Basal cell nevus syndrome 1

Summary

Basal cell nevus syndrome 1 (MONDO:0958174) is a disease caused by PTCH1 (GenCC Definitive), with 4 cohort genes.

At a glance

• Causal gene: PTCH1 (GenCC Definitive)
• Cohort genes: 4
• ClinVar variants: 223

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	basal cell nevus syndrome 1
Mondo ID	MONDO:0958174
OMIM	109400
GARD	0026952
Is cancer (heuristic)	no

Data availability: 223 ClinVar variants · 3 GenCC gene-disease records.

Disease family

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 › basal cell nevus syndrome 1

Related subtypes (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

223 retrieved; paginated sample, class counts are floors:

58 conflicting classifications of pathogenicity, 55 uncertain significance, 38 benign/likely benign, 27 pathogenic, 22 likely pathogenic, 12 benign, 8 pathogenic/likely pathogenic, 2 likely benign, 1 not provided

ClinVar	Variant (HGVS)	Gene	Classification	Review
287019	NM_000264.5(PTCH1):c.2011dup (p.His671fs)	LOC100507346	Pathogenic	criteria provided, multiple submitters, no conflicts
2910229	NM_000264.5(PTCH1):c.1975C>T (p.Gln659Ter)	LOC100507346	Pathogenic	criteria provided, multiple submitters, no conflicts
3901203	NM_000264.5(PTCH1):c.2438del (p.Pro813fs)	LOC100507346	Pathogenic	criteria provided, single submitter
4056127	NM_000264.5(PTCH1):c.2170G>T (p.Glu724Ter)	LOC100507346	Pathogenic	criteria provided, single submitter
4820222	NM_000264.5(PTCH1):c.2513_2514del (p.Lys838fs)	LOC100507346	Pathogenic	criteria provided, single submitter
8212	NM_000264.5(PTCH1):c.2444_2454del (p.Ile815fs)	LOC100507346	Pathogenic	no assertion criteria provided
8216	NM_000264.5(PTCH1):c.2057_2058dup (p.Val687fs)	LOC100507346	Pathogenic	no assertion criteria provided
945805	NM_000264.5(PTCH1):c.2287dup (p.Val763fs)	LOC100507346	Pathogenic	criteria provided, multiple submitters, no conflicts
987139	NM_000264.5(PTCH1):c.2179del (p.Cys727fs)	LOC100507346	Pathogenic	criteria provided, multiple submitters, no conflicts
1068908	NM_000264.5(PTCH1):c.1526G>T (p.Gly509Val)	PTCH1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1074459	NM_000264.5(PTCH1):c.2713C>T (p.Gln905Ter)	PTCH1	Pathogenic	criteria provided, multiple submitters, no conflicts
156352	NM_000264.5(PTCH1):c.1093C>T (p.Gln365Ter)	PTCH1	Pathogenic	criteria provided, single submitter
237465	NM_000264.5(PTCH1):c.202-2A>G	PTCH1	Pathogenic	criteria provided, multiple submitters, no conflicts
2819419	NM_000264.5(PTCH1):c.2917C>T (p.Gln973Ter)	PTCH1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2819522	NM_000264.5(PTCH1):c.1104del (p.Lys370fs)	PTCH1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2835237	NM_000264.5(PTCH1):c.758del (p.Pro253fs)	PTCH1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3242226	NM_000264.5(PTCH1):c.1325T>A (p.Val442Glu)	PTCH1	Pathogenic	no assertion criteria provided
3359135	NM_000264.5(PTCH1):c.3053_3054delinsAA (p.Trp1018Ter)	PTCH1	Pathogenic	criteria provided, single submitter
3382580	NM_000264.5(PTCH1):c.3321_3330del (p.Ile1108fs)	PTCH1	Pathogenic	criteria provided, single submitter
3382899	NM_000264.5(PTCH1):c.563dup (p.His189fs)	PTCH1	Pathogenic	criteria provided, single submitter
37076	NM_000264.5(PTCH1):c.387G>A (p.Trp129Ter)	PTCH1	Pathogenic	criteria provided, multiple submitters, no conflicts
409158	NM_000264.5(PTCH1):c.1602+1G>T	PTCH1	Pathogenic	criteria provided, multiple submitters, no conflicts
409183	NM_000264.5(PTCH1):c.1208_1209del (p.Tyr403fs)	PTCH1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
419508	NM_000264.5(PTCH1):c.1603-2A>G	PTCH1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
453824	NM_000264.5(PTCH1):c.2619C>G (p.Tyr873Ter)	PTCH1	Pathogenic	criteria provided, multiple submitters, no conflicts
4710755	NM_000264.5(PTCH1):c.1501C>T (p.Gln501Ter)	PTCH1	Pathogenic	criteria provided, multiple submitters, no conflicts
488582	NM_000264.5(PTCH1):c.290del (p.Asn97fs)	PTCH1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
524511	NM_000264.5(PTCH1):c.2561-2A>G	PTCH1	Pathogenic	criteria provided, multiple submitters, no conflicts
654759	NM_000264.5(PTCH1):c.1198C>T (p.Gln400Ter)	PTCH1	Pathogenic	criteria provided, multiple submitters, no conflicts
816995	NM_000264.5(PTCH1):c.278dup (p.Tyr93Ter)	PTCH1	Pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 18 · Orphanet: 19 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

