Section 1: Gene Identifiers
| Database | Identifier | Details |
|---|
| HGNC | HGNC:7989 | Approved symbol: NRAS |
| Full Name | NRAS proto-oncogene, GTPase | |
| Ensembl Gene | ENSG00000213281 | |
| NCBI Entrez Gene | 4893 | |
| OMIM | 164790 | Gene/locus |
| COSMIC | NRAS | (via HGNC) |
| VEGA | (linked) | (via HGNC) |
Genomic Location:
| Attribute | Value |
|---|
| Chromosome | 1 |
| Cytogenetic Band | 1p13.2 |
| Start Position | 114,704,468 |
| End Position | 114,716,770 |
| Strand | Minus (-) |
| Genome Assembly | GRCh38 |
| Genomic Accession | NC_000001.11 |
Gene Classification:
- Locus Group: protein-coding gene
- Locus Type: gene with protein product
- Gene Family: RAS type GTPase family
- Status: Approved
Aliases & Previous Names:
| - Aliases | - Previous Names | Total Ensembl Transcripts |
|---|
| N-ras, ALPS4, CMNS, NCMS, NRAS1, NS6 | neuroblastoma RAS viral (v-ras) oncogene homolog | | |
| | Transcript Identifiers** | 4 |
| Transcript ID | Biotype | Start | End | UTR5 | UTR3 |
|---|
| ENST00000369535 ★ | protein_coding | 114,704,469 | 114,716,771 | 114,716,658-114,716,771 | 114,708,531-114,708,534 |
| ENST00000899430 | protein_coding | 114,704,471 | 114,716,756 | 114,716,658-114,716,756 | 114,708,531-114,708,534 |
| ENST00000931009 | protein_coding | 114,704,469 | 114,716,747 | 114,716,658-114,716,747 | 114,708,531-114,708,534 |
| ENST00000931010 | protein_coding | 114,704,472 | 114,716,640 | 114,716,531-114,716,640 | 114,708,531-114,708,534 |
★ = Canonical transcript
RefSeq Transcripts (Human):
| RefSeq ID | Type | Status | MANE Select |
|---|
| NM_002524 | mRNA | REVIEWED | ★ YES |
| NP_002515 | protein | REVIEWED | ★ YES |
CCDS ID: CCDS877
Exons for Canonical Transcript (ENST00000369535):
Total Exon Count: 7
| Exon ID | Start | End | Strand |
|---|
| ENSE00001364464 | 114,716,658 | 114,716,771 | - |
| ENSE00001450282 | 114,716,050 | 114,716,177 | - |
| ENSE00001751295 | 114,713,800 | 114,713,978 | - |
| ENSE00000784343 | 114,709,569 | 114,709,728 | - |
| ENSE00000800104 | 114,708,531 | 114,708,654 | - |
| ENSE00001365300 | 114,708,154 | 114,708,192 | - |
| ENSE00001450280 | 114,704,469 | 114,708,050 | - |
Section 3: Protein Identifiers
UniProt Accessions:
| Accession | Name | Status | Length | Mass |
|---|
| P01111 ★ | GTPase NRas | Reviewed (Swiss-Prot) | 189 aa | 21,229 Da |
| Q5U091 | GTPase NRas | Unreviewed (TrEMBL) | - | - |
★ = Canonical reviewed entry
Alternative Names: Transforming protein N-Ras
RefSeq Protein: NP_002515 (MANE Select)
Protein Domains and Families:
| Database | ID | Name | Type |
|---|
| InterPro | IPR001806 | Small_GTPase | Family |
| InterPro | IPR005225 | Small_GTP-bd | Domain |
| InterPro | IPR020849 | Small_GTPase_Ras-type | Family |
| InterPro | IPR027417 | P-loop_NTPase | Homologous_superfamily |
| Pfam | PF00071 | Ras family | Domain |
| PANTHER | (linked) | | |
| SUPFAM | (linked) | | |
| CDD | (linked) | | |
| SMART | (3 entries) | | |
| CATH-Gene3D | (linked) | | |
Section 4: Structure Identifiers
Total PDB Structures: 29
| PDB ID | Title | Method | Resolution (Å) |
|---|
| 9BG8 | Daraxonrasib/NRAS Q61R/CypA complex | X-RAY | 1.20 |
| 7F68 | NRAS S89D crystal structure | X-RAY | 1.24 |
| 9BG3 | Daraxonrasib/NRAS Q61K/CypA complex | X-RAY | 1.33 |
| 6ZIO | NRAS (C118S) with GDP | X-RAY | 1.55 |
| 8TBI | RMC-7977/NRAS WT/CypA tricomplex | X-RAY | 1.59 |
| 9BG0 | Daraxonrasib/NRAS WT/CypA tricomplex | X-RAY | 1.64 |
| 6WGH | GDP-bound NRAS with ITD | X-RAY | 1.65 |
| 3CON | Human NRAS GTPase with GDP | X-RAY | 1.65 |
| 5UHV | Wild-type NRas with GppNHp | X-RAY | 1.67 |
| 8VM2 | NRAS Q61K with GTP | X-RAY | 1.74 |
