Melanoma, cutaneous malignant, susceptibility to, 1
diseaseOn this page
Also known as CMM1melanoma, cutaneous malignant, 1melanoma, malignant, somatic
Summary
Melanoma, cutaneous malignant, susceptibility to, 1 (MONDO:0007963) is a cancer with 6 cohort genes (5 CIViC-evidence somatic drivers; 238 ClinVar predisposition records).
At a glance
- Classification: Cancer
- Cohort genes: 6
- ClinVar variants: 238
Clinical features
No curated clinical features (Orphanet) for this disease.
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | melanoma, cutaneous malignant, susceptibility to, 1 |
| Mondo ID | MONDO:0007963 |
| OMIM | 155600 |
| SNOMED CT | 254819008 |
| UMLS | C1835047 |
| MedGen | 320506 |
| GARD | 0027782 |
| Is cancer (heuristic) | yes |
Also known as: CMM1 · melanoma, cutaneous malignant, 1 · melanoma, cutaneous malignant, susceptibility to, 1 · melanoma, malignant, somatic
Data availability: 238 ClinVar variants.
Disease family
Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › hereditary neoplastic syndrome › susceptibility to familial cutaneous melanoma › melanoma, cutaneous malignant, susceptibility to, 1
Related subtypes (9): melanoma, cutaneous malignant, susceptibility to, 2, melanoma, cutaneous malignant, susceptibility to, 4, melanoma, cutaneous malignant, susceptibility to, 3, melanoma, cutaneous malignant, susceptibility to, 7, melanoma, cutaneous malignant, susceptibility to, 5, melanoma, cutaneous malignant, susceptibility to, 6, melanoma, cutaneous malignant, susceptibility to, 8, melanoma, cutaneous malignant, susceptibility to, 9, tumor predisposition syndrome 3
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
238 retrieved; paginated sample, class counts are floors:
117 uncertain significance, 54 conflicting classifications of pathogenicity, 24 benign/likely benign, 16 likely benign, 15 pathogenic, 7 likely pathogenic, 3 pathogenic/likely pathogenic, 2 benign
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 13973 | NM_004333.6(BRAF):c.770A>G (p.Gln257Arg) | BRAF | Pathogenic | reviewed by expert panel |
| 13976 | NM_004333.6(BRAF):c.1495A>G (p.Lys499Glu) | BRAF | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 162795 | NM_004333.6(BRAF):c.2135C>A (p.Ala712Asp) | BRAF | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 41446 | NM_004333.6(BRAF):c.1801A>C (p.Lys601Gln) | BRAF | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 52684 | NM_000059.4(BRCA2):c.8817_8820del (p.Lys2939fs) | BRCA2 | Pathogenic | reviewed by expert panel |
| 1445764 | NM_000455.5(STK11):c.29dup (p.Met11fs) | STK11 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1686233 | NM_000455.5(STK11):c.784A>T (p.Lys262Ter) | STK11 | Pathogenic | criteria provided, single submitter |
| 3383032 | NM_000455.5(STK11):c.388dup (p.Glu130fs) | STK11 | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 3600336 | NM_000455.5(STK11):c.876C>A (p.Tyr292Ter) | STK11 | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 3892570 | NM_000455.5(STK11):c.147C>G (p.Tyr49Ter) | STK11 | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 3892950 | NC_000019.9:g.(?1218416)(1222005_?)del | STK11 | Pathogenic | criteria provided, single submitter |
| 3892951 | NC_000019.9:g.1206913_1219412del | STK11 | Pathogenic | criteria provided, single submitter |
| 3892952 | NC_000019.9:g.1206913_1226646del | STK11 | Pathogenic | criteria provided, single submitter |
