Basal cell carcinoma, susceptibility to, 1

disease
On this page

Also known as basal cell carcinoma, somaticBCC1multiple basal cell carcinoma

Summary

Basal cell carcinoma, susceptibility to, 1 (MONDO:0011556) is a cancer with 6 cohort genes (3 CIViC-evidence somatic drivers; 393 ClinVar predisposition records).

At a glance

  • Classification: Cancer
  • Cohort genes: 6
  • ClinVar variants: 393

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

FieldValue
Canonical namebasal cell carcinoma, susceptibility to, 1
Mondo IDMONDO:0011556
OMIM605462
UMLSC2751544
MedGen414403
Is cancer (heuristic)yes

Also known as: basal cell carcinoma, somatic · basal cell carcinoma, susceptibility to, 1 · BCC1 · multiple basal cell carcinoma

Data availability: 393 ClinVar variants.

Disease family

Classification path: disease susceptibility › inherited disease susceptibility › basal cell carcinoma, susceptibility to › basal cell carcinoma, susceptibility to, 1

Related subtypes (6): basal cell carcinoma, susceptibility to, 2, basal cell carcinoma, susceptibility to, 3, basal cell carcinoma, susceptibility to, 4, basal cell carcinoma, susceptibility to, 5, basal cell carcinoma, susceptibility to, 6, basal cell carcinoma, susceptibility to, 7

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

393 retrieved; paginated sample, class counts are floors:

192 uncertain significance, 123 conflicting classifications of pathogenicity, 41 benign/likely benign, 12 pathogenic, 12 benign, 5 likely benign, 5 likely pathogenic, 3 pathogenic/likely pathogenic

ClinVarVariant (HGVS)GeneClassificationReview
213660NM_002890.3(RASA1):c.2131C>T (p.Arg711Ter)CCNHPathogeniccriteria provided, multiple submitters, no conflicts
411713NM_002890.3(RASA1):c.3055C>T (p.Gln1019Ter)CCNHPathogenic/Likely pathogeniccriteria provided, multiple submitters, no conflicts
411714NM_002890.3(RASA1):c.613_617del (p.Leu205fs)CCNHPathogeniccriteria provided, multiple submitters, no conflicts
464870NM_002890.3(RASA1):c.656C>G (p.Ser219Ter)CCNHPathogeniccriteria provided, multiple submitters, no conflicts
565648NM_002890.3(RASA1):c.2245C>T (p.Arg749Ter)CCNHPathogeniccriteria provided, multiple submitters, no conflicts
3774528NM_000264.5(PTCH1):c.2511_2512delinsTT (p.Lys838Ter)LOC100507346Pathogeniccriteria provided, single submitter
409162NM_000264.5(PTCH1):c.2308C>T (p.Arg770Ter)LOC100507346Pathogeniccriteria provided, multiple submitters, no conflicts
931311NM_000264.5(PTCH1):c.2380C>T (p.Gln794Ter)LOC100507346Pathogeniccriteria provided, multiple submitters, no conflicts
3382899NM_000264.5(PTCH1):c.563dup (p.His189fs)PTCH1Pathogeniccriteria provided, single submitter
3774523NM_000264.5(PTCH1):c.1728+1G>TPTCH1Pathogeniccriteria provided, single submitter
409158NM_000264.5(PTCH1):c.1602+1G>TPTCH1Pathogeniccriteria provided, multiple submitters, no conflicts
409183NM_000264.5(PTCH1):c.1208_1209del (p.Tyr403fs)PTCH1Pathogenic/Likely pathogeniccriteria provided, multiple submitters, no conflicts
576491NM_000264.5(PTCH1):c.938C>G (p.Ser313Ter)PTCH1Pathogeniccriteria provided, multiple submitters, no conflicts
837425NM_000264.5(PTCH1):c.724C>T (p.Gln242Ter)PTCH1Pathogenic/Likely pathogeniccriteria provided, multiple submitters, no conflicts
2576566NM_003738.5(PTCH2):c.1302_1305delinsACCA (p.Leu435Pro)PTCH2Pathogeniccriteria provided, single submitter
3222908NM_002890.3(RASA1):c.1454-11_1454-7delCCNHLikely pathogeniccriteria provided, multiple submitters, no conflicts
3592816NM_002890.3(RASA1):c.2604-1_2605delCCNHLikely pathogeniccriteria provided, single submitter
931156NM_002890.3(RASA1):c.2925+1G>ACCNHLikely pathogeniccriteria provided, single submitter
3240212NM_000264.5(PTCH1):c.2004C>G (p.Tyr668Ter)LOC100507346Likely pathogeniccriteria provided, single submitter
3597832NM_000264.5(PTCH1):c.2704-1G>TPTCH1Likely pathogeniccriteria provided, single submitter
1059612NM_000264.5(PTCH1):c.2540A>G (p.Tyr847Cys)LOC100507346Conflicting classifications of pathogenicitycriteria provided, conflicting classifications
1433582NM_000264.5(PTCH1):c.2372T>C (p.Ile791Thr)LOC100507346Conflicting classifications of pathogenicitycriteria provided, conflicting classifications
188061NM_000264.5(PTCH1):c.1942C>G (p.His648Asp)LOC100507346Conflicting classifications of pathogenicitycriteria provided, conflicting classifications
188150NM_000264.5(PTCH1):c.2440A>C (p.Asn814His)LOC100507346Conflicting classifications of pathogenicitycriteria provided, conflicting classifications
215456NM_000264.5(PTCH1):c.1809C>T (p.Arg603=)LOC100507346Conflicting classifications of pathogenicitycriteria provided, conflicting classifications
237462NM_000264.5(PTCH1):c.1989G>C (p.Gln663His)LOC100507346Conflicting classifications of pathogenicitycriteria provided, conflicting classifications
237469NM_000264.5(PTCH1):c.2303C>T (p.Thr768Ile)LOC100507346Conflicting classifications of pathogenicitycriteria provided, conflicting classifications
409133NM_000264.5(PTCH1):c.1855G>A (p.Val619Ile)LOC100507346Conflicting classifications of pathogenicitycriteria provided, conflicting classifications
409209NM_000264.5(PTCH1):c.2174C>G (p.Pro725Arg)LOC100507346Conflicting classifications of pathogenicitycriteria provided, conflicting classifications
453817NM_000264.5(PTCH1):c.2172G>C (p.Glu724Asp)LOC100507346Conflicting classifications of pathogenicitycriteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 16 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Somatic driver evidence (intOGen + CIViC, cohort fanout)

