HRAS

Summary

HRAS (HRas proto-oncogene, GTPase, HGNC:5173) is a protein-coding gene on chromosome 11p15.5, encoding GTPase HRas (P01112). Signal transducer in the Ras-MAPK signaling pathway that regulates cell proliferation and survival. In precision oncology, BRAF V600E OR NRAS Mutation OR HRAS Mutation OR KRAS Mutation OR NF1 Inactivating Mutation confers sensitivity to Selumetinib in Cancer (CIViC Level B); 8 further curated variant–drug associations are listed below.

This gene belongs to the Ras oncogene family, whose members are related to the transforming genes of mammalian sarcoma retroviruses. The products encoded by these genes function in signal transduction pathways. These proteins can bind GTP and GDP, and they have intrinsic GTPase activity. This protein undergoes a continuous cycle of de- and re-palmitoylation, which regulates its rapid exchange between the plasma membrane and the Golgi apparatus. Mutations in this gene cause Costello syndrome, a disease characterized by increased growth at the prenatal stage, growth deficiency at the postnatal stage, predisposition to tumor formation, cognitive disability, skin and musculoskeletal abnormalities, distinctive facial appearance and cardiovascular abnormalities. Defects in this gene are implicated in a variety of cancers, including bladder cancer, follicular thyroid cancer, and oral squamous cell carcinoma. Multiple transcript variants, which encode different isoforms, have been identified for this gene.

Source: NCBI Gene 3265 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Costello syndrome (Definitive, ClinGen) — +2 more curated relationships
• Clinical variants (ClinVar): 668 total — 21 pathogenic, 23 likely-pathogenic (top 5% of genes corpus-wide)
• Regional missense constraint (gnomAD): 1 of 4 regions constrained (≈7% of expected missense variation)
• GTEx eGene: eQTL in 46 tissues, sQTL in 13 (q < 0.05)
• Phenotypes (HPO): 210
• Drug target: yes — 1 via a complex or family; 4 molecules with ChEMBL bioactivity
• Precision-oncology evidence (CIViC): 9 curated variant–drug associations
• Cancer driver (intOGen): activating (oncogene-like) across 14 cancer types (inferred from mutation patterns)
• Dosage sensitivity (ClinGen): haploinsufficiency no evidence, triplosensitivity no evidence
• Constraint (gnomAD): pLI 0.02 (LoF-tolerant), LOEUF 0.89 (unconstrained)
• MANE Select transcript: NM_005343
• Interaction hub: 4,618 STRING partners (top 1% of genes corpus-wide)

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:5173
Approved symbol	HRAS
Name	HRas proto-oncogene, GTPase
Location	11p15.5
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000174775
Ensembl biotype	protein_coding
OMIM	190020
Entrez	3265

Gene structure

Transcript identifiers

Ensembl transcripts: 27 — 21 protein_coding, 4 nonsense_mediated_decay, 1 retained_intron, 1 protein_coding_CDS_not_defined

MANE Select: ENST00000311189 · MANE Plus Clinical: ENST00000417302

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2, TSL 2: 4, TSL 3: 3, TSL 5: 1

ENST00000311189, ENST00000417302, ENST00000397594, ENST00000397596, ENST00000451590, ENST00000462734, ENST00000468682, ENST00000479482, ENST00000482021, ENST00000493230, ENST00000879220, ENST00000879221, ENST00000879222, ENST00000879223, ENST00000879224, ENST00000932528, ENST00000932529, ENST00000932530, ENST00000932531, ENST00000932532, ENST00000979403, ENST00000979404, ENST00001041405, ENST00001041406, ENST00001061984, ENST00001142568, ENST00001142569

RefSeq mRNA: 4 — MANE Select: NM_005343 NM_001130442, NM_001318054, NM_005343, NM_176795

CCDS: CCDS7698, CCDS7699

Canonical transcript exons

ENST00000311189 — 6 exons

Exon	Start	End
ENSE00001503789	535416	535576
ENSE00001529354	532242	532522
ENSE00003561701	532631	532755
ENSE00003603244	533453	533612
ENSE00003921927	533766	533944
ENSE00004014247	534212	534375

Expression profiles

Bgee: expression breadth ubiquitous, 139 present calls, max score 99.01.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 27.6164 / max 180.9101, expressed in 1811 samples.

Highest expression (Bgee): skin of abdomen, skin of leg, zone of skin, lower esophagus mucosa, putamen.

Genetic regulation across tissues (GTEx eQTL / sQTL)

HRAS is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 46 tissues and its splicing (sQTL) in 13 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 59 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Artery Tibial	eqtl	2.2e-56	-0.28	11:534242:A:G
Nerve Tibial	eqtl	1.6e-40	-0.29	11:534242:A:G
Testis	eqtl	1.5e-36	+1.02	11:535026:C:T
Artery Aorta	eqtl	9.9e-33	-0.35	11:539646:G:T
Esophagus Muscularis	eqtl	1.1e-29	-0.28	11:534242:A:G
Thyroid	eqtl	1.7e-25	-0.31	11:545276:G:T
Lung	eqtl	6.0e-24	-0.30	11:539648:G:A
Adipose Subcutaneous	eqtl	1.2e-22	-0.22	11:531224:A:G
Brain Nucleus accumbens basal ganglia	eqtl	1.9e-22	-0.43	11:539058:C:T
Esophagus Gastroesophageal Junction	eqtl	6.8e-18	-0.24	11:534242:A:G
Brain Caudate basal ganglia	eqtl	7.1e-16	-0.37	11:531572:G:A
Muscle Skeletal	eqtl	1.4e-15	-0.17	11:547210:T:C
Heart Atrial Appendage	eqtl	7.6e-15	-0.27	11:545276:G:T
Brain Putamen basal ganglia	eqtl	1.4e-14	-0.40	11:540005:C:T
Colon Transverse	eqtl	3.5e-14	-0.27	11:539648:G:A
Brain Cortex	eqtl	5.4e-14	-0.51	11:521462:C:T
Cells Cultured fibroblasts	eqtl	1.3e-13	-0.12	11:555645:T:G
Brain Cerebellar Hemisphere	eqtl	1.6e-13	-0.19	11:531224:A:G
Colon Sigmoid	eqtl	3.7e-13	-0.20	11:534242:A:G
Brain Hypothalamus	eqtl	4.4e-13	-0.27	11:534242:A:G

FANTOM5 promoters

1 alternative TSS:

Promoter ID	TPM avg	Samples expressed
117775	27.6164	1811

Top tissues by expression

showing 100 of 139 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
skin of abdomen	UBERON:0001416	99.01	gold quality
skin of leg	UBERON:0001511	98.93	gold quality
zone of skin	UBERON:0000014	98.90	gold quality
lower esophagus mucosa	UBERON:0035834	98.90	gold quality
putamen	UBERON:0001874	98.55	gold quality
esophagus mucosa	UBERON:0002469	98.55	gold quality
caudate nucleus	UBERON:0001873	98.38	gold quality
nucleus accumbens	UBERON:0001882	98.28	gold quality
hypothalamus	UBERON:0001898	97.96	gold quality
temporal lobe	UBERON:0001871	97.86	gold quality
amygdala	UBERON:0001876	97.85	gold quality
right hemisphere of cerebellum	UBERON:0014890	97.84	gold quality
substantia nigra	UBERON:0002038	97.77	gold quality
Ammon’s horn	UBERON:0001954	97.73	gold quality
vagina	UBERON:0000996	97.72	gold quality
cerebellar hemisphere	UBERON:0002245	97.71	gold quality
anterior cingulate cortex	UBERON:0009835	97.71	gold quality
cerebellum	UBERON:0002037	97.67	gold quality
cerebellar cortex	UBERON:0002129	97.66	gold quality
right frontal lobe	UBERON:0002810	97.63	gold quality
prefrontal cortex	UBERON:0000451	97.61	gold quality
brain	UBERON:0000955	97.60	gold quality
frontal cortex	UBERON:0001870	97.54	gold quality
metanephros cortex	UBERON:0010533	97.49	gold quality
cerebral cortex	UBERON:0000956	97.45	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	97.42	gold quality
Brodmann (1909) area 9	UBERON:0013540	97.42	gold quality
mucosa of transverse colon	UBERON:0004991	97.38	gold quality
pituitary gland	UBERON:0000007	97.32	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	97.29	gold quality
adenohypophysis	UBERON:0002196	97.27	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	97.26	gold quality
esophagus	UBERON:0001043	97.22	gold quality
apex of heart	UBERON:0002098	96.94	gold quality
prostate gland	UBERON:0002367	96.83	gold quality
right uterine tube	UBERON:0001302	96.62	gold quality
primary visual cortex	UBERON:0002436	96.58	gold quality
tibial nerve	UBERON:0001323	96.39	gold quality
lower esophagus	UBERON:0013473	96.18	gold quality
lower esophagus muscularis layer	UBERON:0035833	96.18	gold quality
superior frontal gyrus	UBERON:0002661	96.09	gold quality
ectocervix	UBERON:0012249	96.09	gold quality
minor salivary gland	UBERON:0001830	96.06	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	95.86	gold quality
fundus of stomach	UBERON:0001160	95.73	gold quality
saliva-secreting gland	UBERON:0001044	95.72	gold quality
cortex of kidney	UBERON:0001225	95.68	gold quality
hindlimb stylopod muscle	UBERON:0004252	95.64	gold quality
left coronary artery	UBERON:0001626	95.62	gold quality
endocervix	UBERON:0000458	95.58	gold quality
right lung	UBERON:0002167	95.52	gold quality
body of stomach	UBERON:0001161	95.45	gold quality
spleen	UBERON:0002106	95.41	gold quality
right lobe of thyroid gland	UBERON:0001119	95.40	gold quality
cortical plate	UBERON:0005343	95.40	gold quality
heart left ventricle	UBERON:0002084	95.38	gold quality
left lobe of thyroid gland	UBERON:0001120	95.34	gold quality
transverse colon	UBERON:0001157	95.34	gold quality
upper lobe of left lung	UBERON:0008952	95.33	gold quality
muscle layer of sigmoid colon	UBERON:0035805	95.33	gold quality
right coronary artery	UBERON:0001625	95.27	gold quality
ascending aorta	UBERON:0001496	95.25	gold quality
thoracic aorta	UBERON:0001515	95.22	gold quality
granulocyte	CL:0000094	95.17	gold quality
body of uterus	UBERON:0009853	95.17	gold quality
popliteal artery	UBERON:0002250	95.15	gold quality
tibial artery	UBERON:0007610	95.14	gold quality
mammary gland	UBERON:0001911	94.92	gold quality
subcutaneous adipose tissue	UBERON:0002190	94.92	gold quality
thoracic mammary gland	UBERON:0005200	94.92	gold quality
small intestine Peyer’s patch	UBERON:0003454	94.87	gold quality
gastrocnemius	UBERON:0001388	94.82	gold quality
mucosa of stomach	UBERON:0001199	94.80	gold quality
descending thoracic aorta	UBERON:0002345	94.74	gold quality
anatomical system	UBERON:0000467	94.73	gold quality
material anatomical entity	UBERON:0000465	94.71	gold quality
multicellular organism	UBERON:0000468	94.71	gold quality
adipose tissue	UBERON:0001013	94.65	gold quality
thyroid gland	UBERON:0002046	94.65	gold quality
muscle of leg	UBERON:0001383	94.51	gold quality
muscle organ	UBERON:0001630	94.45	gold quality
omental fat pad	UBERON:0010414	94.43	gold quality
colon	UBERON:0001155	94.35	gold quality
heart	UBERON:0000948	94.28	gold quality
adult mammalian kidney	UBERON:0000082	94.27	gold quality
left uterine tube	UBERON:0001303	94.25	gold quality
right ovary	UBERON:0002118	94.25	gold quality
left ovary	UBERON:0002119	94.24	gold quality
stromal cell of endometrium	CL:0002255	94.23	gold quality
myometrium	UBERON:0001296	94.14	gold quality
right atrium auricular region	UBERON:0006631	94.13	gold quality
body of pancreas	UBERON:0001150	94.08	gold quality
uterine cervix	UBERON:0000002	94.01	gold quality
small intestine	UBERON:0002108	93.95	gold quality
ganglionic eminence	UBERON:0004023	93.64	gold quality
embryo	UBERON:0000922	93.63	gold quality
intestine	UBERON:0000160	93.56	gold quality
stomach	UBERON:0000945	93.52	gold quality
placenta	UBERON:0001987	93.40	gold quality
right lobe of liver	UBERON:0001114	93.24	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-7008	yes	87.33
E-ANND-3	yes	8.40

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 78 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Caudate putamen	tissue	301.4
Frontal cortex	tissue	187.2
Spinal cord	tissue	57.8
Corpus callosum	tissue	54.9
Medulla oblongata	tissue	51.6
Pons	tissue	51.1
Midbrain	tissue	50.5
Putamen	tissue	50.0
Thalamus	tissue	48.1
Superior colliculi	tissue	46.8
Cerebral cortex	tissue	44.5	medium
Motor cortex	tissue	44.5
Somatosensory cortex	tissue	44.2
Substantia nigra	tissue	42.8
Prefrontal cortex	tissue	39.5
Basal ganglia	tissue	39.2	not detected
Occipital cortex	tissue	39.1
Hippocampal formation	tissue	38.7
Entorhinal cortex	tissue	37.9
Hypothalamus	tissue	37.8
Retrosplenial cortex	tissue	37.6
Temporal cortex	tissue	37.3
Ventral forebrain	tissue	37.2
Vagina	tissue	36.7	not detected
Retrosplenial and cingulate cortex	tissue	36.6
Insular cortex	tissue	36.1
Pituitary gland	tissue	35.6
Locus coeruleus	tissue	34.8
Periaqueductal gray	tissue	34.8
Septum	tissue	34.4
Skeletal muscle	tissue	31.9	low
Amygdala	tissue	30.1
Hippocampus	tissue	29.0	not detected
Heart muscle	tissue	25.0	not detected
Nucleus accumbens	tissue	23.9
Tongue	tissue	23.4
Cerebellum	tissue	22.6	medium
Postcentral gyrus	tissue	19.5
Olfactory bulb	tissue	19.2
Skin 1	tissue	17.4	low
Choroid plexus	tissue	16.7
Esophagus	tissue	12.9	not detected
Parathyroid gland	tissue	11.9	medium
Adipose tissue	tissue	11.3	not detected
Urinary bladder	tissue	11.2	low
Epididymis	tissue	11.2	medium
Seminal vesicle	tissue	10.7	medium
Retina	tissue	9.2
Tonsil	tissue	9.0	low
Thymus	tissue	8.4
Placenta	tissue	8.0	not detected
Colon	tissue	7.9	high
Smooth muscle	tissue	7.8	not detected
Adrenal gland	tissue	7.8	not detected
Fallopian tube	tissue	7.6	medium
Breast	tissue	7.1	not detected
Ovary	tissue	6.8	not detected
Prostate	tissue	6.7	low
Rectum	tissue	6.2	high
Lung	tissue	5.7	not detected

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Ventral spinal cord (57.8), White matter (54.9), Dorsal spinal cord (47.9), Dorsal hippocampus (38.7), Ventral hippocampus (34.5).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, BTG2, ESR1, HNRNPAB, MAZ, PAX1, SP1, STAT3, TP53, ZHX2, ZNF362

miRNA regulators (miRDB)

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

23 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-4699-3P	99.71	70.15	3142
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-6513-5P	99.43	67.81	1071
HSA-MIR-4292	99.16	65.57	1767
HSA-MIR-6791-5P	99.16	65.92	1844
HSA-MIR-6734-3P	99.15	66.27	1627
HSA-MIR-6889-3P	98.84	67.35	1198
HSA-MIR-6529-3P	98.68	66.76	1020
HSA-MIR-1301-3P	98.64	68.27	1071
HSA-MIR-5047	98.64	68.62	1035
HSA-MIR-6868-3P	98.63	69.64	2259
HSA-MIR-4691-5P	98.41	66.77	1343
HSA-MIR-6792-3P	98.41	66.86	1359
HSA-MIR-4768-3P	98.16	66.02	2330
HSA-MIR-6502-3P	97.86	65.43	569
HSA-MIR-4660	97.79	67.44	1328
HSA-MIR-6728-5P	97.79	66.33	891
HSA-MIR-4693-5P	97.35	67.02	1234
HSA-MIR-1306-5P	97.11	64.04	755