| 527834 | NM_000455.5(STK11):c.256C>T (p.Arg86Ter) | STK11 | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 7450 | NM_000455.5(STK11):c.580G>T (p.Asp194Tyr) | STK11 | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 7455 | NM_000455.5(STK11):c.508C>T (p.Gln170Ter) | STK11 | Pathogenic | criteria provided, single submitter |
| 7456 | NM_000455.5(STK11):c.145T>G (p.Tyr49Asp) | STK11 | Pathogenic | no assertion criteria provided |
| 7457 | NM_000455.5(STK11):c.403G>C (p.Gly135Arg) | STK11 | Pathogenic | no assertion criteria provided |
| 40370 | NM_004333.6(BRAF):c.1454T>C (p.Leu485Ser) | BRAF | Likely pathogenic | reviewed by expert panel |
| 182898 | NM_000455.5(STK11):c.487G>C (p.Gly163Arg) | STK11 | Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 220351 | NM_000455.5(STK11):c.923G>T (p.Trp308Leu) | STK11 | Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 2679059 | NM_000455.5(STK11):c.1217del (p.Ala406fs) | STK11 | Likely pathogenic | criteria provided, single submitter |
| 3583467 | NM_000455.5(STK11):c.810del (p.Ser271fs) | STK11 | Likely pathogenic | criteria provided, single submitter |
| 3892572 | NM_000455.5(STK11):c.922T>G (p.Trp308Gly) | STK11 | Likely pathogenic | criteria provided, single submitter |
| 3892953 | NM_000455.5(STK11):c.292_464+1del | STK11 | Likely pathogenic | criteria provided, single submitter |
| 1050230 | NM_004333.6(BRAF):c.1789C>T (p.Leu597=) | BRAF | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1091347 | NM_004333.6(BRAF):c.915G>A (p.Ala305=) | BRAF | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1130636 | NM_004333.6(BRAF):c.1797A>G (p.Thr599=) | BRAF | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1318788 | NM_004333.6(BRAF):c.52C>G (p.Leu18Val) | BRAF | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1339665 | NM_004333.6(BRAF):c.1690A>G (p.Met564Val) | BRAF | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 0 · Orphanet: 44 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0
Somatic driver evidence (intOGen + CIViC, cohort fanout)
| Gene | intOGen role | Cancer types | CIViC |
|---|---|---|---|
| BRAF | Act | BLCA,BRCA,CHOL,CLLSLL,COAD,COADREAD,CSCC,DLBCLNOS,GBM,GIST,HGGNOS,LGGNOS,LUAD,MEL,MLYM,NSCLC,OVT,PAST,PCM,PRAD,PRCC,PROSTATE,READ,SACA,SKCM,STAD,UCEC,WDTC | CIViC #5 |
| BRCA2 | LoF | BLCA,BRCA,CESC,CHOL,HCC,HNSC,LUSC,MBL,OVT,PAAD,PRAD,PROSTATE,RCC,VULVA | CIViC #7 |
| STK11 | LoF | ANSC,CEAD,CESC,CHOL,LUAD,NSCLC,WDTC | CIViC #5534 |
| POT1 | Act | ANGS,CLLSLL,LGGNOS,MEL,SOFT_TISSUE | CIViC #9935 |
| PTEN | LoF | ANGS,BLCA,BRCA,CCRCC,CEAD,CESC,CHOL,CHRCC,COADREAD,CSCC,ESCA,GB,GBM,HCC,HGGNOS,HNSC,LGGNOS,LIPO,LUAD,LUSC,MBL,MEL,MT,NSCLC,OVT,PANET,PAST,PRAD,PRCC,PROSTATE,RCC,SCLC,SKCM,SOFT_TISSUE,STAD,UCEC,UCS,WDTC | CIViC #41 |
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|---|---|
| BRAF | Orphanet:1340 | Cardiofaciocutaneous syndrome |
| BRAF | Orphanet:146 | Differentiated thyroid carcinoma |
| BRAF | Orphanet:251615 | Pilomyxoid astrocytoma |
| BRAF | Orphanet:389 | Langerhans cell histiocytosis |
| BRAF | Orphanet:500 | Noonan syndrome with multiple lentigines |
| BRAF | Orphanet:54595 | Craniopharyngioma |
| BRAF | Orphanet:58017 | Classic hairy cell leukemia |
| BRAF | Orphanet:626 | Large/giant congenital melanocytic nevus |
| BRAF | Orphanet:648 | Noonan syndrome |
| BRAF | Orphanet:840 | Syringocystadenoma papilliferum |
| BRAF | Orphanet:96253 | Cushing disease |
| BRCA2 | Orphanet:1331 | Familial prostate cancer |
| BRCA2 | Orphanet:1333 | Familial pancreatic carcinoma |
