Proteins / KRAS
KRAS
GTPase KRas (KRAS4B)
GTPase
UniProt P01116-2
HSP90 client (literature): unknown
3D structure ↓
99 interaction partners · volcano ↗
Abundance in LZTR1-knockout cells with RAS activation. CIAR (chemically inducible activator of RAS): a small molecule releases a constitutively active SOS1 variant. Scores are WT-relative: 1 = wild type.
4,048 variantsmissense decreased 34% · increased 11%
Other cells fade; highlighted cells are outlined.
Annotation tracks
Structure
Function
Chaperone
Variant effect
Track legend & definitions
Secondary structure
alpha helix3-10 helixpi helixbeta strandbeta bridgeturnbendno_ss
DSSP assignment on the reference structure.
Relative SASA
0.000.250.500.751.00
Side-chain solvent accessibility (0 = buried, 1 = fully exposed). The pipeline calls a residue surface-exposed above 0.25.
pLDDT
50.062.575.087.5100.0
AlphaFold per-residue confidence. The analysis drops residues below 60.
Curated feature
Protein-protein interfaceCatalytic / active siteLigand / substrate pocketRegulatory elementOther annotation
UniProt / literature annotation, coloured by class. Red marks a curated protein-protein interface — the independent comparison for our predicted interfaces.
Annotated interface
yesno
Curated protein-interface residue, independent of any structure prediction in this study.
Active site
yesno
Curated catalytic / active-site residue.
Inter-domain contact
yesno
Residue contacting another domain of the same protein (all-atom), so a variant effect there may be intramolecular rather than at a PPI.
HSP90 contact
TrueFalseUnknown
Contacts HSP90 in the chaperone-client cryo-EM structures ('Unknown' where the protein was not mapped).
CDC37 contact
TrueFalseUnknown
Contacts CDC37. These positions report kinase foldability rather than a canonical binding surface.
Fraction decreased
0%25%50%75%100%
Fraction of variants at this position classified decreased in this assay (2.5th-percentile rule).
Fraction increased
0%25%50%75%100%
Fraction of variants at this position classified increased in this assay.
Click a position for its interactions and annotations
— ■ the Interface strip marks
positions in ≥1 supported interface (darker = more partners)
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One row per interface: complexes of the same pair and source whose interfaces overlap (IoU ≥ 0.3) are merged, as in the Fig. 6c,d volcano plots (median Cohen's d; q from the geometric-mean p). Supported: at least one complex with q < 0.05 and |d| ≥ 0.2 in either basal assay.
| Partner | Source | Activity d | q | Abundance d | q | Interface positions | Supported | |
