Gene | Associated with LEOPARD SYNDROME in | Link to HGNC | Cytogenetic band | Number of associated diseases | Associated diseases |
---|---|---|---|---|---|
PTPN11 | ClinVar, OMIM, HUMSAVAR | HGNC link | 12q24.13 | 4 | PS163950, 607785, 156250, PS151100 |
RAF1 | ClinVar, OMIM, HUMSAVAR | HGNC link | 3p25.2 | 3 | PS163950, PS115200, PS151100 |
BRAF | ClinVar, OMIM, HUMSAVAR | HGNC link | 7q34 | 8 | 605027, PS115150, PS151100, PS155600, 211980, PS188550, PS163950, 114500 |
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Gene1 | Gene2 | Direct Interaction | Number of shared interactors | Shared genes in interaction |
---|---|---|---|---|
PTPN11 | RAF1 | No | 7 | PDGFRB, MAP2K1, JAK1, JAK2, MAP3K5, EGFR, FYN |
PTPN11 | BRAF | No | 1 | MAP2K1 |
RAF1 | BRAF | Yes | 26 | MAP2K2, CDC37, YWHAE, MAPK1, BRAF, NEDD4L, KSR1, RAP1A, HSPA5, YWHAB, YWHAH, PRKCE, BRAP, RAF1, YWHAZ, HRAS, HSP90AA1, AKT1, BAD, HSPA8, MRAS, MAPK3, YWHAG, SFN, YWHAQ, MAP2K1 |
Direct interactions graph
Interactions graph (direct and indirect interactions, when direct are not available)
Gene1 | Gene2 | Direct Interaction | Interaction mode | Number of shared interactors | Shared genes in interaction |
---|---|---|---|---|---|
PTPN11 | RAF1 | No | - | 50 | PIK3R3, FCER1A, RAP1A, MS4A2, PRKCZ, MAPK3, TP53, MAPK1, JAK2, SRC, KRAS, PIK3CG, PRKACA, RAP1B, FCER1G, RPS27A, STAT2, PDGFRB, CXCL12, MAP2K2, PIK3CA, UBA52, MAPK7, INPP5D, LCK, HRAS, NOS3, VAV1, PIK3CB, DOK1, PPP2CA, AKT1, RHOA, PPP2R1A, FYN, MYC, STAT3, IL2, UBB, IL3, IGF1R, HSPA4, GNB2L1, SPRY2, JAK1, IGF1, UBC, PIK3CD, PIK3R5, MAP2K1 |
PTPN11 | BRAF | No | - | 15 | MAP2K2, AKT1, CRK, MAPK1, HRAS, MAPK3, PPP2CA, SPRY2, UBC, KRAS, RAP1A, PPP2R1A, PRKACA, RAP1B, MAP2K1 |
RAF1 | BRAF | Yes | binding | 40 | MAP2K2, HSP90AB1, CDC37, KSR2, YWHAE, MAPK1, PPP2CA, PAK2, KSR1, RAP1A, PRKACA, RAP1B, YWHAB, PRKCE, PRKCD, YWHAH, RRAS, CNKSR3, PRKCG, RHEB, YWHAZ, PRKCA, HRAS, HSP90AA1, PPP2R2B, AKT1, PAK4, PPP2R1A, KRAS, PRKCB, MRAS, MAPK3, SPRY2, YWHAG, SFN, UBC, PRKCQ, PIN1, YWHAQ, MAP2K1 |
Direct interactions graph
Interactions graph (direct and indirect interactions, when direct are not available)
Gene1 | Gene2 | Direct Interaction | Complexes | Number of shared interactors | Shared genes in interaction |
---|---|---|---|---|---|
RAF1 | BRAF | Yes | RAF1-BRAF complex, RAS stimulated;BRAF-RAF1-14-3-3 complex;MAP2K1-BRAF-RAF1-YWHAE-KSR1 complex | 11 | MAP2K2, YWHAH, YWHAE, KSR1, YWHAG, YWHAB, SFN, CNKSR1, YWHAQ, MAP2K1, YWHAZ |
Direct interactions graph
Interactions graph (direct and indirect interactions, when direct are not available)