| BRCA2 | Orphanet:145 | Hereditary breast and/or ovarian cancer syndrome |
| BRCA2 | Orphanet:178 | Chordoma |
| BRCA2 | Orphanet:227535 | Hereditary breast cancer |
| BRCA2 | Orphanet:319462 | Inherited cancer-predisposing syndrome due to biallelic BRCA2 mutations |
| BRCA2 | Orphanet:440437 | Familial colorectal cancer Type X |
| BRCA2 | Orphanet:654 | Nephroblastoma |
| BRCA2 | Orphanet:667662 | Breast implant-associated anaplastic large cell lymphoma |
| BRCA2 | Orphanet:694963 | Inflammatory breast cancer |
| BRCA2 | Orphanet:70567 | Cholangiocarcinoma |
| BRCA2 | Orphanet:84 | Fanconi anemia |
| STK11 | Orphanet:2869 | Peutz-Jeghers syndrome |
| POT1 | Orphanet:251627 | Oligodendroglioma |
| POT1 | Orphanet:251630 | Anaplastic oligodendroglioma |
| POT1 | Orphanet:618 | Familial melanoma |
| POT1 | Orphanet:67038 | B-cell chronic lymphocytic leukemia |
| MC1R | Orphanet:618 | Familial melanoma |
| MC1R | Orphanet:79432 | Oculocutaneous albinism type 2 |
| PTEN | Orphanet:109 | Bannayan-Riley-Ruvalcaba syndrome |
| PTEN | Orphanet:137608 | Segmental outgrowth-lipomatosis-arteriovenous malformation-epidermal nevus syndrome |
| PTEN | Orphanet:145 | Hereditary breast and/or ovarian cancer syndrome |
| PTEN | Orphanet:201 | Cowden syndrome |
| PTEN | Orphanet:210548 | Macrocephaly-intellectual disability-autism syndrome |
| PTEN | Orphanet:2969 | Proteus-like syndrome |
| PTEN | Orphanet:494547 | Squamous cell carcinoma of the hypopharynx |
| PTEN | Orphanet:494550 | Squamous cell carcinoma of the larynx |
| PTEN | Orphanet:500464 | Squamous cell carcinoma of the nasal cavity and paranasal sinuses |
| PTEN | Orphanet:500478 | Squamous cell carcinoma of the oropharynx |
| PTEN | Orphanet:502363 | Squamous cell carcinoma of the oral cavity |
| PTEN | Orphanet:502366 | Squamous cell carcinoma of the lip |
| PTEN | Orphanet:65285 | Lhermitte-Duclos disease |
| PTEN | Orphanet:79076 | Juvenile polyposis of infancy |
Cohort genes → proteins
6 cohort genes, 6 distinct canonical proteins.
Evidence partition
| Subset | Genes |
|---|---|
| multi_evidence | 6 |
Cohort genes (full)
| Symbol | HGNC | Ensembl | UniProt | Name | Evidence |
|---|---|---|---|---|---|
| BRAF | HGNC:1097 | ENSG00000157764 | P15056 | Serine/threonine-protein kinase B-raf | clinvar |
| BRCA2 | HGNC:1101 | ENSG00000139618 | P51587 | Breast cancer type 2 susceptibility protein | clinvar |
| STK11 | HGNC:11389 | ENSG00000118046 | Q15831 | Serine/threonine-protein kinase STK11 | clinvar |
| POT1 | HGNC:17284 | ENSG00000128513 | Q9NUX5 | Protection of telomeres protein 1 | clinvar |
| MC1R | HGNC:6929 | ENSG00000258839 | Q01726 | Melanocyte-stimulating hormone receptor | clinvar |
| PTEN | HGNC:9588 | ENSG00000171862 | P60484 | Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN | clinvar |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| BRAF | Serine/threonine-protein kinase B-raf | Protein kinase involved in the transduction of mitogenic signals from the cell membrane to the nucleus. |
| BRCA2 | Breast cancer type 2 susceptibility protein | Involved in double-strand break repair and/or homologous recombination. |
| STK11 | Serine/threonine-protein kinase STK11 | Tumor suppressor serine/threonine-protein kinase that controls the activity of AMP-activated protein kinase (AMPK) family members, thereby playing a role in various processes such as cell metabolism, cell polarity, apoptosis and DNA damage… |