|---|---|---|---|---|---|---|---|---|
| IL1RAP | AF-M | -0.86 | 1.2e-54 | +0.40 | 0.061 | 9 | supported | Structure ↗ |
| RAPGEF2 | AF-M | -0.44 | 1.3e-46 | +0.58 | 6.4e-11 | 24 | supported | Structure ↗ |
| SNAP47 | AF-M | -0.94 | 9.7e-42 | -0.16 | 0.002 | 6 | supported | Structure ↗ |
| TTC4 | AF-M | -0.28 | 1.0e-07 | +2.11 | 1.6e-41 | 6 | supported | Structure ↗ |
| PTPN1 H_N_K_Ras_like #2 | AF-M | -0.80 | 5.0e-41 | +0.21 | 0.789 | 8 | supported | Structure ↗ |
| PIK3R4 | AF-M | -0.69 | 2.6e-40 | +0.90 | 2.0e-21 | 12 | supported | Structure ↗ |
| RPS10 | AF-M | -0.46 | 2.0e-16 | +1.50 | 4.0e-40 | 9 | supported | Structure ↗ |
| AFDN | AF-M | -0.73 | 8.1e-40 | +0.61 | 2.0e-07 | 11 | supported | Structure ↗ |
| DCUN1D3 | RF2-PPI | -1.30 | 9.0e-40 | -0.16 | 0.023 | 5 | supported | Structure ↗ |
| USO1 | AF-M | -0.73 | 1.5e-39 | +1.47 | 2.1e-35 | 10 | supported | Structure ↗ |
| RIN1 | AF-M | -0.76 | 2.9e-39 | +0.37 | 5.0e-05 | 6 | supported | Structure ↗ |
| CYFIP1 | AF-M | -0.77 | 4.1e-39 | +0.45 | 0.010 | 9 | supported | Structure ↗ |
| EXOSC5 | AF-M | -0.55 | 7.1e-26 | +1.43 | 6.2e-38 | 10 | supported | Structure ↗ |
| SOS1 H_N_K_Ras_like #2 | AF-M | -0.65 | 4.5e-37 | +0.07 | 0.365 | 16 | supported | Structure ↗ |
| FRMPD1 | AF-M | -0.83 | 1.4e-36 | +0.45 | 0.012 | 8 | supported | Structure ↗ |
| PIK3CB | AF-M | -0.77 | 1.5e-36 | +0.14 | 0.524 | 7 | supported | Structure ↗ |
| LRP8 | AF-M | -0.26 | 1.0e-05 | +2.22 | 5.9e-36 | 4 | supported | Structure ↗ |
| RAPGEF6 | AF-M | -0.41 | 8.3e-36 | +0.60 | 2.2e-10 | 19 | supported | Structure ↗ |
| SOS1 H_N_K_Ras_like | AF-M | -0.31 | 1.7e-35 | +0.53 | 2.4e-08 | 20 | supported | Structure ↗ |
| RGL2 | PDB | -0.66 | 8.0e-35 | -0.09 | 0.032 | 10 | supported | Structure ↗ |
| EEF1AKMT1 | AF-M | -0.80 | 8.2e-35 | -0.48 | 1.1e-09 | 7 | supported | Structure ↗ |
| RRAS2 H_N_K_Ras_like | AF-M | -0.80 | 1.3e-33 | +0.10 | 0.444 | 8 | supported | Structure ↗ |
| BRAF | PDB | -0.72 | 5.3e-33 | +0.27 | 0.160 | 7 | supported | Structure ↗ |
| EIF2S2 | AF-M | -0.73 | 6.3e-33 | +0.18 | 0.403 | 6 | supported | Structure ↗ |
| RASGEF1C | AF-M | -0.30 | 9.5e-33 | +0.79 | 1.9e-20 | 18 | supported | Structure ↗ |
| RASGEF1A | AF-M | -0.39 | 5.4e-28 | +1.12 | 3.6e-32 | 14 | supported | Structure ↗ |
| SIPA1L1 H_N_K_Ras_like #3 | AF-M | -0.50 | 7.1e-32 | +0.41 | 1.9e-04 | 15 | supported | Structure ↗ |
| NRAS | AF-M | -0.67 | 7.4e-32 | +0.18 | 0.440 | 10 | supported | Structure ↗ |
| MAPKAP1 H_N_K_Ras_like | PDB | -0.61 | 7.8e-32 | +0.48 | 8.7e-06 | 10 | supported | Structure ↗ |
| TIAM1 | AF-M | -0.40 | 1.3e-31 | +1.00 | 2.2e-18 | 12 | supported | Structure ↗ |
