar pits	Very frequent (80-99%)
HP:0000256	Macrocephaly	Frequent (30-79%)
HP:0000431	Wide nasal bridge	Frequent (30-79%)
HP:0000464	Abnormality of the neck	Frequent (30-79%)
HP:0000772	Abnormal rib morphology	Frequent (30-79%)
HP:0000892	Bifid ribs	Frequent (30-79%)
HP:0000902	Rib fusion	Frequent (30-79%)
HP:0000907	Anterior rib cupping	Frequent (30-79%)
HP:0001156	Brachydactyly	Frequent (30-79%)
HP:0002650	Scoliosis	Frequent (30-79%)
HP:0002671	Basal cell carcinoma	Frequent (30-79%)
HP:0002948	Vertebral fusion	Frequent (30-79%)
HP:0005462	Calcification of falx cerebri	Frequent (30-79%)
HP:0008422	Vertebral wedging	Frequent (30-79%)
HP:0010603	Odontogenic keratocysts of the jaw	Frequent (30-79%)
HP:0000028	Cryptorchidism	Occasional (5-29%)
HP:0000044	Hypogonadotropic hypogonadism	Occasional (5-29%)
HP:0000202	Orofacial cleft	Occasional (5-29%)
HP:0000238	Hydrocephalus	Occasional (5-29%)
HP:0000248	Brachycephaly	Occasional (5-29%)
HP:0000280	Coarse facial features	Occasional (5-29%)
HP:0000286	Epicanthus	Occasional (5-29%)
HP:0000303	Mandibular prognathia	Occasional (5-29%)
HP:0000316	Hypertelorism	Occasional (5-29%)
HP:0000486	Strabismus	Occasional (5-29%)
HP:0000501	Glaucoma	Occasional (5-29%)
HP:0000506	Telecanthus	Occasional (5-29%)
HP:0000518	Cataract	Occasional (5-29%)
HP:0000612	Iris coloboma	Occasional (5-29%)
HP:0000670	Carious teeth	Occasional (5-29%)
HP:0001166	Arachnodactyly	Occasional (5-29%)
HP:0001249	Intellectual disability	Occasional (5-29%)
HP:0002007	Frontal bossing	Occasional (5-29%)
HP:0002858	Meningioma	Occasional (5-29%)
HP:0002937	Hemivertebrae	Occasional (5-29%)
HP:0003468	Abnormal vertebral morphology	Occasional (5-29%)
HP:0004408	Abnormality of the sense of smell	Occasional (5-29%)
HP:0005449	Bridged sella turcica	Occasional (5-29%)
HP:0010618	Ovarian fibroma	Occasional (5-29%)
HP:0002885	Medulloblastoma	Very rare (<1-4%)
HP:0010617	Cardiac fibroma	Very rare (<1-4%)

Identifiers

Disease identifiers

Field	Value
Canonical name	nevoid basal cell carcinoma syndrome
Mondo ID	MONDO:0007187
MeSH	D001478
OMIM	109400
Orphanet	377
DOID	DOID:0070365, DOID:2512
ICD-11	1012745138
NCIT	C2892
SNOMED CT	69408002
UMLS	C0004779
MedGen	2554
GARD	0007166
MedDRA	10062804
NORD	1507
Is cancer (heuristic)	yes

Also known as: basal cell nevus syndrome · BCNS · Gorlin syndrome · Gorlin-Goltz syndrome · multiple basal cell carcinomas · NBCCS · nevoid basal cell cancer syndrome · nevoid basal cell carcinoma syndrome

Data availability: 6,834 ClinVar variants · 11 GenCC gene-disease records · 46 cell lines.

Disease family

An umbrella term covering 2 Mondo subtypes.

