Familial atypical multiple mole melanoma syndrome

Summary

Familial atypical multiple mole melanoma syndrome (MONDO:0018453) is a cancer with 1 cohort gene (1 CIViC-evidence somatic driver).

At a glance

• Classification: Cancer
• Prevalence: Unknown (Worldwide)
• Cohort genes: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	familial atypical multiple mole melanoma syndrome
Mondo ID	MONDO:0018453
Orphanet	404560
NCIT	C27264
UMLS	C2314896
MedGen	389220
GARD	0009281
Is cancer (heuristic)	yes

Also known as: B-K mole syndrome · familial atypical mole melanoma syndrome · familial atypical mole syndrome · familial atypical multiple mole melanoma-pancreatic carcinoma syndrome · familial Clark nevus syndrome · familial dysplastic nevus syndrome · FAMM syndrome · FAMM-PC syndrome · FAMMM syndrome · melanoma-pancreatic cancer syndrome

Data availability: 1 GenCC gene-disease record.

Disease family

An umbrella term covering 1 Mondo subtype.

Classification path: disease › human disease › disease by body system or component › integumentary system disorder › familial atypical multiple mole melanoma syndrome

Related subtypes (35): Neu-Laxova syndrome, cutaneous mycosis, integumentary system benign neoplasm, integumentary system cancer, nipple neoplasm, nail disorder, disorder of pilosebaceous unit, Bartholin duct cyst, benign mammary dysplasia, skin disorder, breast fibrosis, breast mucosa-associated lymphoid tissue lymphoma, panniculitis, alopecia-epilepsy-pyorrhea-intellectual disability syndrome, autosomal dominant deafness - onychodystrophy syndrome, keratoderma hereditarium mutilans, Rombo syndrome, Sjogren-Larsson syndrome, mucosulfatidosis, ichthyosis prematurity syndrome, ANE syndrome, frontonasal dysplasia with alopecia and genital anomaly, peeling skin-leukonuchia-acral punctate keratoses-cheilitis-knuckle pads syndrome, mandibulofacial dysostosis with alopecia, cutis laxa, X-linked ichthyosis syndrome, demodicidosis, Proteus-like syndrome, familial tumoral calcinosis, subcutaneous tissue disorder, Bartholin gland neoplasm, pseudoxanthoma elasticum (inherited or acquired), skin appendage disorder, keratinization disease, paraneoplastic cutaneous syndrome

Subtypes (1): melanoma-pancreatic cancer syndrome

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

No tiered GWAS variants or ClinVar records for this disease.

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 7 · Orphanet: 8 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
CDKN2A	LoF	ACYC,BLCA,BRCA,CHOL,COAD,COADREAD,CSCC,EGC,ESCA,ESCC,GBM,HCC,HNSC,LGGNOS,LUAD,LUSC,MEL,MLYM,NPC,NSCLC,OS,PAAD,PANCREAS,RCC,SKCM,SKIN,STAD,STOMACH,WDTC	CIViC #14

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
CDKN2A	Definitive	Autosomal dominant	melanoma-pancreatic cancer syndrome	7

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CDKN2A	Orphanet:1333	Familial pancreatic carcinoma
CDKN2A	Orphanet:1501	Adrenocortical carcinoma
CDKN2A	Orphanet:252206	Melanoma and neural system tumor syndrome
CDKN2A	Orphanet:404560	Familial atypical multiple mole melanoma syndrome
CDKN2A	Orphanet:524	Li-Fraumeni syndrome
CDKN2A	Orphanet:585909	B-lymphoblastic leukemia/lymphoma with t(9;22)(q34.1;q11.2)
CDKN2A	Orphanet:618	Familial melanoma
CDKN2A	Orphanet:99861	Precursor T-cell acute lymphoblastic leukemia

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
CDKN2A	HGNC:1787	ENSG00000147889	P42771	Cyclin-dependent kinase inhibitor 2A	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CDKN2A	Cyclin-dependent kinase inhibitor 2A	Acts as a negative regulator of the proliferation of normal cells by interacting strongly with CDK4 and CDK6.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 0 · 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
Scaffold/PPI	1	17.3×	0.058

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CDKN2A	Scaffold/PPI	no		Ankyrin_rpt-contain_sf, Ank_Repeat/CDKN_Inhibitor, Tumor_suppres_ARF

Expression context

Cohort genes with no expression data: 0.

1 cohort gene 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)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
cervix squamous epithelium	1
parotid gland	1
pituitary gland	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CDKN2A	220	ubiquitous	marker	parotid gland, cervix squamous epithelium, pituitary gland