Functional genomics

gnomAD constraint: pLI 0.0173, LOEUF 0.893, missense Z 1.46 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000311189 splits into 4 regions with different missense tolerance; 1 is missense-constrained (≈7% of the expected missense variation). Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
11:532,639–533,803	142 / 141.1	1.01	no
11:533,804–534,239	51 / 79.0	0.65	no
11:534,240–534,283	1 / 17.8	0.06	yes (p 6.9e-05)
11:534,284–534,322	10 / 18.0	0.56	no
ClinGen dosage: haploinsufficiency 0 (no evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• The Tg.AC (v-Ha-ras) transgenic mouse model provides a reporter phenotype of skin papillomas in response to either genotoxic or nongenotoxic carcinogens. (PMID:11695562)
• The Tg.Ac (v-Ha-ras) mouse model was not overly sensitive and possesses utility as an adjunct to the battery of toxicity studies used to establish carcinogenic risk. (PMID:11695563)
• immunohistochemical analysis reveals a protective effect of H-ras expression mediated via apoptosis in node-negative breast cancer patients (PMID:11788888)
• molecular dynamics simulations to show that Ras, a monomeric G protein, can generate mechanical force upon hydrolysis (PMID:11904419)
• Point mutations were identified in DNA from two of the 115 normal individuals. Both mutations resulted in an amino acid substitution at position 12 in H RAS. (PMID:11920220)
• H-Ras/mitogen-activated protein kinase pathway inhibits integrin-mediated adhesion and induces apoptosis in osteoblasts (PMID:11934900)
• H-Ras mutations at the binding site for the GTP nucleotide ring in a human multiple myeloma line leads to transformation and factor-independent cell growth (PMID:12569357)
• HRAS genes are biallelically expressed in multiple fetal and adult tissues both in humans and in mice (PMID:12589428)
• overexpression of PPARalpha or the c-Ha-ras transgene is not associated with the liver tumorigenesis induced by DEHP in rasH2 mice (PMID:12668284)
• steady-state structure of the switch I region of the protein in both the inactive GDP-bound conformation as in the active GTP-bound conformation. (PMID:12717016)
• Ha-ras mutations detected in HPV-induced cervical intraepithelial neoplasia grade II and invasive squamous cell carcinoma (PMID:12878090)
• Results demonstrate the close relationship between Ha-ras expression level and sensitization of 5-flurouracil (5-FU)-treated cells. (PMID:12915131)
• using fragments of the human c-Ha-ras gene containing 8-hydroxyguanine (8-OH-G) in codon 12, evidence for the highly complex biochemical events leading to activation of the oncogene (PMID:14576295)
• the human c-Ha-ras proto-oncogene product does not influence the androgen-dependence of prostate carcinogenesis due to the probasin-mediated SV40 T antigen. (PMID:14662018)
• Ras activates the MAP kinase cascade through simultaneous dual effector interactions: induction of Raf kinase activity and derepression of Raf-MEK complex formation (PMID:14724641)
• When mutated, causes hepatocarcinogenesis in transgenic mice. (PMID:14729607)
• complete loss of p53 is a prerequisite for collaborating with activated Ha-ras to promote bladder tumorigenesis (PMID:14737103)
• H-ras mutations have a role in malignant transformation of aerodigestive spindle cell carcinoma (PMID:14767509)
• a domain of Rap1 acts dominantly on COOH-terminal lipid modification of Ha-Ras, which has been considered to be essential and sufficient for the plasma membrane localization (PMID:15031297)
• Changes in flexibility upon protein-protein complex formation of H-Ras & the Ras-binding domain of C-Raf1 have been investigated using the molecular framework approach FIRST and molecular dynamics simulations of in total approximately 35 ns length. (PMID:15211515)
• ras gene alterations have a specific and early role in the development of follicular type of thyroid tumors in Taiwan. (PMID:15320975)
• Myc rescued cell growth inhibition induced by Ras (PMID:15528212)
• RAS appears to be a pejorative prognostic factor in terms of survival in NSCLC globally, in ADC and when it is studied by PCR. (PMID:15597105)
• No significant correlations were found between mutations in colorect cancer. (PMID:15638373)
• H-Ras-specific activation of Rac-MKK3/6-p38 pathway has a role in invasion and migration of breast epithelial cells (PMID:15677464)
• the mechanism of O2*-mediated Ras guanine nucleotide dissociation is similar to that of NO/O2-mediated Ras guanine nucleotide dissociation (PMID:15684418)
• Ras exists in (at least) two conformational states identifiable by nuclear magnetic resonance spectroscopy: state 2 represents the high-affinity binding state for effectors, while state 1 represents a weak binding state. (PMID:15697248)
• We found mutations in p53, K-ras, and BRAF genes in 35%, 30%, and 4% of tumors, respectively, and observed a minimal or no co-presence of these gene alterations. (PMID:15702478)
• RAS-MEK-ERK1/2 signaling pathway can sensitize cells to TRAIL-induced apoptosis by up-regulating DR4 and DR5 (PMID:15757891)
• reduced Ras activation in cells harbouring the Hepatitis C virus subgenomic replicon (PMID:15784896)
• K-ras mutations are found in plasma after colorectal tumor resection (PMID:15816642)
• the mechanism for Ras-mediated down-regulation of Par-4 is by promoter methylation (PMID:15831492)
• Ras isoforms have distinct and separate cellular and subcellular distribution that may persist even in the malignantly transformed state in pancreatic disease (PMID:15855817)
• In this study, we probe the cellular and molecular mechanisms of RAS-mediated transformation. (PMID:15940260)
• HRAS oncogene could play an important role in the development of cervical cancer, in addition to the presence of HPV, by reducing the G1 phase and accelerating the G1/S transition of infected cells (PMID:15950068)
• N-Ras(L61) transformed cells lack a G0-G1 arrest upon TGF-beta treatment due to absence of p27. (PMID:15963850)
• Ras activity regulates Fbw7-mediated cyclin E proteolysis; impaired cyclin E proteolysis is a mechanism through which Ras mutations promote tumorigenesis. (PMID:15980150)
• RIG1 exerts inhibitory effect at the level of Ras activation, which is independent of Ras subtype but dependent on membrane localization of RIG1. It may be mediated through downregulation of Ras levels and alteration of Ras subcellular distribution. (PMID:16005186)
• studies provide evidence for the existence of human-specific mechanisms that resist Ras/MEK/ERK-mediated transformation (PMID:16007212)
• in primary fibroblasts stabilization of Ras protein by ROS and ERK1/2 amplifies the response of the cells to growth factors and in systemic sclerosis represents a critical factor in the onset and progression of the disease (PMID:16081426)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	hrasb	ENSDARG00000005651
danio_rerio	hrasa	ENSDARG00000098497
mus_musculus	Hras	ENSMUSG00000025499
rattus_norvegicus	Hras	ENSRNOG00000016611
rattus_norvegicus	Hrasl1	ENSRNOG00000018301
drosophila_melanogaster	Ras85D	FBGN0003205
caenorhabditis_elegans		WBGENE00002335

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), DIRAS1 (ENSG00000176490), RAP2B (ENSG00000181467), ERAS (ENSG00000187682), NKIRAS1 (ENSG00000197885), NRAS (ENSG00000213281), RASL10B (ENSG00000270885)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:96224) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 63 distinct phenotype terms.

Mouse phenotype (MP)	Records
postnatal growth retardation	2
premature death	2
abnormal ameloblast morphology	2
abnormal enamel mineralization	2
short premaxilla	1
short maxilla	1
abnormal frontal bone morphology	1
abnormal tooth development	1
malocclusion	1
hypertension	1
abnormal heart morphology	1
heart right ventricle hypertrophy	1
abnormal cranium morphology	1
domed cranium	1
abnormal mammary gland development	1
mammary gland hyperplasia	1
abnormal branching of the mammary ductal tree	1
ataxia	1
abnormal suckling behavior	1
abnormal blood vessel morphology	1
edema	1
increased mammary adenocarcinoma incidence	1
hydrocephaly	1
increased papilloma incidence	1
increased skin papilloma incidence	1

+38 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
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
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
Harvey murine sarcoma virus	P01115	98.9%	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
LMNTD2	protein-coding	256329
ANO9	protein-coding	338440
RNH1	protein-coding	6050
LMNTD2-AS1	ncRNA	692247
RASSF7	protein-coding	8045
PTDSS2	protein-coding	81490
LRRC56	protein-coding	115399
SIGIRR	protein-coding	59307
MIR210HG	ncRNA	100506211
MIR210	ncRNA	406992

Protein

Protein identifiers

GTPase HRas — P01112 (reviewed: P01112)

Alternative names: H-Ras-1, Ha-Ras, Transforming protein p21, c-H-ras, p21ras

All UniProt accessions (5): A0A804HJ06, A0A804HKM6, A0A8C8MQR2, P01112, X5D945

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. In its GTP-bound form interacts with PLCE1. Interacts with TBC1D10C. Interacts with RGL3. Interacts with HSPD1. Found in a complex with at least BRAF, HRAS, MAP2K1, MAPK3 and RGS14. Interacts (active GTP-bound form) with RGS14 (via RBD 1 domain). Forms a signaling complex with RASGRP1 and DGKZ. Interacts with RASSF5. Interacts with PDE6D. Interacts with IKZF3. Interacts with RACK1. Interacts with PIK3CG; the interaction is required for membrane recruitment and beta-gamma G protein dimer-dependent activation of the PI3K gamma complex PIK3CG:PIK3R6. Interacts with RAPGEF2. 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 (GTP-bound form) with MAPKAP1/SIN1; inhibiting H-Ras/HRAS activity. Interacts (GDP-bound form) with LZTR1; this interaction mediates HRAS ubiquitination by BCR E3 ligase complex.

