Nevus, epidermal
diseaseOn this page
Also known as Epidermal Nevusepidermal nevus, somaticnevus sebaceous or woolly hair nevus, somaticnevus sebaceous or wooly hair nevus, somaticnevus, epidermal, somaticNevus, woolly hair
Summary
Nevus, epidermal (MONDO:0008093) is a disease with 8 cohort genes. The dominant Reactome pathway is Signaling by FGFR3 in disease (5 cohort genes).
At a glance
- Cohort genes: 8
- ClinVar variants: 90
Clinical features
No curated clinical features (Orphanet) for this disease.
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | nevus, epidermal |
| Mondo ID | MONDO:0008093 |
| MeSH | C580062 |
| OMIM | 162900 |
| DOID | DOID:0111162 |
| NCIT | C4088 |
| UMLS | C0334082 |
| MedGen | 83106 |
| GARD | 0024601 |
| Is cancer (heuristic) | no |
Also known as: Epidermal Nevus · epidermal nevus, somatic · nevus sebaceous or woolly hair nevus, somatic · nevus sebaceous or wooly hair nevus, somatic · nevus, epidermal · nevus, epidermal, somatic · Nevus, woolly hair
Data availability: 90 ClinVar variants.
Disease family
An umbrella term covering 1 Mondo subtype.
Classification path: disease › human disease › disease by body system or component › integumentary system disorder › integumentary system benign neoplasm › benign neoplasm of skin › melanocytic nevus › nevus, epidermal
Related subtypes (27): conjunctival nevus, blue nevus, halo nevus, intradermal nevus, pigmented spindle cell nevus, neurocutaneous melanocytosis, neutrophil actin dysfunction, CHILD syndrome, Becker nevus syndrome, CLOVES syndrome, nevus comedonicus syndrome, segmental outgrowth-lipomatosis-arteriovenous malformation-epidermal nevus syndrome, congenital panfollicular nevus, porokeratotic eccrine ostial and dermal duct nevus, hereditary mucosal leukokeratosis, linear verrucous nevus syndrome, nevus of Ota, nevus of Ito, phakomatosis pigmentokeratotica, PENS syndrome, Angora hair nevus, didymosis aplasticosebacea, scalp syndrome, Nevada syndrome, palpebral nevus, large congenital melanocytic nevus, benign melanocytic skin nevus
Subtypes (1): wooly hair nevus
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
90 retrieved; paginated sample, class counts are floors:
42 uncertain significance, 22 pathogenic, 8 conflicting classifications of pathogenicity, 7 pathogenic/likely pathogenic, 6 benign/likely benign, 3 benign, 2 likely pathogenic
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 16327 | NM_000142.5(FGFR3):c.1138G>A (p.Gly380Arg) | FGFR3 | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 16331 | NM_000142.5(FGFR3):c.1948A>G (p.Lys650Glu) | FGFR3 | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 16332 | NM_000142.5(FGFR3):c.742C>T (p.Arg248Cys) | FGFR3 | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 16335 | NM_000142.5(FGFR3):c.2419T>A (p.Ter807Arg) | FGFR3 | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 16338 | NM_000142.5(FGFR3):c.1620C>G (p.Asn540Lys) | FGFR3 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 16339 | NM_000142.5(FGFR3):c.746C>G (p.Ser249Cys) | FGFR3 | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 16340 | NM_000142.5(FGFR3):c.749C>G (p.Pro250Arg) | FGFR3 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 16341 | NM_000142.5(FGFR3):c.1949A>T (p.Lys650Met) | FGFR3 | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 16347 | NM_000142.5(FGFR3):c.1950G>C (p.Lys650Asn) | FGFR3 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 16359 | NM_000142.5(FGFR3):c.1108G>T (p.Gly370Cys) | FGFR3 | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 65562 | NM_000142.5(FGFR3):c.2420G>T (p.Ter807Leu) | FGFR3 | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 65855 | NM_000142.5(FGFR3):c.1949A>C (p.Lys650Thr) | FGFR3 | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 12600 | NM_005343.4(HRAS):c.35G>T (p.Gly12Val) | HRAS | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 12601 | NM_005343.4(HRAS):c.181C>A (p.Gln61Lys) | HRAS | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 12602 | NM_005343.4(HRAS):c.34G>A (p.Gly12Ser) | HRAS | Pathogenic | reviewed by expert panel |
| 12603 | NM_005343.4(HRAS):c.35G>C (p.Gly12Ala) | HRAS | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 12604 | NM_005343.4(HRAS):c.38G>A (p.Gly13Asp) | HRAS | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 12606 | NM_005343.4(HRAS):c.37G>T (p.Gly13Cys) | HRAS | Pathogenic | reviewed by expert panel |
