NRAS

Summary

NRAS (NRAS proto-oncogene, GTPase, HGNC:7989) is a protein-coding gene on chromosome 1p13.2, encoding GTPase NRas (P01111). Signal transducer in the Ras-MAPK signaling pathway that regulates cell proliferation and survival. In precision oncology, NRAS Mutation is associated with resistance to Panitumumab + Cetuximab in Colorectal Cancer (CIViC Level A); 75 further curated variant–drug associations are listed below.

This is an N-ras oncogene encoding a membrane protein that shuttles between the Golgi apparatus and the plasma membrane. This shuttling is regulated through palmitoylation and depalmitoylation by the ZDHHC9-GOLGA7 complex. The encoded protein, which has intrinsic GTPase activity, is activated by a guanine nucleotide-exchange factor and inactivated by a GTPase activating protein. Mutations in this gene have been associated with somatic rectal cancer, follicular thyroid cancer, autoimmune lymphoproliferative syndrome, Noonan syndrome, and juvenile myelomonocytic leukemia.

Source: NCBI Gene 4893 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Noonan syndrome (Definitive, ClinGen) — +4 more curated relationships
• GWAS associations: 4
• Clinical variants (ClinVar): 346 total — 11 pathogenic, 9 likely-pathogenic (top 9% of genes corpus-wide)
• GTEx eGene: eQTL in 6 tissues, sQTL in 1 (q < 0.05)
• Phenotypes (HPO): 244
• Drug target: yes — 1 via a complex or family; 1 molecules with ChEMBL bioactivity
• Precision-oncology evidence (CIViC): 76 curated variant–drug associations
• Cancer driver (intOGen): activating (oncogene-like) across 22 cancer types (inferred from mutation patterns)
• Dosage sensitivity (ClinGen): haploinsufficiency no evidence, triplosensitivity no evidence
• Constraint (gnomAD): pLI 0.94 (loss-of-function intolerant), LOEUF 0.55 (moderately constrained)
• MANE Select transcript: NM_002524
• Interaction hub: 4,752 STRING partners (top 1% of genes corpus-wide)

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7989
Approved symbol	NRAS
Name	NRAS proto-oncogene, GTPase
Location	1p13.2
Locus type	gene with protein product
Status	Approved
Aliases	N-ras
Ensembl gene	ENSG00000213281
Ensembl biotype	protein_coding
OMIM	164790
Entrez	4893

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 4 protein_coding, 3 nonsense_mediated_decay

MANE Select: ENST00000369535

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1

ENST00000369535, ENST00000899430, ENST00000931009, ENST00000931010, ENST00000995004, ENST00001081567, ENST00001081568

RefSeq mRNA: 1 — MANE Select: NM_002524 NM_002524

CCDS: CCDS877

Canonical transcript exons

ENST00000369535 — 7 exons

Exon	Start	End
ENSE00000784343	114709569	114709728
ENSE00000800104	114708531	114708654
ENSE00001364464	114716658	114716771
ENSE00001365300	114708154	114708192
ENSE00001450280	114704469	114708050
ENSE00001450282	114716050	114716177
ENSE00001751295	114713800	114713978

Expression profiles

Bgee: expression breadth ubiquitous, 278 present calls, max score 96.10.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 39.5218 / max 448.9475, expressed in 1809 samples.

Highest expression (Bgee): gingival epithelium, epithelium of nasopharynx, secondary oocyte, amniotic fluid, colonic mucosa.

Genetic regulation across tissues (GTEx eQTL / sQTL)

NRAS is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 6 tissues and its splicing (sQTL) in 1 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

7 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Esophagus Mucosa	eqtl	4.7e-04	+0.28	1:114468247:G:A
Skin Sun Exposed Lower leg	eqtl	6.7e-03	+0.19	1:114693284:A:G
Thyroid	eqtl	1.2e-02	+0.28	1:115594899:A:G
Skin Sun Exposed Lower leg	sqtl	1.9e-02	-0.72	1:114683656:G:A
Cells EBV-transformed lymphocytes	eqtl	3.1e-02	+0.39	1:114378436:A:G
Brain Spinal cord cervical c-1	eqtl	3.8e-02	-0.37	1:114320582:T:C
Whole Blood	eqtl	4.7e-02	+0.12	1:114511463:C:T

FANTOM5 promoters

2 alternative TSS:

Promoter ID	TPM avg	Samples expressed
13958	37.9598	1809
13959	1.5619	893

Top tissues by expression

showing 100 of 293 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
gingival epithelium	UBERON:0001949	96.10	gold quality
epithelium of nasopharynx	UBERON:0001951	95.64	gold quality
secondary oocyte	CL:0000655	95.63	gold quality
amniotic fluid	UBERON:0000173	95.62	gold quality
colonic mucosa	UBERON:0000317	95.54	gold quality
mucosa of sigmoid colon	UBERON:0004993	95.52	gold quality
gingiva	UBERON:0001828	95.45	gold quality
esophagus squamous epithelium	UBERON:0006920	95.20	gold quality
germinal epithelium of ovary	UBERON:0001304	95.02	gold quality
upper leg skin	UBERON:0004262	94.53	gold quality
ganglionic eminence	UBERON:0004023	93.84	gold quality
parietal pleura	UBERON:0002400	93.75	gold quality
tibia	UBERON:0000979	93.58	gold quality
visceral pleura	UBERON:0002401	93.56	gold quality
ventricular zone	UBERON:0003053	93.55	gold quality
adrenal tissue	UBERON:0018303	93.50	gold quality
oocyte	CL:0000023	93.13	gold quality
endothelial cell	CL:0000115	93.02	gold quality
cortical plate	UBERON:0005343	93.00	gold quality
trabecular bone tissue	UBERON:0002483	92.69	gold quality
islet of Langerhans	UBERON:0000006	92.65	gold quality
oral cavity	UBERON:0000167	92.57	gold quality
pleura	UBERON:0000977	92.48	gold quality
skin of hip	UBERON:0001554	92.32	gold quality
monocyte	CL:0000576	92.27	gold quality
mononuclear cell	CL:0000842	92.12	gold quality
palpebral conjunctiva	UBERON:0001812	91.97	gold quality
leukocyte	CL:0000738	91.94	gold quality
endometrium	UBERON:0001295	91.89	gold quality
mammary duct	UBERON:0001765	91.72	gold quality
jejunal mucosa	UBERON:0000399	91.64	gold quality
rectum	UBERON:0001052	91.35	gold quality
bone marrow	UBERON:0002371	91.15	gold quality
lower lobe of lung	UBERON:0008949	90.97	gold quality
embryo	UBERON:0000922	90.95	gold quality
epithelium of esophagus	UBERON:0001976	90.89	gold quality
mucosa of paranasal sinus	UBERON:0005030	90.75	gold quality
penis	UBERON:0000989	90.43	gold quality
placenta	UBERON:0001987	90.25	gold quality
cartilage tissue	UBERON:0002418	90.13	gold quality
substantia nigra pars reticulata	UBERON:0001966	90.09	gold quality
tonsil	UBERON:0002372	90.02	gold quality
synovial joint	UBERON:0002217	89.94	gold quality
buccal mucosa cell	CL:0002336	89.91	gold quality
substantia nigra pars compacta	UBERON:0001965	89.35	gold quality
pharyngeal mucosa	UBERON:0000355	89.25	gold quality
caput epididymis	UBERON:0004358	89.03	gold quality
epithelium of mammary gland	UBERON:0003244	88.92	gold quality
subthalamic nucleus	UBERON:0001906	88.84	gold quality
corpus epididymis	UBERON:0004359	88.81	gold quality
lymph node	UBERON:0000029	88.64	gold quality
mammalian vulva	UBERON:0000997	88.63	gold quality
superior surface of tongue	UBERON:0007371	88.33	gold quality
ileal mucosa	UBERON:0000331	88.28	gold quality
medial globus pallidus	UBERON:0002477	88.10	gold quality
thoracic mammary gland	UBERON:0005200	87.85	gold quality
mammary gland	UBERON:0001911	87.83	gold quality
globus pallidus	UBERON:0001875	87.82	gold quality
superficial temporal artery	UBERON:0001614	87.76	gold quality
cauda epididymis	UBERON:0004360	87.74	gold quality
endometrium epithelium	UBERON:0004811	87.71	gold quality
squamous epithelium	UBERON:0006914	87.69	gold quality
duodenum	UBERON:0002114	87.56	gold quality
gall bladder	UBERON:0002110	87.40	gold quality
caecum	UBERON:0001153	87.36	gold quality
jejunum	UBERON:0002115	87.29	gold quality
bronchial epithelial cell	CL:0002328	87.21	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.16	gold quality
nipple	UBERON:0002030	87.12	gold quality
colonic epithelium	UBERON:0000397	87.11	gold quality
trigeminal ganglion	UBERON:0001675	86.89	gold quality
lateral globus pallidus	UBERON:0002476	86.89	gold quality
Brodmann (1909) area 23	UBERON:0013554	86.85	gold quality
mucosa of transverse colon	UBERON:0004991	86.77	gold quality
superior vestibular nucleus	UBERON:0007227	86.66	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	86.48	gold quality
inferior vagus X ganglion	UBERON:0005363	86.45	gold quality
lower esophagus mucosa	UBERON:0035834	86.22	gold quality
decidua	UBERON:0002450	86.17	gold quality
pigmented layer of retina	UBERON:0001782	86.15	gold quality
stromal cell of endometrium	CL:0002255	86.11	gold quality
vermiform appendix	UBERON:0001154	86.10	gold quality
tendon	UBERON:0000043	86.09	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	86.03	gold quality
calcaneal tendon	UBERON:0003701	85.81	gold quality
esophagus mucosa	UBERON:0002469	85.80	gold quality
pylorus	UBERON:0001166	85.67	gold quality
spinal cord	UBERON:0002240	85.59	gold quality
renal medulla	UBERON:0000362	85.55	gold quality
pancreas	UBERON:0001264	85.44	gold quality
adult organism	UBERON:0007023	85.38	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	85.31	gold quality
tongue	UBERON:0001723	85.20	gold quality
tendon of biceps brachii	UBERON:0008188	85.20	gold quality
pons	UBERON:0000988	85.18	gold quality
nasal cavity mucosa	UBERON:0001826	85.00	gold quality
lateral nuclear group of thalamus	UBERON:0002736	84.92	gold quality
bone marrow cell	CL:0002092	84.90	gold quality
granulocyte	CL:0000094	84.87	gold quality
connective tissue	UBERON:0002384	84.61	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.34

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 78 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Bone marrow	tissue	55.2	medium
Thymus	tissue	36.4
Caudate putamen	tissue	30.4
Lymph node	tissue	28.5	medium
Tonsil	tissue	27.8	low
Placenta	tissue	26.6	not detected
Frontal cortex	tissue	26.4
Colon	tissue	26.1	high
Corpus callosum	tissue	26.1
Rectum	tissue	25.0	high
Appendix	tissue	24.3	high
Liver	tissue	23.3	not detected
Spinal cord	tissue	21.9
Small intestine	tissue	21.2	high
Urinary bladder	tissue	20.8	low
Stomach 1	tissue	20.6	medium
Duodenum	tissue	20.2	high
Substantia nigra	tissue	20.1
Midbrain	tissue	19.5
Kidney	tissue	19.5	medium
Esophagus	tissue	19.4	not detected
Locus coeruleus	tissue	19.1
Skin 1	tissue	18.7	low
Medulla oblongata	tissue	18.4
Pons	tissue	18.1
Adipose tissue	tissue	17.8	not detected
Lung	tissue	17.5	not detected
Spleen	tissue	17.5	not detected
Thalamus	tissue	17.4
Superior colliculi	tissue	17.0
Breast	tissue	16.9	not detected
Periaqueductal gray	tissue	16.6
Hypothalamus	tissue	16.4
Putamen	tissue	16.3
Gallbladder	tissue	16.1	high
Septum	tissue	15.6
Ventral forebrain	tissue	15.2
Thyroid gland	tissue	15.1	low
Hippocampal formation	tissue	13.7
Cerebral cortex	tissue	13.3	medium
Motor cortex	tissue	13.3
Amygdala	tissue	13.3
Retrosplenial cortex	tissue	13.3
Smooth muscle	tissue	13.2	not detected
Entorhinal cortex	tissue	13.2
Somatosensory cortex	tissue	13.2
Occipital cortex	tissue	13.1
Postcentral gyrus	tissue	13.0
Olfactory bulb	tissue	13.0
Prefrontal cortex	tissue	12.9
Nucleus accumbens	tissue	12.9
Insular cortex	tissue	12.9
Retrosplenial and cingulate cortex	tissue	12.7
Hippocampus	tissue	12.5	not detected
Basal ganglia	tissue	12.4	not detected
Temporal cortex	tissue	12.4
Cervix	tissue	11.7	not detected
Endometrium 1	tissue	11.6	not detected
Ovary	tissue	11.4	not detected
Choroid plexus	tissue	11.1

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — White matter (26.1), Ventral spinal cord (21.9), Dorsal spinal cord (21.3), Lateral funiculus (white matter) (21.0), Dorsal funiculus (white matter) (20.6).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AR, MYB, MYC, NR1H2

miRNA regulators (miRDB)

Targeting NRAS by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 224 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-196A-5P	100.00	68.16	684
HSA-MIR-196B-5P	100.00	68.16	681
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939