Subcellular location. Cell membrane. Golgi apparatus. Golgi apparatus membrane Nucleus. Cytoplasm. Perinuclear region.

Tissue specificity. Widely expressed.

Post-translational modifications. Palmitoylated by the ZDHHC9-GOLGA7 complex. A continuous cycle of de- and re-palmitoylation regulates rapid exchange between plasma membrane and Golgi. S-nitrosylated; critical for redox regulation. Important for stimulating guanine nucleotide exchange. No structural perturbation on nitrosylation. The covalent modification of cysteine by 15-deoxy-Delta12,14-prostaglandin-J2 is autocatalytic and reversible. It may occur as an alternative to other cysteine modifications, such as S-nitrosylation and S-palmitoylation. Acetylation at Lys-104 prevents interaction with guanine nucleotide exchange factors (GEFs). Fatty-acylated at 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. (Microbial infection) Glucosylated at Thr-35 by P.sordellii toxin TcsL. Monoglucosylation completely prevents the recognition of the downstream effector, blocking the GTPases in their inactive form, leading to inhibit Ras signaling.

Disease relevance. Costello syndrome (CSTLO) [MIM:218040] A rare condition characterized by prenatally increased growth, postnatal growth deficiency, intellectual disability, distinctive facial appearance, cardiovascular abnormalities (typically pulmonic stenosis, hypertrophic cardiomyopathy and/or atrial tachycardia), tumor predisposition, skin and musculoskeletal abnormalities. The disease is caused by variants affecting the gene represented in this entry. Congenital myopathy with excess of muscle spindles (CMEMS) [MIM:218040] Variant of Costello syndrome. 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. Mutations which change positions 12, 13 or 61 activate the potential of HRAS to transform cultured cells and are implicated in a variety of human tumors. Bladder cancer (BLC) [MIM:109800] A malignancy originating in tissues of the urinary bladder. It often presents with multiple tumors appearing at different times and at different sites in the bladder. Most bladder cancers are transitional cell carcinomas that begin in cells that normally make up the inner lining of the bladder. Other types of bladder cancer include squamous cell carcinoma (cancer that begins in thin, flat cells) and adenocarcinoma (cancer that begins in cells that make and release mucus and other fluids). Bladder cancer is a complex disorder with both genetic and environmental influences. Disease susceptibility is associated with variants affecting the gene represented in this entry. Schimmelpenning-Feuerstein-Mims syndrome (SFM) [MIM:163200] A disease characterized by sebaceous nevi, often on the face, associated with variable ipsilateral abnormalities of the central nervous system, ocular anomalies, and skeletal defects. Many oral manifestations have been reported, not only including hypoplastic and malformed teeth, and mucosal papillomatosis, but also ankyloglossia, hemihyperplastic tongue, intraoral nevus, giant cell granuloma, ameloblastoma, bone cysts, follicular cysts, oligodontia, and odontodysplasia. Sebaceous nevi follow the lines of Blaschko and these can continue as linear intraoral lesions, as in mucosal papillomatosis. The disease is caused by 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).

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

Isoforms (2)

UniProt ID	Names	Canonical?
P01112-1	1, H-Ras4A, p21	yes
P01112-2	2, H-RasIDX, p19

RefSeq proteins (4): NP_001123914, NP_001304983, NP_005334, NP_789765 (=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

Enzyme classification (BRENDA)

• EC 3.6.5.2 — small monomeric GTPase (BRENDA: 49 organisms, 138 substrates, 55 inhibitors, 5 Km, 1 kcat entries)

Substrate kinetics (BRENDA)

1 substrates with measured Km, best-characterized 1. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
GTP	—	0

Catalyzed reactions (Rhea)

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

UniProt features (82 total): mutagenesis site 22, sequence variant 19, strand 11, helix 6, binding site 5, modified residue 4, lipid moiety-binding region 4, chain 2, turn 2, initiator methionine 1, glycosylation site 1, cross-link 1, splice variant 1, propeptide 1, region of interest 1, short sequence motif 1

Structure

Experimental structures (PDB)

showing 30 of 256 structures by resolution:

PDB	Title	Method	Resolution (Å)
2CE2	CRYSTAL STRUCTURE ANALYSIS OF A FLUORESCENT FORM OF H-RAS P21 IN COMPLEX WITH GDP	X-RAY DIFFRACTION	1
2EVW	Crystal structure analysis of a fluorescent form of H-Ras p21 in complex with R-caged GTP	X-RAY DIFFRACTION	1.05
24SQ	Human HRAS WT (GDP-bound) in complex with macrocyclic peptide inhibitor AP6296	X-RAY DIFFRACTION	1.08
8TBG	Tricomplex of RMC-7977, HRAS WT, and CypA	X-RAY DIFFRACTION	1.2
2CLD	CRYSTAL STRUCTURE ANALYSIS OF A FLUORESCENT FORM OF H-RAS P21 IN COMPLEX WITH GDP (2)	X-RAY DIFFRACTION	1.22
2CL6	CRYSTAL STRUCTURE ANALYSIS OF A FLUORESCENT FORM OF H-RAS P21 IN COMPLEX WITH S-caged GTP	X-RAY DIFFRACTION	1.24
2CL7	CRYSTAL STRUCTURE ANALYSIS OF A FLUORESCENT FORM OF H-RAS P21 IN COMPLEX WITH GTP	X-RAY DIFFRACTION	1.25
5WDQ	H-Ras mutant L120A bound to GMP-PNP at 100K	X-RAY DIFFRACTION	1.25
1CTQ	STRUCTURE OF P21RAS IN COMPLEX WITH GPPNHP AT 100 K	X-RAY DIFFRACTION	1.26
2CLC	CRYSTAL STRUCTURE ANALYSIS OF A FLUORESCENT FORM OF H-RAS P21 IN COMPLEX WITH GTP (2)	X-RAY DIFFRACTION	1.3
3K8Y	Allosteric modulation of H-Ras GTPase	X-RAY DIFFRACTION	1.3
3OIW	H-RasG12V with allosteric switch in the “on” state	X-RAY DIFFRACTION	1.3
3TGP	Room temperature H-ras	X-RAY DIFFRACTION	1.31
4DLR	H-Ras PEG 400/Ca(OAc)2, ordered off	X-RAY DIFFRACTION	1.32
3OIU	H-RasQ61L with allosteric switch in the “on” state	X-RAY DIFFRACTION	1.32
8BWG	HRas (1-166) Y64 phosphorylation	X-RAY DIFFRACTION	1.32
2RGB	Crystal structure of H-RasQ61K-GppNHp	X-RAY DIFFRACTION	1.35
5P21	REFINED CRYSTAL STRUCTURE OF THE TRIPHOSPHATE CONFORMATION OF H-RAS P21 AT 1.35 ANGSTROMS …	X-RAY DIFFRACTION	1.35
5WDP	H-Ras mutant L120A bound to GMP-PNP at 277K	X-RAY DIFFRACTION	1.35
8CNJ	HRas(1-166) in complex with GDP and BeF3-	X-RAY DIFFRACTION	1.35
3I3S	Crystal Structure of H-Ras with Thr50 replaced by Isoleucine	X-RAY DIFFRACTION	1.36
2RGE	Crystal structure of H-Ras-GppNHp	X-RAY DIFFRACTION	1.4
3RS0	H-Ras soaked in neat cyclopentanol: one of 10 in MSCS set	X-RAY DIFFRACTION	1.4
9PU1	HRAS complex with UM0140401 compound	X-RAY DIFFRACTION	1.4
9PU8	HRAS complex with UM0140693 compound	X-RAY DIFFRACTION	1.4
5E95	Crystal Structure of Mb(NS1)/H-Ras Complex	X-RAY DIFFRACTION	1.4
3L8Z	H-Ras wildtype new crystal form	X-RAY DIFFRACTION	1.44
2RGG	Crystal structure of H-RasQ61I-GppNHp, trigonal crystal form	X-RAY DIFFRACTION	1.45
8CNN	BeF3 Phospho-HRas GSA complex	X-RAY DIFFRACTION	1.48
2QUZ	Crystal Structure of the activating H-RasK117R mutant in Costello Syndrome, bound to …	X-RAY DIFFRACTION	1.49