| MAD2L1 H_N_K_Ras_like | AF-M | -0.32 | 1.7e-04 | +1.25 | 2.1e-31 | 9 | supported | Structure ↗ |
| NRXN3 | AF-M | -0.83 | 6.7e-31 | -0.05 | 0.046 | 7 | supported | Structure ↗ |
| CRAF | PDB | -0.71 | 8.5e-31 | +0.29 | 0.022 | 7 | supported | Structure ↗ |
| KRAS H_N_K_Ras_like #3 | PDB | -0.72 | 8.8e-31 | +0.16 | 0.524 | 6 | supported | Structure ↗ |
| ADGRG1 | AF-M | -0.31 | 1.4e-11 | +1.22 | 9.5e-31 | 8 | supported | Structure ↗ |
| DAB2IP | AF-M | -0.77 | 1.3e-30 | +0.31 | 0.095 | 10 | supported | Structure ↗ |
| ITSN1 | AF-M | -0.38 | 4.6e-30 | +0.75 | 1.4e-07 | 9 | supported | Structure ↗ |
| TAOK3 | AF-M | -0.42 | 4.0e-12 | +1.41 | 8.1e-30 | 7 | supported | Structure ↗ |
| HRAS | AF-M | -0.65 | 9.2e-30 | +0.12 | 0.561 | 12 | supported | Structure ↗ |
| EXOC1 | AF-M | -0.62 | 1.9e-29 | +0.68 | 1.0e-07 | 8 | supported | Structure ↗ |
| NME6 H_N_K_Ras_like #2 | AF-M | -0.26 | 9.8e-18 | +1.29 | 3.8e-29 | 10 | supported | Structure ↗ |
| YKT6 | AF-M | -0.24 | 6.8e-14 | +1.46 | 8.7e-29 | 8 | supported | Structure ↗ |
| RAP2C | AF-M | -0.64 | 1.3e-28 | +0.21 | 0.403 | 12 | supported | Structure ↗ |
| MCF2L | AF-M | -0.36 | 2.2e-27 | +1.00 | 2.8e-16 | 11 | supported | Structure ↗ |
| CRAF | AF-M | -0.51 | 4.1e-27 | +0.04 | 0.195 | 15 | supported | Structure ↗ |
| RAPH1 | AF-M | -0.66 | 4.9e-27 | +0.26 | 0.104 | 7 | supported | Structure ↗ |
| MAPKAP1 | AF-M | -0.49 | 6.7e-27 | +1.08 | 1.7e-22 | 12 | supported | Structure ↗ |
| ATP5F1A | AF-M | -0.58 | 6.7e-27 | +0.92 | 3.5e-17 | 12 | supported | Structure ↗ |
| PIK3CA | AF-M | -0.58 | 8.4e-26 | +0.23 | 0.099 | 10 | supported | Structure ↗ |
| PTPN14 | RF2-PPI | -0.60 | 1.3e-25 | +0.04 | 0.723 | 11 | supported | Structure ↗ |
| UTP6 | AF-M | -0.31 | 3.5e-10 | +1.12 | 1.3e-25 | 11 | supported | Structure ↗ |
| ARAF | AF-M | -0.50 | 2.1e-25 | +0.07 | 0.437 | 15 | supported | Structure ↗ |
| BRAF | AF-M | -0.53 | 4.3e-25 | +0.07 | 0.880 | 12 | supported | Structure ↗ |
| KIF11 | AF-M | -0.75 | 7.7e-25 | -0.21 | 5.4e-04 | 7 | supported | Structure ↗ |
| USE1 | AF-M | -0.38 | 4.9e-10 | +1.52 | 9.0e-25 | 5 | supported | Structure ↗ |
| RASGRF2 | AF-M | -0.13 | 1.0e-24 | +0.30 | 0.006 | 22 | supported | Structure ↗ |
| RAP1A | AF-M | -0.60 | 1.0e-24 | +0.14 | 0.213 | 11 | supported | Structure ↗ |
| NME6 H_N_K_Ras_like | AF-M | -0.80 | 1.4e-24 | +1.15 | 4.6e-12 | 6 | supported | Structure ↗ |
| RASAL2 | AF-M | -0.04 | 3.7e-24 | +0.35 | 0.024 | 10 | supported | Structure ↗ |
| NPM1 | AF-M | -0.62 | 7.8e-24 | +0.88 | 1.1e-14 | 10 | supported | Structure ↗ |
| LZTR1 | PDB | -0.24 | 8.1e-24 | +0.62 | 4.7e-11 | 13 | supported | Structure ↗ |