Functional genomics

gnomAD constraint: pLI 0.937, LOEUF 0.55, missense Z 2.24 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000369535 — one region, missense o/e 0.62. ClinGen dosage: haploinsufficiency 0 (no evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• Mutations were detected by using allele-specific amplification method. (PMID:11524732)
• BMECs co-expressing SV40T, hTERT and N-ras exhibited an overtly transformed phenotype; forming very large colonies with an altered morphology and generating rapidly growing tumours in vivo. (PMID:12082607)
• Regulation of Fas-mediated apoptosis by N-ras in melanoma. (PMID:12230495)
• Protein kinase C mediates mutant N-Ras-induced developmental abnormalities erythropoiesis, giving rise to phenotypic and functional abnormalities commonly observed in preleukemia. (PMID:12393454)
• role of interleukin-6 in activation of expression (PMID:12483530)
• HDL induced a potent signal through a Ras/MAPK pathway mediated by a pertussis toxin-sensitive G-protein coupled receptor to the angiogenic phenotype in HCECs. (PMID:12637339)
• high frequency of NRAS codon 61 mutations detected in primary hereditary melanomas may be the result of a hypermutability phenotype associated with a hereditary predisposition for melanoma development in patients with germline CDKN2A mutations (PMID:12783933)
• NRAS and BRAF mutations arise early during melanoma pathogenesis and are preserved throughout tumor progression (PMID:14695152)
• Acquisition of N-ras mutation is frequently associated with progression of myelodysplastic syndrome to acute myeloid leukemia (PMID:14737077)
• Mutations in N-ras gene is associated with malignant melanomas (PMID:14961576)
• Data show that Golgi-associated N-Ras is the critical Ras isoform and intracellular pool for low-grade T cell receptor signaling in Jurkat T cells. (PMID:15060167)
• Low frequency of NRAS and KRAS2 gene mutations in childhood myelodysplastic syndromes. (PMID:15474158)
• NRAS mutations are frequent in acute myeloblastic leukemia with normal karyotype. (PMID:15674343)
• oncogenic NRAS is important for avoidance of apoptosis in melanomas that harbor the codon 61 NRAS mutation (PMID:15688405)
• Although BRAF and NRAS mutations are likely to be important for the initiation and maintenance of some melanomas, other factors might be more significant for proliferation and prognosis in subgroups of aggressive melanoma (PMID:16098042)
• Overactivation of N-Ras61K induces cytoplasmic mislocalization of p27 and disrupts TGF-beta-mediated Smad nuclear translocation by activation of the Mek/Erk pathway. (PMID:16135812)
• Ras mutations do not play a significant role in the pathogenesis of multiple myeloma in the Spanish population (PMID:16142319)
• NRAS and BRAF activating mutations can coexist in the same melanoma, but are mutually exclusive at the single-cell level (PMID:16462768)
• In 239 Thai adult AML cases, 35 RAS mutations were found in 32 cases (13%) predominantly classified as M1/M2 (53%) followed by M4/M5 (38%). Ten cases were positive for NRAS codon 12, 11 for NRAS codon 61, 13 for NRAS codon 13, and one for KRAS codon 13. (PMID:16573741)
• ras may be involved in early stages of larynx carcinogenesis and may be activated by other mechanisms different from mutations, such as epigenetic events (PMID:16761621)
• NRAS mutation is associated with melanoma and melanocytic nevi. (PMID:16845322)
• The chemical properties and stucture of the membrane bound C-terminus of N-ras is reported. (PMID:16847854)
• Ras gene mutations, mostly involving the N-Ras gene, were detected in 20% of the multiple myeloma patients; Ras gene mutations are not likely to represent a master lesion in MM (PMID:17036375)
• NRAS mutations were associated with a significantly higher Clark level of invasion in melanoma tumours (PMID:17119447)
• Our data suggest that the activity of specific RAS isoforms is context-dependent and provide a possible explanation for the prevalence of NRAS mutations in melanoma. (PMID:17297468)
• patients having juvenile myelomonocytic leukemia with NRAS or KRAS2 glycine to serine substitution received no chemotherapy, but hematologic improvement was observed during a 2- to 4-year follow up (PMID:17332249)
• data indicate that both early-life UV exposure and nevus propensity contribute to occurrence of BRAF+ melanoma, whereas nevus propensity and later-life sun exposure influence the occurrence of NRAS+ melanoma (PMID:17507627)
• observations on the effects of NRAS activation indicate that RAS-inactivating drugs, such as farnesyltransferase inhibitors should be examined in human autoimmune and lymphocyte homeostasis disorders (PMID:17517660)
• Nras gene mutation might be one of the mechanisms of oncogenesis of lung adenocarcinoma. (PMID:17671710)
• No mutations in NRAS was found in pilocytic astrocytomas. (PMID:17712732)
• Ras mutations were found in 33% of the papillary thyroid carcinomas (PMID:17786355)
• CD155, at least in part, enhances the proliferation of ras-mutated cells (PMID:17893876)
• expression of RET, nuclearRAS, and ERK proteins is greatly enhanced in papillary thyroid carcinoma cells and Hashimoto’s thyroiditis oxyphil cells. (PMID:17900235)
• Frequently mutated in high hyperdiploid childhood acute lymphoblastic leukemia. (PMID:17910045)
• Data indicate that a critical component of Ras signaling is the activation of PLD. (PMID:17949898)
• 54% of childhood CBF-AML had RTKs and/or Ras mutations (PMID:17960171)
• 16k PRL inhibits cell migration by blocking the Ras-Tiam1-Rac1-Pak1 signaling pathway in endothelial cells (PMID:18006851)
• mutation of N-RAS or B-RAF, signature genetic lesions present in most MMs, potently induced the expression of cell-surface CD200, a repressor of DC function. (PMID:18008004)
• NRAS mutation is not associated with cutaneous melanoma (PMID:18227705)
• N-ras mutation is associated with familial non-medullary thyroid carcinoma (PMID:18310288)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	nras	ENSDARG00000038225
mus_musculus	Nras	ENSMUSG00000027852
rattus_norvegicus	Nras	ENSRNOG00000023079

Paralogs (35): RALA (ENSG00000006451), REM1 (ENSG00000088320), RASL10A (ENSG00000100276), RASD2 (ENSG00000100302), RASL12 (ENSG00000103710), RHEB (ENSG00000106615), RASD1 (ENSG00000108551), RERGL (ENSG00000111404), RAP1A (ENSG00000116473), RASL11A (ENSG00000122035), RAP2C (ENSG00000123728), RAP2A (ENSG00000125249), RRAS (ENSG00000126458), RAP1B (ENSG00000127314), RASL11B (ENSG00000128045), KRAS (ENSG00000133703), RRAS2 (ENSG00000133818), RERG (ENSG00000134533), REM2 (ENSG00000139890), RIT1 (ENSG00000143622), RALB (ENSG00000144118), RIT2 (ENSG00000152214), MRAS (ENSG00000158186), DIRAS3 (ENSG00000162595), GEM (ENSG00000164949), DIRAS2 (ENSG00000165023), RRAD (ENSG00000166592), RHEBL1 (ENSG00000167550), NKIRAS2 (ENSG00000168256), HRAS (ENSG00000174775), DIRAS1 (ENSG00000176490), RAP2B (ENSG00000181467), ERAS (ENSG00000187682), NKIRAS1 (ENSG00000197885), RASL10B (ENSG00000270885)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:97376) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 59 distinct phenotype terms.

Mouse phenotype (MP)	Records
enlarged spleen	2
premature death	2
abnormal definitive hematopoiesis	2
preweaning lethality, complete penetrance	2
abnormal leukocyte cell number	1
increased leukocyte cell number	1
increased neutrophil cell number	1
increased monocyte cell number	1
decreased monocyte cell number	1
abnormal heart morphology	1
abnormal heart development	1
thin ventricular wall	1
double outlet right ventricle	1
increased granulocyte number	1
abnormal cranium morphology	1
small liver	1
pale liver	1
abnormal thymus morphology	1
tremors	1
hyperpigmentation	1
decreased body weight	1
weight loss	1
impaired coordination	1
abnormal gait	1
increased circulating HDL cholesterol level	1

+34 more (showing top 25).

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Pan troglodytes	A5A6J7	100.0%	Diamond
Coprinopsis cinerea okayama7#130	A8NU18	100.0%	Diamond
Drosophila ananassae	B3M185	100.0%	Diamond
Drosophila erecta	B3NZR4	100.0%	Diamond
Drosophila persimilis	B4GFJ8	100.0%	Diamond
Drosophila sechellia	B4HKC7	100.0%	Diamond
Drosophila yakuba	B4PUP5	100.0%	Diamond
Crocodylus siamensis	C0HM48	100.0%	Diamond
Gallus gallus	P08642	100.0%	Diamond
Drosophila melanogaster	P08646	100.0%	Diamond
Cryptococcus deneoformans JEC21	P0CQ42	100.0%	Diamond
Cryptococcus deneoformans B-3501A	P0CQ43	100.0%	Diamond
Candida albicans	P0CY32	100.0%	Diamond
Bos taurus	P61223	100.0%	Diamond
Saguinus oedipus	P63320	100.0%	Diamond
Drosophila simulans	P83831	100.0%	Diamond
Drosophila mauritiana	P83832	100.0%	Diamond
Coprinopsis cinerea	Q05058	100.0%	Diamond
Sus scrofa	Q06AU2	100.0%	Diamond
Drosophila pseudoobscura pseudoobscura	Q295X7	100.0%	Diamond
Macaca fascicularis	Q4R9D4	100.0%	Diamond
Candida albicans SC5314	Q59XU5	100.0%	Diamond
Pongo abelii	Q5R4B8	100.0%	Diamond
Mesocricetus auratus	Q60529	100.0%	Diamond
Xenopus tropicalis	Q640R7	100.0%	Diamond
Xenopus laevis	Q7ZXH7	100.0%	Diamond
Drosophila grimshawi	B4JFU8	99.5%	Diamond
Drosophila virilis	B4LY29	99.5%	Diamond
Cavia porcellus	P12825	99.5%	Diamond
Candida albicans WO-1	C4YKT4	99.0%	Diamond
Oryzias latipes	O42277	99.0%	Diamond
Carassius auratus	P05774	99.0%	Diamond
Meleagris gallopavo	P79800	99.0%	Diamond
Monodelphis domestica	Q07983	99.0%	Diamond
Kryptolebias marmoratus	Q5EFX7	99.0%	Diamond
Cyprinus carpio	Q9YH38	99.0%	Diamond
Drosophila willistoni	B4NJ72	97.9%	Diamond
NS.C58 murine sarcoma virus	P23175	99.5%	Diamond
Moloney murine sarcoma virus	P01113	99.0%	Diamond
Rasheed rat sarcoma virus	P01114	99.0%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
CSDE1	protein-coding	7812
SIKE1	protein-coding	80143
AMPD1	protein-coding	270
SYCP1	protein-coding	6847
DENND2C	protein-coding	163259

Protein

Protein identifiers

GTPase NRas — P01111 (reviewed: P01111)

Alternative names: Transforming protein N-Ras

All UniProt accessions (2): P01111, Q5U091

UniProt curated annotations — full annotation on UniProt →

Function. Signal transducer in the Ras-MAPK signaling pathway that regulates cell proliferation and survival. Ras proteins bind GDP/GTP and possess intrinsic GTPase activity. Recognized by LZTR1 that mediates its ubiquitination by a BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex.

Subunit / interactions. Interacts (active GTP-bound form preferentially) with RGS14. Interacts (active GTP-bound form) with RASSF7. Interacts (active GTP-bound form) with both SHOC2 and PP1c (all isoforms) to form a tertiary complex; SHOC2 and PP1c preferably bind M-Ras/MRAS, but they also bind K-Ras/KRAS, N-Ras/NRAS and H-Ras/HRAS. Interacts (GDP-bound form) with LZTR1; this interaction mediates NRAS ubiquitination by BCR E3 ligase complex.

Subcellular location. Cell membrane. Golgi apparatus membrane.

Post-translational modifications. Palmitoylated by the ZDHHC9-GOLGA7 complex. Depalmitoylated by ABHD17A, ABHD17B and ABHD17C. A continuous cycle of de- and re-palmitoylation regulates rapid exchange between plasma membrane and Golgi. Acetylation at Lys-104 prevents interaction with guanine nucleotide exchange factors (GEFs). Fatty-acylated at Lys-169 and/or Lys-170. Ubiquitinated by the BCR(LZTR1) E3 ubiquitin ligase complex at Lys-170 in a non-degradative manner, leading to inhibit Ras signaling by decreasing Ras association with membranes. Phosphorylation at Ser-89 enhances NRAS association with its downstream effectors. (Microbial infection) Glucosylated at Thr-35 by P.sordellii toxin TcsL.