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P01112-F1	92.50	0.79

Antibody-complex structures (SAbDab)

2 antibodies co-crystallized with this protein: 2UZI, 2VH5

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Hydrolases, Predicted intracellular proteins, Plasma proteins, RAS pathway related proteins, Cancer-related genes, Candidate cancer biomarkers, 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

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): cytosol; basal body; nucleoplasm

Antibody reliability (HPA): IH supported · 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 (5)

Position	Role
145–147	GTP
13–18	GTP
29–35	GTP
59–60	GTP
116–119	GTP

Post-translational modifications (9)

Type	Positions
N-acetylmethionine	1
N-acetylthreonine	2
S-nitrosocysteine	118
Cysteine methyl ester	186
S-palmitoyl cysteine	181, 184
S-(15-deoxy-delta12,14-prostaglandin j2-9-yl)cysteine	184
S-farnesyl cysteine	186
Glycyl lysine isopeptide (lys-gly) (interchain with g-cter in ubiquitin)	170

Glycosylation sites (1)

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

Mutagenesis-validated functional residues (22)

Position	Phenotype
17	dominant negative. prevents plce1 egf-induced recruitment to plasma membrane. no effect on subcellular location of isoform 2.
26	loss of interaction with plce1; when associated with v-12.
29	no effect on interaction with plce1; when associated with v-12.
32	loss of interaction and recruitment to plasma membrane of plce1; when associated with v-12.
34	no effect on interaction with plce1; when associated with v-12.
35	loss of interaction with plce1; when associated with v-12.
37	no effect on interaction with plce1; when associated with v-12.
38	no effect on interaction with plce1; when associated with v-12.
39	no effect on interaction with plce1; when associated with v-12.
59	loss of gtpase activity and creation of an autophosphorylation site.
61	moderately increased transformation of cultured cell lines.
61	promotes interaction with shoc2 and pp1c.
61	strongly increased transformation of cultured cell lines.
83	gtp-binding activity reduced by factor of 30.
118	abolishes s-nitrosylation. no stimulation of guanine nucleotide exchange.
119	loss of gtp-binding activity.
144	gtp-binding activity reduced by factor of 25.
164–165	loss of gtp-binding activity.
167–185	in h-ras-3kr mutant; decreased fatty-acylation.
170	increased ras signaling due to impaired ubiquitination.
181	exclusively localized in golgi. non-specifically localized on all endomembranes; when associated with s-184.
184	loss of s-(15-deoxy-delta12,14-prostaglandin j2-9-yl)cysteine stimulation of ras-gtpase activity. mainly localized in golgi …

Function

Pathways and Gene Ontology

Reactome pathways

56 curated (TAS) of 142; 37 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

showing 60 of 142 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-3928662	EPHB-mediated forward signaling	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-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: 1170 (showing top): PID_BCR_5PATHWAY, PID_SHP2_PATHWAY, REACTOME_SIGNALING_BY_INSULIN_RECEPTOR, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_NEGATIVE_REGULATION_OF_NEURON_APOPTOTIC_PROCESS, GOBP_RESPONSE_TO_IONIZING_RADIATION, BIOCARTA_FMLP_PATHWAY, MODY_HIPPOCAMPUS_POSTNATAL, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_REGULATION_OF_WOUND_HEALING, BIOCARTA_MAL_PATHWAY, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_REGULATION_OF_NEURONAL_SYNAPTIC_PLASTICITY, KEGG_MAPK_SIGNALING_PATHWAY

GO Biological Process (31): MAPK cascade (GO:0000165), regulation of transcription by RNA polymerase II (GO:0006357), chemotaxis (GO:0006935), signal transduction (GO:0007165), cell surface receptor signaling pathway (GO:0007166), Ras protein signal transduction (GO:0007265), positive regulation of cell population proliferation (GO:0008284), negative regulation of cell population proliferation (GO:0008285), insulin receptor signaling pathway (GO:0008286), animal organ morphogenesis (GO:0009887), negative regulation of gene expression (GO:0010629), Schwann cell development (GO:0014044), positive regulation of cell migration (GO:0030335), regulation of actin cytoskeleton organization (GO:0032956), regulation of cell population proliferation (GO:0042127), myelination (GO:0042552), positive regulation of MAPK cascade (GO:0043410), positive regulation of transcription by RNA polymerase II (GO:0045944), positive regulation of JNK cascade (GO:0046330), positive regulation of Ras protein signal transduction (GO:0046579), positive regulation of epithelial cell proliferation (GO:0050679), regulation of cell cycle (GO:0051726), adipose tissue development (GO:0060612), positive regulation of ERK1 and ERK2 cascade (GO:0070374), cellular response to gamma radiation (GO:0071480), positive regulation of wound healing (GO:0090303), positive regulation of protein targeting to membrane (GO:0090314), cellular senescence (GO:0090398), regulation of neurotransmitter receptor localization to postsynaptic specialization membrane (GO:0098696), positive regulation of ruffle assembly (GO:1900029), positive regulation of miRNA metabolic process (GO:2000630)

GO Molecular Function (9): GTPase activity (GO:0003924), G protein activity (GO:0003925), GTP binding (GO:0005525), GDP binding (GO:0019003), protein-membrane adaptor activity (GO:0043495), phospholipase C activator activity (GO:0160185), nucleotide binding (GO:0000166), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (12): Golgi membrane (GO:0000139), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), endoplasmic reticulum membrane (GO:0005789), Golgi apparatus (GO:0005794), cytosol (GO:0005829), plasma membrane (GO:0005886), perinuclear region of cytoplasm (GO:0048471), glutamatergic synapse (GO:0098978), nucleus (GO:0005634), endomembrane system (GO:0012505), membrane (GO:0016020)

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
EPH-Ephrin signaling	1
CREB1 phosphorylation through NMDA receptor-mediated activation of RAS signaling	1

GO top-level categories

showing 60 of 72 GO namespaces:

Category	Terms
cellular anatomical structure	6
cell population proliferation	3
cytoplasm	3
transcription by RNA polymerase II	2
regulation of cellular process	2
regulation of cell population proliferation	2
guanyl ribonucleotide binding	2
anion binding	2
intracellular membrane-bounded organelle	2
intracellular signaling cassette	1
regulation of DNA-templated transcription	1
response to chemical	1
taxis	1
cell communication	1
cellular process	1
signaling	1
cellular response to stimulus	1
signal transduction	1
small GTPase-mediated signal transduction	1
positive regulation of cellular process	1
negative regulation of cellular process	1
cell surface receptor protein tyrosine kinase signaling pathway	1
cellular response to insulin stimulus	1
anatomical structure morphogenesis	1
animal organ development	1
gene expression	1
regulation of gene expression	1
negative regulation of macromolecule biosynthetic process	1
Schwann cell differentiation	1
glial cell development	1
cell migration	1
regulation of cell migration	1
positive regulation of cell motility	1
actin cytoskeleton organization	1
regulation of actin filament-based process	1
regulation of cytoskeleton organization	1
axon ensheathment	1
MAPK cascade	1
regulation of MAPK cascade	1
positive regulation of intracellular signal transduction	1
regulation of transcription by RNA polymerase II	1
positive regulation of DNA-templated transcription	1
JNK cascade	1
positive regulation of MAPK cascade	1
regulation of JNK cascade	1
Ras protein signal transduction	1
regulation of Ras protein signal transduction	1
positive regulation of small GTPase mediated signal transduction	1
ribonucleoside triphosphate phosphatase activity	1
GTPase activity	1
molecular function regulator activity	1
purine ribonucleoside triphosphate binding	1
protein-macromolecule adaptor activity	1
C-type glycerophospholipase activity	1
phospholipase activator activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
catalytic activity	1
Golgi apparatus	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 30 of 52 annotations. The rest are phylogenetic / computational / electronic (IEA).