| PTPN1 H_N_K_Ras_like | AF-M | -0.38 | 5.2e-23 | +0.35 | 0.018 | 10 | supported | Structure ↗ |
| YWHAE | RF2-PPI | -0.88 | 9.0e-23 | +0.89 | 4.8e-07 | 5 | supported | Structure ↗ |
| RASGRF1 | AF-M | -0.00 | 2.5e-22 | +0.41 | 4.6e-06 | 21 | supported | Structure ↗ |
| WBP4 | AF-M | -0.56 | 4.2e-22 | +0.16 | 0.278 | 8 | supported | Structure ↗ |
| RALGPS2 | AF-M | +0.09 | 4.7e-21 | +0.47 | 8.0e-06 | 17 | supported | Structure ↗ |
| TRIO H_N_K_Ras_like | AF-M | -0.17 | 2.8e-17 | +1.06 | 9.2e-21 | 10 | supported | Structure ↗ |
| C2orf72 H_N_K_Ras_like | AF-M | -0.50 | 1.6e-13 | +1.57 | 3.0e-20 | 4 | supported | Structure ↗ |
| FGD6 | AF-M | -0.32 | 3.4e-20 | +0.68 | 4.9e-06 | 8 | supported | Structure ↗ |
| FGD1 | AF-M | -0.22 | 1.1e-19 | +0.83 | 2.8e-11 | 10 | supported | Structure ↗ |
| RGL2 | AF-M | +0.08 | 6.3e-19 | +0.29 | 0.012 | 26 | supported | Structure ↗ |
| PLAAT3 | PDB | +1.30 | 1.3e-08 | -0.81 | 1.9e-18 | 9 | supported | Structure ↗ |
| OSBPL10 H_N_K_Ras_like #2 | AF-M | -0.63 | 2.1e-18 | +0.63 | 1.2e-06 | 6 | supported | Structure ↗ |
| ARHGAP39 H_N_K_Ras_like #2 | AF-M | -0.61 | 1.5e-13 | +1.53 | 2.4e-18 | 4 | supported | Structure ↗ |
| RALGDS | AF-M | +0.14 | 7.1e-18 | +0.37 | 0.003 | 24 | supported | Structure ↗ |
| SGSM2 | AF-M | -0.06 | 1.8e-17 | +0.58 | 3.6e-08 | 13 | supported | Structure ↗ |
| C2orf72 H_N_K_Ras_like #2 | AF-M | -0.00 | 3.0e-06 | +0.95 | 1.9e-17 | 9 | supported | Structure ↗ |
| ARHGDIA | AF-M | -0.27 | 1.6e-12 | +0.98 | 3.3e-17 | 9 | supported | Structure ↗ |
| TBC1D10B | AF-M | +0.11 | 7.7e-17 | +0.51 | 3.2e-05 | 15 | supported | Structure ↗ |
| SLC4A2 | RF2-PPI | -0.97 | 9.0e-17 | -0.52 | 0.003 | 3 | supported | Structure ↗ |
| TBC1D10A | AF-M | +0.15 | 1.1e-16 | +0.68 | 6.9e-08 | 14 | supported | Structure ↗ |
| RASGRP4 | AF-M | +0.18 | 1.7e-14 | +0.30 | 0.031 | 23 | supported | Structure ↗ |
| TBC1D5 | AF-M | -0.14 | 3.4e-14 | +0.67 | 7.9e-05 | 11 | supported | Structure ↗ |
| ATP5F1B H_N_K_Ras_like | AF-M | -0.47 | 1.1e-13 | -0.04 | 0.006 | 6 | supported | Structure ↗ |
| SOS1 | PDB | +0.15 | 2.7e-13 | +0.46 | 3.3e-07 | 22 | supported | Structure ↗ |
| OSBPL10 H_N_K_Ras_like | AF-M | -0.47 | 2.7e-13 | +0.39 | 0.011 | 4 | supported | Structure ↗ |
| RASGRP1 | AF-M | +0.22 | 5.7e-12 | +0.30 | 0.027 | 23 | supported | Structure ↗ |
| RGL1 | AF-M | +0.17 | 1.0e-11 | +0.26 | 0.028 | 21 | supported | Structure ↗ |
| RBM12 | AF-M | -0.24 | 2.0e-11 | +0.36 | 2.9e-04 | 14 | supported | Structure ↗ |
| ZDHHC5 | AF-M | -0.44 | 6.8e-11 | -0.36 | 1.2e-04 | 5 | supported | Structure ↗ |
| RASGRP3 | AF-M | +0.28 | 3.2e-10 | +0.32 | 0.015 | 21 | supported | Structure ↗ |