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CDKN2A	9,311

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CDKN2A	P42771	5

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 58. 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
Evasion of Oncogene Induced Senescence Due to p14ARF Defects	1	11420.0×	0.001	CDKN2A
Evasion of Oxidative Stress Induced Senescence Due to p14ARF Defects	1	11420.0×	0.001	CDKN2A
Evasion of Oncogene Induced Senescence Due to Defective p16INK4A binding to CDK4	1	5710.0×	0.001	CDKN2A
Evasion of Oxidative Stress Induced Senescence Due to Defective p16INK4A binding to CDK4	1	5710.0×	0.001	CDKN2A
Defective Intrinsic Pathway for Apoptosis Due to p14ARF Loss of Function	1	5710.0×	0.001	CDKN2A
Diseases of Cellular Senescence	1	3806.7×	0.001	CDKN2A
Evasion of Oncogene Induced Senescence Due to p16INK4A Defects	1	3806.7×	0.001	CDKN2A
Evasion of Oncogene Induced Senescence Due to Defective p16INK4A binding to CDK4 and CDK6	1	3806.7×	0.001	CDKN2A
Evasion of Oxidative Stress Induced Senescence Due to p16INK4A Defects	1	3806.7×	0.001	CDKN2A
Evasion of Oxidative Stress Induced Senescence Due to Defective p16INK4A binding to CDK4 and CDK6	1	3806.7×	0.001	CDKN2A
Diseases of cellular response to stress	1	3806.7×	0.001	CDKN2A
RUNX3 regulates p14-ARF	1	1142.0×	0.004	CDKN2A
Apoptotic factor-mediated response	1	878.5×	0.005	CDKN2A
Stabilization of p53	1	761.3×	0.005	CDKN2A
Defective Intrinsic Pathway for Apoptosis	1	761.3×	0.005	CDKN2A
p53-Dependent G1 DNA Damage Response	1	713.8×	0.005	CDKN2A
p53-Dependent G1/S DNA damage checkpoint	1	713.8×	0.005	CDKN2A
G1/S DNA Damage Checkpoints	1	671.8×	0.005	CDKN2A
Diseases of programmed cell death	1	634.4×	0.005	CDKN2A
SUMOylation of transcription factors	1	571.0×	0.005	CDKN2A
Regulation of MITF-M-dependent genes involved in cell cycle and proliferation	1	571.0×	0.005	CDKN2A
Regulation of TP53 Expression and Degradation	1	519.1×	0.005	CDKN2A
G1 Phase	1	393.8×	0.006	CDKN2A
Oncogene Induced Senescence	1	335.9×	0.007	CDKN2A
Nuclear events mediated by NFE2L2	1	335.9×	0.007	CDKN2A
Intrinsic Pathway for Apoptosis	1	292.8×	0.007	CDKN2A
Regulation of TP53 Degradation	1	292.8×	0.007	CDKN2A
Transcriptional regulation by RUNX3	1	271.9×	0.008	CDKN2A
Transcriptional Regulation by VENTX	1	265.6×	0.008	CDKN2A
Cyclin D associated events in G1	1	233.1×	0.008	CDKN2A

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
nuclear body organization	1	8426.0×	0.002	CDKN2A
apoptotic process involved in mammary gland involution	1	5617.3×	0.002	CDKN2A
positive regulation of macrophage apoptotic process	1	5617.3×	0.002	CDKN2A
positive regulation of apoptotic process involved in mammary gland involution	1	4213.0×	0.002	CDKN2A
obsolete negative regulation of proteolysis involved in protein catabolic process	1	4213.0×	0.002	CDKN2A
negative regulation of mammary gland epithelial cell proliferation	1	3370.4×	0.002	CDKN2A
negative regulation of immature T cell proliferation in thymus	1	2808.7×	0.002	CDKN2A
positive regulation of smooth muscle cell apoptotic process	1	2407.4×	0.002	CDKN2A
mitochondrial depolarization	1	2407.4×	0.002	CDKN2A
oncogene-induced cell senescence	1	2407.4×	0.002	CDKN2A
negative regulation of cyclin-dependent protein serine/threonine kinase activity	1	2106.5×	0.002	CDKN2A
obsolete regulation of protein targeting to mitochondrion	1	2106.5×	0.002	CDKN2A
regulation of nucleocytoplasmic transport	1	1872.4×	0.002	CDKN2A
mammary gland epithelial cell proliferation	1	1532.0×	0.002	CDKN2A
regulation of protein export from nucleus	1	1532.0×	0.002	CDKN2A
somatic stem cell division	1	1532.0×	0.002	CDKN2A
protein localization to nucleolus	1	1532.0×	0.002	CDKN2A
positive regulation of protein sumoylation	1	1296.3×	0.002	CDKN2A
positive regulation of signal transduction by p53 class mediator	1	1203.7×	0.002	CDKN2A
rRNA transcription	1	991.3×	0.002	CDKN2A
positive regulation of DNA damage response, signal transduction by p53 class mediator	1	991.3×	0.002	CDKN2A
replicative senescence	1	991.3×	0.002	CDKN2A
negative regulation of B cell proliferation	1	936.2×	0.002	CDKN2A
negative regulation of cell-matrix adhesion	1	887.0×	0.002	CDKN2A
negative regulation of ubiquitin-dependent protein catabolic process	1	842.6×	0.003	CDKN2A
autophagy of mitochondrion	1	732.7×	0.003	CDKN2A
amyloid fibril formation	1	601.9×	0.003	CDKN2A
keratinocyte proliferation	1	581.1×	0.003	CDKN2A
positive regulation of protein localization to nucleus	1	391.9×	0.005	CDKN2A
protein localization to nucleus	1	351.1×	0.005	CDKN2A

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
CDKN2A	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
CDKN2A	2	Binding:2

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).

Drug repurposing candidates

0 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.

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	CDKN2A

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)
CDKN2A	2	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.