KEGG term | KEGG term ID | IC | Number of genes with the same term | Genes |
---|---|---|---|---|
Neurotrophin signaling pathway | hsa04722 | 5.78 | 3 | PTPN11, BRAF, RAF1 |
Natural killer cell mediated cytotoxicity | hsa04650 | 5.53 | 3 | PTPN11, BRAF, RAF1 |
Renal cell carcinoma | hsa05211 | 6.6 | 3 | PTPN11, BRAF, RAF1 |
Proteoglycans in cancer | hsa05205 | 5.02 | 3 | PTPN11, BRAF, RAF1 |
Chronic myeloid leukemia | hsa05220 | 6.48 | 3 | PTPN11, BRAF, RAF1 |
Melanoma | hsa05218 | 6.56 | 2 | BRAF, RAF1 |
Bladder cancer | hsa05219 | 7.38 | 2 | BRAF, RAF1 |
Focal adhesion | hsa04510 | 4.92 | 2 | BRAF, RAF1 |
Pancreatic cancer | hsa05212 | 6.56 | 2 | BRAF, RAF1 |
Endometrial cancer | hsa05213 | 6.81 | 2 | BRAF, RAF1 |
Colorectal cancer | hsa05210 | 6.52 | 2 | BRAF, RAF1 |
Glioma | hsa05214 | 6.66 | 2 | BRAF, RAF1 |
Prostate cancer | hsa05215 | 6.11 | 2 | BRAF, RAF1 |
Long-term potentiation | hsa04720 | 6.64 | 2 | BRAF, RAF1 |
FoxO signaling pathway | hsa04068 | 5.63 | 2 | BRAF, RAF1 |
Serotonergic synapse | hsa04726 | 5.84 | 2 | BRAF, RAF1 |
Chemokine signaling pathway | hsa04062 | 5.19 | 2 | BRAF, RAF1 |
Progesterone-mediated oocyte maturation | hsa04914 | 6.18 | 2 | BRAF, RAF1 |
Hepatitis C | hsa05160 | 5.68 | 2 | BRAF, RAF1 |
Vascular smooth muscle contraction | hsa04270 | 5.74 | 2 | BRAF, RAF1 |
Pathways in cancer | hsa05200 | 3.98 | 2 | BRAF, RAF1 |
Rap1 signaling pathway | hsa04015 | 4.97 | 2 | BRAF, RAF1 |
Ras signaling pathway | hsa04014 | 4.9 | 2 | PTPN11, RAF1 |
Non-small cell lung cancer | hsa05223 | 6.88 | 2 | BRAF, RAF1 |
ErbB signaling pathway | hsa04012 | 6.15 | 2 | BRAF, RAF1 |
Acute myeloid leukemia | hsa05221 | 6.74 | 2 | BRAF, RAF1 |
MAPK signaling pathway | hsa04010 | 4.63 | 2 | BRAF, RAF1 |
Long-term depression | hsa04730 | 6.74 | 2 | BRAF, RAF1 |
Regulation of actin cytoskeleton | hsa04810 | 4.9 | 2 | BRAF, RAF1 |
Insulin signaling pathway | hsa04910 | 5.55 | 2 | BRAF, RAF1 |
cAMP signaling pathway | hsa04024 | 5.05 | 2 | BRAF, RAF1 |
Alcoholism | hsa05034 | 5.59 | 2 | BRAF, RAF1 |
REACTOME term | REACTOME term ID | IC | Number of genes with the same term | Genes |
---|---|---|---|---|
Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R) | R-HSA-2404192 | 4.85 | 3 | PTPN11, BRAF, RAF1 |
Signaling by Interleukins | R-HSA-449147 | 4.71 | 3 | PTPN11, BRAF, RAF1 |
Signaling by Leptin | R-HSA-2586552 | 5.1 | 3 | PTPN11, BRAF, RAF1 |
Cytokine Signaling in Immune system | R-HSA-1280215 | 3.74 | 3 | PTPN11, BRAF, RAF1 |
IGF1R signaling cascade | R-HSA-2428924 | 4.85 | 3 | PTPN11, BRAF, RAF1 |
Downstream signal transduction | R-HSA-186763 | 4.65 | 3 | PTPN11, BRAF, RAF1 |