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › autosomal genetic disease › autosomal dominant disease › nevoid basal cell carcinoma syndrome

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

Subtypes (2): basal cell nevus syndrome 1, basal cell nevus syndrome 2

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

600 retrieved; paginated sample, class counts are floors:

238 uncertain significance, 214 likely benign, 83 pathogenic, 55 conflicting classifications of pathogenicity, 5 likely pathogenic, 3 benign/likely benign, 2 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1037360	NM_000264.5(PTCH1):c.2532G>C (p.Trp844Cys)	LOC100507346	Pathogenic	criteria provided, single submitter
1070252	NM_000264.5(PTCH1):c.2484del (p.Asn828fs)	LOC100507346	Pathogenic	criteria provided, single submitter
1070553	NM_000264.5(PTCH1):c.2296del (p.Tyr766fs)	LOC100507346	Pathogenic	criteria provided, single submitter
1070827	NM_000264.5(PTCH1):c.1847+2T>G	LOC100507346	Pathogenic	criteria provided, single submitter
1071127	NM_000264.5(PTCH1):c.2322dup (p.Leu775fs)	LOC100507346	Pathogenic	criteria provided, single submitter
1071471	NM_000264.5(PTCH1):c.2369_2370del (p.Phe790fs)	LOC100507346	Pathogenic	criteria provided, single submitter
1072168	NM_000264.5(PTCH1):c.2382del (p.Gln794fs)	LOC100507346	Pathogenic	criteria provided, single submitter
1072438	NM_000264.5(PTCH1):c.2204_2205del (p.Phe735fs)	LOC100507346	Pathogenic	criteria provided, single submitter
1072729	NM_000264.5(PTCH1):c.2332dup (p.Thr778fs)	LOC100507346	Pathogenic	criteria provided, multiple submitters, no conflicts
1072731	NM_000264.5(PTCH1):c.2178dup (p.Cys727fs)	LOC100507346	Pathogenic	criteria provided, multiple submitters, no conflicts
1073589	NM_000264.5(PTCH1):c.2493T>A (p.Tyr831Ter)	LOC100507346	Pathogenic	criteria provided, single submitter
1074462	NM_000264.5(PTCH1):c.2477del (p.Phe826fs)	LOC100507346	Pathogenic	criteria provided, single submitter
1074759	NM_000264.5(PTCH1):c.2107G>T (p.Glu703Ter)	LOC100507346	Pathogenic	criteria provided, single submitter
1075361	NM_000264.5(PTCH1):c.2370del (p.Phe790fs)	LOC100507346	Pathogenic	criteria provided, single submitter
1075463	NM_000264.5(PTCH1):c.2172dup (p.Pro725fs)	LOC100507346	Pathogenic	criteria provided, single submitter
1076107	NM_000264.5(PTCH1):c.2199_2203del (p.Ser734fs)	LOC100507346	Pathogenic	criteria provided, single submitter
1076315	NM_000264.5(PTCH1):c.2144del (p.Phe715fs)	LOC100507346	Pathogenic	criteria provided, single submitter
1072595	NM_016169.4(SUFU):c.37_53del (p.Thr13fs)	LOC130004614	Pathogenic	criteria provided, multiple submitters, no conflicts
1020298	NM_000264.5(PTCH1):c.1524TGGTGT[1] (p.509GV[1])	PTCH1	Pathogenic	criteria provided, single submitter
1068532	NM_000264.5(PTCH1):c.654+1G>A	PTCH1	Pathogenic	criteria provided, multiple submitters, no conflicts
1068897	NM_000264.5(PTCH1):c.3030del (p.Asn1011fs)	PTCH1	Pathogenic	criteria provided, single submitter
1068908	NM_000264.5(PTCH1):c.1526G>T (p.Gly509Val)	PTCH1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1068949	NC_000009.12:g.95449841dup	PTCH1	Pathogenic	criteria provided, single submitter
1069018	NM_000264.5(PTCH1):c.1480dup (p.Ser494fs)	PTCH1	Pathogenic	criteria provided, single submitter
1069312	NC_000009.12:g.95482041_95482042insGCTCTCCCTCTCCCTCTCCCTCTCCCTCTCCCTCTCCCTCCCCCTCCCTCTCCCTCTCCCTCTCCCTCTACCTCCACGGTCNNNNNNNNNNAAAAAAAAAAAAAAAAAAAAAAAGATATTCTATTATC	PTCH1	Pathogenic	criteria provided, single submitter
1069426	NM_000264.5(PTCH1):c.1603-1G>A	PTCH1	Pathogenic	criteria provided, single submitter
1069671	NC_000009.11:g.(?98229392)(98232219_?)del	PTCH1	Pathogenic	criteria provided, single submitter
1069761	NM_000264.5(PTCH1):c.1068-2A>G	PTCH1	Pathogenic	criteria provided, single submitter
1069765	NM_000264.5(PTCH1):c.554_584+1dup	PTCH1	Pathogenic	criteria provided, single submitter
1069985	NM_000264.5(PTCH1):c.376G>T (p.Glu126Ter)	PTCH1	Pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 34 · Orphanet: 21 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
SUFU	LoF	PAST	CIViC #12074
PTCH1	LoF	ANGS,BCC,CHOL,ESCA,MBL,NPC,OS,PAST,PLMESO,SKIN,WDTC	CIViC #4645
FANCC			CIViC #1811