| 12613 | NM_005343.4(HRAS):c.34G>T (p.Gly12Cys) | HRAS | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 35554 | NM_005343.4(HRAS):c.37G>C (p.Gly13Arg) | HRAS | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 391700 | NM_005343.4(HRAS):c.179G>T (p.Gly60Val) | HRAS | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 12582 | NM_004985.5(KRAS):c.35G>A (p.Gly12Asp) | KRAS | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 13900 | NM_002524.5(NRAS):c.182A>G (p.Gln61Arg) | NRAS | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 39647 | NM_002524.5(NRAS):c.101C>T (p.Pro34Leu) | NRAS | Pathogenic | no assertion criteria provided |
| 39648 | NM_002524.5(NRAS):c.35G>A (p.Gly12Asp) | NRAS | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 13656 | NM_006218.4(PIK3CA):c.1634A>G (p.Glu545Gly) | PIK3CA | Pathogenic | criteria provided, single submitter |
| 376050 | NM_006218.4(PIK3CA):c.1035T>A (p.Asn345Lys) | PIK3CA | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 39704 | NM_006218.4(PIK3CA):c.1133G>A (p.Cys378Tyr) | PIK3CA | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 39705 | NM_006218.4(PIK3CA):c.3139C>T (p.His1047Tyr) | PIK3CA | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 160364 | NM_005343.4(HRAS):c.182A>G (p.Gln61Arg) | HRAS | Likely pathogenic | criteria provided, multiple submitters, no conflicts |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 0 · Orphanet: 72 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0
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 |
| COL7A1 | Orphanet:158673 | Localized dystrophic epidermolysis bullosa, acral form |
| COL7A1 | Orphanet:158676 | Localized dystrophic epidermolysis bullosa, nails only |
| COL7A1 | Orphanet:231568 | Autosomal dominant generalized dystrophic epidermolysis bullosa |
| COL7A1 | Orphanet:79408 | Autosomal recessive generalized dystrophic epidermolysis bullosa, severe form |
| COL7A1 | Orphanet:79409 | Recessive dystrophic epidermolysis bullosa inversa |
| COL7A1 | Orphanet:79410 | Localized dystrophic epidermolysis bullosa, pretibial form |
| COL7A1 | Orphanet:79411 | Self-improving dystrophic epidermolysis bullosa |
| COL7A1 | Orphanet:89842 | Autosomal recessive generalized dystrophic epidermolysis bullosa, intermediate form |
| COL7A1 | Orphanet:89843 | Dystrophic epidermolysis bullosa pruriginosa |
| LRRC56 | Orphanet:244 | Primary ciliary dyskinesia |
| FGFR3 | Orphanet:15 | Achondroplasia |
| FGFR3 | Orphanet:1860 | Thanatophoric dysplasia type 1 |
| FGFR3 | Orphanet:2363 | Lacrimoauriculodentodigital syndrome |
| FGFR3 | Orphanet:251576 | Gliosarcoma |
| FGFR3 | Orphanet:251579 | Giant cell glioblastoma |
| FGFR3 | Orphanet:35099 | Non-syndromic bicoronal craniosynostosis |
| FGFR3 | Orphanet:429 | Hypochondroplasia |
| FGFR3 | Orphanet:53271 | Muenke syndrome |
| FGFR3 | Orphanet:794 | Saethre-Chotzen syndrome |
| FGFR3 | Orphanet:85164 | Camptodactyly-tall stature-scoliosis-hearing loss syndrome |
| FGFR3 | Orphanet:85165 | Severe achondroplasia-developmental delay-acanthosis nigricans syndrome |
| FGFR3 | Orphanet:93262 | Crouzon syndrome-acanthosis nigricans syndrome |
| FGFR3 | Orphanet:93274 | Thanatophoric dysplasia type 2 |
| HRAS | Orphanet:146 | Differentiated thyroid carcinoma |
| HRAS | Orphanet:2612 | Linear nevus sebaceus syndrome |
| HRAS | Orphanet:2874 | Phakomatosis pigmentokeratotica |
| HRAS | Orphanet:3071 | Costello syndrome |
| HRAS | Orphanet:79414 | Woolly hair nevus |
| KRAS | Orphanet:1333 | Familial pancreatic carcinoma |
| KRAS | Orphanet:1340 | Cardiofaciocutaneous syndrome |
| KRAS | Orphanet:144 | Lynch syndrome |
| KRAS | Orphanet:146 | Differentiated thyroid carcinoma |
| KRAS | Orphanet:2396 | Encephalocraniocutaneous lipomatosis |
| KRAS | Orphanet:251615 | Pilomyxoid astrocytoma |
| KRAS | Orphanet:2612 | Linear nevus sebaceus syndrome |
| KRAS | Orphanet:268114 | RAS-associated autoimmune leukoproliferative disease |
| KRAS | Orphanet:3339 | Oculoectodermal syndrome |
| KRAS | Orphanet:648 | Noonan syndrome |
| KRAS | Orphanet:86834 | Juvenile myelomonocytic leukemia |
Cohort genes → proteins
8 cohort genes, 8 distinct canonical proteins.