IRS-related events triggered by IGF1R | R-HSA-2428928 | 4.85 | 3 | PTPN11, BRAF, RAF1 |
Signaling by ERBB4 | R-HSA-1236394 | 4.7 | 3 | PTPN11, BRAF, RAF1 |
Signaling by Insulin receptor | R-HSA-74752 | 4.73 | 3 | PTPN11, BRAF, RAF1 |
Developmental Biology | R-HSA-1266738 | 3.48 | 3 | PTPN11, BRAF, RAF1 |
Insulin receptor signalling cascade | R-HSA-74751 | 4.85 | 3 | PTPN11, BRAF, RAF1 |
Downstream signaling of activated FGFR1 | R-HSA-5654687 | 4.71 | 3 | PTPN11, BRAF, RAF1 |
MAPK family signaling cascades | R-HSA-5683057 | 4.89 | 3 | PTPN11, BRAF, RAF1 |
Signalling by NGF | R-HSA-166520 | 4.23 | 3 | PTPN11, BRAF, RAF1 |
MAPK1/MAPK3 signaling | R-HSA-5684996 | 5.11 | 3 | PTPN11, BRAF, RAF1 |
IRS-mediated signalling | R-HSA-112399 | 4.87 | 3 | PTPN11, BRAF, RAF1 |
FRS-mediated FGFR2 signaling | R-HSA-5654700 | 5.14 | 3 | PTPN11, BRAF, RAF1 |
FRS-mediated FGFR4 signaling | R-HSA-5654712 | 5.14 | 3 | PTPN11, BRAF, RAF1 |
FRS-mediated FGFR3 signaling | R-HSA-5654706 | 5.14 | 3 | PTPN11, BRAF, RAF1 |
Downstream signaling of activated FGFR3 | R-HSA-5654708 | 4.71 | 3 | PTPN11, BRAF, RAF1 |
Signaling by FGFR4 | R-HSA-5654743 | 4.69 | 3 | PTPN11, BRAF, RAF1 |
Signaling by FGFR3 | R-HSA-5654741 | 4.69 | 3 | PTPN11, BRAF, RAF1 |
Signaling by FGFR | R-HSA-190236 | 4.67 | 3 | PTPN11, BRAF, RAF1 |
Fc epsilon receptor (FCERI) signaling | R-HSA-2454202 | 4.03 | 3 | PTPN11, BRAF, RAF1 |
Immune System | R-HSA-168256 | 2.37 | 3 | PTPN11, BRAF, RAF1 |
Innate Immune System | R-HSA-168249 | 3.17 | 3 | PTPN11, BRAF, RAF1 |
Signaling by SCF-KIT | R-HSA-1433557 | 4.73 | 3 | PTPN11, BRAF, RAF1 |
Signaling by PDGF | R-HSA-186797 | 4.53 | 3 | PTPN11, BRAF, RAF1 |
DAP12 signaling | R-HSA-2424491 | 4.64 | 3 | PTPN11, BRAF, RAF1 |
Interleukin-3, 5 and GM-CSF signaling | R-HSA-512988 | 4.99 | 3 | PTPN11, BRAF, RAF1 |
Downstream signaling of activated FGFR2 | R-HSA-5654696 | 4.71 | 3 | PTPN11, BRAF, RAF1 |
Signaling by EGFR | R-HSA-177929 | 4.59 | 3 | PTPN11, BRAF, RAF1 |
NGF signalling via TRKA from the plasma membrane | R-HSA-187037 | 4.51 | 3 | PTPN11, BRAF, RAF1 |
FRS-mediated FGFR1 signaling | R-HSA-5654693 | 5.14 | 3 | PTPN11, BRAF, RAF1 |
Signaling by FGFR2 | R-HSA-5654738 | 4.68 | 3 | PTPN11, BRAF, RAF1 |
Signaling by FGFR1 | R-HSA-5654736 | 4.69 | 3 | PTPN11, BRAF, RAF1 |
DAP12 interactions | R-HSA-2172127 | 4.56 | 3 | PTPN11, BRAF, RAF1 |
Downstream signaling of activated FGFR4 | R-HSA-5654716 | 4.71 | 3 | PTPN11, BRAF, RAF1 |
Signaling by ERBB2 | R-HSA-1227986 | 4.66 | 3 | PTPN11, BRAF, RAF1 |
Axon guidance | R-HSA-422475 | 3.93 | 3 | PTPN11, BRAF, RAF1 |
Signal Transduction | R-HSA-162582 | 1.78 | 3 | PTPN11, BRAF, RAF1 |