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
PTCH1	Definitive	Autosomal dominant	nevoid basal cell carcinoma syndrome	12
SUFU	Definitive	Autosomal dominant	nevoid basal cell carcinoma syndrome	16
PTCH2	Moderate	Autosomal dominant	nevoid basal cell carcinoma syndrome	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
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
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
PTCH2	Orphanet:141276	Tessier number 7 facial cleft
PTCH2	Orphanet:377	Gorlin syndrome
FANCC	Orphanet:84	Fanconi anemia
ARL3	Orphanet:475	Isolated Joubert syndrome
ARL3	Orphanet:791	Retinitis pigmentosa

Cohort genes → proteins

7 cohort genes, 7 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	7

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SUFU	HGNC:16466	ENSG00000107882	Q9UMX1	Suppressor of fused homolog	gencc,clinvar
PTCH1	HGNC:9585	ENSG00000185920	Q13635	Protein patched homolog 1	gencc,clinvar
PTCH2	HGNC:9586	ENSG00000117425	Q9Y6C5	Protein patched homolog 2	gencc,clinvar
AOPEP	HGNC:1361	ENSG00000148120	Q8N6M6	Aminopeptidase O	clinvar
ANP32B	HGNC:16677	ENSG00000136938	Q92688	Acidic leucine-rich nuclear phosphoprotein 32 family member B	clinvar
FANCC	HGNC:3584	ENSG00000158169	Q00597	Fanconi anemia group C protein	clinvar
ARL3	HGNC:694	ENSG00000138175	P36405	ADP-ribosylation factor-like protein 3	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SUFU	Suppressor of fused homolog	Negative regulator in the hedgehog/smoothened signaling pathway.
PTCH1	Protein patched homolog 1	Acts as a receptor for sonic hedgehog (SHH), indian hedgehog (IHH) and desert hedgehog (DHH).
PTCH2	Protein patched homolog 2	Plays a role in the control of cellular growth.
AOPEP	Aminopeptidase O	Aminopeptidase which catalyzes the hydrolysis of amino acid residues from the N-terminus of peptide or protein substrates.
ANP32B	Acidic leucine-rich nuclear phosphoprotein 32 family member B	Multifunctional protein that is involved in the regulation of many processes including cell proliferation, apoptosis, cell cycle progression or transcription.
FANCC	Fanconi anemia group C protein	DNA repair protein that may operate in a postreplication repair or a cell cycle checkpoint function.
ARL3	ADP-ribosylation factor-like protein 3	Small GTP-binding protein which cycles between an inactive GDP-bound and an active GTP-bound form, and the rate of cycling is regulated by guanine nucleotide exchange factors (GEF) and GTPase-activating proteins (GAP).