| 9BGD | Daraxonrasib/NRAS Q61L/CypA complex | X-RAY | 1.76 |
| 6ZIZ | NRAS Q61R with GTP and compound 18 | X-RAY | 1.79 |
| 7OW4 | HLA-A*11:01 with KRAS G12D peptide | X-RAY | 1.81 |
| 9GLX | NRas-Q61R-GTP with peptide MPB3 | X-RAY | 1.85 |
| 6ULI | TCR/HLA-A*11:01/KRAS-G12D | X-RAY | 1.88 |
| 6ZIR | NRAS (C118S) with GDP/compound 18 | X-RAY | 1.90 |
| 6ULK | TCR/HLA-A*11:01/KRAS-G12D | X-RAY | 1.90 |
| 6E6H | NRAS G13D with GppNHp | X-RAY | 1.99 |
| 6ULN | TCR/HLA-A*11:01/KRAS-G12D | X-RAY | 2.01 |
| 9GLW | NRas-Q61R-GTP with peptide MPB2 | X-RAY | 2.10 |
| 7OW3 | HLA-A*11:01 with KRAS peptide | X-RAY | 2.46 |
| 7OW5 | TCR/HLA-A*11:01/KRAS peptide | X-RAY | 2.58 |
| 7OW6 | TCR/HLA-A*11:01/KRAS G12D peptide | X-RAY | 2.64 |
| 9BTM | NRas Q61R with Shoc2 | X-RAY | 2.73 |
| 6ULR | TCR/HLA-A*11:01/KRAS-G12D | X-RAY | 3.20 |
| 7PB2 | JDI TCR/HLA-A*11:01/KRAS G12D | X-RAY | 3.41 |
| 6UON | TCR/HLA-A*11:01/KRAS-G12D | X-RAY | 3.50 |
| 2N9C | NRAS Isoform 5 | SOLUTION NMR | - |
| 6MPP | HLA-A*01:01/NRAS Q61K peptide | SOLUTION NMR | - |
AlphaFold Predicted Structure:
| Entry | pLDDT Score | Sequence Length | Fraction Very High Confidence |
|---|
| AF-P01111 | 92.56 | 1484* | 0.81 (81%) |
| *Note |
|---|
| AlphaFold model includes full-length isoform | |
| Cross-Species Orthologs** |
| Organism | Gene ID | Symbol | Type |
|---|
| Mouse (Mus musculus) | ENSMUSG00000027852 | Nras | protein_coding |
| Rat (Rattus norvegicus) | ENSRNOG00000023079 | Kras | protein_coding |
| Zebrafish (Danio rerio) | ENSDARG00000038225 | nras | protein_coding |
| Fruit fly (Drosophila) | No direct ortholog | - | (see paralogs) |
| C. elegans | No direct ortholog | - | (RAS pathway conserved) |
| S. cerevisiae | No direct ortholog | - | (RAS1/RAS2 functional analogs) |
| Total paralogs in human |
|---|
| 35 (RAS family members including HRAS, KRAS) | |
| Clinical Variants & AI Predictions** |
ClinVar Variants
Total ClinVar Variants: 330
Classification Breakdown:
| Classification | Count |
|---|
| Pathogenic | 10 |
| Likely pathogenic | 10 |
| Pathogenic/Likely pathogenic | 2 |
| Uncertain significance (VUS) | ~150 |
| Conflicting classifications | ~20 |
| Likely benign | ~100 |
| Benign | ~10 |
| Benign/Likely benign | ~5 |
Pathogenic Variants (10 total)
| Variant ID | HGVS Notation | Protein Change | Review Status |
|---|
| 177778 | c.34G>A | p.Gly12Ser | Reviewed by expert panel |
| 40468 | c.34G>T | p.Gly12Cys | Criteria provided |
| 40469 | c.34G>C | p.Gly12Arg | Multiple submitters |
| 13900 | c.182A>G | p.Gln61Arg | Multiple submitters |
| 280409 | c.182A>C | p.Gln61Pro | Single submitter |
| 13902 | c.149C>T | p.Thr50Ile | Reviewed by expert panel |
| 13903 | c.179G>A | p.Gly60Glu | Reviewed by expert panel |
| 1070042 | c.173C>T | p.Thr58Ile | Reviewed by expert panel |
| 39647 | c.101C>T | p.Pro34Leu | No criteria |
| 40472 | c.112-1_113dup | Splice site | Single submitter |
Likely Pathogenic Variants (10 total)
| Variant ID | HGVS Notation | Protein Change | Review Status |
|---|
| 13899 | c.37G>C | p.Gly13Arg | Multiple submitters |
| 375876 | c.38G>T | p.Gly13Val | Single submitter |
| 222971 | c.71T>A | p.Ile24Asn | Reviewed by expert panel |
| 1335888 | c.108A>G | p.Ile36Met | Single submitter |
| 812886 | c.176C>A | p.Ala59Asp | No criteria |
| 561786 | c.178G>A | p.Gly60Arg | Multiple submitters |
| 981556 | c.204A>T | p.Arg68Ser | No criteria |
| 1320232 | c.449A>G | p.Gln150Arg | Single submitter |
| 2672090 | c.191_196dup | p.Ser65_Ala66insAspSer | Single submitter |
| 3029607 | c.34_35delinsTT | p.Gly12Phe | No criteria |
SpliceAI Predictions
Total Splice Predictions: 577