Gastrin-CREB signalling pathway via PKC and MAPK | R-HSA-881907 | 4.26 | 2 | BRAF, RAF1 |
Interleukin-2 signaling | R-HSA-451927 | 5.05 | 2 | BRAF, RAF1 |
Frs2-mediated activation | R-HSA-170968 | 5.12 | 2 | BRAF, RAF1 |
MAP2K and MAPK activation | R-HSA-5674135 | 7.66 | 2 | BRAF, RAF1 |
Post NMDA receptor activation events | R-HSA-438064 | 7.85 | 2 | BRAF, RAF1 |
CREB phosphorylation through the activation of Ras | R-HSA-442742 | 8.23 | 2 | BRAF, RAF1 |
RAF activation | R-HSA-5673000 | 8.34 | 2 | BRAF, RAF1 |
RAF/MAP kinase cascade | R-HSA-5673001 | 5.15 | 2 | BRAF, RAF1 |
Signaling by VEGF | R-HSA-194138 | 4.66 | 2 | BRAF, RAF1 |
Signalling to p38 via RIT and RIN | R-HSA-187706 | 5.12 | 2 | BRAF, RAF1 |
Platelet activation, signaling and aggregation | R-HSA-76002 | 5.15 | 2 | PTPN11, RAF1 |
FCERI mediated MAPK activation | R-HSA-2871796 | 4.32 | 2 | BRAF, RAF1 |
Negative regulation of FGFR1 signaling | R-HSA-5654726 | 7.98 | 2 | PTPN11, BRAF |
Negative regulation of FGFR2 signaling | R-HSA-5654727 | 7.89 | 2 | PTPN11, BRAF |
Adaptive Immune System | R-HSA-1280218 | 3.19 | 2 | PTPN11, RAF1 |
Neuronal System | R-HSA-112316 | 4.82 | 2 | BRAF, RAF1 |
Neurotransmitter Receptor Binding And Downstream Transmission In The Postsynaptic Cell | R-HSA-112314 | 5.85 | 2 | BRAF, RAF1 |
Transmission across Chemical Synapses | R-HSA-112315 | 5.28 | 2 | BRAF, RAF1 |
VEGFA-VEGFR2 Pathway | R-HSA-4420097 | 4.7 | 2 | BRAF, RAF1 |
Spry regulation of FGF signaling | R-HSA-1295596 | 9.18 | 2 | PTPN11, BRAF |
GRB2 events in ERBB2 signaling | R-HSA-1963640 | 5.15 | 2 | BRAF, RAF1 |
Interleukin receptor SHC signaling | R-HSA-912526 | 5.09 | 2 | BRAF, RAF1 |
Negative feedback regulation of MAPK pathway | R-HSA-5674499 | 10.4 | 2 | BRAF, RAF1 |
NCAM signaling for neurite out-growth | R-HSA-375165 | 4.9 | 2 | BRAF, RAF1 |
Signalling to RAS | R-HSA-167044 | 5.08 | 2 | BRAF, RAF1 |
Activation of NMDA receptor upon glutamate binding and postsynaptic events | R-HSA-442755 | 7.7 | 2 | BRAF, RAF1 |
SHC1 events in EGFR signaling | R-HSA-180336 | 5.15 | 2 | BRAF, RAF1 |
Prolonged ERK activation events | R-HSA-169893 | 5.11 | 2 | BRAF, RAF1 |
Negative regulation of MAPK pathway | R-HSA-5675221 | 7.66 | 2 | BRAF, RAF1 |
Signalling to ERKs | R-HSA-187687 | 5.04 | 2 | BRAF, RAF1 |
Signaling by GPCR | R-HSA-372790 | 2.68 | 2 | BRAF, RAF1 |
GRB2 events in EGFR signaling | R-HSA-179812 | 5.15 | 2 | BRAF, RAF1 |
SHC1 events in ERBB2 signaling | R-HSA-1250196 | 5.15 | 2 | BRAF, RAF1 |
Negative regulation of FGFR4 signaling | R-HSA-5654733 | 8.03 | 2 | PTPN11, BRAF |
Negative regulation of FGFR3 signaling | R-HSA-5654732 | 8.12 | 2 | PTPN11, BRAF |