Disease relevance. Leukemia, juvenile myelomonocytic (JMML) [MIM:607785] An aggressive pediatric myelodysplastic syndrome/myeloproliferative disorder characterized by malignant transformation in the hematopoietic stem cell compartment with proliferation of differentiated progeny. Patients have splenomegaly, enlarged lymph nodes, rashes, and hemorrhages. The disease is caused by variants affecting the gene represented in this entry. Noonan syndrome 6 (NS6) [MIM:613224] A form of Noonan syndrome, a disease characterized by short stature, facial dysmorphic features such as hypertelorism, a downward eyeslant and low-set posteriorly rotated ears, and a high incidence of congenital heart defects and hypertrophic cardiomyopathy. Other features can include a short neck with webbing or redundancy of skin, deafness, motor delay, variable intellectual deficits, multiple skeletal defects, cryptorchidism, and bleeding diathesis. Individuals with Noonan syndrome are at risk of juvenile myelomonocytic leukemia, a myeloproliferative disorder characterized by excessive production of myelomonocytic cells. The disease is caused by variants affecting the gene represented in this entry. RAS-associated autoimmune leukoproliferative disorder (RALD) [MIM:614470] A disorder of apoptosis, characterized by chronic accumulation of non-malignant lymphocytes, defective lymphocyte apoptosis, and an increased risk for the development of hematologic malignancies. The disease is caused by variants affecting the gene represented in this entry. Melanocytic nevus syndrome, congenital (CMNS) [MIM:137550] A syndrome characterized by congenital pigmentary skin lesions which can occur at any site and can cover most of the body surface. These lesions may or may not be hairy. Congenital melanocytic nevi are associated with neuromelanosis (the presence of melanin-producing cells within the brain parenchyma or leptomeninges). Less commonly they are associated with malignant melanoma in childhood, both in the skin and the central nervous system. CMNS patients also tend to have a characteristic facial appearance, including wide or prominent forehead, periorbital fullness, small short nose with narrow nasal bridge, round face, full cheeks, prominent premaxilla, and everted lower lip. The disease is caused by variants affecting the gene represented in this entry. Melanosis, neurocutaneous (NCMS) [MIM:249400] A rare congenital disease characterized by the presence of giant or multiple melanocytic nevi on the skin, foci of melanin-producing cells within the brain parenchyma, and infiltration of leptomeninges by abnormal melanin deposits. Neurologic abnormalities include seizures, hydrocephalus, arachnoid cysts, tumors, and syringomyelia. Some patients may develop malignant melanoma. The disease is caused by variants affecting the gene represented in this entry. Keratinocytic non-epidermolytic nevus (KNEN) [MIM:162900] Epidermal nevi of the common, non-organoid and non-epidermolytic type are benign skin lesions and may vary in their extent from a single (usually linear) lesion to widespread and systematized involvement. They may be present at birth or develop early during childhood. The disease is caused by variants affecting the gene represented in this entry. Thyroid cancer, non-medullary, 2 (NMTC2) [MIM:188470] A form of non-medullary thyroid cancer (NMTC), a cancer characterized by tumors originating from the thyroid follicular cells. NMTCs represent approximately 95% of all cases of thyroid cancer and are classified into papillary, follicular, Hurthle cell, and anaplastic neoplasms. Disease susceptibility is associated with variants affecting the gene represented in this entry.

Activity regulation. Alternates between an inactive form bound to GDP and an active form bound to GTP. Activated by a guanine nucleotide-exchange factor (GEF) and inactivated by a GTPase-activating protein (GAP).

Miscellaneous. Mutations which change AA 12, 13 or 61 activate the potential of Ras to transform cultured cells and are implicated in a variety of human tumors.

Similarity. Belongs to the small GTPase superfamily. Ras family.

RefSeq proteins (1): NP_002515* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001806	Small_GTPase	Family
IPR005225	Small_GTP-bd	Domain
IPR020849	Small_GTPase_Ras-type	Family
IPR027417	P-loop_NTPase	Homologous_superfamily

Pfam: PF00071

Catalyzed reactions (Rhea)

• GTP + H2O = GDP + phosphate + H(+) (RHEA:19669)

UniProt features (40 total): sequence variant 9, helix 7, strand 6, mutagenesis site 4, binding site 4, lipid moiety-binding region 2, chain 1, propeptide 1, glycosylation site 1, cross-link 1, region of interest 1, short sequence motif 1, turn 1, modified residue 1

Structure

Experimental structures (PDB)

showing 30 of 36 structures by resolution:

PDB	Title	Method	Resolution (Å)
9BG8	Tri-complex of Daraxonrasib (RMC-6236), NRAS Q61R, and CypA	X-RAY DIFFRACTION	1.2
24SR	Human NRAS WT (GDP-bound) in complex with macrocyclic peptide inhibitor AP6296	X-RAY DIFFRACTION	1.23
7F68	Crystal structure of N-ras S89D	X-RAY DIFFRACTION	1.24
9BG3	Tri-complex of Daraxonrasib (RMC-6236), NRAS Q61K, and CypA	X-RAY DIFFRACTION	1.33
6ZIO	CRYSTAL STRUCTURE OF NRAS (C118S) IN COMPLEX WITH GDP	X-RAY DIFFRACTION	1.55
9Y3W	Crystal structure of NRas-G12D in complex with GDP and compound 13	X-RAY DIFFRACTION	1.56
8TBI	Tricomplex of RMC-7977, NRAS WT, and CypA	X-RAY DIFFRACTION	1.59
9BG0	Tri-complex of Daraxonrasib (RMC-6236), NRAS WT, and CypA	X-RAY DIFFRACTION	1.64
3CON	Crystal structure of the human NRAS GTPase bound with GDP	X-RAY DIFFRACTION	1.65
6WGH	Crystal structure of GDP-bound NRAS with ten residues long internal tandem duplication in …	X-RAY DIFFRACTION	1.65
5UHV	wild-type NRas bound to GppNHp	X-RAY DIFFRACTION	1.67
9Y1Y	Crystal structure of NRas-G12D in complex with GDP and compound 7	X-RAY DIFFRACTION	1.7
9Y1X	Crystal structure of NRas-G12D in complex with GDP and IACS-56676	X-RAY DIFFRACTION	1.72
8VM2	Crystal Structure of NRAS Q61K bound to GTP	X-RAY DIFFRACTION	1.74
9BGD	Tri-complex of Daraxonrasib (RMC-6236), NRAS Q61L, and CypA	X-RAY DIFFRACTION	1.76
6ZIZ	CRYSTAL STRUCTURE OF NRAS Q61R IN COMPLEX WITH GTP AND COMPOUND 18	X-RAY DIFFRACTION	1.78
9Y0G	Crystal structure of NRas-G12D in complex with GDP and compound 1	X-RAY DIFFRACTION	1.8
7OW4	Crystal structure of HLA-A*11:01 in complex with KRAS G12D peptide (VVVGADGVGK)	X-RAY DIFFRACTION	1.81
9GLX	NRas-Q61R-GTP in complex with the peptide MPB3	X-RAY DIFFRACTION	1.85
6ULI	Molecular basis for tumor infiltrating TCR recognition of hotspot KRAS-G12D mutation	X-RAY DIFFRACTION	1.88
6ULK	Molecular basis for tumor infiltrating TCR recognition of hotspot KRAS-G12D mutation	X-RAY DIFFRACTION	1.9
6ZIR	CRYSTAL STRUCTURE OF NRAS (C118S) IN COMPLEX WITH GDP AND COMPOUND 18	X-RAY DIFFRACTION	1.9
9Y1Z	Crystal structure of NRas-G12D in complex with GDP and compound 5	X-RAY DIFFRACTION	1.92
9Y1W	Crystal structure of NRas-G12D in complex with GDP and compound 27	X-RAY DIFFRACTION	1.95
6E6H	NRAS G13D bound to GppNHp (N13GNP)	X-RAY DIFFRACTION	1.99
6ULN	Molecular basis for tumor infiltrating TCR recognition of hotspot KRAS-G12D mutation	X-RAY DIFFRACTION	2.01
9GLW	NRas-Q61R-GTP in complex with the peptide MPB2	X-RAY DIFFRACTION	2.1
7OW3	Crystal structure of HLA-A*11:01 in complex with KRAS peptide (VVVGAGGVGK)	X-RAY DIFFRACTION	2.46
7OW5	Crystal structure of a TCR in complex with HLA-A*11:01 bound to KRAS peptide (VVVGAGGVGK)	X-RAY DIFFRACTION	2.58
7OW6	Crystal structure of a TCR in complex with HLA-A*11:01 bound to KRAS G12D peptide …	X-RAY DIFFRACTION	2.64

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P01111-F1	92.56	0.81

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Hydrolases, Predicted intracellular proteins, RAS pathway related proteins, Cancer-related genes, Mutated cancer genes, Mutational cancer driver genes, Disease related genes, Potential drug targets, Human disease related genes, Congenital malformations, Congenital malformations of skin, Other congenital malformations, Primary immunodeficiency

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): plasma membrane; cytosol

Antibody reliability (HPA): IH uncertain · IF supported

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (4)

Position	Role
10–18	GTP
29–30	GTP
57–61	GTP
116–119	GTP

Post-translational modifications (4)

Type	Positions
S-farnesyl cysteine	186
Glycyl lysine isopeptide (lys-gly) (interchain with g-cter in ubiquitin)	170
Phosphoserine	89
S-palmitoyl cysteine	181

Glycosylation sites (1)

Type	Positions
(microbial infection) o-linked (glc) threonine	35

Mutagenesis-validated functional residues (4)

Position	Phenotype
89	abolished phosphorylation by stk19.
164	loss of gtp-binding activity.
169–170	in n-ras-2kr mutant; decreased fatty-acylation.
181	loss of plasma membrane localization.

Function

Pathways and Gene Ontology

Reactome pathways

56 curated (TAS) of 141; 37 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

showing 60 of 141 pathways:

ID	Pathway	Evidence
R-HSA-5637810	Constitutive Signaling by EGFRvIII ⚕	curated
R-HSA-1236382	Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants ⚕	curated
R-HSA-9634285	Constitutive Signaling by Overexpressed ERBB2 ⚕	curated
R-HSA-6802955	Paradoxical activation of RAF signaling by kinase inactive BRAF ⚕	curated
R-HSA-6802953	RAS signaling downstream of NF1 loss-of-function variants ⚕	curated
R-HSA-6802952	Signaling by BRAF and RAF1 fusions ⚕	curated
R-HSA-9665348	Signaling by ERBB2 ECD mutants ⚕	curated
R-HSA-9664565	Signaling by ERBB2 KD Mutants ⚕	curated
R-HSA-9665686	Signaling by ERBB2 TMD/JMD mutants ⚕	curated
R-HSA-5655302	Signaling by FGFR1 in disease ⚕	curated
R-HSA-5655253	Signaling by FGFR2 in disease ⚕	curated
R-HSA-5655332	Signaling by FGFR3 in disease ⚕	curated
R-HSA-5655291	Signaling by FGFR4 in disease ⚕	curated
R-HSA-9703648	Signaling by FLT3 ITD and TKD mutants ⚕	curated
R-HSA-9703465	Signaling by FLT3 fusion proteins ⚕	curated
R-HSA-9673770	Signaling by PDGFRA extracellular domain mutants ⚕	curated
R-HSA-9673767	Signaling by PDGFRA transmembrane, juxtamembrane and kinase domain mutants ⚕	curated
R-HSA-9656223	Signaling by RAF1 mutants ⚕	curated
R-HSA-9753510	Signaling by RAS GAP mutants ⚕	curated
R-HSA-9753512	Signaling by RAS GTPase mutants ⚕	curated
R-HSA-6802948	Signaling by high-kinase activity BRAF mutants ⚕	curated
R-HSA-6802946	Signaling by moderate kinase activity BRAF mutants ⚕	curated
R-HSA-9670439	Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants ⚕	curated
R-HSA-9649948	Signaling downstream of RAS mutants ⚕	curated
R-HSA-1169092	Activation of RAS in B cells	curated
R-HSA-5621575	CD209 (DC-SIGN) signaling	curated
R-HSA-2424491	DAP12 signaling	curated
R-HSA-186763	Downstream signal transduction	curated
R-HSA-2179392	EGFR Transactivation by Gastrin	curated
R-HSA-9634635	Estrogen-stimulated signaling through PRKCZ	curated
R-HSA-2871796	FCERI mediated MAPK activation	curated
R-HSA-9607240	FLT3 Signaling	curated
R-HSA-5654693	FRS-mediated FGFR1 signaling	curated
R-HSA-5654700	FRS-mediated FGFR2 signaling	curated
R-HSA-5654706	FRS-mediated FGFR3 signaling	curated
R-HSA-5654712	FRS-mediated FGFR4 signaling	curated
R-HSA-179812	GRB2 events in EGFR signaling	curated
R-HSA-5674135	MAP2K and MAPK activation	curated
R-HSA-8851805	MET activates RAS signaling	curated
R-HSA-375165	NCAM signaling for neurite out-growth	curated
R-HSA-5675221	Negative regulation of MAPK pathway	curated
R-HSA-6798695	Neutrophil degranulation	curated
R-HSA-8849471	PTK6 Regulates RHO GTPases, RAS GTPase and MAP kinases	curated
R-HSA-5673000	RAF activation	curated
R-HSA-5673001	RAF/MAP kinase cascade	curated
R-HSA-9648002	RAS processing	curated
R-HSA-5658442	Regulation of RAS by GAPs	curated
R-HSA-5654688	SHC-mediated cascade:FGFR1	curated
R-HSA-5654699	SHC-mediated cascade:FGFR2	curated
R-HSA-5654704	SHC-mediated cascade:FGFR3	curated
R-HSA-5654719	SHC-mediated cascade:FGFR4	curated
R-HSA-180336	SHC1 events in EGFR signaling	curated
R-HSA-1250347	SHC1 events in ERBB4 signaling	curated
R-HSA-1433557	Signaling by SCF-KIT	curated
R-HSA-210993	Tie2 Signaling	curated
R-HSA-5218921	VEGFR2 mediated cell proliferation	curated
R-HSA-1643685	Disease ⚕	—
R-HSA-5663202	Diseases of signal transduction by growth factor receptors and second messengers ⚕	—
R-HSA-9682385	FLT3 signaling in disease ⚕	—
R-HSA-6802957	Oncogenic MAPK signaling ⚕	—

MSigDB gene sets: 1022 (showing top): PID_SHP2_PATHWAY, RNGTGGGC_UNKNOWN, MODULE_97, RRAGTTGT_UNKNOWN, REACTOME_SIGNALING_BY_INSULIN_RECEPTOR, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, ACTACCT_MIR196A_MIR196B, REACTOME_INNATE_IMMUNE_SYSTEM, WWTAAGGC_UNKNOWN, HNF3ALPHA_Q6, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOCC_SECRETORY_GRANULE, HOFMANN_CELL_LYMPHOMA_UP

GO Biological Process (6): MAPK cascade (GO:0000165), positive regulation of endothelial cell proliferation (GO:0001938), Ras protein signal transduction (GO:0007265), positive regulation of cell population proliferation (GO:0008284), positive regulation of Ras protein signal transduction (GO:0046579), signal transduction (GO:0007165)