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
PTCH2	Moderate	Autosomal dominant	nevoid basal cell carcinoma syndrome	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
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
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
HMGCR	Orphanet:653725	Autosomal recessive limb-girdle muscular dystrophy, type 28

Cohort genes → proteins

4 cohort genes, 4 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	4

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
PTCH1	HGNC:9585	ENSG00000185920	Q13635	Protein patched homolog 1	gencc,clinvar
PTCH2	HGNC:9586	ENSG00000117425	Q9Y6C5	Protein patched homolog 2	gencc,clinvar
SUFU	HGNC:16466	ENSG00000107882	Q9UMX1	Suppressor of fused homolog	clinvar
HMGCR	HGNC:5006	ENSG00000113161	P04035	3-hydroxy-3-methylglutaryl-coenzyme A reductase	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
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.
SUFU	Suppressor of fused homolog	Negative regulator in the hedgehog/smoothened signaling pathway.
HMGCR	3-hydroxy-3-methylglutaryl-coenzyme A reductase	Catalyzes the conversion of (3S)-hydroxy-3-methylglutaryl-CoA (HMG-CoA) to mevalonic acid, the rate-limiting step in the synthesis of cholesterol and other isoprenoids, thus plays a critical role in cellular cholesterol homeostasis.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 3 · Druggable fraction: 0.25

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
Enzyme (other)	1	3.0×	0.404
Other/Unknown	3	1.3×	0.404

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
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
SUFU	Other/Unknown	no		Suppressor_of_fused, Suppressor_of_fused_euk, SUFU-like_domain
HMGCR	Enzyme (other)	yes	1.1.1.34	SSD, HMG_CoA_Rdtase, HMG_CoA_Rdtase_eu_arc

Expression context

Cohort genes with no expression data: 0.

3 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)	4
unknown	0

Top tissues across cohort

Tissue	Cohort genes
dorsal root ganglion	1
tibia	1
trigeminal ganglion	1
left testis	1
male germ line stem cell (sensu Vertebrata) in testis	1
right ovary	1
kidney epithelium	1
upper arm skin	1
vena cava	1
adrenal tissue	1
cortical plate	1
ventricular zone	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
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
SUFU	226	ubiquitous	yes	upper arm skin, kidney epithelium, vena cava
HMGCR	286	ubiquitous	marker	adrenal tissue, ventricular zone, cortical plate

Protein interactions among cohort

Intra-cohort edges: 2.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
HMGCR	5,062
PTCH1	3,368
SUFU	2,188
PTCH2	1,199

Intra-cohort edges

A	B	Sources
PTCH1	SUFU	string_interaction
PTCH2	SUFU	string_interaction

Structural data

PDB: 3 · AlphaFold-only: 1 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
HMGCR	P04035	24
PTCH1	Q13635	16
SUFU	Q9UMX1	10