Evidence partition
| Subset | Genes |
|---|---|
| multi_evidence | 8 |
Cohort genes (full)
| Symbol | HGNC | Ensembl | UniProt | Name | Evidence |
|---|---|---|---|---|---|
| BRAF | HGNC:1097 | ENSG00000157764 | P15056 | Serine/threonine-protein kinase B-raf | clinvar |
| COL7A1 | HGNC:2214 | ENSG00000114270 | Q02388 | Collagen alpha-1(VII) chain | clinvar |
| LRRC56 | HGNC:25430 | ENSG00000161328 | Q8IYG6 | Leucine-rich repeat-containing protein 56 | clinvar |
| FGFR3 | HGNC:3690 | ENSG00000068078 | P22607 | Fibroblast growth factor receptor 3 | clinvar |
| HRAS | HGNC:5173 | ENSG00000174775 | P01112 | GTPase HRas | clinvar |
| KRAS | HGNC:6407 | ENSG00000133703 | P01116 | GTPase KRas | clinvar |
| NRAS | HGNC:7989 | ENSG00000213281 | P01111 | GTPase NRas | clinvar |
| PIK3CA | HGNC:8975 | ENSG00000121879 | P42336 | Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform | 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. |
| COL7A1 | Collagen alpha-1(VII) chain | Stratified squamous epithelial basement membrane protein that forms anchoring fibrils which may contribute to epithelial basement membrane organization and adherence by interacting with extracellular matrix (ECM) proteins such as type IV c… |
| LRRC56 | Leucine-rich repeat-containing protein 56 | Required for the assembly of dynein arms. |
| FGFR3 | Fibroblast growth factor receptor 3 | Tyrosine-protein kinase that acts as a cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of cell proliferation, differentiation and apoptosis. |
| HRAS | GTPase HRas | Involved in the activation of Ras protein signal transduction. |
| KRAS | GTPase KRas | Ras proteins bind GDP/GTP and possess intrinsic GTPase activity. |
| NRAS | GTPase NRas | Ras proteins bind GDP/GTP and possess intrinsic GTPase activity. |
| PIK3CA | Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform | Phosphoinositide-3-kinase (PI3K) phosphorylates phosphatidylinositol (PI) and its phosphorylated derivatives at position 3 of the inositol ring to produce 3-phosphoinositides. |
Protein-family classification
Druggable: 6 · Difficult: 0 · Unknown: 2 · Druggable fraction: 0.75
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 | 3 | 10.4× | 0.009 |
| Enzyme (other) | 2 | 3.0× | 0.278 |
| Antibody/Immunoglobulin | 1 | 3.6× | 0.325 |
| Other/Unknown | 2 | 0.5× | 0.984 |
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 |
| COL7A1 | Antibody/Immunoglobulin | yes | VWF_A, Kunitz_BPTI, FN3_dom | |
| LRRC56 | Other/Unknown | no | Leu-rich_rpt, Leu-rich_rpt_4, LRR_dom_sf | |
| FGFR3 | Kinase | yes | 2.7.10.1 | Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Ig_sub2 |
| HRAS | Enzyme (other) | yes | 3.6.5.2 | Small_GTPase, Small_GTP-bd, Small_GTPase_Ras-type |
| KRAS | Enzyme (other) | yes | 3.6.5.2 | Small_GTPase, Small_GTP-bd, Small_GTPase_Ras-type |
| NRAS | Other/Unknown | no | Small_GTPase, Small_GTP-bd, Small_GTPase_Ras-type | |
| PIK3CA | Kinase | yes | 2.7.1.137 | PI3K_Ras-bd_dom, PI3/4_kinase_cat_dom, PI3K_accessory_dom |
Expression context
Cohort genes with no expression data: 0.