| SIPA1L2 | AF-M | +0.45 | 3.5e-10 | +0.25 | 0.185 | 14 | supported | Structure ↗ |
| ARHGAP32 | AF-M | -0.06 | 5.4e-10 | +0.63 | 1.1e-06 | 8 | supported | Structure ↗ |
| KRAS H_N_K_Ras_like | PDB | +0.18 | 6.1e-10 | -0.08 | 0.234 | 7 | supported | Structure ↗ |
| ARHGAP31 | AF-M | -0.16 | 1.3e-06 | +0.70 | 2.1e-09 | 9 | supported | Structure ↗ |
| PPIA | PDB | -0.39 | 3.1e-09 | +0.09 | 0.023 | 4 | supported | Structure ↗ |
| SIPA1L1 H_N_K_Ras_like | AF-M | -0.60 | 6.6e-09 | +0.01 | 0.432 | 4 | supported | Structure ↗ |
| RASA1 | AF-M | +0.23 | 5.3e-08 | -0.16 | 0.006 | 15 | supported | Structure ↗ |
| KRAS H_N_K_Ras_like #2 | PDB | -0.55 | 8.2e-08 | -0.17 | 0.093 | 4 | supported | Structure ↗ |
| PLXNA1 | AF-M | +0.39 | 8.9e-06 | -0.32 | 9.4e-08 | 14 | supported | Structure ↗ |
| ATP5F1B H_N_K_Ras_like #2 | AF-M | -0.40 | 7.9e-07 | +0.04 | 0.712 | 3 | supported | Structure ↗ |
| PLXNC1 | AF-M | +0.26 | 1.3e-06 | -0.10 | 0.005 | 20 | supported | Structure ↗ |
| SIPA1L1 H_N_K_Ras_like #2 | AF-M | +0.45 | 2.6e-06 | +0.22 | 0.327 | 14 | supported | Structure ↗ |
| PLXNB2 | AF-M | +0.39 | 2.6e-05 | -0.08 | 0.017 | 16 | supported | Structure ↗ |
| FAM91A1 | AF-M | +1.15 | 0.021 | +0.62 | 3.6e-05 | 7 | supported | Structure ↗ |
| PLXNA2 | AF-M | +0.43 | 4.0e-04 | -0.24 | 1.5e-04 | 15 | supported | Structure ↗ |
| CHN1 | AF-M | +0.90 | 1.7e-04 | -0.31 | 9.9e-04 | 6 | supported | Structure ↗ |
| CHERP | AF-M | -0.40 | 1.9e-04 | -0.03 | 0.096 | 4 | supported | Structure ↗ |
| NF1 | AF-M | +0.55 | 2.3e-04 | +0.03 | 0.358 | 12 | supported | Structure ↗ |
| ARHGAP21 | AF-M | +0.89 | 2.4e-04 | +0.01 | 8.6e-04 | 11 | supported | Structure ↗ |
| IQGAP1 | AF-M | +0.53 | 4.2e-04 | +0.27 | 0.098 | 9 | supported | Structure ↗ |
| MAD2L1 res 2-184 | AF-M | -0.16 | 0.176 | +0.38 | 6.0e-04 | 8 | supported | Structure ↗ |
| TRIO H_N_K_Ras_like #2 | AF-M | +0.98 | 0.159 | -0.26 | 7.5e-04 | 6 | supported | Structure ↗ |
| PPP1CA | PDB | -0.34 | 9.3e-04 | -0.22 | 0.020 | 4 | supported | Structure ↗ |
| RRAS2 H_N_K_Ras_like #2 | AF-M | -0.03 | 0.008 | -0.26 | 0.001 | 8 | supported | Structure ↗ |
| RALGAPA2 | AF-M | +0.44 | 0.003 | -0.04 | 0.433 | 10 | supported | Structure ↗ |
| USP6NL | AF-M | +0.61 | 0.022 | +0.11 | 0.206 | 10 | supported | Structure ↗ |
| ARHGAP39 H_N_K_Ras_like | AF-M | +0.59 | 0.055 | +0.26 | 0.054 | 8 | supported | Structure ↗ |
| RGL3 | AF-M | +0.07 | 2.5e-19 | +0.23 | 0.236 | 23 | not supported | Structure ↗ |
| MAPKAP1 H_N_K_Ras_like #2 | PDB | -0.30 | 0.110 | -0.17 | 0.069 | 4 | not supported | Structure ↗ |
| RALGAPA1 | AF-M | +0.69 | 0.218 | +0.05 | 0.618 | 7 | not supported | Structure ↗ |