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
PTCH2	Q9Y6C5	79.25

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 15. Enrichment computed across 4 evidence-associated genes (4 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 4 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	815.7×	3e-05	PTCH1, PTCH2
Class B/2 (Secretin family receptors)	2	95.2×	9e-04	PTCH1, PTCH2
Hedgehog ‘off’ state	2	89.2×	9e-04	PTCH1, SUFU
Hedgehog ‘on’ state	2	79.3×	9e-04	PTCH1, SUFU
Ligand-receptor interactions	1	356.9×	0.008	PTCH1
Lanosterol biosynthesis	1	190.3×	0.013	HMGCR
Activation of SMO	1	158.6×	0.013	PTCH1
EGR2 and SOX10-mediated initiation of Schwann cell myelination	1	92.1×	0.020	HMGCR
Activation of gene expression by SREBF (SREBP)	1	64.9×	0.022	HMGCR
Degradation of GLI1 by the proteasome	1	56.0×	0.022	SUFU
Degradation of GLI2 by the proteasome	1	56.0×	0.022	SUFU
GLI3 is processed to GLI3R by the proteasome	1	56.0×	0.022	SUFU
Signaling by Hedgehog	1	46.0×	0.025	SUFU
PPARA activates gene expression	1	23.6×	0.045	HMGCR
Signal Transduction	1	2.5×	0.339	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 4 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	341.6×	3e-06	PTCH1, PTCH2, SUFU
epidermal cell fate specification	2	1685.2×	2e-05	PTCH1, PTCH2
positive regulation of epidermal cell differentiation	2	1053.2×	3e-05	PTCH1, PTCH2
cell fate determination	2	468.1×	1e-04	PTCH1, PTCH2
dorsal/ventral neural tube patterning	2	401.2×	1e-04	PTCH1, SUFU
skin development	2	221.7×	4e-04	PTCH2, SUFU
negative regulation of osteoblast differentiation	2	147.8×	8e-04	PTCH1, SUFU
neural tube closure	2	93.6×	0.002	PTCH1, SUFU
positive regulation of cellular response to drug	1	4213.0×	0.002	SUFU
spermatid development	2	72.6×	0.002	PTCH1, SUFU
response to chlorate	1	2106.5×	0.002	PTCH1
smoothened signaling pathway involved in ventral spinal cord interneuron specification	1	2106.5×	0.002	SUFU
smoothened signaling pathway involved in spinal cord motor neuron cell fate specification	1	2106.5×	0.002	SUFU
neural plate axis specification	1	2106.5×	0.002	PTCH1
cell proliferation involved in metanephros development	1	2106.5×	0.002	PTCH1
maintenance of protein localization in organelle	1	2106.5×	0.002	SUFU
cell differentiation involved in kidney development	1	1404.3×	0.003	PTCH1
coenzyme A metabolic process	1	842.6×	0.005	HMGCR
neural tube patterning	1	702.2×	0.006	PTCH1
hindlimb morphogenesis	1	702.2×	0.006	PTCH1
negative regulation of cell division	1	601.9×	0.006	PTCH1
mammary gland duct morphogenesis	1	601.9×	0.006	PTCH1
isoprenoid biosynthetic process	1	421.3×	0.007	HMGCR
sterol biosynthetic process	1	421.3×	0.007	HMGCR
metanephric collecting duct development	1	421.3×	0.007	PTCH1
negative regulation of amyloid-beta clearance	1	421.3×	0.007	HMGCR
response to alkaloid	1	383.0×	0.008	PTCH1
prostate gland development	1	351.1×	0.008	PTCH1
mammary gland epithelial cell differentiation	1	300.9×	0.009	PTCH1
negative regulation of multicellular organism growth	1	280.9×	0.009	PTCH1

Therapeutics

Drug target analysis

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

Druggability breadth: 3 of 4 evidence-associated genes (75%) 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
HMGCR	SIMVASTATIN

Top cohort targets by molecule count

Symbol	Molecules	Max phase
HMGCR	15	4
PTCH1	0	0
PTCH2	0	0
SUFU	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
SIMVASTATIN	4	HMGCR
PRAVASTATIN	4	HMGCR
PITAVASTATIN CALCIUM	4	HMGCR
CERIVASTATIN	4	HMGCR
ATORVASTATIN	4	HMGCR
ROSUVASTATIN	4	HMGCR
CISAPRIDE	4	HMGCR
FLUVASTATIN	4	HMGCR
LOVASTATIN	4	HMGCR
TANNIC ACID	4	HMGCR
PRAVASTATIN SODIUM	4	HMGCR
GLENVASTATIN	2	HMGCR
MEGLUTOL	2	HMGCR
MEVASTATIN	2	HMGCR
APOMINE	1	HMGCR

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
HMGCR	153	Binding:148, Functional:5
PTCH1	4	Binding:4
SUFU	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
HMGCR	1.1.1.34	hydroxymethylglutaryl-CoA reductase (NADPH)

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
HMGCR	153

Pharmacogenomics

Cohort genes with a PharmGKB record: 4; with CPIC/DPWG dosing guidelines: 1.

Cohort genes with a CPIC/DPWG dosing guideline

Symbol	CPIC guidelines
HMGCR	1

Chemical tractability of cohort targets

15 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)
SIMVASTATIN	4	HMGCR
PRAVASTATIN	4	HMGCR
PITAVASTATIN CALCIUM	4	HMGCR
CERIVASTATIN	4	HMGCR
ATORVASTATIN	4	HMGCR
ROSUVASTATIN	4	HMGCR
CISAPRIDE	4	HMGCR
FLUVASTATIN	4	HMGCR
LOVASTATIN	4	HMGCR
TANNIC ACID	4	HMGCR
PRAVASTATIN SODIUM	4	HMGCR
GLENVASTATIN	2	HMGCR
MEGLUTOL	2	HMGCR
MEVASTATIN	2	HMGCR
APOMINE	1	HMGCR

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	HMGCR
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	3	PTCH1, PTCH2, SUFU

Undrugged target profiles

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

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

Clinical trials & evidence

Clinical trials

Clinical trials: 0.