TOP 50 High-Impact Splice-Altering Variants:
| Variant | Effect | Delta Score |
|---|
| 1:114707945:TAAAC:T | donor_gain | 1.00 |
| 1:114707948:A:C | donor_gain | 0.99 |
| 1:114708048:CAGCT:C | acceptor_loss | 0.99 |
| 1:114708049:AGCTG:A | acceptor_loss | 0.99 |
| 1:114708050:GCTGA:G | acceptor_loss | 0.99 |
| 1:114708046:TGCAG:T | acceptor_gain | 0.99 |
| 1:114708051:CTG:C | acceptor_loss | 0.99 |
| 1:114708052:T:A | acceptor_loss | 0.99 |
| 1:114708047:GCAG:G | acceptor_gain | 0.98 |
| 1:114708048:CAG:C | acceptor_gain | 0.99 |
| 1:114708150:CTA:C | donor_loss | 0.98 |
| 1:114708151:TACCT:T | donor_loss | 0.98 |
| 1:114708153:C:G | donor_loss | 0.98 |
| 1:114708051:C:CC | acceptor_gain | 0.98 |
| 1:114707949:C:CT | donor_gain | 0.97 |
| 1:114707950:T:TT | donor_gain | 0.97 |
| 1:114708056:A:AC | acceptor_gain | 0.97 |
| 1:114708153:CCT:C | acceptor_loss | 0.97 |
| 1:114708189:GTAT:G | acceptor_gain | 0.97 |
| 1:114708154:C:A | acceptor_loss | 0.96 |
| 1:114708152:ACCTT:A | acceptor_loss | 0.96 |
| 1:114707979:T:TA | donor_gain | 0.95 |
| 1:114708149:CCTA:C | acceptor_loss | 0.95 |
| 1:114708150:CTAC:C | acceptor_loss | 0.95 |
| 1:114707951:A:AC | donor_gain | 0.94 |
| 1:114707952:C:CC | donor_gain | 0.94 |
| 1:114708013:T:TA | donor_gain | 0.94 |
| 1:114708049:A:T | acceptor_gain | 0.94 |
| 1:114708151:TACC:T | acceptor_loss | 0.94 |
| 1:114708148:TCCTA:T | acceptor_loss | 0.92 |
| 1:114708189:GTATC:G | donor_loss | 0.92 |
| 1:114707944:CTAAA:C | donor_gain | 0.90 |
| 1:114708188:AGTAT:A | acceptor_gain | 0.86 |
| 1:114708064:A:T | acceptor_gain | 0.82 |
| 1:114708147:GTCCT:G | acceptor_loss | 0.82 |
| 1:114705423:T:G | acceptor_gain | 0.80 |
| 1:114708056:A:C | acceptor_gain | 0.79 |
| 1:114707946:A:T | donor_gain | 0.78 |
| 1:114708063:C:CT | acceptor_gain | 0.76 |
| 1:114708155:TTGA:T | donor_loss | 0.54 |
| (showing top 40 with delta score ≥0.54) | | |
AlphaMissense Predictions
Total AlphaMissense Predictions: 1,251
TOP 50 Predicted Pathogenic Missense Variants:
| Variant | Protein Change | AM Score | Class |
|---|
| 1:114709582:G:T | A146D | 1.000 | likely_pathogenic |
| 1:114709586:A:G | S145P | 1.000 | likely_pathogenic |
| 1:114708637:A:C | F156L | 0.999 | likely_pathogenic |
| 1:114708637:A:T | F156L | 0.999 | likely_pathogenic |
| 1:114708629:A:G | L159P | 0.999 | likely_pathogenic |
| 1:114708638:A:G | F156S | 0.998 | likely_pathogenic |
| 1:114709585:G:A | S145L | 0.998 | likely_pathogenic |
| 1:114708614:C:G | R164P | 0.998 | likely_pathogenic |
| 1:114708626:A:T | V160E | 0.997 | likely_pathogenic |
| 1:114709578:C:A | K147N | 0.997 | likely_pathogenic |
| 1:114709582:G:A | A146V | 0.996 | likely_pathogenic |
| 1:114708629:A:C | L159R | 0.996 | likely_pathogenic |
| 1:114708629:A:T | L159Q | 0.996 | likely_pathogenic |
| 1:114708651:C:A | V152F | 0.996 | likely_pathogenic |
| 1:114709617:A:T | I163K | 0.995 | likely_pathogenic |
| 1:114709580:T:C | K147E | 0.994 | likely_pathogenic |
| 1:114709583:C:T | A146T | 0.994 | likely_pathogenic |
| 1:114709573:C:A | R149I | 0.993 | likely_pathogenic |
| 1:114708617:A:C | I163R | 0.992 | likely_pathogenic |
| 1:114708638:A:C | F156C | 0.991 | likely_pathogenic |
| 1:114709579:T:G | K147T | 0.990 | likely_pathogenic |
| 1:114708622:T:A | R161S | 0.989 | likely_pathogenic |
| 1:114708623:C:A | R161I | 0.989 | likely_pathogenic |
| 1:114709596:G:A | T144I | 0.989 | likely_pathogenic |
| 1:114708642:C:G | A155P | 0.988 | likely_pathogenic |
| 1:114708651:C:G | V152L | 0.987 | likely_pathogenic |
| 1:114708639:A:T | F156I | 0.987 | likely_pathogenic |
| 1:114708617:A:G | I163T | 0.985 | likely_pathogenic |
| 1:114708615:G:T | R164S | 0.984 | likely_pathogenic |