30 experimentally-supported GO terms:

GO term	NS	Evidence
Ras protein signal transduction	BP	direct assay
cellular response to gamma radiation	BP	direct assay
cellular senescence	BP	direct assay
negative regulation of cell population proliferation	BP	direct assay
negative regulation of gene expression	BP	direct assay
positive regulation of ERK1 and ERK2 cascade	BP	direct assay
positive regulation of JNK cascade	BP	direct assay
positive regulation of MAPK cascade	BP	direct assay
positive regulation of cell migration	BP	direct assay
positive regulation of cell population proliferation	BP	direct assay
positive regulation of epithelial cell proliferation	BP	mutant phenotype
positive regulation of miRNA metabolic process	BP	direct assay
positive regulation of protein targeting to membrane	BP	mutant phenotype
positive regulation of ruffle assembly	BP	direct assay
positive regulation of transcription by RNA polymerase II	BP	direct assay
positive regulation of wound healing	BP	direct assay
regulation of actin cytoskeleton organization	BP	direct assay
regulation of cell cycle	BP	direct assay
regulation of cell population proliferation	BP	direct assay
regulation of neurotransmitter receptor localization to postsynaptic specialization membrane	BP	direct assay
regulation of transcription by RNA polymerase II	BP	direct assay
Golgi apparatus	CC	direct assay
cytosol	CC	direct assay
glutamatergic synapse	CC	direct assay
nucleoplasm	CC	direct assay
plasma membrane	CC	direct assay
GDP binding	MF	mutant phenotype
GTP binding	MF	direct assay
GTPase activity	MF	direct assay
phospholipase C activator activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 4,618 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HRAS	BRAF	P15056	929
HRAS	TP53	P04637	883
HRAS	MYC	P01106	849
HRAS	EGFR	P00533	831
HRAS	MAP2K1	Q02750	828
HRAS	PTPN11	Q06124	827
HRAS	PIK3CA	P42336	826
HRAS	CDKN2A	P42771	821
HRAS	RAF1	P04049	813
HRAS	AKT1	P31749	811
HRAS	SOS1	Q07889	807
HRAS	PTEN	P60484	798
HRAS	RALGDS	Q12967	773
HRAS	NF1	P21359	745
HRAS	CTNNB1	P35222	741

IntAct

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

showing 30 of 184 partners by confidence:

Partner	Interaction type	MIscore	Records
RAF1	physical association	0.980	28
SOS1	direct interaction	0.940	11
BRAF	direct interaction	0.940	7
RIN1	physical association	0.930	8
ARAF	direct interaction	0.850	3
RGL1	direct interaction	0.740	3
MTHFD2	association	0.730	3
RAP1GDS1	physical association	0.690	2
RASSF1	physical association	0.680	7
RALGDS	direct interaction	0.680	3
MRFAP1	physical association	0.670	3
BLZF1	physical association	0.660	3
CHMP7	physical association	0.660	3
RGL2	association	0.660	3
STIM1	physical association	0.660	3
NF1	physical association	0.600	2
RASSF5	physical association	0.590	4
UBIAD1	colocalization	0.580	9
FANCI	proximity	0.570	5
RALA	direct interaction	0.570	1
SRC	direct interaction	0.570	1
PCDHGC3	physical association	0.560	4
AKAP9	physical association	0.560	3
AP3M2	physical association	0.560	3
ARHGEF38	physical association	0.560	3
ATP5IF1	physical association	0.560	3
AUNIP	physical association	0.560	3
BEX3	physical association	0.560	3
BRMS1L	physical association	0.560	3
BRPF3	physical association	0.560	3

BioGRID (996 interactions; top human partners by supporting records in a sample of 600 records): RAF1 (Affinity Capture-Western; 13 records), LZTR1 (Affinity Capture-MS; 8 records), BRAF (Affinity Capture-MS; 5 records), MTOR (Proximity Label-MS; 5 records), BSG (Proximity Label-MS; 3 records), F11R (Proximity Label-MS; 3 records), FAM129B (Affinity Capture-Western; 3 records), LYN (Proximity Label-MS; 3 records), MARK2 (Proximity Label-MS; 3 records), MPZL1 (Proximity Label-MS; 3 records), NOTCH1 (Proximity Label-MS; 3 records), NUMB (Proximity Label-MS; 3 records), PI4KA (Proximity Label-MS; 3 records), PVRL2 (Proximity Label-MS; 3 records), RALGDS (Two-hybrid; 3 records)

SIGNOR signaling

showing 35 of 43 signaling interactions:

A	Effect	B	Mechanism
RIN1	up-regulates	HRAS	binding
HRAS	“up-regulates activity”	BRAF	binding
HRAS	up-regulates	BRAF	binding
RASGEF1C	up-regulates	HRAS	binding
HRAS	up-regulates	ARAF	binding
HRAS	“up-regulates activity”	PIK3CB	binding
HRAS	up-regulates	PIK3CD	binding
HRAS	up-regulates	PIK3CG	binding
SOS2	up-regulates	HRAS	“guanine nucleotide exchange factor”
RAPGEF5	up-regulates	HRAS	“guanine nucleotide exchange factor”
RAPGEF6	up-regulates	HRAS	“guanine nucleotide exchange factor”
RASGEF1A	up-regulates	HRAS	binding
RASGEF1B	up-regulates	HRAS	binding
NF1	“down-regulates activity”	HRAS	“gtpase-activating protein”
HRAS	up-regulates	RAF1	binding
FNTB	“up-regulates activity”	HRAS
FNTA	“up-regulates activity”	HRAS
SRC	“down-regulates activity”	HRAS	phosphorylation
PTPN11	“up-regulates activity”	HRAS	dephosphorylation
DAB2IP	“down-regulates activity”	HRAS	“gtpase-activating protein”
NF1	“down-regulates activity”	HRAS
UBIAD1	“down-regulates activity”	HRAS	binding
HRAS	“up-regulates activity”	GATA2	phosphorylation
GOLGA7	“up-regulates activity”	HRAS	palmitoylation
ZDHHC9	“up-regulates activity”	HRAS	palmitoylation
NIBAN2	“up-regulates activity”	HRAS	binding
HRAS	up-regulates	PIK3CA	binding
SOS1	“up-regulates activity”	HRAS	“guanine nucleotide exchange factor”
RASA1	down-regulates	HRAS	binding
GNAQ	up-regulates	HRAS	binding
PLCE1	up-regulates	HRAS	“guanine nucleotide exchange factor”
HRAS	“up-regulates activity”	JUN	phosphorylation
HRAS	“up-regulates activity”	PIK3CA	binding
HRAS	“up-regulates activity”	PI3K	binding
MVD	“up-regulates quantity by stabilization”	HRAS

Protein complexes (CORUM) (6)

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

6 complexes by size:

Complex	Subunits	Members
HRAS-IRAK1-IRAK2-TRAF6 complex	4	HRAS, IRAK1, IRAK2, TRAF6
ABL2-HRAS-RIN1 complex	3	ABL2, HRAS, RIN1
DGKZ-RASGRP1-HRAS complex	3	DGKZ, HRAS, RASGRP1
★ AURKA-HRAS-RAF1 complex	3	HRAS, RAF1, AURKA
HRAS-PPP1CC-SHOC2 complex	3	HRAS, PPP1CC, SHOC2
★ HRAS-RAF1 complex	2	HRAS, RAF1

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 184 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
CD28 dependent PI3K/Akt signaling	7	22.2×	8e-06
RAF activation	6	16.2×	1e-04
Downstream signal transduction	5	15.3×	8e-04
Oncogenic MAPK signaling	7	14.0×	8e-05
FLT3 Signaling	5	13.9×	1e-03
Signaling by CSF1 (M-CSF) in myeloid cells	5	13.9×	1e-03
Bacterial Infection Pathways	5	13.5×	1e-03
Signaling by EGFR	5	13.2×	1e-03

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of peptidyl-serine phosphorylation	5	23.2×	1e-03
mismatch repair	5	19.6×	1e-03
insulin-like growth factor receptor signaling pathway	5	15.0×	4e-03
Ras protein signal transduction	12	14.9×	4e-08
positive regulation of miRNA transcription	6	10.6×	4e-03
epidermal growth factor receptor signaling pathway	7	10.5×	1e-03
phosphatidylinositol 3-kinase/protein kinase B signal transduction	7	8.9×	3e-03
MAPK cascade	9	8.4×	1e-03

Disease & clinical

Cancer significance

From CIViC — curated cancer-variant interpretation:

HRAS is a member of the small GTPase family that upon activation by receptor tyrosine kinases stimulates downstream pathways including RAF-MEK-ERK and PI3K-AKT. In cancer, recurrent gain-of-function mutations at positions G12, G13, and Q61 result in an accumulation of GTP-bound HRAS, constitutive downstream signaling, and transformation. In TCGA, HRAS mutations were found more frequently in head and neck squamous cell carcinoma, bladder urothelial carcinoma, thyroid carcinoma, thymoma, skin cutaneous carcinoma, and pheochromocytoma/paraganglioma. Although development of HRAS inhibitors has not been possible, targeting the enzyme essential for farnesylating HRAS has recently shown benefit in HRAS driven cancers. The farnesyltransferase inhibitor (FTi) tipifarnib has been shown to cause HRAS mislocalization, decrease downstream signaling, and selectively impair proliferation, survival, and transformation of HRAS-mutant cells. Tipifarnib is in clinical development for HRAS-mutant cancers.