GO Molecular Function (7): GTPase activity (GO:0003924), G protein activity (GO:0003925), GTP binding (GO:0005525), protein-containing complex binding (GO:0044877), nucleotide binding (GO:0000166), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (8): Golgi membrane (GO:0000139), endoplasmic reticulum membrane (GO:0005789), Golgi apparatus (GO:0005794), cytosol (GO:0005829), plasma membrane (GO:0005886), membrane (GO:0016020), extracellular exosome (GO:0070062), tertiary granule membrane (GO:0070821)

Reactome top-level categories

18 top-level categories:

Category	Pathways
Signaling by ERBB2	2
Signaling by EGFR	2
IRS-mediated signalling	1
Downstream signaling events of B Cell Receptor (BCR)	1
Signaling by Ligand-Responsive EGFR Variants in Cancer	1
Signaling by ERBB4	1
Signaling by Receptor Tyrosine Kinases	1
Signalling to ERKs	1
Signalling to RAS	1
Signaling by PDGF	1
Cell surface interactions at the vascular wall	1
Gastrin-CREB signalling pathway via PKC and MAPK	1
DAP12 interactions	1
IGF1R signaling cascade	1
Fc epsilon receptor (FCERI) signaling	1
Axon guidance	1
CREB1 phosphorylation through NMDA receptor-mediated activation of RAS signaling	1
VEGFA-VEGFR2 Pathway	1

GO top-level categories

40 GO namespaces:

Category	Terms
binding	2
cytoplasm	2
cellular anatomical structure	2
intracellular signaling cassette	1
endothelial cell proliferation	1
regulation of endothelial cell proliferation	1
positive regulation of epithelial cell proliferation	1
small GTPase-mediated signal transduction	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
Ras protein signal transduction	1
regulation of Ras protein signal transduction	1
positive regulation of small GTPase mediated signal transduction	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
ribonucleoside triphosphate phosphatase activity	1
GTPase activity	1
molecular function regulator activity	1
guanyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
anion binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
catalytic activity	1
Golgi apparatus	1
bounding membrane of organelle	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
endomembrane system	1
intracellular membrane-bounded organelle	1
membrane	1
cell periphery	1
extracellular vesicle	1
secretory granule membrane	1
tertiary granule	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 8 of 21 annotations. The rest are phylogenetic / computational / electronic (IEA).

8 experimentally-supported GO terms:

GO term	NS	Evidence
Ras protein signal transduction	BP	direct assay
positive regulation of endothelial cell proliferation	BP	mutant phenotype
Golgi apparatus	CC	direct assay
extracellular exosome	CC	high-throughput assay
membrane	CC	high-throughput assay
plasma membrane	CC	direct assay
GTPase activity	MF	direct assay
protein-containing complex binding	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 4,752 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NRAS	BRAF	P15056	974
NRAS	PTPN11	Q06124	881
NRAS	EGFR	P00533	870
NRAS	NF1	P21359	870
NRAS	TP53	P04637	858
NRAS	ZDHHC9	Q9Y397	842
NRAS	PTEN	P60484	840
NRAS	ASXL1	Q8IXJ9	834
NRAS	SOS1	Q07889	821
NRAS	PIK3CA	P42336	800
NRAS	PAX8	Q06710	798
NRAS	KIT	P10721	798
NRAS	SHOC2	Q9UQ13	795
NRAS	MAP2K1	Q02750	791
NRAS	FLT3	P36888	777

IntAct

Human interaction partners of NRAS in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

showing 30 of 50 partners by confidence:

Partner	Interaction type	MIscore	Records
RAF1	physical association	0.930	9
BRAF	physical association	0.860	6
RIN1	physical association	0.840	9
RAP1GDS1	physical association	0.560	6
ARAF	physical association	0.560	3
PIK3R1	physical association	0.560	3
RGL3	physical association	0.560	3
FNTA	physical association	0.560	1
RGL2	association	0.550	2
AKT1	proximity	0.520	2
RADIL	physical association	0.500	1
ESYT2	proximity	0.480	1
EGFR	proximity	0.410	1
FMO3	physical association	0.400	1
GPR31	physical association	0.400	1
GRB10	physical association	0.400	1
GRB14	physical association	0.400	1
PAPOLA	physical association	0.400	1
PPP1CA	physical association	0.400	1
SHOC2	physical association	0.400	1
ALDOB	physical association	0.370	1
AOPEP	physical association	0.370	1
CCDC180	physical association	0.370	1
CORO2A	physical association	0.370	1
CYLC2	physical association	0.370	1
FANCC	physical association	0.370	1
FBP2	physical association	0.370	1
FRAT2	physical association	0.370	1
HEMGN	physical association	0.370	1
LEF1	physical association	0.370	1

BioGRID (920 interactions; top human partners by supporting records in a sample of 600 records): LZTR1 (Affinity Capture-MS; 8 records), BRAF (Affinity Capture-Western; 5 records), MTOR (Proximity Label-MS; 5 records), BSG (Proximity Label-MS; 4 records), MAPKAP1 (Co-localization; 4 records), RICTOR (Proximity Label-MS; 4 records), FLVCR1 (Proximity Label-MS; 3 records), GORASP2 (Proximity Label-MS; 3 records), ITGB1 (Proximity Label-MS; 3 records), LYN (Proximity Label-MS; 3 records), MPZL1 (Proximity Label-MS; 3 records), PVRL2 (Proximity Label-MS; 3 records), RAF1 (Synthetic Lethality; 3 records), SEMA4C (Proximity Label-MS; 3 records), SLC12A2 (Proximity Label-MS; 3 records)

SIGNOR signaling

showing 22 of 23 signaling interactions:

A	Effect	B	Mechanism
SOS1	“up-regulates activity”	NRAS	“guanine nucleotide exchange factor”
NRAS	up-regulates	GLI1
RASGEF1B	up-regulates	NRAS	binding
RASGEF1C	up-regulates	NRAS	binding
NRAS	up-regulates	ARAF	binding
NRAS	“up-regulates activity”	BRAF	binding
NRAS	“up-regulates activity”	PIK3CA	binding
NRAS	up-regulates	PIK3CB	binding
NRAS	up-regulates	PIK3CG	binding
NRAS	up-regulates	RAF1	relocalization
RAPGEF5	up-regulates	NRAS	“guanine nucleotide exchange factor”
RAPGEF6	up-regulates	NRAS	“guanine nucleotide exchange factor”
RASGEF1A	up-regulates	NRAS	binding
NRAS	“up-regulates activity”	PI3K	binding
AR	“down-regulates quantity by repression”	NRAS	“transcriptional regulation”
DAB2IP	“down-regulates activity”	NRAS	“gtpase-activating protein”
PTPN11	“up-regulates activity”	NRAS	dephosphorylation
GOLGA7	“up-regulates activity”	NRAS	palmitoylation
ZDHHC9	“up-regulates activity”	NRAS	palmitoylation
STK19	“up-regulates activity”	NRAS	phosphorylation
BCR-ABL	“up-regulates activity”	NRAS
MVD	“up-regulates quantity by stabilization”	NRAS

Protein complexes (CORUM) (1)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

1 complexes by size:

Complex	Subunits	Members
NRAS-PPP1CC-SHOC2 complex	3	NRAS, PPP1CC, SHOC2

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 50 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
RAF activation	5	42.0×	2e-05
RAF/MAP kinase cascade	7	10.7×	3e-04

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of peptidyl-serine phosphorylation	5	79.8×	2e-06
insulin receptor signaling pathway	5	23.1×	5e-04
MAPK cascade	5	16.0×	2e-03
intracellular signal transduction	8	6.3×	3e-03
negative regulation of apoptotic process	8	5.8×	4e-03

Disease & clinical

Cancer significance

From CIViC — curated cancer-variant interpretation:

Mutations in the RAS family of proteins have frequently been observed across cancer types. The amino acid positions G12, G13 and Q61 account for the overwhelming majority of these mutations. The isoforms, despite their raw similarity, also behave very differently when expressed in non-native tissue types, likely due to differences in the C-terminal hyper-variable regions. Mis-regulation of isoform expression has been shown to be a driving event in cancer, as well as missense mutations at the three hotspots previously mentioned. While highly recurrent in cancer, targeting these RAS mutants has also been very elusive, and has not yet become common practice in the clinic.

From intOGen — cancer-driver classification: activating (oncogene-like) across 22 cancer types — ALL, AML, ANGS, CHOL, CLLSLL, COAD, COADREAD, GBM, HCC, LGGNOS, LUAD, LUSC…(+10 more).

intOGen’s role is a computational inference from cohort mutation patterns and may diverge from the gene’s curated/literature role; read it alongside the evidence above.

Genetic variants

Variant evidence for NRAS: 346 ClinVar records (20 pathogenic / likely pathogenic); 15 ClinGen expert-panel interpretations; 14 CIViC cancer variants; 1 PharmGKB clinical annotation; 4 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

346 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	11
Likely pathogenic	9
Uncertain significance	157
Likely benign	92
Benign	18

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 20 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
177778	NM_002524.5(NRAS):c.34G>A (p.Gly12Ser)	Pathogenic	reviewed by expert panel	13
13903	NM_002524.5(NRAS):c.179G>A (p.Gly60Glu)	Pathogenic	reviewed by expert panel	11
13902	NM_002524.5(NRAS):c.149C>T (p.Thr50Ile)	Pathogenic	reviewed by expert panel	10
1070042	NM_002524.5(NRAS):c.173C>T (p.Thr58Ile)	Pathogenic	reviewed by expert panel	7
222971	NM_002524.5(NRAS):c.71T>A (p.Ile24Asn)	Likely pathogenic	reviewed by expert panel	3
13900	NM_002524.5(NRAS):c.182A>G (p.Gln61Arg)	Pathogenic	criteria provided, multiple submitters, no conflicts	22
40469	NM_002524.5(NRAS):c.34G>C (p.Gly12Arg)	Pathogenic	criteria provided, multiple submitters, no conflicts	7
40468	NM_002524.5(NRAS):c.34G>T (p.Gly12Cys)	Pathogenic	criteria provided, multiple submitters, no conflicts	6
561786	NM_002524.5(NRAS):c.178G>A (p.Gly60Arg)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
280409	NM_002524.5(NRAS):c.182A>C (p.Gln61Pro)	Pathogenic	criteria provided, single submitter	2
40472	NM_002524.5(NRAS):c.112-1_113dup	Pathogenic	criteria provided, single submitter	1
1320232	NM_002524.5(NRAS):c.449A>G (p.Gln150Arg)	Likely pathogenic	criteria provided, single submitter	1
1335888	NM_002524.5(NRAS):c.108A>G (p.Ile36Met)	Likely pathogenic	criteria provided, single submitter	1
2672090	NM_002524.5(NRAS):c.191_196dup (p.Ser65_Ala66insAspSer)	Likely pathogenic	criteria provided, single submitter	1
4799925	NM_002524.5(NRAS):c.149C>A (p.Thr50Asn)	Likely pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

Explore NRAS’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

ClinGen expert-panel interpretations (15)

Expert ACMG interpretations from RASopathy VCEP for Noonan syndrome; RASopathy — a higher-authority tier than individual ClinVar submissions.

Assertion	Variants
Pathogenic	4
Likely Pathogenic	1
Uncertain Significance	5
Likely Benign	3
Benign	2

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 36 predictions of 287):

Position(s)	Effect	Δscore	Sites
1:114708529–114708530	donor_loss	1.0000	5
1:114708655–114708657	acceptor_gain	1.0000	2
1:114709567–114709568	donor_loss	1.0000	4
1:114709729–114709730	acceptor_loss	1.0000	5
1:114713985	acceptor_gain	1.0000
1:114716048–114716049	donor_loss	1.0000	5
1:114716178–114716179	acceptor_loss	1.0000	6
1:114707948	donor_gain	0.9900
1:114708051–114708052	acceptor_loss	0.9900	6
1:114708566	donor_gain	0.9900

AlphaMissense

826 missense substitutions predicted likely pathogenic (of 1,251 scored), across 155 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M72	9	0.950	0.999
M67	9	0.943	0.999
D57	8	1.000	1.000
D38	8	0.999	1.000
D33	8	0.998	1.000
D119	8	0.998	0.999
D54	8	0.993	0.999
D69	8	0.992	0.999
N116	8	0.989	1.000
F28	8	0.986	1.000
F78	8	0.985	1.000
D47	8	0.984	0.998
F156	8	0.975	0.999
S17	8	0.948	1.000
D105	8	0.837	0.971
K16	7	0.997	1.000
F82	7	0.997	0.999
E37	7	0.994	0.999
R73	7	0.988	0.999
E63	7	0.986	0.998

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

5 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	3.94e-07
Kidney Chromophobe (TCGA)	unfavorable	1.11e-06
Liver Hepatocellular Carcinoma (TCGA)	unfavorable	1.92e-06
Liver Hepatocellular Carcinoma (validation)	unfavorable	0.000291
Lung Adenocarcinoma (TCGA)	unfavorable	0.000575

Disease associations

OMIM: gene MIM:164790 | disease phenotypes: MIM:114500, MIM:163950, MIM:613224, MIM:163200, MIM:601626, MIM:137550, MIM:162900, MIM:188470, MIM:249400, MIM:607785, MIM:614470, MIM:608232

GenCC curated gene-disease

5 curated gene-disease records:

Disease	Classification	Inheritance	Records
Noonan syndrome	Definitive	Autosomal dominant	2
Noonan syndrome 6	Definitive	Autosomal dominant	4
cardiofaciocutaneous syndrome	Strong	Autosomal dominant	2
Noonan syndrome with multiple lentigines	Limited	Autosomal dominant
Costello syndrome	Limited	Autosomal dominant