| POT1 | Protection of telomeres protein 1 | Component of the telomerase ribonucleoprotein (RNP) complex that is essential for the replication of chromosome termini. |
| MC1R | Melanocyte-stimulating hormone receptor | G protein-coupled receptor that binds melanocyte-stimulating hormones (alpha, beta, and gamma-MSH) and adrenocorticotropic hormone/ACTH, which are peptide products of the POMC precursor protein. |
| PTEN | Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN | Dual-specificity protein phosphatase, dephosphorylating tyrosine-, serine- and threonine-phosphorylated proteins. |
Protein-family classification
Druggable: 4 · Difficult: 0 · Unknown: 2 · Druggable fraction: 0.67
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 |
|---|---|---|---|
| Kinase | 2 | 9.2× | 0.071 |
| Phosphatase | 1 | 14.0× | 0.139 |
| GPCR | 1 | 4.0× | 0.301 |
| Other/Unknown | 2 | 0.6× | 0.936 |
Per-gene assignment
| Symbol | Family | Druggable? | EC | InterPro (top 3) |
|---|---|---|---|---|
| BRAF | Kinase | yes | 2.7.10.2 | Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, PKC_DAG/PE |
| BRCA2 | Other/Unknown | no | BRCA2_repeat, NA-bd_OB-fold, BRCA2_OB_1 | |
| STK11 | Kinase | yes | 2.7.11.1 | Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf |
| POT1 | Other/Unknown | no | Telomer_end-bd_POT1/Cdc13, NA-bd_OB-fold, POT1 | |
| MC1R | GPCR | yes | GPCR_Rhodpsn, MSH_rcpt, Melcrt_ACTH_rcpt | |
| PTEN | Phosphatase | yes | 3.1.3.16 | Tyr_Pase_dom, Tyr_Pase_cat, Tensin_C2-dom |
Expression context
Cohort genes with no expression data: 0.
5 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) | 6 |
| unknown | 0 |
Top tissues across cohort
| Tissue | Cohort genes |
|---|---|
| calcaneal tendon | 3 |
| secondary oocyte | 2 |
| left testis | 2 |
| buccal mucosa cell | 1 |
| colonic epithelium | 1 |
| male germ line stem cell (sensu Vertebrata) in testis | 1 |
| ventricular zone | 1 |
| hindlimb stylopod muscle | 1 |
| right testis | 1 |
| germinal epithelium of ovary | 1 |
| granulocyte | 1 |
| right uterine tube | 1 |
| endothelial cell | 1 |
| sperm | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| BRAF | 265 | ubiquitous | marker | buccal mucosa cell, colonic epithelium, calcaneal tendon |
| BRCA2 | 184 | ubiquitous | marker | male germ line stem cell (sensu Vertebrata) in testis, secondary oocyte, ventricular zone |
| STK11 | 238 | ubiquitous | marker | left testis, right testis, hindlimb stylopod muscle |
| POT1 | 279 | ubiquitous | marker | secondary oocyte, germinal epithelium of ovary, calcaneal tendon |
| MC1R | 180 | broad | yes | granulocyte, right uterine tube, left testis |
| PTEN | 256 | ubiquitous | marker | sperm, endothelial cell, calcaneal tendon |
Protein interactions among cohort
Intra-cohort edges: 4.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| PTEN | 11,626 |
| BRAF | 7,394 |
| STK11 | 5,146 |
| BRCA2 | 4,839 |
| POT1 | 1,842 |
| MC1R | 1,169 |
Intra-cohort edges
| A | B | Sources |
|---|---|---|
| BRAF | BRCA2 | biogrid_interaction |
| BRAF | PTEN | biogrid_interaction, string_interaction |
| BRCA2 | STK11 | string_interaction |
| PTEN | STK11 | string_interaction |
Structural data
PDB: 6 · AlphaFold-only: 0 · No structure: 0
Cohort genes with PDB structures (top 30)
| Symbol | UniProt | PDB entries |
|---|---|---|
| BRAF | P15056 | 131 |
| BRCA2 | P51587 | 14 |
| POT1 | Q9NUX5 | 14 |
| PTEN | P60484 | 12 |
| MC1R | Q01726 | 5 |
| STK11 | Q15831 | 4 |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 114. 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.