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 6 · Druggable fraction: 0.14

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
Protease	1	5.2×	0.176
Other/Unknown	6	1.5×	0.176

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SUFU	Other/Unknown	no		Suppressor_of_fused, Suppressor_of_fused_euk, SUFU-like_domain
PTCH1	Other/Unknown	no		SSD, TM_rcpt_patched, HMGCR/SNAP/NPC1-like_SSD
PTCH2	Other/Unknown	no		SSD, TM_rcpt_patched, HMGCR/SNAP/NPC1-like_SSD
AOPEP	Protease	yes		Peptidase_M1_dom, Peptidase_M1_C, ARM-type_fold
ANP32B	Other/Unknown	no		Leu-rich_rpt, U2A’_phosphoprotein32A_C, LRR_dom_sf
FANCC	Other/Unknown	no		FANCC
ARL3	Other/Unknown	no		Small_GTP-bd, Small_GTPase_ARF/SAR, P-loop_NTPase

Expression context

Cohort genes with no expression data: 0.

6 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)	7
unknown	0

Top tissues across cohort

Tissue	Cohort genes
male germ line stem cell (sensu Vertebrata) in testis	2
kidney epithelium	1
upper arm skin	1
vena cava	1
dorsal root ganglion	1
tibia	1
trigeminal ganglion	1
left testis	1
right ovary	1
apex of heart	1
ascending aorta	1
right coronary artery	1
cranial nerve II	1
tendon of biceps brachii	1
trabecular bone tissue	1
pancreatic ductal cell	1
right lobe of liver	1
bronchial epithelial cell	1
epithelium of bronchus	1
mucosa of paranasal sinus	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SUFU	226	ubiquitous	yes	upper arm skin, kidney epithelium, vena cava
PTCH1	275	ubiquitous	marker	tibia, dorsal root ganglion, trigeminal ganglion
PTCH2	162	broad	marker	male germ line stem cell (sensu Vertebrata) in testis, left testis, right ovary
AOPEP	224	ubiquitous	marker	apex of heart, right coronary artery, ascending aorta
ANP32B	295	ubiquitous	marker	tendon of biceps brachii, trabecular bone tissue, cranial nerve II
FANCC	195	ubiquitous	marker	pancreatic ductal cell, right lobe of liver, male germ line stem cell (sensu Vertebrata) in testis
ARL3	299	ubiquitous	marker	bronchial epithelial cell, mucosa of paranasal sinus, epithelium of bronchus

Protein interactions among cohort

Intra-cohort edges: 2.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PTCH1	3,368
ARL3	2,651
SUFU	2,188
FANCC	1,470
PTCH2	1,199
AOPEP	991
ANP32B	339

Intra-cohort edges

A	B	Sources
PTCH1	SUFU	string_interaction
PTCH2	SUFU	string_interaction

Structural data

PDB: 4 · AlphaFold-only: 3 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PTCH1	Q13635	16
SUFU	Q9UMX1	10
FANCC	Q00597	6
ANP32B	Q92688	4

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ARL3	P36405	92.73
AOPEP	Q8N6M6	83.36
PTCH2	Q9Y6C5	79.25

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 18. Enrichment computed across 7 evidence-associated genes (5 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 5 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
GLI proteins bind promoters of Hh responsive genes to promote transcription	2	652.6×	6e-05	PTCH1, PTCH2
Class B/2 (Secretin family receptors)	2	76.1×	0.002	PTCH1, PTCH2
Hedgehog ‘off’ state	2	71.4×	0.002	SUFU, PTCH1
Hedgehog ‘on’ state	2	63.4×	0.002	SUFU, PTCH1
Trafficking of myristoylated proteins to the cilium	1	456.8×	0.008	ARL3
Ligand-receptor interactions	1	285.5×	0.010	PTCH1
Activation of SMO	1	126.9×	0.020	PTCH1
Fanconi Anemia Pathway	1	55.7×	0.033	FANCC
Cargo trafficking to the periciliary membrane	1	49.6×	0.033	ARL3
Degradation of GLI1 by the proteasome	1	44.8×	0.033	SUFU
Degradation of GLI2 by the proteasome	1	44.8×	0.033	SUFU
GLI3 is processed to GLI3R by the proteasome	1	44.8×	0.033	SUFU
Signaling by Hedgehog	1	36.8×	0.035	SUFU
TP53 Regulates Transcription of DNA Repair Genes	1	36.2×	0.035	FANCC
PKR-mediated signaling	1	28.2×	0.042	FANCC
Cilium Assembly	1	21.8×	0.051	ARL3
Organelle biogenesis and maintenance	1	13.2×	0.078	ARL3
Signal Transduction	1	2.0×	0.404	SUFU