ClinGen Gene-Disease Validity

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

4 validity classifications:

Disease	Classification	Inheritance
Costello syndrome	Limited	AD
Noonan syndrome	Definitive	AD
cardiofaciocutaneous syndrome	Limited	AD
Noonan syndrome with multiple lentigines	Limited	AD

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (19 panels, 17 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

19 panels:

Panel	Rating
Adult solid tumours cancer susceptibility	green
Childhood solid tumours cancer susceptibility	green
DDG2P	green
Fetal anomalies	green
Fetal hydrops	green
Hypotonic infant	green
IUGR and IGF abnormalities	green
Intellectual disability	green
Leukodystrophy, childhood onset	green
Monogenic short stature	green
Mosaic skin disorders - Deep sequencing	green
Paediatric disorders	green
Paediatric or syndromic cardiomyopathy	green
Pigmentary skin disorders	green
Primary lymphoedema	green
RASopathies	green
Unexplained death in infancy and sudden unexplained death in childhood	green
COVID-19 research	amber
Primary immunodeficiency or monogenic inflammatory bowel disease	amber

Mondo (24): colorectal cancer (MONDO:0005575), Noonan syndrome 1 (MONDO:0008104), Noonan syndrome (MONDO:0018997), Noonan syndrome and Noonan-related syndrome (MONDO:0020297), RASopathy (MONDO:0021060), Noonan syndrome 6 (MONDO:0013186), colon carcinoma (MONDO:0002032), linear nevus sebaceous syndrome (MONDO:0008097), acute myeloid leukemia (MONDO:0018874), large congenital melanocytic nevus (MONDO:0044792), non-small cell lung carcinoma (MONDO:0005233), nevus, epidermal (MONDO:0008093), thyroid cancer, nonmedullary, 2 (MONDO:0008566), neurocutaneous melanocytosis (MONDO:0009578), vascular malformation (MONDO:0024291), juvenile myelomonocytic leukemia (MONDO:0011908), autoimmune lymphoproliferative syndrome type 4 (MONDO:0013767), acute megakaryoblastic leukemia in down syndrome (MONDO:0020526), pyogenic granuloma (MONDO:0022096), chronic myeloid leukemia (MONDO:0011996), anemia (MONDO:0002280), Noonan syndrome with multiple lentigines (MONDO:0007893), Costello syndrome (MONDO:0009026), cardiofaciocutaneous syndrome (MONDO:0015280)

Orphanet (14): RASopathy (Orphanet:536391), Noonan syndrome (Orphanet:648), Noonan syndrome and Noonan-related syndrome (Orphanet:98733), Linear nevus sebaceus syndrome (Orphanet:2612), Acute myeloid leukemia (Orphanet:519), Large/giant congenital melanocytic nevus (Orphanet:626), Neurocutaneous melanocytosis (Orphanet:2481), Woolly hair nevus (Orphanet:79414), RAS-associated autoimmune leukoproliferative disease (Orphanet:268114), Juvenile myelomonocytic leukemia (Orphanet:86834), Acute megakaryoblastic leukemia in children with Down syndrome (Orphanet:99887), Chronic myeloid leukemia (Orphanet:521), NON RARE IN EUROPE: Colorectal cancer (Orphanet:466667), NON RARE IN EUROPE: Non-small cell lung cancer (Orphanet:488201)

HPO phenotypes

showing 60 of 244 phenotypes (HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000028	Cryptorchidism
HP:0000044	Hypogonadotropic hypogonadism
HP:0000078	Abnormality of the genital system
HP:0000085	Horseshoe kidney
HP:0000155	Oral ulcer
HP:0000179	Thick lower lip vermilion
HP:0000194	Open mouth
HP:0000218	High palate
HP:0000232	Everted lower lip vermilion
HP:0000238	Hydrocephalus
HP:0000256	Macrocephaly
HP:0000267	Cranial asymmetry
HP:0000269	Prominent occiput
HP:0000286	Epicanthus
HP:0000293	Full cheeks
HP:0000311	Round face
HP:0000316	Hypertelorism
HP:0000324	Facial asymmetry
HP:0000325	Triangular face
HP:0000337	Broad forehead
HP:0000343	Long philtrum
HP:0000347	Micrognathia
HP:0000348	High forehead
HP:0000358	Posteriorly rotated ears
HP:0000365	Hearing impairment
HP:0000369	Low-set ears
HP:0000391	Thickened helices
HP:0000407	Sensorineural hearing impairment
HP:0000418	Narrow nasal ridge
HP:0000431	Wide nasal bridge
HP:0000455	Broad nasal tip
HP:0000463	Anteverted nares
HP:0000465	Webbed neck
HP:0000470	Short neck
HP:0000474	Thickened nuchal skin fold
HP:0000476	Cystic hygroma
HP:0000478	Abnormality of the eye
HP:0000483	Astigmatism
HP:0000486	Strabismus
HP:0000494	Downslanted palpebral fissures
HP:0000504	Abnormality of vision
HP:0000506	Telecanthus
HP:0000508	Ptosis
HP:0000520	Proptosis
HP:0000545	Myopia
HP:0000563	Keratoconus
HP:0000568	Microphthalmia
HP:0000589	Coloboma
HP:0000602	Ophthalmoplegia
HP:0000612	Iris coloboma
HP:0000629	Periorbital fullness
HP:0000635	Blue irides
HP:0000639	Nystagmus
HP:0000708	Atypical behavior
HP:0000750	Delayed speech and language development
HP:0000766	Abnormal sternum morphology
HP:0000767	Pectus excavatum
HP:0000768	Pectus carinatum
HP:0000826	Precocious puberty

GWAS associations

4 associations:

Study	Trait	p-value
GCST010988_246	Adult body size	7e-10
GCST002268_1	Autism	3e-8
GCST002268_10	Autism	4e-8
GCST002268_2	Autism	9e-8

MeSH disease descriptors

15 disease descriptors:

Descriptor	Name	Tree numbers
D000740	Anemia	C15.378.050
D002289	Carcinoma, Non-Small-Cell Lung	C04.588.894.797.520.109.220.249; C08.381.540.140.500; C08.785.520.100.220.500
D056685	Costello Syndrome	C05.660.207.219; C16.131.077.256; C16.320.188
D017789	Granuloma, Pyogenic	C23.550.382.937
D044542	LEOPARD Syndrome	C05.660.207.525; C14.240.400.695; C14.280.400.695; C14.280.484.716.525; C16.131.077.525; C16.131.240.400.685; C16.131.621.207.525; C17.800.621.430.530.550.525
D015470	Leukemia, Myeloid, Acute	C04.557.337.539.275; C15.378.508.539.275
D054429	Leukemia, Myelomonocytic, Juvenile	C04.557.337.539.525; C15.378.190.615.520; C15.378.508.539.525
D009634	Noonan Syndrome	C05.660.207.690; C14.240.400.787; C14.280.400.787; C16.131.240.400.784; C16.131.621.207.690; C17.300.690
D054079	Vascular Malformations	C14.240.850; C16.131.240.850
C535579	Cardiofaciocutaneous syndrome *(supp.)*
C580062	Epidermal Nevus *(supp.)*
C537387	Neurocutaneous melanosis *(supp.)*
C548084	Noonan Syndrome 6 *(supp.)*
C537846	Noonan like syndrome *(supp.)*
C572845	Thyroid cancer, follicular *(supp.)*

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (4): CHEMBL2079845 (SINGLE PROTEIN), CHEMBL4524006 (PROTEIN FAMILY), CHEMBL6193817 (PROTEIN-PROTEIN INTERACTION), CHEMBL6195563 (PROTEIN-PROTEIN INTERACTION)

Drugs acting on a complex or family that includes this protein

Curated ChEMBL mechanism-of-action drugs whose target is a protein complex or family of ≤10 members that includes NRAS — the drug acts on the assembly or class, not necessarily on this subunit alone.

1 drugs via a complex or family:

Drug	Target (ChEMBL)	Members	Max phase
SALIRASIB	RAS	3	2

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 341 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

1 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL279433	L-778123 FREE BASE	1	341

Clinical evidence (CIViC)

Drug × variant × indication, from 88 curated evidence items; also 10 prognostic, 2 diagnostic, 2 functional, 2 predisposing. CIViC evidence level: A (validated) → B (clinical) → C (case study) → D (preclinical) → E (inferential).

showing 30 of 76 predictive associations by evidence level:

Variant	Therapy	Indication	Effect	Level	CIViC
NRAS Mutation	Panitumumab + Cetuximab	Colorectal Cancer	Resistance	CIViC A	EID5344
NRAS Mutation	Binimetinib	Skin Melanoma	Sensitivity/Response	CIViC B	EID1472 +1
NRAS Q61K	Dactolisib	Colorectal Cancer	Sensitivity/Response	CIViC B	EID2194 +1
BRAF V600E OR NRAS Mutation OR HRAS Mutation OR KRAS Mutation OR NF1 Inactivating Mutation	Selumetinib	Cancer	Sensitivity/Response	CIViC B	EID11696
BRAF V600E OR NRAS Mutation OR HRAS Mutation OR KRAS Mutation OR NF1 Mutation	Selumetinib	Cancer	Sensitivity/Response	CIViC B	EID11681
NRAS Mutation	Binimetinib	Solid Tumor	Sensitivity/Response	CIViC B	EID11674
NRAS Mutation	Docetaxel + Trametinib	Skin Melanoma	Sensitivity/Response	CIViC B	EID1225
NRAS Mutation	Trametinib	Melanoma	Sensitivity/Response	CIViC B	EID1227
NRAS Mutation	Trametinib	Low-grade Serous Ovarian Carcinoma	Sensitivity/Response	CIViC B	EID13128
NRAS Mutation	Binimetinib + Ribociclib	Skin Melanoma	Sensitivity/Response	CIViC B	EID2931
NRAS Mutation	Belvarafenib	Melanoma	Sensitivity/Response	CIViC B	EID7452
NRAS Q61	Binimetinib	Skin Melanoma	Sensitivity/Response	CIViC B	EID1226
NRAS Q61H	Ipilimumab	Melanoma	Sensitivity/Response	CIViC B	EID7333
NRAS G12D	Cetuximab	Colorectal Cancer	Resistance	CIViC B	EID3693 +2
NRAS Q61K	Cetuximab	Colorectal Cancer	Resistance	CIViC B	EID3833 +1
BRAF V600E AND NRAS Mutation	Vemurafenib + Dabrafenib	Melanoma	Resistance	CIViC B	EID6263
NRAS Mutation	Cetuximab + Chemotherapy	Colorectal Cancer	Resistance	CIViC B	EID2210
NRAS Q179*	Cetuximab	Colorectal Cancer	Resistance	CIViC B	EID4785
NRAS Q61	Cetuximab	Colorectal Cancer	Resistance	CIViC B	EID124
NRAS Q61	Vemurafenib	Melanoma	Resistance	CIViC B	EID14
NRAS Q61	Cetuximab + Chemotherapy	Colorectal Cancer	Resistance	CIViC B	EID36
NRAS Q61K	Trametinib + Dabrafenib	Melanoma	Resistance	CIViC B	EID7678
NRAS G13D	Tanespimycin	Melanoma	Sensitivity/Response	CIViC C	EID21
NRAS G13R	Belvarafenib	Acral Lentiginous Melanoma	Sensitivity/Response	CIViC C	EID13214
NRAS Q61	Selumetinib	Skin Melanoma	Sensitivity/Response	CIViC C	EID1473
NRAS Q61K	Belvarafenib	Acral Lentiginous Melanoma	Sensitivity/Response	CIViC C	EID13218
NRAS Q61K	Trametinib	Ovary Serous Adenocarcinoma	Sensitivity/Response	CIViC C	EID8933
NRAS Q61L	Belvarafenib	Mucosal Melanoma	Sensitivity/Response	CIViC C	EID13215
NRAS Q61L	Temozolomide	Melanoma	Sensitivity/Response	CIViC C	EID22
NRAS Q61R	Belvarafenib	Melanoma	Sensitivity/Response	CIViC C	EID13220

CIViC column: a representative evidence item (EID); +N = additional CIViC items supporting the same association.

Clinical-actionability assertions (CIViC AMP/ASCO/CAP)

Curated AMP/ASCO/CAP tier assertions — the clinical-actionability classification (Tier I highest) for this gene’s variants, distilling the CIViC evidence above into a tiered call.

1 CIViC assertions:

Molecular profile	Disease	Therapy	Type	AMP tier	Significance
NRAS Q61R	Cancer		Oncogenic		Oncogenic

CIViC curated variants (14)

Named clinical variants curated in CIViC for this gene (the catalogue beneath the predictive evidence above):

Q179* (stop gained), Mutation (gain of function variant,transcript variant), Q61K (missense variant), Gain, G12/G13 (protein altering variant), G12D (missense variant), Q61H (missense variant), G13R (missense variant), G12C (missense variant), G12 (missense variant), G13D (missense variant), Q61 (missense variant), Q61L (missense variant), Q61R (missense variant).

PharmGKB: 1 entry (CPIC guideline: no)

PharmGKB clinical annotations

1 annotations by evidence level (1 strongest → 4):

Variant	Association	Level	Drugs	Phenotypes
rs1065634	Efficacy	3	carboplatin;cisplatin;gemcitabine	Non-Small Cell Lung Carcinoma

PharmGKB variants

1 variants:

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1065634	CSDE1, NRAS	3	2.75	1	carboplatin;cisplatin;gemcitabine

PharmGKB variant annotations

Per-publication pharmacogenomic findings for this gene (significant associations).