GeneintOGen roleCancer typesCIViC
SMOActBCC,GB,HCC,MBL,PAST,PLMESO,SKINCIViC #5365
PTCH1LoFANGS,BCC,CHOL,ESCA,MBL,NPC,OS,PAST,PLMESO,SKIN,WDTCCIViC #4645
RASA1LoFHNSC,LUSCCIViC #4791

Orphanet rare-disease linkage (cohort genes)

GeneOrphanet IDRare disease
SMOOrphanet:1553Curry-Jones syndrome
SMOOrphanet:2495Meningioma
SMOOrphanet:388Hirschsprung disease
PTCH1Orphanet:220386Semilobar holoprosencephaly
PTCH1Orphanet:2353Schilbach-Rott syndrome
PTCH1Orphanet:280195Septopreoptic holoprosencephaly
PTCH1Orphanet:280200Microform holoprosencephaly
PTCH1Orphanet:377Gorlin syndrome
PTCH1Orphanet:77301Monosomy 9q22.3 syndrome
PTCH1Orphanet:93924Lobar holoprosencephaly
PTCH1Orphanet:93925Alobar holoprosencephaly
PTCH1Orphanet:93926Midline interhemispheric variant of holoprosencephaly
PTCH2Orphanet:141276Tessier number 7 facial cleft
PTCH2Orphanet:377Gorlin syndrome
RASA1Orphanet:693907RASA1-related capillary malformation-arteriovenous malformation
RASA1Orphanet:90307Parkes Weber syndrome

Cohort genes → proteins

6 cohort genes, 6 distinct canonical proteins.