| Pathway | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| PTEN Loss of Function in Cancer | 1 | 951.7× | 0.037 | PTEN |
| Impaired BRCA2 translocation to the nucleus | 1 | 634.4× | 0.037 | BRCA2 |
| Impaired BRCA2 binding to SEM1 (DSS1) | 1 | 634.4× | 0.037 | BRCA2 |
| Signaling by MRAS-complex mutants | 1 | 475.8× | 0.037 | BRAF |
| Signalling to p38 via RIT and RIN | 1 | 380.7× | 0.037 | BRAF |
| Negative feedback regulation of MAPK pathway | 1 | 317.2× | 0.037 | BRAF |
| ARMS-mediated activation | 1 | 271.9× | 0.037 | BRAF |
| AMPK inhibits chREBP transcriptional activation activity | 1 | 237.9× | 0.037 | STK11 |
| Prolonged ERK activation events | 1 | 237.9× | 0.037 | BRAF |
| SHOC2 M1731 mutant abolishes MRAS complex function | 1 | 237.9× | 0.037 | BRAF |
| Gain-of-function MRAS complexes activate RAF signaling | 1 | 237.9× | 0.037 | BRAF |
| Signaling by FGFR3 | 1 | 190.3× | 0.037 | BRAF |
| Regulation of PTEN mRNA translation | 1 | 190.3× | 0.037 | PTEN |
| Signaling by FGFR4 | 1 | 173.0× | 0.037 | BRAF |
| Regulation of PTEN localization | 1 | 173.0× | 0.037 | PTEN |
| Frs2-mediated activation | 1 | 158.6× | 0.037 | BRAF |
| Defective homologous recombination repair (HRR) due to PALB2 loss of function | 1 | 158.6× | 0.037 | BRCA2 |
| HDR through MMEJ (alt-NHEJ) | 1 | 146.4× | 0.037 | BRCA2 |
| Telomere C-strand synthesis initiation | 1 | 135.9× | 0.037 | POT1 |
| Signaling by FGFR1 | 1 | 135.9× | 0.037 | BRAF |
| Diseases of DNA Double-Strand Break Repair | 1 | 135.9× | 0.037 | BRCA2 |
| Defective homologous recombination repair (HRR) due to BRCA2 loss of function | 1 | 135.9× | 0.037 | BRCA2 |
| Processive synthesis on the C-strand of the telomere | 1 | 126.9× | 0.037 | POT1 |
| Telomere C-strand (Lagging Strand) Synthesis | 1 | 126.9× | 0.037 | POT1 |
| Spry regulation of FGF signaling | 1 | 119.0× | 0.037 | BRAF |
| FOXO-mediated transcription of cell death genes | 1 | 119.0× | 0.037 | STK11 |
| Removal of the Flap Intermediate from the C-strand | 1 | 105.7× | 0.038 | POT1 |
| Resolution of D-Loop Structures | 1 | 105.7× | 0.038 | BRCA2 |
| Signalling to ERKs | 1 | 100.2× | 0.039 | BRAF |
| Diseases of DNA repair | 1 | 95.2× | 0.039 | BRCA2 |
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 term | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| establishment of protein localization to telomere | 2 | 702.2× | 5e-04 | BRCA2, POT1 |
| regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction | 2 | 234.1× | 0.003 | STK11, PTEN |
| positive regulation of axonogenesis | 2 | 193.7× | 0.003 | BRAF, STK11 |
| positive regulation of DNA strand elongation | 1 | 2808.7× | 0.009 | POT1 |
| positive regulation of vesicle transport along microtubule | 1 | 2808.7× | 0.009 | STK11 |
| positive regulation of telomeric D-loop disassembly | 1 | 2808.7× | 0.009 | POT1 |
| protein dephosphorylation | 2 | 73.9× | 0.009 | STK11, PTEN |
| mitotic recombination-dependent replication fork processing | 1 | 1404.3× | 0.013 | BRCA2 |
| negative regulation of synaptic vesicle clustering | 1 | 1404.3× | 0.013 | PTEN |
| T cell receptor signaling pathway | 2 | 50.6× | 0.013 | BRAF, STK11 |