| 1:114709573:C:G | R149T | 0.983 | likely_pathogenic |
| 1:114709596:G:T | T144N | 0.982 | likely_pathogenic |
| 1:114708623:C:G | R161T | 0.980 | likely_pathogenic |
| 1:114708650:A:G | V152A | 0.980 | likely_pathogenic |
| 1:114708639:A:C | F156V | 0.977 | likely_pathogenic |
| 1:114708614:C:A | R164L | 0.937 | likely_pathogenic |
| 1:114708627:C:A | V160L | 0.971 | likely_pathogenic |
| 1:114708605:C:G | R167P | 0.971 | likely_pathogenic |
| 1:114709577:T:G | T148P | 0.970 | likely_pathogenic |
| 1:114708624:T:C | R161G | 0.967 | likely_pathogenic |
| 1:114709570:T:G | Q150P | 0.965 | likely_pathogenic |
| 1:114708615:G:C | R164G | 0.963 | likely_pathogenic |
| 1:114709572:T:A | R149S | 0.963 | likely_pathogenic |
| 1:114708650:A:C | V152G | 0.960 | likely_pathogenic |
| 1:114708653:C:A | G151V | 0.948 | likely_pathogenic |
| 1:114709579:T:A | K147M | 0.945 | likely_pathogenic |
| 1:114708648:C:T | E153K | 0.944 | likely_pathogenic |
| 1:114708633:T:G | T158P | 0.941 | likely_pathogenic |
| 1:114708626:A:C | V160G | 0.941 | likely_pathogenic |
| 1:114708626:A:G | V160A | 0.938 | likely_pathogenic |
| 1:114709580:T:G | K147Q | 0.933 | likely_pathogenic |
Section 7: Biological Pathways & Gene Ontology
Reactome Pathways
Total Pathways: 68
| Pathway ID | Pathway Name | Disease Pathway |
|---|
| R-HSA-9753512 | Signaling by RAS GTPase mutants | Yes |
| R-HSA-9649948 | Signaling downstream of RAS mutants | Yes |
| R-HSA-9648002 | RAS processing | No |
| R-HSA-5658442 | Regulation of RAS by GAPs | No |
| R-HSA-5673001 | RAF/MAP kinase cascade | No |
| R-HSA-5673000 | RAF activation | No |
| R-HSA-5674135 | MAP2K and MAPK activation | No |
| R-HSA-167044 | Signalling to RAS | No |
| R-HSA-112412 | SOS-mediated signalling | No |
| R-HSA-6802946 | Signaling by moderate kinase activity BRAF mutants | Yes |
| R-HSA-6802948 | Signaling by high-kinase activity BRAF mutants | Yes |
| R-HSA-6802952 | Signaling by BRAF and RAF1 fusions | Yes |
| R-HSA-6802953 | RAS signaling downstream of NF1 loss-of-function | Yes |
| R-HSA-6802955 | Paradoxical RAF activation by kinase inactive BRAF | Yes |
| R-HSA-9656223 | Signaling by RAF1 mutants | Yes |
| R-HSA-9753510 | Signaling by RAS GAP mutants | Yes |
| R-HSA-1236382 | Constitutive Signaling by EGFR Cancer Variants | Yes |
| R-HSA-5637810 | Constitutive Signaling by EGFRvIII | Yes |
| R-HSA-9634285 | Constitutive Signaling by Overexpressed ERBB2 | Yes |
| R-HSA-1169092 | Activation of RAS in B cells | No |
| R-HSA-171007 | p38MAPK events | No |
| R-HSA-000165 | MAPK cascade | No |
| R-HSA-179812 | GRB2 events in EGFR signaling | No |
| R-HSA-180336 | SHC1 events in EGFR signaling | No |
| R-HSA-186763 | Downstream signal transduction | No |
| R-HSA-5675221 | Negative regulation of MAPK pathway | No |
| R-HSA-6798695 | Neutrophil degranulation | No |
| R-HSA-74751 | Insulin receptor signalling cascade | No |
| R-HSA-8851805 | MET activates RAS signaling | No |
| R-HSA-9027284 | Erythropoietin activates RAS | No |
| R-HSA-9607240 | FLT3 Signaling | No |
| R-HSA-210993 | Tie2 Signaling | No |
| R-HSA-375165 | NCAM signaling for neurite out-growth | No |
| R-HSA-442982 | Ras activation upon Ca2+ influx through NMDA receptor | No |
| R-HSA-5218921 | VEGFR2 mediated cell proliferation | No |
| R-HSA-5621575 | CD209 (DC-SIGN) signaling | No |
| (and 32 more pathways...) | | |
Gene Ontology Annotations
Total GO Terms: 16
Biological Process (4):
| GO ID | Term |
|---|
| GO:0007265 | Ras protein signal transduction |
| GO:0000165 | MAPK cascade |
| GO:0001938 | positive regulation of endothelial cell proliferation |
Molecular Function (5):