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 7 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
negative regulation of smoothened signaling pathway	3	195.2×	3e-05	SUFU, PTCH1, PTCH2
epidermal cell fate specification	2	963.0×	7e-05	PTCH1, PTCH2
positive regulation of epidermal cell differentiation	2	601.9×	1e-04	PTCH1, PTCH2
cell fate determination	2	267.5×	5e-04	PTCH1, PTCH2
dorsal/ventral neural tube patterning	2	229.3×	6e-04	SUFU, PTCH1
skin development	2	126.7×	0.002	SUFU, PTCH2
negative regulation of osteoblast differentiation	2	84.5×	0.003	SUFU, PTCH1
positive regulation of cellular response to drug	1	2407.4×	0.005	SUFU
response to chlorate	1	1203.7×	0.005	PTCH1
smoothened signaling pathway involved in ventral spinal cord interneuron specification	1	1203.7×	0.005	SUFU
smoothened signaling pathway involved in spinal cord motor neuron cell fate specification	1	1203.7×	0.005	SUFU
neural plate axis specification	1	1203.7×	0.005	PTCH1
cell proliferation involved in metanephros development	1	1203.7×	0.005	PTCH1
maintenance of protein localization in organelle	1	1203.7×	0.005	SUFU
neural tube closure	2	53.5×	0.005	SUFU, PTCH1
spermatid development	2	41.5×	0.006	SUFU, PTCH1
cell differentiation involved in kidney development	1	802.5×	0.007	PTCH1
photoreceptor cell development	1	601.9×	0.009	ARL3
protein localization to ciliary membrane	1	481.5×	0.010	ARL3
neural tube patterning	1	401.2×	0.011	PTCH1
hindlimb morphogenesis	1	401.2×	0.011	PTCH1
negative regulation of cell division	1	343.9×	0.012	PTCH1
mammary gland duct morphogenesis	1	343.9×	0.012	PTCH1
metanephric collecting duct development	1	240.7×	0.017	PTCH1
response to alkaloid	1	218.9×	0.018	PTCH1
prostate gland development	1	200.6×	0.018	PTCH1
mammary gland epithelial cell differentiation	1	172.0×	0.019	PTCH1
vasculature development	1	160.5×	0.019	ANP32B
negative regulation of multicellular organism growth	1	160.5×	0.019	PTCH1
somite development	1	160.5×	0.019	PTCH1

Therapeutics

Drugs indicated or in trials for this disease

No drug has an approved disease-direct ChEMBL indication for this disease.

6 drugs in clinical trials for this disease (phase 2–3, investigational): efficacy not established — a trial record, not an indication.

Drug	Highest phase
Patidegib	Phase 3
Verteporfin	Phase 3
Aminolevulinic Acid	Phase 2
Ipilimumab	Phase 2
Nivolumab	Phase 2
Vismodegib	Phase 2

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 1 · Undrugged: 6

Druggability breadth: 4 of 7 evidence-associated genes (57%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ANP32B	1	2
SUFU	0	0
PTCH1	0	0
PTCH2	0	0
AOPEP	0	0
FANCC	0	0
ARL3	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
MOLIBRESIB	2	ANP32B

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
ANP32B	9	Binding:9
PTCH1	4	Binding:4
SUFU	1	Binding:1
AOPEP	1	ADMET:1

Pharmacogenomics

Cohort genes with a PharmGKB record: 7; with CPIC/DPWG dosing guidelines: 0.