8 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) | 8 |
| unknown | 0 |
Top tissues across cohort
| Tissue | Cohort genes |
|---|---|
| calcaneal tendon | 2 |
| skin of abdomen | 2 |
| skin of leg | 2 |
| buccal mucosa cell | 1 |
| colonic epithelium | 1 |
| stromal cell of endometrium | 1 |
| left testis | 1 |
| right testis | 1 |
| right uterine tube | 1 |
| skin of hip | 1 |
| upper arm skin | 1 |
| upper leg skin | 1 |
| zone of skin | 1 |
| nipple | 1 |
| pylorus | 1 |
| trigeminal ganglion | 1 |
| epithelium of nasopharynx | 1 |
| gingival epithelium | 1 |
| secondary oocyte | 1 |
| adrenal tissue | 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 |
| COL7A1 | 267 | ubiquitous | marker | stromal cell of endometrium, skin of abdomen, skin of leg |
| LRRC56 | 129 | broad | marker | right uterine tube, right testis, left testis |
| FGFR3 | 262 | broad | marker | upper leg skin, skin of hip, upper arm skin |
| HRAS | 139 | ubiquitous | marker | skin of abdomen, skin of leg, zone of skin |
| KRAS | 298 | ubiquitous | marker | trigeminal ganglion, pylorus, nipple |
| NRAS | 278 | ubiquitous | marker | gingival epithelium, epithelium of nasopharynx, secondary oocyte |
| PIK3CA | 284 | ubiquitous | marker | calcaneal tendon, adrenal tissue, tendon |
Protein interactions among cohort
Intra-cohort edges: 8.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| KRAS | 14,509 |
| HRAS | 8,064 |
| NRAS | 7,598 |
| BRAF | 7,394 |
| PIK3CA | 5,157 |
| FGFR3 | 4,510 |
| COL7A1 | 1,767 |
| LRRC56 | 914 |
Intra-cohort edges
| A | B | Sources |
|---|---|---|
| BRAF | HRAS | intact, string_interaction |
| BRAF | KRAS | biogrid_interaction, intact, string_interaction |
| BRAF | NRAS | biogrid_interaction, intact, string_interaction |
| BRAF | PIK3CA | biogrid_interaction, string_interaction |
| FGFR3 | PIK3CA | string_interaction |
| KRAS | NRAS | intact |
| KRAS | PIK3CA | string_interaction |
| NRAS | PIK3CA | string_interaction |
Structural data
PDB: 6 · AlphaFold-only: 2 · No structure: 0
Cohort genes with PDB structures (top 30)
| Symbol | UniProt | PDB entries |
|---|---|---|
| KRAS | P01116 | 511 |
| HRAS | P01112 | 246 |
| PIK3CA | P42336 | 135 |
| BRAF | P15056 | 131 |
| NRAS | P01111 | 35 |
| FGFR3 | P22607 | 15 |
AlphaFold-only cohort genes (top 30 by pLDDT)
| Symbol | UniProt | pLDDT |
|---|---|---|
| LRRC56 | Q8IYG6 | 56.07 |
| COL7A1 | Q02388 |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 158. Enrichment computed across 8 evidence-associated genes (7 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 7 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| Pathway | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| Signaling by FGFR3 in disease | 5 | 354.7× | 7e-11 | FGFR3, HRAS, KRAS, NRAS, PIK3CA |
| Signaling by FGFR4 in disease | 4 | 543.8× | 1e-09 | HRAS, KRAS, NRAS, PIK3CA |
| Signaling by PDGFRA transmembrane, juxtamembrane and kinase domain mutants | 4 | 502.0× | 1e-09 | HRAS, KRAS, NRAS, PIK3CA |
| Signaling by PDGFRA extracellular domain mutants | 4 | 502.0× | 1e-09 | HRAS, KRAS, NRAS, PIK3CA |