ARMS-mediated activation | R-HSA-170984 | 5.12 | 2 | BRAF, RAF1 |
SOS-mediated signalling | R-HSA-112412 | 5.15 | 2 | BRAF, RAF1 |
SHC1 events in ERBB4 signaling | R-HSA-1250347 | 5.15 | 2 | BRAF, RAF1 |
VEGFR2 mediated cell proliferation | R-HSA-5218921 | 5.07 | 2 | BRAF, RAF1 |
Hemostasis | R-HSA-109582 | 3.98 | 2 | PTPN11, RAF1 |
Term | New enriched term | IC | P value | Genes |
---|---|---|---|---|
Ras guanyl-nucleotide exchange factor activity (GO:0005088) | NEW | 4.31 | 0.001 | PTPN11, BRAF, RAF1 |
mitogen-activated protein kinase kinase binding (GO:0031434) | - | 6.97 | 0.001 | BRAF, RAF1 |
receptor signaling protein activity (GO:0005057) | - | 4.76 | 0.009 | PTPN11, BRAF, RAF1 |
guanyl-nucleotide exchange factor activity (GO:0005085) | NEW | 4.02 | 0.004 | PTPN11, BRAF, RAF1 |
enzyme binding (GO:0019899) | - | 2.27 | 0.03 | PTPN11, BRAF, RAF1 |
receptor signaling protein serine/threonine kinase activity (GO:0004702) | - | 5.23 | 0.002 | BRAF, RAF1 |
MAP kinase kinase kinase activity (GO:0004709) | - | 6.6 | 0.002 | BRAF, RAF1 |
GO | IC | Number of genes with the same GO | Genes |
---|---|---|---|
cytoplasm (GO:0005737) | 1.01 | 3 | PTPN11, BRAF, RAF1 |
cytosol (GO:0005829) | 1.68 | 3 | PTPN11, BRAF, RAF1 |
intracellular membrane-bounded organelle (GO:0043231) | 0.6 | 3 | PTPN11, BRAF, RAF1 |
nucleus (GO:0005634) | 1.07 | 3 | PTPN11, BRAF, RAF1 |
cell part (GO:0044464) | 0.11 | 3 | PTPN11, BRAF, RAF1 |
cytoplasmic part (GO:0044444) | 0.82 | 3 | PTPN11, BRAF, RAF1 |
mitochondrion (GO:0005739) | 2.42 | 3 | PTPN11, BRAF, RAF1 |
intracellular organelle (GO:0043229) | 0.51 | 3 | PTPN11, BRAF, RAF1 |
intracellular part (GO:0044424) | 0.28 | 3 | PTPN11, BRAF, RAF1 |
membrane-bounded organelle (GO:0043227) | 0.47 | 3 | PTPN11, BRAF, RAF1 |
organelle (GO:0043226) | 0.4 | 3 | PTPN11, BRAF, RAF1 |
cell projection (GO:0042995) | 2.47 | 2 | BRAF, RAF1 |
membrane (GO:0016020) | 0.68 | 2 | BRAF, RAF1 |
plasma membrane (GO:0005886) | 1.39 | 2 | BRAF, RAF1 |
Term | New enriched term | IC | P value | Genes |
---|---|---|---|---|
protein kinase complex (GO:1902911) | NEW | 5.31 | 0.025 | BRAF, RAF1 |
anchoring junction (GO:0070161) | NEW | 3.61 | 0.026 | PTPN11, BRAF, RAF1 |
adherens junction (GO:0005912) | NEW | 3.66 | 0.023 | PTPN11, BRAF, RAF1 |
transferase complex (GO:1990234) | NEW | 3.32 | 0.037 | PTPN11, BRAF, RAF1 |
cell-substrate adherens junction (GO:0005924) | NEW | 3.83 | 0.014 | PTPN11, BRAF, RAF1 |
focal adhesion (GO:0005925) | NEW | 3.83 | 0.013 | PTPN11, BRAF, RAF1 |
cell-substrate junction (GO:0030055) | NEW | 3.82 | 0.015 | PTPN11, BRAF, RAF1 |