| CD4-positive or CD8-positive, alpha-beta T cell lineage commitment | 1 | 936.2× | 0.014 | BRAF |
| negative regulation of keratinocyte migration | 1 | 936.2× | 0.014 | PTEN |
| telomere assembly | 1 | 702.2× | 0.014 | POT1 |
| rhythmic synaptic transmission | 1 | 702.2× | 0.014 | PTEN |
| negative regulation of mammary gland epithelial cell proliferation | 1 | 561.7× | 0.014 | BRCA2 |
| positive regulation of axon regeneration | 1 | 561.7× | 0.014 | BRAF |
| negative regulation of synaptic vesicle exocytosis | 1 | 561.7× | 0.014 | BRAF |
| regulation of double-strand break repair via nonhomologous end joining | 1 | 561.7× | 0.014 | POT1 |
| regulation of telomere maintenance via telomerase | 1 | 468.1× | 0.014 | POT1 |
| central nervous system myelin maintenance | 1 | 468.1× | 0.014 | PTEN |
| CD4-positive, alpha-beta T cell differentiation | 1 | 468.1× | 0.014 | BRAF |
| negative regulation of epithelial cell proliferation involved in prostate gland development | 1 | 468.1× | 0.014 | STK11 |
| myeloid progenitor cell differentiation | 1 | 401.2× | 0.014 | BRAF |
| negative regulation of cell cycle G1/S phase transition | 1 | 401.2× | 0.014 | PTEN |
| negative regulation of wound healing, spreading of epidermal cells | 1 | 401.2× | 0.014 | PTEN |
| positive regulation of feeding behavior | 1 | 401.2× | 0.014 | MC1R |
| positive regulation of D-glucose transmembrane transport | 1 | 351.1× | 0.014 | BRAF |
| Golgi localization | 1 | 351.1× | 0.014 | STK11 |
| head morphogenesis | 1 | 351.1× | 0.014 | BRAF |
| epithelial cell proliferation involved in prostate gland development | 1 | 351.1× | 0.014 | STK11 |
Therapeutics
Drug target analysis
Approved (phase 4): 3 · Phase ≥3: 3 · Phased (≥1): 3 · Undrugged: 3
Druggability breadth: 5 of 6 evidence-associated genes (83%) 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 |
|---|---|
| BRAF | VEMURAFENIB |
| STK11 | FEDRATINIB |
| MC1R | BREMELANOTIDE |
Top cohort targets by molecule count
| Symbol | Molecules | Max phase |
|---|---|---|
| BRAF | 48 | 4 |
| STK11 | 17 | 4 |
| MC1R | 6 | 4 |
| BRCA2 | 0 | 0 |
| POT1 | 0 | 0 |
| PTEN | 0 | 0 |
Drugs targeting cohort genes (top 30)
| Molecule | Max phase | Targets in cohort |
|---|---|---|
| VEMURAFENIB | 4 | BRAF |
| PONATINIB | 4 | BRAF |
| FEDRATINIB | 4 | BRAF, STK11 |
| SORAFENIB | 4 | BRAF |
| DASATINIB ANHYDROUS | 4 | BRAF |
| RUXOLITINIB | 4 | BRAF |
| INFIGRATINIB PHOSPHATE | 4 | BRAF |
| INFIGRATINIB | 4 | BRAF |
| REGORAFENIB | 4 | BRAF |
| DABRAFENIB | 4 | BRAF |
| COBIMETINIB | 4 | BRAF |
| NILOTINIB | 4 | BRAF |
| ABEMACICLIB | 4 | BRAF |
| ENCORAFENIB | 4 | BRAF |
| TOVORAFENIB | 4 | BRAF |
| PAZOPANIB | 4 | BRAF |
| DASATINIB | 4 | BRAF |
| ERLOTINIB | 4 | BRAF |
| GEFITINIB | 4 | BRAF |
| IMATINIB | 4 | BRAF |
| PACRITINIB | 4 | STK11 |
| NINTEDANIB | 4 | STK11 |
| SUNITINIB | 4 | STK11 |
| MIDOSTAURIN | 4 | STK11 |
| BREMELANOTIDE | 4 | MC1R |
| SETMELANOTIDE | 4 | MC1R |
| AFAMELANOTIDE | 4 | MC1R |
| MASITINIB | 3 | BRAF |
| AVUTOMETINIB | 3 | BRAF |
| NAPORAFENIB | 3 | BRAF |
Bioactivity and enzyme data
Enzyme cohort genes (≥1 EC): 3.