| Signaling by FLT3 ITD and TKD mutants | 4 | 435.1× | 2e-09 | HRAS, KRAS, NRAS, PIK3CA |
| Signaling by RAS GAP mutants | 3 | 1631.4× | 2e-09 | HRAS, KRAS, NRAS |
| Signaling by RAS GTPase mutants | 3 | 1631.4× | 2e-09 | HRAS, KRAS, NRAS |
| Constitutive Signaling by EGFRvIII | 4 | 407.9× | 2e-09 | HRAS, KRAS, NRAS, PIK3CA |
| Signaling by ERBB2 ECD mutants | 4 | 383.9× | 2e-09 | HRAS, KRAS, NRAS, PIK3CA |
| RAF/MAP kinase cascade | 6 | 52.4× | 2e-09 | BRAF, FGFR3, HRAS, KRAS, NRAS, PIK3CA |
| Tie2 Signaling | 4 | 343.5× | 3e-09 | HRAS, KRAS, NRAS, PIK3CA |
| SHC-mediated cascade:FGFR3 | 4 | 343.5× | 3e-09 | FGFR3, HRAS, KRAS, NRAS |
| Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants | 4 | 326.3× | 3e-09 | HRAS, KRAS, NRAS, PIK3CA |
| Signaling by FLT3 fusion proteins | 4 | 326.3× | 3e-09 | HRAS, KRAS, NRAS, PIK3CA |
| FRS-mediated FGFR3 signaling | 4 | 310.8× | 3e-09 | FGFR3, HRAS, KRAS, NRAS |
| Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants | 4 | 296.6× | 4e-09 | HRAS, KRAS, NRAS, PIK3CA |
| Signaling by ERBB2 KD Mutants | 4 | 241.7× | 8e-09 | HRAS, KRAS, NRAS, PIK3CA |
| Activation of RAS in B cells | 3 | 978.9× | 1e-08 | HRAS, KRAS, NRAS |
| Downstream signal transduction | 4 | 217.5× | 1e-08 | HRAS, KRAS, NRAS, PIK3CA |
| DAP12 signaling | 4 | 210.5× | 1e-08 | HRAS, KRAS, NRAS, PIK3CA |
| FLT3 Signaling | 4 | 197.8× | 2e-08 | HRAS, KRAS, NRAS, PIK3CA |
| RAF activation | 4 | 191.9× | 2e-08 | BRAF, HRAS, KRAS, NRAS |
| Signaling by high-kinase activity BRAF mutants | 4 | 181.3× | 2e-08 | BRAF, HRAS, KRAS, NRAS |
| Signaling by FGFR1 in disease | 4 | 167.3× | 3e-08 | HRAS, KRAS, NRAS, PIK3CA |
| RAS signaling downstream of NF1 loss-of-function variants | 3 | 699.2× | 3e-08 | HRAS, KRAS, NRAS |
| Estrogen-stimulated signaling through PRKCZ | 3 | 699.2× | 3e-08 | HRAS, KRAS, NRAS |
| MAP2K and MAPK activation | 4 | 163.1× | 3e-08 | BRAF, HRAS, KRAS, NRAS |
| Signaling by RAF1 mutants | 4 | 159.2× | 3e-08 | BRAF, HRAS, KRAS, NRAS |
| Signaling by FGFR2 in disease | 4 | 151.8× | 3e-08 | HRAS, KRAS, NRAS, PIK3CA |
| Negative regulation of MAPK pathway | 4 | 151.8× | 3e-08 | BRAF, HRAS, KRAS, NRAS |
GO biological processes by enrichment
Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 8 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| GO term | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| MAPK cascade | 5 | 95.8× | 1e-07 | BRAF, FGFR3, HRAS, KRAS, NRAS |
| negative regulation of neuron apoptotic process | 4 | 55.4× | 3e-05 | BRAF, HRAS, KRAS, PIK3CA |
| Ras protein signal transduction | 3 | 77.1× | 3e-04 | HRAS, KRAS, NRAS |
| T cell receptor signaling pathway | 3 | 56.9× | 6e-04 | BRAF, HRAS, PIK3CA |
| regulation of long-term neuronal synaptic plasticity | 2 | 247.8× | 9e-04 | HRAS, KRAS |
| positive regulation of ERK1 and ERK2 cascade | 3 | 31.9× | 0.002 | BRAF, FGFR3, HRAS |
| adipose tissue development | 2 | 100.3× | 0.004 | HRAS, PIK3CA |
| visual learning | 2 | 76.6× | 0.006 | BRAF, KRAS |
| response to muscle inactivity | 1 | 2106.5× | 0.006 | PIK3CA |