| GO ID | Term |
|---|
| GO:0003924 | GTPase activity |
| GO:0003925 | G protein activity |
| GO:0005525 | GTP binding |
| GO:0019003 | GDP binding |
| GO:0044877 | protein-containing complex binding |
Cellular Component (8):
| GO ID | Term |
|---|
| GO:0005886 | plasma membrane |
| GO:0005829 | cytosol |
| GO:0005794 | Golgi apparatus |
| GO:0000139 | Golgi membrane |
| GO:0005789 | endoplasmic reticulum membrane |
| GO:0016020 | membrane |
| GO:0070062 | extracellular exosome |
| GO:0070821 | tertiary granule membrane |
Section 8: Protein Interactions & Molecular Networks
STRING Protein-Protein Interactions
Total STRING Interactions: 6,520+
TOP 50 Highest-Confidence Interacting Proteins:
| UniProt | Gene | Score |
|---|
| P15056 | BRAF | 973 |
| P42336 | PIK3CA | 921 |
| Q9Y397 | PREX1 | 901 |
| P00533 | EGFR | 900 |
| P04049 | RAF1 | 900 |
| Q06124 | PTPN11 | 892 |
| Q07889 | SOS1 | 887 |
| P07557 | BMX | 886 |
| P21359 | NF1 | 886 |
| P04637 | TP53 | 871 |
| P48736 | PIK3CG | 870 |
| P60484 | PTEN | 861 |
| Q7Z5G4 | RASGRP4 | 860 |
| Q9UM73 | ALK | 854 |
| Q12967 | DAB2 | 846 |
| P42771 | CDKN2A | 838 |
| P06748 | NPM1 | 823 |
| Q02750 | MAP2K1 | 814 |
| P10721 | KIT | 813 |
| Q9UQ13 | LZTR1 | 812 |
| P22607 | FGFR3 | 806 |
| Q06710 | PAX3 | 803 |
| P36888 | FLT3 | 794 |
| P29992 | GNA11 | 790 |
| P04626 | ERBB2 | 788 |
| Q15910 | EZH2 | 788 |
| Q8IXJ9 | SASH1 | 782 |
| P24385 | CCND1 | 781 |
| P07949 | RET | 777 |
| P19544 | WT1 | 774 |
| P31749 | AKT1 | 774 |
| O75874 | IDH1 | 773 |
| P11802 | CDK4 | 771 |
| P18443 | SOS2 | 767 |
| Q6N021 | RHOD | 765 |
| P20936 | RASA1 | 764 |
| P48735 | IDH2 | 764 |
| P10415 | BCL2 | 763 |
| P50148 | GNAQ | 747 |
| Q01196 | RUNX1 | 727 |
| Q9Y6K1 | PDPK1 | 724 |
| Q01081 | U2AF1 | 712 |
| P08922 | ROS1 | 705 |
| Q969H0 | FBXW7 | 701 |
| Q01130 | SRSF2 | 697 |
| P04198 | MYCN | 685 |
| O60674 | JAK2 | 683 |
| O75534 | CSDE1 | 677 |
| P35222 | CTNNB1 | 676 |
| O14746 | TERT | 675 |
BioGRID Interactions
Total BioGRID Interactions: 914
Key Interactors by Experimental System:
| Interactor | Experimental System |
|---|
| RAF1 | Affinity Capture-Western, Synthetic Lethality |
| BRAF | Affinity Capture-Western, Two-hybrid |
| MAP2K7 | Affinity Capture-Western |
| LZTR1 | Affinity Capture-Western, Luminescence, Co-localization |
| CBL | Affinity Capture-MS, Affinity Capture-Western |
| RAP1GDS1 | Two-hybrid |
| RCE1 | Synthetic Lethality |
| ICMT | Synthetic Lethality |
| SHOC2 | Synthetic Lethality |
| PREX1 | Synthetic Lethality |
| GOLGA7 | Synthetic Lethality |
| GRB2 | Proximity Label-MS |
| ROCK1/2 | Proximity Label-MS |
| PI4KA | Proximity Label-MS |
| RICTOR | Proximity Label-MS |
| BTK | Proximity Label-MS |
| AKT pathway | Multiple |
IntAct Interactions
Total IntAct Interactions: 160
Highest Confidence Interactions:
| Interaction ID | Partner | Score | Type |
|---|
| EBI-15716891 | RAF1 | 0.930 | physical association |
| EBI-24691741 | RAF1 | 0.930 | physical association |
| EBI-44458443 | RAF1 | 0.930 | association |
| EBI-15920564 | BRAF | 0.860 | physical association |
| EBI-28931955 | BRAF | 0.860 | association |
| EBI-32717084 | BRAF | 0.860 | physical association |
| EBI-24445028 | RIN1 | 0.840 | physical association |
| EBI-25265548 | ARAF | 0.560 | physical association |
| EBI-25882313 | PIK3R1 | 0.560 | physical association |
| EBI-24552005 | RAP1GDS1 | 0.560 | physical association |
| EBI-24713213 | RGL3 | 0.560 | physical association |
| EBI-21916458 | FNTA | 0.560 | physical association |
| EBI-3932755 | RGL2 | 0.550 | physical association |
Protein Similarity
ESM2 Structural/Embedding Similarity:
Total Similar Proteins: 74
| UniProt | Top Similarity | Avg Similarity |
|---|
| P01111 | 1.0000 | 0.9941 |
| P08556 (Bovine NRAS) | 0.9998 | 0.9942 |
| Q04970 (Rat NRAS) | 0.9999 | 0.9942 |
| Q95ME4 (Pig NRAS) | 0.9998 | 0.9941 |
| P01112 (HRAS) | 1.0000 | 0.9932 |
| P01116 (KRAS) | 0.9999 | 0.9933 |
| P01113 | 0.9989 | 0.9925 |
| P61223 (RAP1B) | 1.0000 | 0.9907 |
| P62833-6 (RAP2 family) | 1.0000 | 0.9898 |
DIAMOND Sequence Similarity:
Total Homologous Proteins: 168+
| UniProt | Gene | Identity (%) | Bitscore |
|---|
| P01111 | NRAS | 100.00 | 379 |
| P01112 | HRAS | 100.00 | 383 |
| P01116 | KRAS | 99.00 | 372 |
| P08642 | | 100.00 | 378 |
| P62070/P62071 | RRAS2 | 100.00 | 399 |
| P08556 | Bovine NRAS | 98.40 | 375 |
| P12825 | | 99.50 | 379 |
| P36860 | | 98.50 | 385 |
Section 9: Transcription Factor Regulatory Data
Note: NRAS is NOT a transcription factor; it is a GTPase signaling protein.
Upstream Transcriptional Regulators of NRAS
CollecTRI Data (TFs regulating NRAS):
| TF Gene | Regulation | Confidence |
|---|
| AR (Androgen Receptor) | Repression | - |
| MYB | Repression | High |
| MYC | Unknown | High |
| NR1H2 (LXRβ) | - | High |
SIGNOR Signaling Interactions
Upstream Regulators of NRAS Activity:
| Regulator | Effect | Mechanism | Direct | Score |
|---|
| SOS1 | up-regulates activity | GEF | Yes | 0.78 |
| RASGEF1A | up-regulates | binding | Yes | 0.39 |
| RASGEF1B | up-regulates | binding | Yes | 0.30 |
| RASGEF1C | up-regulates | binding | Yes | 0.20 |
| RAPGEF5 | up-regulates | GEF | Yes | 0.44 |
| RAPGEF6 | up-regulates | GEF | Yes | 0.33 |
| PTPN11 | up-regulates activity | dephosphorylation | Yes | 0.67 |
| DAB2IP | down-regulates activity | GAP | Yes | 0.49 |
| ZDHHC9 | up-regulates activity | palmitoylation | Yes | 0.40 |
| GOLGA7 | up-regulates activity | palmitoylation | Yes | 0.40 |
| STK19 | up-regulates activity | phosphorylation | Yes | 0.31 |
| AR | down-regulates quantity | transcriptional | No | 0.28 |
| BCR-ABL | up-regulates activity | - | No | 0.20 |
| MVD | up-regulates quantity | stabilization | No | 0.20 |
Downstream Targets of NRAS Signaling:
| Target | Effect | Mechanism | Direct | Score |
|---|
| RAF1 | up-regulates | relocalization | Yes | 0.87 |
| BRAF | up-regulates activity | binding | Yes | 0.85 |
| PIK3CA | up-regulates activity | binding | Yes | 0.84 |
| ARAF | up-regulates | binding | Yes | 0.83 |
| PIK3CG | up-regulates | binding | Yes | 0.72 |
| PI3K | up-regulates activity | binding | Yes | 0.68 |
| PIK3CB | up-regulates | binding | Yes | 0.67 |
| GLI1 | up-regulates | - | No | 0.29 |
Section 10: Drug & Pharmacology Data
ChEMBL Target Information
| Target ID | Name | Type |
|---|
| CHEMBL2079845 | GTPase NRas | SINGLE PROTEIN |
| CHEMBL4524006 | RAS | PROTEIN FAMILY |
Targeting Molecules
Total ChEMBL Molecules Targeting NRAS: 100+
Molecules by Development Phase:
| ChEMBL ID | Name | Type | Phase |
|---|
| CHEMBL279433 | L-778123 FREE BASE | Small molecule | Phase 1 |
| CHEMBL2086789 | - | Small molecule | 0 |
| CHEMBL256963 | - | Small molecule | 0 |
| CHEMBL3182364 | - | Small molecule | 0 |
| CHEMBL401633 | - | Small molecule | 0 |
| (+ many research compounds in development) | | | |
Note: Direct NRAS inhibitors have historically been challenging to develop. Recent breakthroughs include:
- RMC-7977 (tricomplex inhibitor with CypA)
- Daraxonrasib (RMC-6236) (pan-RAS inhibitor)
- Multiple compounds targeting mutant-specific NRAS (Q61K, Q61R, Q61L)
BindingDB Data
Total BindingDB Entries: 409
Pharmacogenomics (PharmGKB)
| PharmGKB ID | Symbol | VIP Gene | Has CPIC Guideline |
|---|
| PA31768 | NRAS | Yes | No |
Clinical Relevance:
- NRAS mutations predict response/resistance to targeted therapies
- Key biomarker in melanoma, colorectal cancer, AML treatment decisions
- Mutations associated with resistance to EGFR inhibitors (cetuximab, panitumumab)
- Affects MEK inhibitor sensitivity
Section 11: Expression Profiles
Bgee Expression Summary
| Attribute | Value |
|---|
| Expression Breadth | Ubiquitous |
| Total Present Calls | 278 |
| Max Expression Score | 96.10 |
TOP 30 Tissues by Expression Score
| Tissue/Anatomical Entity | Score | Rank | Quality |
|---|
| Gingival epithelium | 96.10 | 1820 | Gold |
| Epithelium of nasopharynx | 95.64 | 2030 | Gold |
| Amniotic fluid | 95.62 | 2040 | Gold |
| Colonic mucosa | 95.54 | 2080 | Gold |
| Mucosa of sigmoid colon | 95.52 | 2090 | Gold |
| Gingiva | 95.45 | 2120 | Gold |
| Esophagus squamous epithelium | 95.20 | 2240 | Gold |
| Germinal epithelium of ovary | 95.02 | 2320 | Gold |
| Upper leg skin | 94.53 | 2550 | Gold |
| Ganglionic eminence | 93.84 | 2870 | Gold |
| Parietal pleura | 93.75 | 2910 | Gold |
| Tibia | 93.58 | 2990 | Gold |
| Visceral pleura | 93.56 | 3000 | Gold |
| Ventricular zone | 93.55 | 3010 | Gold |
| Adrenal tissue | 93.50 | 3030 | Gold |
| Endothelial cell | 93.02 | 3260 | Gold |
| Cortical plate | 93.00 | 3270 | Gold |
| Trabecular bone tissue | 92.69 | 3410 | Gold |
| Islet of Langerhans | 92.65 | 3430 | Gold |
| Oral cavity | 92.57 | 3460 | Gold |
| Pleura | 92.48 | 3510 | Gold |
| Skin of hip | 92.32 | 3580 | Gold |
| Palpebral conjunctiva | 91.97 | 3750 | Gold |
| Endometrium | 91.89 | 3780 | Gold |
| Mammary duct | 91.72 | 3860 | Gold |
| Jejunal mucosa | 91.64 | 3900 | Gold |
| Rectum | 91.35 | 4030 | Gold |
| Bone marrow | 91.15 | 4130 | Gold |
| Lower lobe of lung | 90.97 | 4210 | Gold |
| Embryo | 90.95 | 4220 | Gold |
TOP 30 Cell Types by Expression
| Cell Type | Score | Quality |
|---|
| Secondary oocyte | 95.63 | Gold |
| Oocyte | 93.13 | Gold |
| Endothelial cell | 93.02 | Gold |
| Monocyte | 92.27 | Gold |
| Mononuclear cell | 92.12 | Gold |
| Leukocyte | 91.94 | Gold |
| Buccal mucosa cell | 89.91 | Gold |
| Bronchial epithelial cell | 87.21 | Gold |
| Primordial germ cell (gonad) | 87.16 | Gold |
| Stromal cell of endometrium | 86.11 | Gold |
| Bone marrow cell | 84.90 | Gold |
| Granulocyte | 84.87 | Gold |
Single-Cell Expression Data
Single Cell Expression Atlas (SCXA): Data available
- Multiple experiments include NRAS expression
- Expression across diverse cell populations
Section 12: Disease Associations
Mendelian/Monogenic Disease Links (GenCC)
| Disease | MONDO/OMIM ID | Classification | MOI | Source |
|---|
| Noonan syndrome 6 | OMIM:613224 | Definitive | AD | G2P |
| Noonan syndrome 6 | OMIM:613224 | Strong | AD | Genomics England |
| Noonan syndrome 6 | OMIM:613224 | Strong | AD | Labcorp/Invitae |
| Noonan syndrome | ORPHANET:648 | Supportive | AD | Orphanet |
| Cardiofaciocutaneous syndrome | MONDO:0015280 | Strong | AD | Genomics England |
AD = Autosomal Dominant
Orphanet Disease Associations (7 total)
| Orphanet ID | Disease Name | Type | Gene Count |
|---|
| 648 | Noonan syndrome | Malformation syndrome | 15 |
| 86834 | Juvenile myelomonocytic leukemia | Disease | 6 |
| 268114 | RAS-associated autoimmune leukoproliferative disease | Disease | 2 |
| 389 | Langerhans cell histiocytosis | Disease | 3 |
| 626 | Large/giant congenital melanocytic nevus | Disease | 7 |
| 2612 | Linear nevus sebaceus syndrome | Disease | 3 |
| 146 | Differentiated thyroid carcinoma | Disease | 29 |
HPO Phenotype Associations
Total Associated Phenotypes: 244
TOP 50 Phenotype Terms:
| HPO ID | Phenotype |
|---|