Cohort genes with ChEMBL bioactivity (full, sorted by assay count)
| Symbol | Assays | Type breakdown |
|---|---|---|
| BRAF | 1,442 | Binding:1400, Functional:37, ADMET:5 |
| MC1R | 319 | Functional:164, Binding:155 |
| STK11 | 244 | Binding:244 |
| PTEN | 8 | Binding:8 |
| POT1 | 1 | Binding:1 |
Cohort enzymes (BRENDA EC)
| Symbol | EC numbers | Names |
|---|---|---|
| BRAF | 2.7.10.2, 2.7.11.1 | non-specific protein-tyrosine kinase, non-specific serine/threonine protein kinase |
| STK11 | 2.7.11.1 | non-specific serine/threonine protein kinase |
| PTEN | 3.1.3.16, 3.1.3.67 | protein-serine/threonine phosphatase, phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase |
Cohort genes with high screening signal
≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.
| Symbol | ChEMBL assays |
|---|---|
| BRAF | 1,442 |
| STK11 | 244 |
| MC1R | 319 |
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.
| Compound | Max phase | Cohort target (bioactivity) |
|---|---|---|
| VEMURAFENIB | 4 | BRAF |
| PONATINIB | 4 | BRAF |
| FEDRATINIB | 4 | BRAF, STK11 |
| SORAFENIB | 4 | BRAF |
| DASATINIB ANHYDROUS | 4 | BRAF |
| RUXOLITINIB | 4 | BRAF |
| INFIGRATINIB PHOSPHATE | 4 | BRAF |
| INFIGRATINIB | 4 | BRAF |
| REGORAFENIB | 4 | BRAF |
| DABRAFENIB | 4 | BRAF |
| COBIMETINIB | 4 | BRAF |
| NILOTINIB | 4 | BRAF |
| ABEMACICLIB | 4 | BRAF |
| ENCORAFENIB | 4 | BRAF |
| TOVORAFENIB | 4 | BRAF |
| PAZOPANIB | 4 | BRAF |
| DASATINIB | 4 | BRAF |
| ERLOTINIB | 4 | BRAF |
| GEFITINIB | 4 | BRAF |
| IMATINIB | 4 | BRAF |
| PACRITINIB | 4 | STK11 |
| NINTEDANIB | 4 | STK11 |
| SUNITINIB | 4 | STK11 |
| MIDOSTAURIN | 4 | STK11 |
| BREMELANOTIDE | 4 | MC1R |
| SETMELANOTIDE | 4 | MC1R |
| AFAMELANOTIDE | 4 | MC1R |
| MASITINIB | 3 | BRAF |
| AVUTOMETINIB | 3 | BRAF |
| NAPORAFENIB | 3 | BRAF |
Druggability pyramid
Cohort genes binned by druggability tier (high → low):
| Tier | Definition | Genes | Symbols |
|---|---|---|---|
| A | Approved (phase 4 drug) | 3 | BRAF, STK11, MC1R |
| B | Phased (≥1) drug, not yet approved | 0 | |
| C | Druggable family + PDB, no drug | 1 | PTEN |
| D | Druggable family + AlphaFold only, no drug | 0 | |
| E | Difficult family or no structure, no drug | 2 | BRCA2, POT1 |
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) |
|---|---|---|
| PTEN | 8 | STK11 |
| BRCA2 | 0 | — |
| POT1 | 1 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 0.