| negative regulation of developmental growth | 1 | 2106.5× | 0.006 | FGFR3 |
| response to mineralocorticoid | 1 | 2106.5× | 0.006 | KRAS |
| response to butyrate | 1 | 2106.5× | 0.006 | PIK3CA |
| epidermal growth factor receptor signaling pathway | 2 | 62.0× | 0.006 | BRAF, PIK3CA |
| liver development | 2 | 55.4× | 0.006 | KRAS, PIK3CA |
| insulin receptor signaling pathway | 2 | 55.4× | 0.006 | HRAS, PIK3CA |
| animal organ morphogenesis | 2 | 47.9× | 0.007 | BRAF, HRAS |
| neuron apoptotic process | 2 | 46.3× | 0.007 | HRAS, KRAS |
| fibroblast growth factor receptor apoptotic signaling pathway | 1 | 1053.2× | 0.008 | FGFR3 |
| forebrain astrocyte development | 1 | 702.2× | 0.010 | KRAS |
| response to L-leucine | 1 | 702.2× | 0.010 | PIK3CA |
| CD4-positive or CD8-positive, alpha-beta T cell lineage commitment | 1 | 702.2× | 0.010 | BRAF |
| bone maturation | 1 | 702.2× | 0.010 | FGFR3 |
| cellular response to hydrostatic pressure | 1 | 702.2× | 0.010 | PIK3CA |
| positive regulation of miRNA metabolic process | 1 | 702.2× | 0.010 | HRAS |
| response to isolation stress | 1 | 526.6× | 0.012 | KRAS |
| regulation of cell population proliferation | 2 | 28.9× | 0.012 | BRAF, HRAS |
| positive regulation of phospholipase activity | 1 | 421.3× | 0.013 | FGFR3 |
| positive regulation of axon regeneration | 1 | 421.3× | 0.013 | BRAF |
| negative regulation of synaptic vesicle exocytosis | 1 | 421.3× | 0.013 | BRAF |
| response to gravity | 1 | 351.1× | 0.014 | KRAS |
Therapeutics
Drug target analysis
Approved (phase 4): 5 · Phase ≥3: 5 · Phased (≥1): 6 · Undrugged: 2
Druggability breadth: 7 of 8 evidence-associated genes (88%) 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 |
| FGFR3 | PONATINIB |
| HRAS | LONAFARNIB |
| KRAS | VEMURAFENIB |
| PIK3CA | IDELALISIB |
Top cohort targets by molecule count
| Symbol | Molecules | Max phase |
|---|---|---|
| PIK3CA | 67 | 4 |
| FGFR3 | 64 | 4 |
| BRAF | 48 | 4 |
| KRAS | 11 | 4 |
| HRAS | 4 | 4 |
| NRAS | 1 | 1 |
| COL7A1 | 0 | 0 |
| LRRC56 | 0 | 0 |
Drugs targeting cohort genes (top 30)
| Molecule | Max phase | Targets in cohort |
|---|---|---|
| VEMURAFENIB | 4 | BRAF, KRAS |
| PONATINIB | 4 | BRAF, FGFR3 |
| FEDRATINIB | 4 | BRAF, FGFR3, PIK3CA |
| SORAFENIB | 4 | BRAF, FGFR3 |
| DASATINIB ANHYDROUS | 4 | BRAF |
| RUXOLITINIB | 4 | BRAF |
| INFIGRATINIB PHOSPHATE | 4 | BRAF, FGFR3 |
| INFIGRATINIB | 4 | BRAF, FGFR3 |
| REGORAFENIB | 4 | BRAF |
| DABRAFENIB | 4 | BRAF, KRAS |
| COBIMETINIB | 4 | BRAF |
| NILOTINIB | 4 | BRAF |
| ABEMACICLIB | 4 | BRAF |
| ENCORAFENIB | 4 | BRAF |
| TOVORAFENIB | 4 | BRAF |
| PAZOPANIB | 4 | BRAF, FGFR3 |
| DASATINIB | 4 | BRAF, FGFR3, PIK3CA |
| ERLOTINIB | 4 | BRAF |
| GEFITINIB | 4 | BRAF |
| IMATINIB | 4 | BRAF |
| PEMIGATINIB | 4 | FGFR3 |
| NINTEDANIB | 4 | FGFR3 |
| LENVATINIB | 4 | FGFR3 |
| AXITINIB | 4 | FGFR3 |
| ENTRECTINIB | 4 | FGFR3 |
| CERITINIB | 4 | FGFR3 |
| VANDETANIB | 4 | FGFR3 |
| NINTEDANIB ESYLATE | 4 | FGFR3 |
| BRIGATINIB | 4 | FGFR3 |
| ERDAFITINIB | 4 | FGFR3 |
Bioactivity and enzyme data
Enzyme cohort genes (≥1 EC): 5.