Evidence partition

SubsetGenes
multi_evidence6

Cohort genes (full)

SymbolHGNCEnsemblUniProtNameEvidence
SMOHGNC:11119ENSG00000128602Q99835Protein smoothenedclinvar
SMOXHGNC:15862ENSG00000088826Q9NWM0Spermine oxidaseclinvar
CCNHHGNC:1594ENSG00000134480P51946Cyclin-Hclinvar
PTCH1HGNC:9585ENSG00000185920Q13635Protein patched homolog 1clinvar
PTCH2HGNC:9586ENSG00000117425Q9Y6C5Protein patched homolog 2clinvar
RASA1HGNC:9871ENSG00000145715P20936Ras GTPase-activating protein 1clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

SymbolProtein nameFunction (lead sentence)
SMOProtein smoothenedG protein-coupled receptor which associates with the patched protein (PTCH) to transduce hedgehog protein signaling.
SMOXSpermine oxidaseFlavoenzyme which catalyzes the oxidation of spermine to spermidine.
CCNHCyclin-HRegulates CDK7, the catalytic subunit of the CDK-activating kinase (CAK) enzymatic complex.
PTCH1Protein patched homolog 1Acts as a receptor for sonic hedgehog (SHH), indian hedgehog (IHH) and desert hedgehog (DHH).
PTCH2Protein patched homolog 2Plays a role in the control of cellular growth.
RASA1Ras GTPase-activating protein 1GTPase-activating protein (GAP) that stimulates the intrinsic GTPase activity of Ras proteins, such as NRAS, facilitating their transition from the active GTP-bound state to the inactive GDP-bound state, thereby terminating Ras signaling.

Protein-family classification

Druggable: 2 · Difficult: 1 · Unknown: 3 · Druggable fraction: 0.33

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.

FamilyGenesFoldFDR
GPCR14.0×0.543
Scaffold/PPI12.9×0.543
Enzyme (other)12.0×0.543
Other/Unknown30.9×0.758

Per-gene assignment

SymbolFamilyDruggable?ECInterPro (top 3)
SMOGPCRyesFrizzled/Smoothened_7TM, Frizzled/SFRP, GPCR_2-like_7TM
SMOXEnzyme (other)yes1.5.3.16Amino_oxidase, FAD/NAD-bd_sf, Flavin_monoamine_oxidase
CCNHOther/UnknownnoCyclin_N, Cyclin-like_dom, CyclinH/Ccl1
PTCH1Other/UnknownnoSSD, TM_rcpt_patched, HMGCR/SNAP/NPC1-like_SSD
PTCH2Other/UnknownnoSSD, TM_rcpt_patched, HMGCR/SNAP/NPC1-like_SSD
RASA1Scaffold/PPInoC2_dom, SH2, SH3_domain

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)

BucketGenes
narrow (1-5 tissues)0
moderate (6-20)0
broad (>20)6
unknown0

Top tissues across cohort

TissueCohort genes
right ovary2
left testis2
left ovary1
ventricular zone1
C1 segment of cervical spinal cord1
amygdala1
lower esophagus mucosa1
calcaneal tendon1
right testis1
dorsal root ganglion1
tibia1
trigeminal ganglion1
male germ line stem cell (sensu Vertebrata) in testis1
choroid plexus epithelium1
endothelial cell1
placenta1

Per-gene tissue summary (top 30)

SymbolBgee breadthFANTOM5 breadthSCXATop tissues
SMO225ubiquitousmarkerventricular zone, left ovary, right ovary
SMOX258ubiquitousmarkeramygdala, lower esophagus mucosa, C1 segment of cervical spinal cord
CCNH297ubiquitousmarkercalcaneal tendon, left testis, right testis
PTCH1275ubiquitousmarkertibia, dorsal root ganglion, trigeminal ganglion
PTCH2162broadmarkermale germ line stem cell (sensu Vertebrata) in testis, left testis, right ovary
RASA1298ubiquitousmarkerendothelial cell, placenta, choroid plexus epithelium

Protein interactions among cohort

Intra-cohort edges: 2.