From intOGen — cancer-driver classification: activating (oncogene-like) across 14 cancer types — ANGS, BLCA, BRCA, COADREAD, CSCC, HNSC, LUSC, NPC, PGNG, PRAD, PROSTATE, THYM…(+2 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 HRAS: 668 ClinVar records (44 pathogenic / likely pathogenic); 13 ClinGen expert-panel interpretations; 7 CIViC cancer variants. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	21
Likely pathogenic	23
Uncertain significance	273
Likely benign	264
Benign	38

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 44 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
12602	NM_005343.4(HRAS):c.34G>A (p.Gly12Ser)	Pathogenic	reviewed by expert panel	50
12606	NM_005343.4(HRAS):c.37G>T (p.Gly13Cys)	Pathogenic	reviewed by expert panel	24
12610	NM_005343.4(HRAS):c.173C>T (p.Thr58Ile)	Pathogenic	reviewed by expert panel	10
12605	NM_005343.4(HRAS):c.350A>G (p.Lys117Arg)	Pathogenic	reviewed by expert panel	6
40435	NM_005343.4(HRAS):c.175G>A (p.Ala59Thr)	Likely pathogenic	reviewed by expert panel	7
12604	NM_005343.4(HRAS):c.38G>A (p.Gly13Asp)	Pathogenic	criteria provided, multiple submitters, no conflicts	22
12613	NM_005343.4(HRAS):c.34G>T (p.Gly12Cys)	Pathogenic	criteria provided, multiple submitters, no conflicts	19
12600	NM_005343.4(HRAS):c.35G>T (p.Gly12Val)	Pathogenic	criteria provided, multiple submitters, no conflicts	13
12603	NM_005343.4(HRAS):c.35G>C (p.Gly12Ala)	Pathogenic	criteria provided, multiple submitters, no conflicts	11
1209208	NM_005343.4(HRAS):c.35_36delinsTT (p.Gly12Val)	Pathogenic	criteria provided, multiple submitters, no conflicts	6
12608	NM_005343.4(HRAS):c.187G>A (p.Glu63Lys)	Pathogenic	criteria provided, multiple submitters, no conflicts	3
40436	NM_005343.4(HRAS):c.179G>A (p.Gly60Asp)	Pathogenic	criteria provided, multiple submitters, no conflicts	3
391700	NM_005343.4(HRAS):c.179G>T (p.Gly60Val)	Pathogenic	criteria provided, multiple submitters, no conflicts	3
1810343	NM_005343.4(HRAS):c.176C>G (p.Ala59Gly)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
160364	NM_005343.4(HRAS):c.182A>G (p.Gln61Arg)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	8

Per-variant reference — Sugi Variant

Explore HRAS’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 (13)

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

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

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 30 predictions of 483):

Position(s)	Effect	Δscore	Sites
11:532756	acceptor_gain	1.0000
11:533452	donor_loss	1.0000
11:533613–533614	acceptor_loss	1.0000	4
11:533945–533946	acceptor_loss	1.0000	5
11:534210–534211	donor_loss	1.0000	2
11:532756–532757	acceptor_loss	0.9900	3
11:533275–533276	donor_loss	0.9900	4
11:533359–533360	acceptor_loss	0.9900	6
11:533451–533452	donor_loss	0.9900	3
11:533455	donor_gain	0.9900

AlphaMissense

852 missense substitutions predicted likely pathogenic (of 1,238 scored), across 154 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	0.958	0.999
M67	9	0.938	1.000
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	0.997	0.999
N116	8	0.991	1.000
D69	8	0.988	0.999
F78	8	0.988	1.000
F28	8	0.987	1.000
D47	8	0.979	0.998
F156	8	0.979	0.999
S17	8	0.958	1.000
F82	8	0.957	0.999
D105	8	0.865	0.977
D92	8	0.799	0.954
K16	7	0.997	1.000
E37	7	0.993	0.999
E62	7	0.989	0.998

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

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

4 prognostic cancer types:

Cancer	Prognostic	p-value
Liver Hepatocellular Carcinoma (TCGA)	unfavorable	5.53e-06
Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma (TCGA)	favorable	1.08e-05
Liver Hepatocellular Carcinoma (validation)	unfavorable	0.000348
Pancreatic Adenocarcinoma (validation)	unfavorable	0.000361

Disease associations

OMIM: gene MIM:190020 | disease phenotypes: MIM:218040, MIM:109800, MIM:162900, MIM:188470, MIM:609942, MIM:163950, MIM:163200, MIM:137550, MIM:236750, MIM:108010

GenCC curated gene-disease

3 curated gene-disease records:

Disease	Classification	Inheritance	Records
Costello syndrome	Definitive	Autosomal dominant	6
rhabdomyosarcoma	Moderate	Autosomal dominant
Noonan syndrome-like disorder with loose anagen hair	Disputed Evidence	Autosomal dominant

ClinGen Gene-Disease Validity

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

2 validity classifications:

Disease	Classification	Inheritance
Costello syndrome	Definitive	AD
Noonan syndrome-like disorder with loose anagen hair	Disputed	AD

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (26 panels, 21 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

26 panels:

Panel	Rating
Adult solid tumours cancer susceptibility	green
Childhood solid tumours	green
Childhood solid tumours cancer susceptibility	green
DDG2P	green
Early onset or syndromic epilepsy	green
Embryonal tumour of possible germline origin	green
Familial rhabdomyosarcoma	green
Fetal anomalies	green
Fetal hydrops	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
Sarcoma of possible germline origin	green
Unexplained death in infancy and sudden unexplained death in childhood	green
Congenital myopathy	amber
Hypotonic infant	amber
Other rare neuromuscular disorders	amber
Sarcoma cancer susceptibility	amber
Sarcoma susceptibility	amber

Mondo (23): Costello syndrome (MONDO:0009026), urinary bladder cancer (MONDO:0001187), nevus, epidermal (MONDO:0008093), myopathy, congenital, with excess of muscle spindles (MONDO:0800299), thyroid cancer, nonmedullary, 2 (MONDO:0008566), Noonan syndrome 3 (MONDO:0012371), spermatocytic seminoma (MONDO:0020513), lip and oral cavity carcinoma (MONDO:0023644), rhabdomyosarcoma (MONDO:0005212), Noonan syndrome 1 (MONDO:0008104), wooly hair nevus (MONDO:0019311), Noonan syndrome and Noonan-related syndrome (MONDO:0020297), RASopathy (MONDO:0021060), linear nevus sebaceous syndrome (MONDO:0008097), large congenital melanocytic nevus (MONDO:0044792), non-immune hydrops fetalis (MONDO:0009369), Noonan syndrome (MONDO:0018997), tumor of salivary gland (MONDO:0021357), vascular malformation (MONDO:0024291), non-small cell lung carcinoma (MONDO:0005233), intramuscular hemangioma (MONDO:0003088), arteriovenous malformations of the brain (MONDO:0007154), Noonan syndrome-like disorder with loose anagen hair (MONDO:0011899)