Cohort genes with ChEMBL bioactivity (full, sorted by assay count)
| Symbol | Assays | Type breakdown |
|---|---|---|
| PIK3CA | 2,034 | Binding:2009, ADMET:19, Toxicity:4, Functional:2 |
| BRAF | 1,442 | Binding:1400, Functional:37, ADMET:5 |
| FGFR3 | 975 | Binding:948, Functional:18, ADMET:9 |
| KRAS | 861 | Binding:829, Functional:32 |
| HRAS | 48 | Binding:45, Functional:3 |
| NRAS | 18 | Binding:18 |
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 |
| FGFR3 | 2.7.10.1 | receptor protein-tyrosine kinase |
| HRAS | 3.6.5.2 | small monomeric GTPase |
| KRAS | 3.6.5.2 | small monomeric GTPase |
| PIK3CA | 2.7.1.137, 2.7.1.153, 2.7.11.1 | phosphatidylinositol 3-kinase, phosphatidylinositol-4,5-bisphosphate 3-kinase, non-specific serine/threonine protein kinase |
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 |
| FGFR3 | 975 |
| KRAS | 861 |
| PIK3CA | 2,034 |
Pharmacogenomics
Cohort genes with a PharmGKB record: 8; with CPIC/DPWG dosing guidelines: 0.
No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).
Chemical tractability of cohort targets
30 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) |
|---|---|---|
| VEMURAFENIB | 4 | BRAF, KRAS |
| PONATINIB | 4 | BRAF, FGFR3 |
| FEDRATINIB | 4 | BRAF, FGFR3, PIK3CA |
| SORAFENIB | 4 | BRAF, FGFR3 |
| DASATINIB ANHYDROUS | 4 | BRAF |
| RUXOLITINIB | 4 | BRAF |
| INFIGRATINIB PHOSPHATE | 4 | BRAF, FGFR3 |
| INFIGRATINIB | 4 | BRAF, FGFR3 |
| REGORAFENIB | 4 | BRAF |
| DABRAFENIB | 4 | BRAF, KRAS |
| COBIMETINIB | 4 | BRAF |
| NILOTINIB | 4 | BRAF |
| ABEMACICLIB | 4 | BRAF |
| ENCORAFENIB | 4 | BRAF |
| TOVORAFENIB | 4 | BRAF |
| PAZOPANIB | 4 | BRAF, FGFR3 |
| DASATINIB | 4 | BRAF, FGFR3, PIK3CA |
| ERLOTINIB | 4 | BRAF |
| GEFITINIB | 4 | BRAF |
| IMATINIB | 4 | BRAF |
| PEMIGATINIB | 4 | FGFR3 |
| NINTEDANIB | 4 | FGFR3 |
| LENVATINIB | 4 | FGFR3 |
| AXITINIB | 4 | FGFR3 |
| ENTRECTINIB | 4 | FGFR3 |
| CERITINIB | 4 | FGFR3 |
| VANDETANIB | 4 | FGFR3 |
| NINTEDANIB ESYLATE | 4 | FGFR3 |
| BRIGATINIB | 4 | FGFR3 |
| ERDAFITINIB | 4 | FGFR3 |
Druggability pyramid
Cohort genes binned by druggability tier (high → low):
| Tier | Definition | Genes | Symbols |
|---|---|---|---|
| A | Approved (phase 4 drug) | 5 | BRAF, FGFR3, HRAS, KRAS, PIK3CA |
| B | Phased (≥1) drug, not yet approved | 1 | NRAS |
| C | Druggable family + PDB, no drug | 0 | |
| D | Druggable family + AlphaFold only, no drug | 1 | COL7A1 |
| E | Difficult family or no structure, no drug | 1 | LRRC56 |
Undrugged target profiles
2 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).
| Symbol | ChEMBL assays | Drugged partners (top 3) |
|---|---|---|
| COL7A1 | 0 | — |
| LRRC56 | 0 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 0.