Hub genes (top 10 by interactor count)

SymbolInteractor count
RASA14,407
PTCH13,368
SMO2,882
CCNH2,116
PTCH21,199
SMOX717

Intra-cohort edges

ABSources
PTCH1SMOintact, string_interaction
PTCH2SMObiogrid_interaction, string_interaction

Structural data

PDB: 5 · AlphaFold-only: 1 · No structure: 0

Cohort genes with PDB structures (top 30)

SymbolUniProtPDB entries
CCNHP5194647
PTCH1Q1363516
SMOQ9983515
RASA1P2093615
SMOXQ9NWM02

AlphaFold-only cohort genes (top 30 by pLDDT)

SymbolUniProtpLDDT
PTCH2Q9Y6C579.25

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.

PathwayCohort genesFoldFDRSample cohort genes
GLI proteins bind promoters of Hh responsive genes to promote transcription2543.8×2e-04PTCH1, PTCH2
Class B/2 (Secretin family receptors)395.2×2e-04SMO, PTCH1, PTCH2
Activation of SMO2211.5×1e-03SMO, PTCH1
Hedgehog ‘off’ state259.5×0.009SMO, PTCH1
Hedgehog ‘on’ state252.9×0.009SMO, PTCH1
PAOs oxidise polyamines to amines1634.4×0.022SMOX
Interconversion of polyamines1475.8×0.025SMOX
Ligand-receptor interactions1237.9×0.043PTCH1
PTK6 Regulates RHO GTPases, RAS GTPase and MAP kinases1135.9×0.049RASA1
VEGFR2 mediated cell proliferation195.2×0.049RASA1
BBSome-mediated cargo-targeting to cilium182.8×0.049SMO
Global Genome Nucleotide Excision Repair (GG-NER)176.1×0.049CCNH
RNA Pol II CTD phosphorylation and interaction with CE during HIV infection168.0×0.049CCNH
RNA Pol II CTD phosphorylation and interaction with CE168.0×0.049CCNH
G1 Phase165.6×0.049CCNH
Downstream signal transduction163.4×0.049RASA1
mRNA Capping163.4×0.049CCNH
Formation of the Early Elongation Complex156.0×0.049CCNH
Formation of the HIV-1 Early Elongation Complex156.0×0.049CCNH
HIV Transcription Elongation156.0×0.049CCNH
RNA Polymerase I Transcription Termination154.4×0.049CCNH
Cyclin A/B1/B2 associated events during G2/M transition151.4×0.049CCNH
RNA Polymerase I Promoter Clearance148.8×0.049CCNH
Nucleotide Excision Repair147.6×0.049CCNH
Cyclin E associated events during G1/S transition147.6×0.049CCNH
RNA Polymerase I Transcription147.6×0.049CCNH
EPHB-mediated forward signaling144.3×0.049RASA1
Transcription-Coupled Nucleotide Excision Repair (TC-NER)144.3×0.049CCNH
Cyclin A:Cdk2-associated events at S phase entry144.3×0.049CCNH
Formation of HIV-1 elongation complex containing HIV-1 Tat143.3×0.049CCNH

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 termCohort genesFoldFDRSample cohort genes
epidermal cell fate specification21123.5×1e-04PTCH1, PTCH2
positive regulation of epidermal cell differentiation2702.2×2e-04PTCH1, PTCH2
mammary gland epithelial cell differentiation2401.2×3e-04SMO, PTCH1
somite development2374.5×3e-04SMO, PTCH1
smooth muscle tissue development2351.1×3e-04SMO, PTCH1
commissural neuron axon guidance2330.4×3e-04SMO, PTCH1
cell fate determination2312.1×3e-04PTCH1, PTCH2
cellular response to cholesterol2280.9×3e-04SMO, PTCH1
dorsal/ventral neural tube patterning2267.5×3e-04SMO, PTCH1
negative regulation of smoothened signaling pathway2151.8×1e-03PTCH1, PTCH2
vasculogenesis285.1×0.003SMO, RASA1
ventral midline determination12808.7×0.004SMO
mesenchymal to epithelial transition involved in metanephric renal vesicle formation12808.7×0.004SMO
regulation of heart morphogenesis12808.7×0.004SMO
response to chlorate11404.3×0.005PTCH1
neural plate axis specification11404.3×0.005PTCH1
negative regulation of hair follicle development11404.3×0.005SMO
cell proliferation involved in metanephros development11404.3×0.005PTCH1
polyamine catabolic process1936.2×0.007SMOX
spermine catabolic process1936.2×0.007SMOX
cell differentiation involved in kidney development1936.2×0.007PTCH1
pancreas morphogenesis1936.2×0.007SMO
regulation of cerebellar granule cell precursor proliferation1702.2×0.008SMO
contact inhibition1702.2×0.008SMO
epithelial-mesenchymal cell signaling1702.2×0.008SMO
response to inositol1702.2×0.008SMO
regulation of somatic stem cell population maintenance1561.7×0.009SMO
polyamine biosynthetic process1468.1×0.009SMOX
neural tube patterning1468.1×0.009PTCH1
cerebellar cortex morphogenesis1468.1×0.009SMO