1 published findings:

Variant	Drug(s)	Category	Finding	PMID
rs1065634	carboplatin, cisplatin, gemcitabine	Efficacy	Genotype CT is associated with decreased overall survival due to carboplatin, cisplatin or gemcitabine in people with Carcinoma, Non-Small-Cell Lung as compared to genotype TT.	PMID:21636554

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — RAS subfamily

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
lonafarnib	Inhibition	8.55	pIC50

Binding affinities (BindingDB)

1108 measured of 1299 human assays (1375 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
4-{5-[4-(3-Chloro-phenyl)-3-oxo-piperazin-1-ylmethyl]-imidazol-1-ylmethyl}-benzonitrile	IC50	2 nM
NCGC 00371957	IC50	8 nM	US-11542261: Substituted Imidazo[1,2-a]-pyridines as IRAK 1/4 and FLT3 inhibitors
NCGC 00371480	IC50	15 nM	US-11542261: Substituted Imidazo[1,2-a]-pyridines as IRAK 1/4 and FLT3 inhibitors
NCGC00371485	IC50	15 nM	US-11542261: Substituted Imidazo[1,2-a]-pyridines as IRAK 1/4 and FLT3 inhibitors
NCGC 00371850	IC50	17 nM	US-11542261: Substituted Imidazo[1,2-a]-pyridines as IRAK 1/4 and FLT3 inhibitors
NCGC 00371483	IC50	20 nM	US-11542261: Substituted Imidazo[1,2-a]-pyridines as IRAK 1/4 and FLT3 inhibitors
(2S,3S)-1-acetyl-N-[(8S,14S)-22-ethyl-4-hydroxy-21-[2-[(1S)-1-methoxyethyl]-3-pyridinyl]-18,18-dimethyl-9,15-dioxo-16-oxa-10,22,28-triazapentacyclo[18.5.2.12,6.110,14.023,27]nonacosa-1(26),2,4,6(29),20,23(27),24-heptaen-8-yl]-3-methylpyrrolidine-2-carboxamide	IC50	23 nM	US-20250195521: USE OF SOS1 INHIBITORS TO TREAT MALIGNANCIES WITH SHP2 MUTATIONS
NCGC 00371484	IC50	30 nM	US-11542261: Substituted Imidazo[1,2-a]-pyridines as IRAK 1/4 and FLT3 inhibitors
NCGC 00249372	IC50	30 nM	US-11542261: Substituted Imidazo[1,2-a]-pyridines as IRAK 1/4 and FLT3 inhibitors
NCGC 00371859	IC50	33 nM	US-11542261: Substituted Imidazo[1,2-a]-pyridines as IRAK 1/4 and FLT3 inhibitors
US20250195521, Example A186	IC50	38 nM	US-20250195521: USE OF SOS1 INHIBITORS TO TREAT MALIGNANCIES WITH SHP2 MUTATIONS
NCGC 00371853	IC50	53 nM	US-11542261: Substituted Imidazo[1,2-a]-pyridines as IRAK 1/4 and FLT3 inhibitors
(3S)-N-[(2S)-1-[[(8S,14S)-22-ethyl-4-hydroxy-21-[2-(methoxymethyl)-3-pyridinyl]-18,18-dimethyl-9,15-dioxo-16-oxa-10,22,28-triazapentacyclo[18.5.2.12,6.110,14.023,27]nonacosa-1(26),2,4,6(29),20,23(27),24-heptaen-8-yl]amino]-3-methyl-1-oxobutan-2-yl]-N-methyl-1-prop-2-enoylpyrrolidine-3-carboxamide	IC50	55 nM	US-11566007: Ras inhibitors
(3S)-N-[(2S)-1-[[(8S,14S)-22-ethyl-4-hydroxy-21-[2-[(1S)-1-methoxyethyl]phenyl]-18,18-dimethyl-9,15-dioxo-16-oxa-10,22,28-triazapentacyclo[18.5.2.12,6.110,14.023,27]nonacosa-1(26),2,4,6(29),20,23(27),24-heptaen-8-yl]amino]-3-methyl-1-oxobutan-2-yl]-N-methyl-1-prop-2-enoylpyrrolidine-3-carboxamide	IC50	55 nM	US-11566007: Ras inhibitors
(3S)-1-[4-(dimethylamino)but-2-ynoyl]-N-[(2S)-1-[[(8S,14S)-22-ethyl-4-hydroxy-21-[2-(2-methoxyethyl)phenyl]-18,18-dimethyl-9,15-dioxo-16-oxa-10,22,28-triazapentacyclo[18.5.2.12,6.110,14.023,27]nonacosa-1(26),2,4,6(29),20,23(27),24-heptaen-8-yl]amino]-3-methyl-1-oxobutan-2-yl]-N-methylpyrrolidine-3-carboxamide	IC50	55 nM	US-11566007: Ras inhibitors
(3S)-1-[(E)-4-(dimethylamino)but-2-enoyl]-N-[(2S)-1-[[(8S,14S)-22-ethyl-4-hydroxy-21-[2-(methoxymethyl)-3-pyridinyl]-18,18-dimethyl-9,15-dioxo-16-oxa-10,22,28-triazapentacyclo[18.5.2.12,6.110,14.023,27]nonacosa-1(26),2,4,6(29),20,23(27),24-heptaen-8-yl]amino]-3-methyl-1-oxobutan-2-yl]-N-methylpyrrolidine-3-carboxamide	IC50	55 nM	US-11566007: Ras inhibitors
(3S)-N-[(2S)-1-[[(8S,14S)-22-ethyl-4-hydroxy-21-[2-(methoxymethyl)cyclohexen-1-yl]-18,18-dimethyl-9,15-dioxo-16-oxa-10,22,28-triazapentacyclo[18.5.2.12,6.110,14.023,27]nonacosa-1(26),2,4,6(29),20,23(27),24-heptaen-8-yl]amino]-3-methyl-1-oxobutan-2-yl]-N-methyl-1-prop-2-enoylpyrrolidine-3-carboxamide	IC50	55 nM	US-11566007: Ras inhibitors
(3S)-1-ethenylsulfonyl-N-[(2S)-1-[[(8S,14S)-22-ethyl-4-hydroxy-21-[2-(methoxymethyl)-3-pyridinyl]-18,18-dimethyl-9,15-dioxo-16-oxa-10,22,28-triazapentacyclo[18.5.2.12,6.110,14.023,27]nonacosa-1(26),2,4,6(29),20,23(27),24-heptaen-8-yl]amino]-3-methyl-1-oxobutan-2-yl]-N-methylpyrrolidine-3-carboxamide	IC50	55 nM	US-11566007: Ras inhibitors
(3S)-N-[(2S)-1-[[(8S,14S)-22-(2-cyanopropan-2-yl)-4-hydroxy-18,18-dimethyl-9,15-dioxo-21-pyridin-3-yl-16-oxa-10,22,28-triazapentacyclo[18.5.2.12,6.110,14.023,27]nonacosa-1(26),2,4,6(29),20,23(27),24-heptaen-8-yl]amino]-3-methyl-1-oxobutan-2-yl]-N-methyl-1-prop-2-enoylpyrrolidine-3-carboxamide	IC50	55 nM	US-11566007: Ras inhibitors
(3S)-N-[(2S)-1-[[(8S,14S)-22-ethyl-4-hydroxy-21-[4-[(1S)-1-methoxyethyl]-3-pyridinyl]-18,18-dimethyl-9,15-dioxo-16-oxa-10,22,28-triazapentacyclo[18.5.2.12,6.110,14.023,27]nonacosa-1(26),2,4,6(29),20,23(27),24-heptaen-8-yl]amino]-3-methyl-1-oxobutan-2-yl]-N-methyl-1-prop-2-enoylpyrrolidine-3-carboxamide	IC50	55 nM	US-11566007: Ras inhibitors
(3S)-N-[(2S)-1-[[(8S,14S)-22-ethyl-4-hydroxy-18,18-dimethyl-21-(4-methyl-3-pyridinyl)-9,15-dioxo-16-oxa-10,22,28-triazapentacyclo[18.5.2.12,6.110,14.023,27]nonacosa-1(26),2,4,6(29),20,23(27),24-heptaen-8-yl]amino]-3-methyl-1-oxobutan-2-yl]-N-methyl-1-prop-2-enoylpyrrolidine-3-carboxamide	IC50	55 nM	US-11566007: Ras inhibitors
(3S)-N-[(2S)-1-[[(8S,14S)-22-ethyl-21-[5-fluoro-2-(methoxymethyl)-3-pyridinyl]-4-hydroxy-18,18-dimethyl-9,15-dioxo-16-oxa-10,22,28-triazapentacyclo[18.5.2.12,6.110,14.023,27]nonacosa-1(26),2,4,6(29),20,23(27),24-heptaen-8-yl]amino]-3-methyl-1-oxobutan-2-yl]-N-methyl-1-prop-2-enoylpyrrolidine-3-carboxamide	IC50	55 nM	US-11566007: Ras inhibitors
(3S)-N-[(2S)-1-[[(8S,14S)-22-ethyl-4-hydroxy-21-[5-(methoxymethyl)-3-pyridinyl]-18,18-dimethyl-9,15-dioxo-16-oxa-10,22,28-triazapentacyclo[18.5.2.12,6.110,14.023,27]nonacosa-1(26),2,4,6(29),20,23(27),24-heptaen-8-yl]amino]-3-methyl-1-oxobutan-2-yl]-N-methyl-1-prop-2-enoylpyrrolidine-3-carboxamide	IC50	55 nM	US-11566007: Ras inhibitors
(3S)-N-[(2S)-1-[[(8S,14S)-22-(2-cyanopropan-2-yl)-4-hydroxy-18,18-dimethyl-9,15-dioxo-21-pyridin-4-yl-16-oxa-10,22,28-triazapentacyclo[18.5.2.12,6.110,14.023,27]nonacosa-1(26),2,4,6(29),20,23(27),24-heptaen-8-yl]amino]-3-methyl-1-oxobutan-2-yl]-N-methyl-1-prop-2-enoylpyrrolidine-3-carboxamide	IC50	55 nM	US-11566007: Ras inhibitors
(3S)-1-[(E)-4-(dimethylamino)but-2-enoyl]-N-[(2S)-1-[[(8S,14S)-22-ethyl-4-hydroxy-21-[4-(methoxymethyl)-3-pyridinyl]-18,18-dimethyl-9,15-dioxo-16-oxa-10,22,28-triazapentacyclo[18.5.2.12,6.110,14.023,27]nonacosa-1(26),2,4,6(29),20,23(27),24-heptaen-8-yl]amino]-3-methyl-1-oxobutan-2-yl]-N-methylpyrrolidine-3-carboxamide	IC50	55 nM	US-11566007: Ras inhibitors
(3S)-N-[(2S)-1-[[(8S,14S)-21-[6-[(dimethylamino)methyl]-2-(methoxymethyl)-3-pyridinyl]-22-ethyl-4-hydroxy-18,18-dimethyl-9,15-dioxo-16-oxa-10,22,28-triazapentacyclo[18.5.2.12,6.110,14.023,27]nonacosa-1(26),2,4,6(29),20,23(27),24-heptaen-8-yl]amino]-3-methyl-1-oxobutan-2-yl]-N-methyl-1-prop-2-enoylpyrrolidine-3-carboxamide	IC50	55 nM	US-11566007: Ras inhibitors
(3S)-N-[(2S)-1-[[(8S,14S)-22-ethyl-4-hydroxy-21-[4-(3-methoxyazetidin-1-yl)-2-pyridinyl]-18,18-dimethyl-9,15-dioxo-16-oxa-10,22,28-triazapentacyclo[18.5.2.12,6.110,14.023,27]nonacosa-1(26),2,4,6(29),20,23(27),24-heptaen-8-yl]amino]-3-methyl-1-oxobutan-2-yl]-N-methyl-1-prop-2-enoylpyrrolidine-3-carboxamide	IC50	55 nM	US-11566007: Ras inhibitors
(3S)-N-[(2S)-1-[[(8S,14S)-21-[5-cyano-2-(methoxymethyl)-3-pyridinyl]-22-ethyl-4-hydroxy-18,18-dimethyl-9,15-dioxo-16-oxa-10,22,28-triazapentacyclo[18.5.2.12,6.110,14.023,27]nonacosa-1(26),2,4,6(29),20,23(27),24-heptaen-8-yl]amino]-3-methyl-1-oxobutan-2-yl]-N-methyl-1-prop-2-enoylpyrrolidine-3-carboxamide	IC50	55 nM	US-11566007: Ras inhibitors
(3S)-1-[4-(dimethylamino)but-2-ynoyl]-N-[(2S)-1-[[(8S,14S)-22-ethyl-21-[2-[(1S)-1-methoxyethyl]-3-pyridinyl]-18,18-dimethyl-9,15-dioxo-16-oxa-10,22,28-triazapentacyclo[18.5.2.12,6.110,14.023,27]nonacosa-1(26),2,4,6(29),20,23(27),24-heptaen-8-yl]amino]-3-methyl-1-oxobutan-2-yl]-N-methylpyrrolidine-3-carboxamide	IC50	55 nM	US-11566007: Ras inhibitors
(3S)-1-[4-(dimethylamino)but-2-ynoyl]-N-[(2S)-1-[[(8S,14S)-22-ethyl-4-hydroxy-21-[4-[(1S)-1-methoxyethyl]-3-pyridinyl]-18,18-dimethyl-9,15-dioxo-16-oxa-10,22,28-triazapentacyclo[18.5.2.12,6.110,14.023,27]nonacosa-1(26),2,4,6(29),20,23(27),24-heptaen-8-yl]amino]-3-methyl-1-oxobutan-2-yl]-N-methylpyrrolidine-3-carboxamide	IC50	55 nM	US-11566007: Ras inhibitors
5-[[(E)-4-(dimethylamino)but-2-enoyl]amino]-N-[(2R)-1-[[(8S,14S)-21-[2-[(dimethylamino)methyl]phenyl]-22-ethyl-4-hydroxy-18,18-dimethyl-9,15-dioxo-16-oxa-10,22,28-triazapentacyclo[18.5.2.12,6.110,14.023,27]nonacosa-1(26),2,4,6(29),20,23(27),24-heptaen-8-yl]amino]-3-methyl-1-oxobutan-2-yl]-N,1-dimethylimidazole-2-carboxamide	IC50	55 nM	US-11566007: Ras inhibitors
(3S)-N-[(2S)-1-[[(8S,14S)-21-[2-[(dimethylamino)methyl]-4-(methoxymethyl)phenyl]-22-ethyl-4-hydroxy-18,18-dimethyl-9,15-dioxo-16-oxa-10,22,28-triazapentacyclo[18.5.2.12,6.110,14.023,27]nonacosa-1(26),2,4,6(29),20,23(27),24-heptaen-8-yl]amino]-3-methyl-1-oxobutan-2-yl]-N-methyl-1-prop-2-enoylpyrrolidine-3-carboxamide	IC50	55 nM	US-11566007: Ras inhibitors
(3S)-N-[(2S)-1-[[(8S,14S)-21-[3-[(dimethylamino)methyl]-4-pyridinyl]-22-ethyl-4-hydroxy-18,18-dimethyl-9,15-dioxo-16-oxa-10,22,28-triazapentacyclo[18.5.2.12,6.110,14.023,27]nonacosa-1(26),2,4,6(29),20,23(27),24-heptaen-8-yl]amino]-3-methyl-1-oxobutan-2-yl]-N-methyl-1-prop-2-enoylpyrrolidine-3-carboxamide	IC50	55 nM	US-11566007: Ras inhibitors
(3S)-1-ethenylsulfonyl-N-[(2S)-1-[[(8S,14S)-22-ethyl-4-hydroxy-21-[2-[(1S)-1-methoxyethyl]-3-pyridinyl]-18,18-dimethyl-9,15-dioxo-16-oxa-10,22,28-triazapentacyclo[18.5.2.12,6.110,14.023,27]nonacosa-1(26),2,4,6(29),20,23(27),24-heptaen-8-yl]amino]-3-methyl-1-oxobutan-2-yl]-N-methylpyrrolidine-3-carboxamide	IC50	55 nM	US-11566007: Ras inhibitors
(3S)-N-[(1S)-1-cyclopentyl-2-[[(8S,14S)-22-ethyl-21-[4-[(1S)-1-methoxyethyl]-3-pyridinyl]-18,18-dimethyl-9,15-dioxo-16-oxa-10,22,28-triazapentacyclo[18.5.2.12,6.110,14.023,27]nonacosa-1(26),2,4,6(29),20,23(27),24-heptaen-8-yl]amino]-2-oxoethyl]-1-[4-(dimethylamino)but-2-ynoyl]-N-methylpyrrolidine-3-carboxamide	IC50	55 nM	US-11566007: Ras inhibitors
(3S)-N-[(2S)-1-[[(8S,14S)-22-ethyl-4-hydroxy-21-[2-(methoxymethyl)-3-pyridinyl]-18,18-dimethyl-9,15-dioxo-16-oxa-10,22,28-triazapentacyclo[18.5.2.12,6.110,14.023,27]nonacosa-1(26),2,4,6(29),20,23(27),24-heptaen-8-yl]amino]-3-methyl-1-oxobutan-2-yl]-N-methyl-1-[(E)-4-morpholin-4-ylbut-2-enoyl]pyrrolidine-3-carboxamide	IC50	55 nM	US-11566007: Ras inhibitors
(3S)-N-[(2S)-1-[[(8S,14S)-22-ethyl-4-hydroxy-21-[2-(methoxymethyl)-3-pyridinyl]-18,18-dimethyl-9,15-dioxo-16-oxa-10,22,28-triazapentacyclo[18.5.2.12,6.110,14.023,27]nonacosa-1(26),2,4,6(29),20,23(27),24-heptaen-8-yl]amino]-3-methyl-1-oxobutan-2-yl]-1-(4-methoxybut-2-ynoyl)-N-methylpyrrolidine-3-carboxamide	IC50	55 nM	US-11566007: Ras inhibitors
(3S)-1-[4-(dimethylamino)but-2-ynoyl]-N-[(2S)-1-[[(8S,14S)-22-ethyl-21-[2-(methoxymethyl)-3-pyridinyl]-18,18-dimethyl-9,15-dioxo-16-oxa-10,22,28-triazapentacyclo[18.5.2.12,6.110,14.023,27]nonacosa-1(26),2,4,6(29),20,23(27),24-heptaen-8-yl]amino]-3-methyl-1-oxobutan-2-yl]-N-methylpyrrolidine-3-carboxamide	IC50	55 nM	US-11566007: Ras inhibitors
(3S)-1-[4-(dimethylamino)but-2-ynoyl]-N-[(2S)-1-[[(8S,14S)-22-ethyl-21-[4-(methoxymethyl)-3-pyridinyl]-18,18-dimethyl-9,15-dioxo-16-oxa-4,10,22,28-tetrazapentacyclo[18.5.2.12,6.110,14.023,27]nonacosa-1(26),2,4,6(29),20,23(27),24-heptaen-8-yl]amino]-3-methyl-1-oxobutan-2-yl]-N-methylpyrrolidine-3-carboxamide	IC50	55 nM	US-11566007: Ras inhibitors
(3S)-1-[4-(dimethylamino)but-2-ynoyl]-N-[(2S)-1-[[(8S,14S)-22-ethyl-4-hydroxy-18,18-dimethyl-9,15-dioxo-21-pyridin-3-yl-16-oxa-10,22,28-triazapentacyclo[18.5.2.12,6.110,14.023,27]nonacosa-1(26),2,4,6(29),20,23(27),24-heptaen-8-yl]amino]-3-methyl-1-oxobutan-2-yl]-N-methylpyrrolidine-3-carboxamide	IC50	55 nM	US-11566007: Ras inhibitors
(3S)-N-[(2S)-1-[[(8S,14S)-21-[5-[(dimethylamino)methyl]-2-methoxy-3-pyridinyl]-22-ethyl-4-hydroxy-18,18-dimethyl-9,15-dioxo-16-oxa-10,22,28-triazapentacyclo[18.5.2.12,6.110,14.023,27]nonacosa-1(26),2,4,6(29),20,23(27),24-heptaen-8-yl]amino]-3-methyl-1-oxobutan-2-yl]-N-methyl-1-prop-2-enoylpyrrolidine-3-carboxamide	IC50	55 nM	US-11566007: Ras inhibitors
(3S)-N-[(2S)-1-[[(8S,14S)-22-ethyl-4-hydroxy-21-[4-[(1S)-1-methoxyethyl]-3-pyridinyl]-18,18-dimethyl-9,15-dioxo-16-oxa-10,22,28-triazapentacyclo[18.5.2.12,6.110,14.023,27]nonacosa-1(26),2,4,6(29),20,23(27),24-heptaen-8-yl]amino]-3-methyl-1-oxobutan-2-yl]-N-methyl-1-prop-2-ynoylpyrrolidine-3-carboxamide	IC50	55 nM	US-11566007: Ras inhibitors
(3S)-1-[4-(dimethylamino)but-2-ynoyl]-N-[(2S)-1-[[(8S,14S)-22-ethyl-18,18-dimethyl-9,15-dioxo-21-pyridin-3-yl-16-oxa-10,22,28-triazapentacyclo[18.5.2.12,6.110,14.023,27]nonacosa-1(26),2,4,6(29),20,23(27),24-heptaen-8-yl]amino]-3-methyl-1-oxobutan-2-yl]-N-methylpyrrolidine-3-carboxamide	IC50	55 nM	US-11566007: Ras inhibitors
(3S)-1-[2-(dimethylamino)-2-methylpropanoyl]-N-[(2S)-1-[[(8S,14S)-22-ethyl-4-hydroxy-21-[4-(methoxymethyl)-3-pyridinyl]-18,18-dimethyl-9,15-dioxo-16-oxa-10,22,28-triazapentacyclo[18.5.2.12,6.110,14.023,27]nonacosa-1(26),2,4,6(29),20,23(27),24-heptaen-8-yl]amino]-3-methyl-1-oxobutan-2-yl]-N-methylpyrrolidine-3-carboxamide	IC50	55 nM	US-11566007: Ras inhibitors
(3S)-N-[(2S)-1-[[(8S,14S)-22-ethyl-4-hydroxy-21-[3-[(1S)-1-methoxyethyl]-1-methylpyrazol-4-yl]-18,18-dimethyl-9,15-dioxo-16-oxa-10,22,28-triazapentacyclo[18.5.2.12,6.110,14.023,27]nonacosa-1(26),2,4,6(29),20,23(27),24-heptaen-8-yl]amino]-3-methyl-1-oxobutan-2-yl]-N-methyl-1-prop-2-enoylpyrrolidine-3-carboxamide	IC50	55 nM	US-11566007: Ras inhibitors
(3S)-1-[4-(dimethylamino)but-2-ynoyl]-N-[(2S)-1-[[(8S,14S)-22-ethyl-4-hydroxy-18,18-dimethyl-9,15-dioxo-21-(4-propan-2-ylpyrimidin-5-yl)-16-oxa-10,22,28-triazapentacyclo[18.5.2.12,6.110,14.023,27]nonacosa-1(26),2,4,6(29),20,23(27),24-heptaen-8-yl]amino]-3-methyl-1-oxobutan-2-yl]-N-methylpyrrolidine-3-carboxamide	IC50	55 nM	US-11566007: Ras inhibitors
(3S)-1-[4-(dimethylamino)but-2-ynoyl]-N-[(2S)-1-[[(8S,14S)-22-ethyl-21-[2-(methoxymethyl)-3-pyridinyl]-4,18,18-trimethyl-9,15-dioxo-16-oxa-10,22,28-triazapentacyclo[18.5.2.12,6.110,14.023,27]nonacosa-1(26),2,4,6(29),20,23(27),24-heptaen-8-yl]amino]-3-methyl-1-oxobutan-2-yl]-N-methylpyrrolidine-3-carboxamide	IC50	55 nM	US-11566007: Ras inhibitors
(3S,5R)-N-[(2S)-1-[[(8S,14S)-22-ethyl-4-hydroxy-21-[2-(methoxymethyl)-3-pyridinyl]-18,18-dimethyl-9,15-dioxo-16-oxa-10,22,28-triazapentacyclo[18.5.2.12,6.110,14.023,27]nonacosa-1(26),2,4,6(29),20,23(27),24-heptaen-8-yl]amino]-3-methyl-1-oxobutan-2-yl]-N,5-dimethyl-1-prop-2-enoylpyrrolidine-3-carboxamide	IC50	55 nM	US-11566007: Ras inhibitors
(1S)-3-[(Z)-4-(dimethylamino)but-2-enoyl]-N-[(2S)-1-[[(8S,14S)-22-ethyl-4-hydroxy-21-[2-(methoxymethyl)-3-pyridinyl]-18,18-dimethyl-9,15-dioxo-16-oxa-10,22,28-triazapentacyclo[18.5.2.12,6.110,14.023,27]nonacosa-1(26),2,4,6(29),20,23(27),24-heptaen-8-yl]amino]-3-methyl-1-oxobutan-2-yl]-N-methylcyclopentane-1-carboxamide	IC50	55 nM	US-11566007: Ras inhibitors
(3S,5R)-1-[4-(dimethylamino)but-2-ynoyl]-N-[(2R)-1-[[(8S,14S)-22-ethyl-4-hydroxy-21-[2-(methoxymethyl)-3-pyridinyl]-18,18-dimethyl-9,15-dioxo-16-oxa-10,22,28-triazapentacyclo[18.5.2.12,6.110,14.023,27]nonacosa-1(26),2,4,6(29),20,23(27),24-heptaen-8-yl]amino]-3-methyl-1-oxobutan-2-yl]-N,5-dimethylpyrrolidine-3-carboxamide	IC50	55 nM	US-11566007: Ras inhibitors