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

Drug repurposing candidates

1 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)
MOLIBRESIB	2	ANP32B

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	1	ANP32B
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	1	AOPEP
E	Difficult family or no structure, no drug	5	SUFU, PTCH1, PTCH2, FANCC, ARL3

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
SUFU	1	—
PTCH1	4	—
PTCH2	0	—
AOPEP	1	—
FANCC	0	—
ARL3	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 22.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2	8
Not specified	8
PHASE3	4
PHASE1/PHASE2	1
PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT06050122	PHASE3	ACTIVE_NOT_RECRUITING	Efficacy and Safety of Patidegib Gel 2% for Preventing Basal Cell Carcinomas on the Face of Adults With Gorlin Syndrome
NCT00049959	PHASE3	TERMINATED	Two Studies to Determine if Verteporfin PDT is Effective & Safe in Treating Multiple Basal Cell Carcinoma of the Skin.
NCT03703310	PHASE3	COMPLETED	Study of Patidegib Topical Gel, 2%, for the Reduction of Disease Burden of Persistently Developing Basal Cell Carcinomas (BCCs) in Subjects With Basal Cell Nevus Syndrome (Gorlin Syndrome)
NCT04308395	PHASE3	TERMINATED	Extension Study of Patidegib Topical Gel, 2% in Subjects With Gorlin Syndrome (Basal Cell Nevus Syndrome)
NCT00957229	PHASE2	COMPLETED	To Determine The Efficacy and Safety of GDC-0449 in Patients With Basal Cell Nevus Syndrome (BCNS)
NCT01350115	PHASE2	COMPLETED	Efficacy, Safety and Pharmacokinetics of Oral LDE225 in Treatment of Patients With Nevoid Basal Cell Carcinoma Syndrome (NBCCS)
NCT01556009	PHASE2	COMPLETED	Trial Comparing the Effects of Intermittent Vismodegib vs. PDT in Patients With Multiple Basal Cell Carcinomas
NCT02017964	PHASE2	COMPLETED	Combination Chemotherapy in Treating Younger Patients With Newly Diagnosed, Non-metastatic Desmoplastic Medulloblastoma
NCT02303041	PHASE2	TERMINATED	Pilot Study of Sonidegib and Buparlisib in Treating Patients With Advanced or Metastatic Basal Cell Carcinoma
NCT02550678	PHASE1/PHASE2	COMPLETED	A Study of the Efficacy and Safety of ASN-002 in Adult Patients With Low-risk Nodular Basal Cell Carcinoma
NCT02762084	PHASE2	COMPLETED	Trial of Patidegib Gel 2%, 4%, and Vehicle to Decrease the Number of Surgically Eligible Basal Cell Carcinomas in Gorlin Syndrome Patients
NCT03767439	PHASE2	WITHDRAWN	Nivolumab With Vismodegib in Patients With Basal Cell Nevus Syndrome
NCT04416516	PHASE2	COMPLETED	Safety and Efficacy of ASN-002 Combined With a Hedgehog Pathway Inhibitor
NCT03467789	PHASE1	COMPLETED	Vitamin D as a Nutritional Neoadjuvant During Photodynamic Therapy of Basal Cell Carcinoma
NCT03050268	Not specified	RECRUITING	Familial Investigations of Childhood Cancer Predisposition
NCT05463757	Not specified	RECRUITING	Oral Hedgehog Inhibitors in the Treatment of Basal Cell Carcinoma in the Netherlands: a Prospective Registration Study
NCT06330324	Not specified	ENROLLING_BY_INVITATION	Reproductive Options in Inherited Skin Diseases
NCT06330350	Not specified	RECRUITING	Qualitative Study in Patients With Genodermatoses and Healthcare Professionals on Reproductive Counselling
NCT00555633	Not specified	COMPLETED	Use of an SPF30 Sunscreen and an After-sun-lotion in Skin Cancer Risk Patients
NCT02100371	Not specified	COMPLETED	Study of BMS-833923 in Two Specific Patients With Basal Cell Nevus Syndrome
NCT02157623	Not specified	COMPLETED	Blue vs Red Light During Levulan Based Photodynamic Therapy in Patients With Basal Cell Nevus Syndrome
NCT05898347	Not specified	UNKNOWN	Nevoid Basal Cell Carcinomas in Gorlin Syndrome

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
VISMODEGIB	4	4
SONIDEGIB	4	3
AMINOLEVULINIC ACID	4	2
BUPARLISIB	3	1
PATIDEGIB	3	1
GUSACITINIB	2	2
BMS-833923	2	1
VEHICLE	0	1