Therapeutics

Drug target analysis

Approved (phase 4): 2 · Phase ≥3: 2 · Phased (≥1): 2 · Undrugged: 4

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.

SymbolExample approved molecule
SMOINFIGRATINIB
CCNHABEMACICLIB

Top cohort targets by molecule count

SymbolMoleculesMax phase
CCNH284
SMO114
SMOX00
PTCH100
PTCH200
RASA100

Drugs targeting cohort genes (top 30)

MoleculeMax phaseTargets in cohort
INFIGRATINIB4SMO
SONIDEGIB4SMO
SONIDEGIB PHOSPHATE4SMO
VISMODEGIB4SMO
ABEMACICLIB4CCNH
QUIZARTINIB4CCNH
ADAGRASIB4CCNH
LINIFANIB3SMO
PATIDEGIB3SMO
ALVOCIDIB3CCNH
DINACICLIB3CCNH
LEROCICLIB3CCNH
FORETINIB2SMO
CEP-324962SMO
TALADEGIB2SMO
SELICICLIB2CCNH
ASNUCICLIB2CCNH
CYC-0652CCNH
ULECACICLIB2CCNH
RONICICLIB2CCNH
AT-75192CCNH
INIXACICLIB2CCNH
ISTISOCICLIB2CCNH
MILCICLIB2CCNH
ZOTIRACICLIB2CCNH
NARAZACICLIB2CCNH
CT-70012CCNH
ZEMIRCICLIB2CCNH
TAK-4411SMO
LEQ5061SMO

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

SymbolAssaysType breakdown
CCNH348Binding:346, Functional:2
SMO131Binding:111, Functional:20
SMOX18Binding:15, ADMET:3
PTCH14Binding:4

Cohort enzymes (BRENDA EC)

SymbolEC numbersNames
SMOX1.5.3.16spermine oxidase

Cohort genes with high screening signal

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

SymbolChEMBL assays
SMO131
CCNH348

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).

Drug repurposing candidates

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

CompoundMax phaseCohort target (bioactivity)
INFIGRATINIB4SMO
SONIDEGIB4SMO
SONIDEGIB PHOSPHATE4SMO
VISMODEGIB4SMO
ABEMACICLIB4CCNH
QUIZARTINIB4CCNH
ADAGRASIB4CCNH
LINIFANIB3SMO
PATIDEGIB3SMO
ALVOCIDIB3CCNH
DINACICLIB3CCNH
LEROCICLIB3CCNH
FORETINIB2SMO
CEP-324962SMO
TALADEGIB2SMO
SELICICLIB2CCNH
ASNUCICLIB2CCNH
CYC-0652CCNH
ULECACICLIB2CCNH
RONICICLIB2CCNH
AT-75192CCNH
INIXACICLIB2CCNH
ISTISOCICLIB2CCNH
MILCICLIB2CCNH
ZOTIRACICLIB2CCNH
NARAZACICLIB2CCNH
CT-70012CCNH
ZEMIRCICLIB2CCNH
TAK-4411SMO
LEQ5061SMO

Druggability pyramid

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

TierDefinitionGenesSymbols
AApproved (phase 4 drug)2SMO, CCNH
BPhased (≥1) drug, not yet approved0
CDruggable family + PDB, no drug1SMOX
DDruggable family + AlphaFold only, no drug0
EDifficult family or no structure, no drug3PTCH1, PTCH2, RASA1

Undrugged target profiles

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

SymbolChEMBL assaysDrugged partners (top 3)
PTCH14SMO
SMOX18
PTCH20
RASA10

Clinical trials & evidence

Clinical trials

Clinical trials: 0.