ChEMBL bioactivities

336 potent at pChembl≥5 of 359 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.52	Ki	0.3	nM	L-778123 FREE BASE
8.70	IC50	2	nM	CHEMBL6038112
7.26	IC50	55	nM	CHEMBL5863589
7.26	IC50	55	nM	CHEMBL5805515
7.26	IC50	55	nM	CHEMBL5750957
7.26	IC50	55	nM	CHEMBL5901194
7.26	IC50	55	nM	CHEMBL5906199
7.26	IC50	55	nM	CHEMBL5916613
7.26	IC50	55	nM	CHEMBL5792114
7.26	IC50	55	nM	CHEMBL6042397
7.26	IC50	55	nM	CHEMBL5935060
7.26	IC50	55	nM	CHEMBL5877158
7.26	IC50	55	nM	CHEMBL5946158
7.26	IC50	55	nM	CHEMBL5753950
7.26	IC50	55	nM	CHEMBL6056472
7.26	IC50	55	nM	CHEMBL6007436
7.26	IC50	55	nM	CHEMBL5750007
7.26	IC50	55	nM	CHEMBL5981374
7.26	IC50	55	nM	CHEMBL6018688
7.26	IC50	55	nM	CHEMBL6008925
7.26	IC50	55	nM	CHEMBL5828567
7.26	IC50	55	nM	CHEMBL5746155
7.26	IC50	55	nM	CHEMBL5990708
7.26	IC50	55	nM	CHEMBL6008715
7.26	IC50	55	nM	CHEMBL5824251
7.26	IC50	55	nM	CHEMBL6033993
7.26	IC50	55	nM	CHEMBL5831167
7.26	IC50	55	nM	CHEMBL5979311
7.26	IC50	55	nM	CHEMBL5936777
7.26	IC50	55	nM	CHEMBL6044428
7.26	IC50	55	nM	CHEMBL6023023
7.26	IC50	55	nM	CHEMBL6052700
7.26	IC50	55	nM	CHEMBL5867756
7.26	IC50	55	nM	CHEMBL6043630
7.26	IC50	55	nM	CHEMBL5856243
7.26	IC50	55	nM	CHEMBL5840072
7.26	IC50	55	nM	CHEMBL5841454
7.26	IC50	55	nM	CHEMBL5991616
7.26	IC50	55	nM	CHEMBL5757361
7.26	IC50	55	nM	CHEMBL5887007
7.26	IC50	55	nM	CHEMBL5966197
7.26	IC50	55	nM	CHEMBL5873051
7.26	IC50	55	nM	CHEMBL5895869
7.26	IC50	55	nM	CHEMBL5829698
7.26	IC50	55	nM	CHEMBL6037737
7.26	IC50	55	nM	CHEMBL6043222
7.26	IC50	55	nM	CHEMBL5784621
7.26	IC50	55	nM	CHEMBL5915901
7.26	IC50	55	nM	CHEMBL5835747
7.26	IC50	55	nM	CHEMBL5956737

