Basal cell nevus syndrome 2

Summary

Basal cell nevus syndrome 2 (MONDO:0958189) is a disease caused by SUFU (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: SUFU (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 45

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	basal cell nevus syndrome 2
Mondo ID	MONDO:0958189
OMIM	620343
DOID	DOID:0070366
UMLS	C5830451
MedGen	1841087
GARD	0026965
Is cancer (heuristic)	no

Data availability: 45 ClinVar variants · 1 GenCC gene-disease record.

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 2

Related subtypes (1): basal cell nevus syndrome 1

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

45 retrieved; paginated sample, class counts are floors:

13 conflicting classifications of pathogenicity, 11 uncertain significance, 8 likely pathogenic, 7 pathogenic, 4 benign/likely benign, 1 pathogenic/likely pathogenic, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1072595	NM_016169.4(SUFU):c.37_53del (p.Thr13fs)	LOC130004614	Pathogenic	criteria provided, multiple submitters, no conflicts
3573	NM_016169.4(SUFU):c.71del (p.Pro24fs)	LOC130004614	Pathogenic	criteria provided, multiple submitters, no conflicts
3574	NM_016169.4(SUFU):c.71dup (p.Ala25fs)	LOC130004614	Pathogenic	criteria provided, multiple submitters, no conflicts
2577897	NM_016169.4(SUFU):c.1147_1150del (p.Leu383fs)	SUFU	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3571	NM_016169.4(SUFU):c.1022+1G>A	SUFU	Pathogenic	criteria provided, multiple submitters, no conflicts
406388	NM_016169.4(SUFU):c.436C>T (p.Arg146Ter)	SUFU	Pathogenic	criteria provided, multiple submitters, no conflicts
4277724	NM_016169.4(SUFU):c.1123C>T (p.Gln375Ter)	SUFU	Pathogenic	criteria provided, single submitter
822842	NM_016169.4(SUFU):c.895C>T (p.Arg299Ter)	SUFU	Pathogenic	criteria provided, multiple submitters, no conflicts
2501297	NM_016169.4(SUFU):c.946_952del (p.Leu316fs)	SUFU	Likely pathogenic	criteria provided, single submitter
406381	NM_016169.4(SUFU):c.1023-2A>T	SUFU	Likely pathogenic	criteria provided, multiple submitters, no conflicts
4759327	NM_016169.4(SUFU):c.841_842delinsA (p.Pro281fs)	SUFU	Likely pathogenic	criteria provided, single submitter
4759328	NM_016169.4(SUFU):c.1271dup (p.Tyr424Ter)	SUFU	Likely pathogenic	criteria provided, single submitter
4759329	NM_016169.4(SUFU):c.1092del (p.Gln365fs)	SUFU	Likely pathogenic	criteria provided, single submitter
4759330	NM_016169.4(SUFU):c.598-1G>T	SUFU	Likely pathogenic	criteria provided, single submitter
4759331	NM_016169.4(SUFU):c.338_339dup (p.Ser114fs)	SUFU	Likely pathogenic	criteria provided, single submitter
647265	NM_016169.4(SUFU):c.684-2A>G	SUFU	Likely pathogenic	criteria provided, multiple submitters, no conflicts
524666	NM_016169.4(SUFU):c.26C>T (p.Ala9Val)	LOC130004614	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
802631	NM_016169.4(SUFU):c.37A>C (p.Thr13Pro)	LOC130004614	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1319742	NM_016169.4(SUFU):c.31G>C (p.Gly11Arg)	SUFU	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
135286	NM_016169.4(SUFU):c.1105G>A (p.Val369Ile)	SUFU	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
241083	NM_016169.4(SUFU):c.169A>G (p.Ile57Val)	SUFU	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3337641	NM_016169.4(SUFU):c.264G>A (p.Trp88Ter)	SUFU	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
406377	NM_016169.4(SUFU):c.992G>A (p.Arg331Gln)	SUFU	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
406392	NM_016169.4(SUFU):c.275G>C (p.Ser92Thr)	SUFU	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
406400	NM_016169.4(SUFU):c.1429G>A (p.Val477Met)	SUFU	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
413911	NM_016169.4(SUFU):c.1445C>T (p.Pro482Leu)	SUFU	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
413912	NM_016169.4(SUFU):c.600C>T (p.Ile200=)	SUFU	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
453966	NM_016169.4(SUFU):c.529A>G (p.Met177Val)	SUFU	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
663073	NM_016169.4(SUFU):c.1016G>A (p.Arg339Gln)	SUFU	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
582859	NM_016169.4(SUFU):c.32G>A (p.Gly11Asp)	LOC130004614	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 16 · Orphanet: 7 · 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
SUFU	Definitive	Autosomal dominant	nevoid basal cell carcinoma syndrome	16

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

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SUFU	HGNC:16466	ENSG00000107882	Q9UMX1	Suppressor of fused homolog	gencc,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.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

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	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SUFU	Other/Unknown	no		Suppressor_of_fused, Suppressor_of_fused_euk, SUFU-like_domain

Expression context

Cohort genes with no expression data: 0.

Breadth distribution (Bgee present_calls)

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

Top tissues across cohort

Tissue	Cohort genes
kidney epithelium	1
upper arm skin	1
vena cava	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

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SUFU	2,188

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SUFU	Q9UMX1	10

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 7. Enrichment computed across 1 evidence-associated genes (1 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 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Degradation of GLI1 by the proteasome	1	223.9×	0.007	SUFU
Degradation of GLI2 by the proteasome	1	223.9×	0.007	SUFU
GLI3 is processed to GLI3R by the proteasome	1	223.9×	0.007	SUFU
Signaling by Hedgehog	1	184.2×	0.007	SUFU
Hedgehog ‘off’ state	1	178.4×	0.007	SUFU
Hedgehog ‘on’ state	1	158.6×	0.007	SUFU
Signal Transduction	1	10.2×	0.098	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 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
positive regulation of cellular response to drug	1	16852.0×	6e-04	SUFU
smoothened signaling pathway involved in ventral spinal cord interneuron specification	1	8426.0×	6e-04	SUFU
smoothened signaling pathway involved in spinal cord motor neuron cell fate specification	1	8426.0×	6e-04	SUFU
maintenance of protein localization in organelle	1	8426.0×	6e-04	SUFU
negative regulation of protein import into nucleus	1	936.2×	0.003	SUFU
negative regulation of ubiquitin-dependent protein catabolic process	1	842.6×	0.003	SUFU
dorsal/ventral neural tube patterning	1	802.5×	0.003	SUFU
coronary vasculature development	1	624.1×	0.004	SUFU
aorta development	1	561.7×	0.004	SUFU
ventricular septum development	1	495.6×	0.004	SUFU
negative regulation of smoothened signaling pathway	1	455.5×	0.004	SUFU
skin development	1	443.5×	0.004	SUFU
negative regulation of osteoblast differentiation	1	295.6×	0.005	SUFU
heart looping	1	267.5×	0.005	SUFU
neural tube closure	1	187.2×	0.007	SUFU
spermatid development	1	145.3×	0.008	SUFU
regulation of DNA-templated transcription	1	31.6×	0.035	SUFU
negative regulation of transcription by RNA polymerase II	1	17.7×	0.060	SUFU
signal transduction	1	16.1×	0.062	SUFU

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SUFU	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
SUFU	1	Binding:1

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

0 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.

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	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	SUFU

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
SUFU	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.