| HP:0000006 | Autosomal dominant inheritance |
| HP:0001249 | Intellectual disability |
| HP:0001263 | Global developmental delay |
| HP:0001252 | Hypotonia |
| HP:0001290 | Generalized hypotonia |
| HP:0001250 | Seizure |
| HP:0000256 | Macrocephaly |
| HP:0000316 | Hypertelorism |
| HP:0000508 | Ptosis |
| HP:0000465 | Webbed neck |
| HP:0000470 | Short neck |
| HP:0000767 | Pectus excavatum |
| HP:0000768 | Pectus carinatum |
| HP:0001382 | Joint hypermobility |
| HP:0000957 | Cafe-au-lait spot |
| HP:0001004 | Lymphedema |
| HP:0000347 | Micrognathia |
| HP:0000494 | Downslanted palpebral fissures |
| HP:0000486 | Strabismus |
| HP:0000369 | Low-set ears |
| HP:0000337 | Broad forehead |
| HP:0000348 | High forehead |
| HP:0000325 | Triangular face |
| HP:0000311 | Round face |
| HP:0000293 | Full cheeks |
| HP:0000218 | High palate |
| HP:0000750 | Delayed speech and language development |
| HP:0001156 | Brachydactyly |
| HP:0000028 | Cryptorchidism |
| HP:0000995 | Melanocytic nevus |
| HP:0001003 | Multiple lentigines |
| HP:0000238 | Hydrocephalus |
| HP:0001028 | Hemangioma |
| HP:0000978 | Bruising susceptibility |
| HP:0000639 | Nystagmus |
| HP:0001270 | Motor delay |
| HP:0001324 | Muscle weakness |
| HP:0001347 | Hyperreflexia |
| HP:0000968 | Eczematoid dermatitis |
| HP:0000826 | Precocious puberty |
| HP:0000545 | Myopia |
| HP:0000407 | Sensorineural hearing impairment |
| HP:0000365 | Hearing impairment |
| HP:0001987 | Placenta abnormality |
| HP:0000476 | Cystic hygroma |
| HP:0001195 | Single umbilical artery |
| HP:0000044 | Hypogonadotropic hypogonadism |
| HP:0000998 | Hypertrichosis |
| HP:0001054 | Numerous nevi |
| HP:0000589 | Coloboma |
GWAS Associations (4 studies)
| Study ID | Trait | P-value | Mapped Gene |
|---|
| GCST010988_371 | Adult body size | 7.0×10⁻¹⁰ | NRAS |
| GCST002268_1 | Autism | 3.0×10⁻⁸ | CSDE1; AMPD1 |
| GCST002268_10 | Autism | 4.0×10⁻⁸ | AMPD1 |
| GCST002268_2 | Autism | 9.0×10⁻⁸ | CSDE1; AMPD1 |
Cancer Associations (Somatic Mutations)
NRAS is one of the most frequently mutated oncogenes. Key cancer types with NRAS mutations:
| Cancer Type | Mutation Frequency |
|---|
| Melanoma | 15-25% |
| Acute Myeloid Leukemia (AML) | 10-15% |
| Colorectal Cancer | 3-5% |
| Thyroid Cancer | 5-10% |
| Multiple Myeloma | 20-25% |
| Juvenile Myelomonocytic Leukemia (JMML) | 15-20% |
Hotspot Mutations:
- G12 (codons 12): G12D, G12S, G12C, G12A, G12V
- G13 (codon 13): G13D, G13R, G13V
- Q61 (codon 61): Q61R, Q61K, Q61L, Q61H (most common in melanoma)
SUMMARY STATISTICS
| Category | Count |
|---|
| Ensembl Transcripts | 4 |
| RefSeq Transcripts (Human) | 2 (NM/NP) |
| CCDS IDs | 1 |
| Exons (canonical) | 7 |
| UniProt Entries | 2 |
| InterPro Domains | 4 |
| PDB Structures | 29 |
| Orthologs (key species) | 3 |
| Paralogs (human) | 35 |
| ClinVar Variants | 330 |
| Pathogenic/Likely Pathogenic | 20 |
| SpliceAI Predictions | 577 |
| AlphaMissense Predictions | 1,251 |
| Reactome Pathways | 68 |
| GO Terms | 16 |
| STRING Interactions | 6,520+ |
| BioGRID Interactions | 914 |
| IntAct Interactions | 160 |
| SIGNOR Interactions | 23 |
| ChEMBL Targeting Molecules | 100+ |
| BindingDB Entries | 409 |
| HPO Phenotypes | 244 |
| GWAS Associations | 4 |
| Orphanet Diseases | 7 |
| GenCC Disease-Gene Relations | 5 |
| Bgee Expression Calls | 278 |
Data Sources: HGNC, Ensembl, NCBI Entrez, UniProt, OMIM, RefSeq, CCDS, PDB, AlphaFold, InterPro, Pfam, ClinVar, AlphaMissense, SpliceAI, Reactome, Gene Ontology, STRING, BioGRID, IntAct, SIGNOR,
ChEMBL, BindingDB, PharmGKB, Bgee, HPO, Orphanet, GenCC, GWAS Catalog
Generated: 2026-03-27 via Biobtree cross-database mapping