PubChem BioAssay actives

2 with measured affinity, of 17 total; 2 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-[[5-[[4-(3-chlorophenyl)-3-oxopiperazin-1-yl]methyl]imidazol-1-yl]methyl]benzonitrile	1893893: Binding affinity to NRAS (unknown origin) assessed as inhibition constant	ki	0.0003	uM
4-(hydroxyamino)-N-(2-naphthalen-2-yloxyethyl)-N-[(2R,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]benzenesulfonamide	682552: Inhibition of N-Ras expressed in Escherichia coli using [3H]GDP and [3H]GTP assessed as inhibition of intrinsic nucleotide exchange by scintillation counting	ic50	0.5000	uM

CTD chemical–gene interactions

71 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, decreases methylation, affects expression	4
sodium arsenite	decreases expression, increases expression	2
Copper	affects binding, increases expression, decreases expression	2
Nickel	increases expression	2
Quercetin	decreases expression	2
Tobacco Smoke Pollution	increases expression	2
Particulate Matter	decreases expression, increases abundance, increases expression	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
ammonium 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)-propanoate	affects cotreatment, affects expression	1
moringin	affects cotreatment, decreases expression	1
BI-2852	affects binding	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
methylparaben	increases expression	1
perfluorooctanoic acid	affects expression, affects cotreatment	1
ochratoxin A	affects binding	1
hydroquinone	decreases expression	1
mitomycin C-DNA adduct	decreases expression	1
cyanoginosin LR	increases expression	1
10-decarbamoylmitomycin C	decreases expression	1
perfluorooctane sulfonic acid	affects expression, affects cotreatment	1
L 744832	decreases prenylation, increases reaction	1
deguelin	decreases expression	1
emamectin benzoate	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
GGTI 2147	decreases prenylation, increases reaction	1
perfluorobutanesulfonic acid	affects expression, affects cotreatment	1
asparanin A	decreases expression	1
AC 93253	decreases expression	1

ChEMBL screening assays

18 unique, capped per target: 18 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2089526	Binding	Inhibition of N-Ras expressed in Escherichia coli using [3H]GDP and [3H]GTP assessed as inhibition of intrinsic nucleotide exchange by scintillation counting	Ras inhibition via direct Ras binding–is there a path forward? — *Bioorg Med Chem Lett*

Cellosaurus cell lines

1,739 cell lines: 1,703 cancer cell line, 22 transformed cell line, 8 induced pluripotent stem cell, 4 spontaneously immortalized cell line, 2 undefined cell line type

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_0002	HL-60	Cancer cell line	Female
CVCL_0006	THP-1	Cancer cell line	Male
CVCL_0013	MOLT-4	Cancer cell line	Male
CVCL_0027	Hep-G2	Cancer cell line	Male
CVCL_0039	SK-MEL-30	Cancer cell line	Male
CVCL_0060	NCI-H1299	Cancer cell line	Male
CVCL_0069	SK-MEL-2	Cancer cell line	Male
CVCL_0092	NALM-6	Cancer cell line	Male
CVCL_0115	2fTGH	Cancer cell line	Male
CVCL_0195	C8166/45	Transformed cell line	Male

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

showing 60 of 323 trials:

NCT	Phase	Status	Title
NCT04586348	Phase 4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	Phase 4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT00114829	Phase 4	UNKNOWN	Preoperative Assessment of Colon Tumor
NCT00114842	Phase 4	COMPLETED	Magnetic Resonance (MR) Colonography With Fecal Tagging
NCT00114946	Phase 4	TERMINATED	A Study to Compare Two Avastin-Based Treatment Regimens for the Treatment of Metastatic Colorectal Cancer
NCT00122720	Phase 4	COMPLETED	The Effect of Darbepoetin Upon Rehabilitation for Colorectal Cancer Surgery
NCT00129870	Phase 4	TERMINATED	CONCEPT: Comparison of Oxaliplatin vs Conventional Methods With Calcium/Magnesium in First-Line Metastatic Colorectal Cancer
NCT00138060	Phase 4	COMPLETED	Toxicity/Benefit Ratio Optimization of Chemotherapy in Colorectal Cancer (CRC) Patients by Determination of Individual Genotypic Determinants
NCT00216424	Phase 4	TERMINATED	Capecitabine (Xeloda) and Radiation for Patients With Rectosigmoid Carcinoma
NCT00327093	Phase 4	TERMINATED	Elaboration of a Model for Predicting Efficacy of Monoclonal Antibodies (Cetuximab and Bevacizumab) in Patients With Colorectal Cancer and Liver Metastases
NCT00332943	Phase 4	COMPLETED	MR Colonography With Fecal Tagging. Barium vs. BariumFerumoxsil
NCT00441311	Phase 4	COMPLETED	Dissemination of Colorectal Cancer Screening to Primary Care Physicians
NCT00460837	Phase 4	WITHDRAWN	Comparison of Bowel Preparation in Virtual Colonoscopy (VC) - Patient Experience
NCT00473980	Phase 4	COMPLETED	Preoperative Non-steroidal Anti-inflammatory Drugs(NSAID) to Colorectal Cancer Patients
NCT00488904	Phase 4	COMPLETED	Omega-3 Fatty Acids and Postoperative Complications After Colorectal Surgery
NCT00496678	Phase 4	COMPLETED	Trial of Patient Navigation-Activation
NCT00502671	Phase 4	COMPLETED	A Study of Xeloda (Capecitabine) as Adjuvant Monotherapy in Patients With Colon Cancer.
NCT00559676	Phase 4	COMPLETED	Study of Biomarkers in Patients Undergoing Chemotherapy for Metastatic Colorectal Cancer
NCT00577031	Phase 4	COMPLETED	OBELIX Study: A Study of Avastin (Bevacizumab) in Combination With XELOX in Patients With Metastatic Cancer of the Colon or Rectum.
NCT00626054	Phase 4	COMPLETED	Comparison of Two Methods of Administration of a PEG Solution
NCT00812864	Phase 4	COMPLETED	Pharmacokinetic Study of Capecitabine in Elderly Cancer Patient (≥ 75 Years)
NCT00868569	Phase 4	UNKNOWN	Transhepatic Arterial Chemotherapy (TAC) Versus Transcatheter Arterial Chemoembolization (TACE) Plus Folfox4 as the Treatment of Unresectable Liver Metastasis of Colorectal Cancer
NCT00868816	Phase 4	COMPLETED	Oxaliplatine Based Adjuvant Chemotherapy for Stage II/III Colorectal Cancer: 8 Cycles Versus 12 Cycles
NCT00874406	Phase 4	UNKNOWN	Preoperative Transhepatic Arterial Chemotherapy (TAC) in the Treatment of Liver Metastasis of Resectable Colorectal Cancer
NCT00928928	Phase 4	COMPLETED	Oxidative Stress Markers in Open and Laparoscopic Colectomy for Cancer
NCT00942461	Phase 4	COMPLETED	Inflammatory Response in Laparoscopic and Open Colectomy
NCT01023633	Phase 4	UNKNOWN	OPTIMOX1 in Chinese mCRC Patients
NCT01271582	Phase 4	UNKNOWN	Investigation of Association Between UGT1A1 Polymorphisms and Irinotecan Toxicity in Korean Patients
NCT01315990	Phase 4	UNKNOWN	FOLFIRI in Combination With Cetuximab in the First-line Treatment of Metastatic Colorectal Cancer Including a Regular Dermal Prophylaxis to Prevent Acneiforme Follicular Exanthema
NCT01493713	Phase 4	COMPLETED	Correlation Between RECIST, Morphologic Response by CT- Histopathologic Response in Hepatic Metastasis Secondary to Colorectal Cancer
NCT01609660	Phase 4	COMPLETED	Impact of Probiotics on the Intestinal Microbiota
NCT01641458	Phase 4	COMPLETED	Pharmacology-driven Dosing of Fluoropyrimidines in Cancer Patients
NCT01689792	Phase 4	COMPLETED	A Multi-centre Study Comparing the Polyp Detection Rate of Two Different Types of Bowel Preparation: a 2-litre Solution (MOVIPREP®) Versus a Hyperosmotic and Stimulant Combined Low Volume Bowel Preparation (Sodium Picosulfate and Magnesium Citrate)
NCT01695772	Phase 4	COMPLETED	A Study of Bevacizumab Plus 5-Flurouracil (5-FU) Based Doublet Chemotherapy as Neoadjuvant Therapy for Participants With Previously Untreated Unresectable Liver-Only Metastases From Colorectal Cancer
NCT01695863	Phase 4	COMPLETED	Efficacy and Patient Satisfaction of Miralax and Gatorade Versus Movi Prep
NCT01706822	Phase 4	TERMINATED	Radial Reload Laparoscopic LAR Case Series
NCT01740947	Phase 4	TERMINATED	Does Administration of Antibiotics in Patients Undergoing Surgery for Colorectal Cancer Result in Less Complications and Better Prognosis?
NCT01831310	Phase 4	COMPLETED	Nutrition for Colorectal Cancer Patients and Neutrophil Functions
NCT01841294	Phase 4	UNKNOWN	NK Activity Modulation Induced by Intravenous Lidocaine During Colorectal Laparoscopic Surgery
NCT01959061	Phase 4	UNKNOWN	Efficacy and Safety of Raltitrexed-based Transarterial Chemoembolisation(TACE)for Colorectal Cancer Liver Metastases
NCT02032953	Phase 4	UNKNOWN	Enhancing the Anabolic Effect of Perioperative Nutrition With Insulin While Maintaining Normoglycemia
NCT02567331	Phase 4	COMPLETED	A Study of Capecitabine (Xeloda) in Patients With Metastatic Colorectal Cancer
NCT02575378	Phase 4	UNKNOWN	Maintenance Treatment With Capecitabine Metronomic Chemotherapy and Chinese Traditional Medicine in Metastatic Colorectal Cancer
NCT02581423	Phase 4	COMPLETED	A Study of Capecitabine (Xeloda) in the Adjuvant Treatment of Participants With Resected Colon Cancer
NCT02582970	Phase 4	COMPLETED	A Study of Bevacizumab (Avastin) in Combination With Chemotherapy in Participants With Metastatic Cancer of the Colon or Rectum
NCT03084809	Phase 4	COMPLETED	Chemotherapy Combined With CIK Treating Colon Cancer
NCT03130634	Phase 4	COMPLETED	The Efficacy of Silymarin as Adjuvant Therapy on Colorectal Cancer Patients Undergoing FOLFIRI Treatment
NCT03298945	Phase 4	COMPLETED	Comparative Effectiveness of Split-Dose Colonoscopy Bowel Preparation Regimens
NCT03465202	Phase 4	UNKNOWN	Association of Capecitabine Pharmacokinetics and Toxicity With Aging
NCT03564938	Phase 4	COMPLETED	Regorafenib in Indian Patients With Metastatic Colorectal Cancer (mCRC).
NCT03700411	Phase 4	COMPLETED	Influence of Opioid Analgesia on Circulating Tumor Cells in Open Colorectal Cancer Surgery
NCT03700541	Phase 4	COMPLETED	Influence of Opioid Analgesia on Circulating Tumor Cells in Laparoscopic Colorectal Cancer Surgery
NCT03723447	Phase 4	COMPLETED	Intraoperative TAP Block With Bupivacaine/Dexamethasone Against Liposomal Bupivacaine (Exparel®)
NCT04074460	Phase 4	COMPLETED	Volatile Anaesthesia and Perioperative Outcomes Related to Cancer Feasibility Study
NCT04281667	Phase 4	ACTIVE_NOT_RECRUITING	Mechanical Bowel Preparation and Oral Antibiotics Versus Mechanical Bowel Preparation Only Prior Rectal Surgery
NCT04297423	Phase 4	COMPLETED	Two Low Volume Regimens for Colorectal Cancer Screening Colonoscopy
NCT04874207	Phase 4	COMPLETED	Evaluation of Treatment PERSOnalization Based on Its Therapeutic Monitoring in Patients With Metastatic Colorectal Cancer Treated With REgorafenib
NCT04874883	Phase 4	UNKNOWN	Effect of the Use of Symbiotics in Patients With Colon Cancer
NCT04973007	Phase 4	TERMINATED	Comparison of Contrast Agents in Liver Magnetic Resonance (MR) for the Detection of Hepatic Metastases
NCT05661357	Phase 4	UNKNOWN	Disitamab Vedotin Combined With Fruquintinib for mCRC With HER2 Expression

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for NRAS across ~30M SureChEMBL compounds — explore on Sugi Predict.