Orphanet (13): Costello syndrome (Orphanet:3071), Woolly hair nevus (Orphanet:79414), Noonan syndrome (Orphanet:648), Spermatocytic seminoma (Orphanet:99865), RASopathy (Orphanet:536391), Rhabdomyosarcoma (Orphanet:780), Noonan syndrome and Noonan-related syndrome (Orphanet:98733), Linear nevus sebaceus syndrome (Orphanet:2612), Large/giant congenital melanocytic nevus (Orphanet:626), Non-immune hydrops fetalis (Orphanet:363999), Brain arteriovenous malformation (Orphanet:46724), NON RARE IN EUROPE: Bladder cancer (Orphanet:157980), NON RARE IN EUROPE: Non-small cell lung cancer (Orphanet:488201)

HPO phenotypes

showing 60 of 210 phenotypes (HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000028	Cryptorchidism
HP:0000083	Renal insufficiency
HP:0000085	Horseshoe kidney
HP:0000158	Macroglossia
HP:0000164	Abnormality of the dentition
HP:0000179	Thick lower lip vermilion
HP:0000189	Narrow palate
HP:0000194	Open mouth
HP:0000218	High palate
HP:0000232	Everted lower lip vermilion
HP:0000238	Hydrocephalus
HP:0000256	Macrocephaly
HP:0000260	Wide anterior fontanel
HP:0000267	Cranial asymmetry
HP:0000269	Prominent occiput
HP:0000280	Coarse facial features
HP:0000286	Epicanthus
HP:0000293	Full cheeks
HP:0000307	Pointed chin
HP:0000311	Round face
HP:0000316	Hypertelorism
HP:0000324	Facial asymmetry
HP:0000337	Broad forehead
HP:0000343	Long philtrum
HP:0000347	Micrognathia
HP:0000358	Posteriorly rotated ears
HP:0000369	Low-set ears
HP:0000418	Narrow nasal ridge
HP:0000455	Broad nasal tip
HP:0000463	Anteverted nares
HP:0000465	Webbed neck
HP:0000470	Short neck
HP:0000474	Thickened nuchal skin fold
HP:0000478	Abnormality of the eye
HP:0000483	Astigmatism
HP:0000486	Strabismus
HP:0000494	Downslanted palpebral fissures
HP:0000501	Glaucoma
HP:0000504	Abnormality of vision
HP:0000506	Telecanthus
HP:0000508	Ptosis
HP:0000540	Hypermetropia
HP:0000543	Optic disc pallor
HP:0000545	Myopia
HP:0000563	Keratoconus
HP:0000568	Microphthalmia
HP:0000589	Coloboma
HP:0000602	Ophthalmoplegia
HP:0000612	Iris coloboma
HP:0000629	Periorbital fullness
HP:0000639	Nystagmus
HP:0000682	Abnormal dental enamel morphology
HP:0000768	Pectus carinatum
HP:0000826	Precocious puberty
HP:0000938	Osteopenia
HP:0000951	Abnormality of the skin
HP:0000953	Hyperpigmentation of the skin
HP:0000956	Acanthosis nigricans
HP:0000962	Hyperkeratosis

MeSH disease descriptors

11 disease descriptors:

Descriptor	Name	Tree numbers
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
D002538	Intracranial Arteriovenous Malformations	C10.228.140.300.520; C10.500.190.500; C14.240.850.750.295; C14.240.850.875.500; C14.907.150.295; C14.907.253.560.400; C16.131.240.850.750.295; C16.131.240.850.875.500; C16.131.666.190.500
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
D012208	Rhabdomyosarcoma	C04.557.450.590.550.660; C04.557.450.795.550.660
D054079	Vascular Malformations	C14.240.850; C16.131.240.850
C580062	Epidermal Nevus *(supp.)*
C537846	Noonan like syndrome *(supp.)*
C537847	Noonan syndrome 3 *(supp.)*
C564342	Noonan-Like Syndrome With Loose Anagen Hair *(supp.)*
C572845	Thyroid cancer, follicular *(supp.)*

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (4): CHEMBL2167 (SINGLE PROTEIN), CHEMBL4524006 (PROTEIN FAMILY), CHEMBL6193817 (PROTEIN-PROTEIN INTERACTION), CHEMBL6195565 (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 HRAS — 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: 15,683 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

4 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL298734	LONAFARNIB	4	13,020
CHEMBL11252	STALLIMYCIN	2	1,919
CHEMBL351706	BMS-214662	1	403
CHEMBL279433	L-778123 FREE BASE	1	341

Clinical evidence (CIViC)

Drug × variant × indication, from 9 curated evidence items; also 1 functional, 1 oncogenic, 1 prognostic. CIViC evidence level: A (validated) → B (clinical) → C (case study) → D (preclinical) → E (inferential).

9 predictive associations by evidence level:

Variant	Therapy	Indication	Effect	Level	CIViC
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
HRAS Mutation	Tipifarnib	Bladder Urothelial Carcinoma	Sensitivity/Response	CIViC B	EID9632
HRAS Mutation	Tipifarnib	Head And Neck Squamous Cell Carcinoma	Sensitivity/Response	CIViC B	EID9633
HRAS G13D	Vemurafenib	Skin Squamous Cell Carcinoma	Resistance	CIViC C	EID3851
HRAS G13D	Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor	Colorectal Cancer	Resistance	CIViC C	EID699
HRAS Q61L OR HRAS Q61R OR HRAS G12V	Binimetinib + Mirdametinib + MTOR Kinase Inhibitor AZD8055 + Everolimus + Selumetinib	Cancer	Sensitivity/Response	CIViC D	EID700
HRAS G13D	Cetuximab	Colorectal Cancer	Resistance	CIViC D	EID3852
HRAS G13R	Vemurafenib	Thyroid Gland Carcinoma	Resistance	CIViC D	EID3853

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
HRAS G13R	Cancer		Oncogenic		Oncogenic

CIViC curated variants (7)

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

Q61R, G13R (missense variant), G12V, Q61, G13D (missense variant), Mutation (coding transcript variant), Q61L (missense variant).

PharmGKB: 1 entry (CPIC guideline: no)

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	8.72	pIC50

Binding affinities (BindingDB)

66 measured of 94 human assays (116 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
(R)-3-Benzyl-1-(3H-imidazol-4-ylmethyl)-4-(thiophene-2-sulfonyl)-2,3,4,5-tetrahydro-1H-benzo[e][1,4]diazepine-7-carbonitrile	IC50	1.35 nM
4-{5-[4-(3-Chloro-phenyl)-3-oxo-piperazin-1-ylmethyl]-imidazol-1-ylmethyl}-benzonitrile	IC50	2 nM
5-{4-[Bis-(2-chloro-ethyl)-amino]-benzoylamino}-1H-benzoimidazole-2-carboxylic acid (5-{5-[5-(2-carbamimidoyl-ethylcarbamoyl)-1-methyl-1H-pyrrol-3-ylcarbamoyl]-1-methyl-1H-pyrrol-3-ylcarbamoyl}-1-methyl-1H-pyrrol-3-yl)-amide; hydrochloride	IC50	15 nM
5-{4-[Bis-(2-chloro-ethyl)-amino]-benzoylamino}-1-methyl-1H-indole-2-carboxylic acid (5-{5-[5-(2-carbamimidoyl-ethylcarbamoyl)-1-methyl-1H-pyrrol-3-ylcarbamoyl]-1-methyl-1H-pyrrol-3-ylcarbamoyl}-1-methyl-1H-pyrrol-3-yl)-amide; hydrochloride	IC50	15 nM
5-{4-[Bis-(2-chloro-ethyl)-amino]-benzoylamino}-benzofuran-2-carboxylic acid (5-{5-[5-(2-carbamimidoyl-ethylcarbamoyl)-1-methyl-1H-pyrrol-3-ylcarbamoyl]-1-methyl-1H-pyrrol-3-ylcarbamoyl}-1-methyl-1H-pyrrol-3-yl)-amide; hydrochloride	IC50	15 nM
5-{4-[Bis-(2-chloro-ethyl)-amino]-benzoylamino}-1H-indole-2-carboxylic acid (5-{5-[5-(2-carbamimidoyl-ethylcarbamoyl)-1-methyl-1H-pyrrol-3-ylcarbamoyl]-1-methyl-1H-pyrrol-3-ylcarbamoyl}-1-methyl-1H-pyrrol-3-yl)-amide; hydrochloride	IC50	15 nM
5-[Bis-(2-chloro-ethyl)-amino]-benzofuran-2-carboxylic acid (5-{5-[5-(2-carbamimidoyl-ethylcarbamoyl)-1-methyl-1H-pyrrol-3-ylcarbamoyl]-1-methyl-1H-pyrrol-3-ylcarbamoyl}-1-methyl-1H-pyrrol-3-yl)-amide; hydrochloride	IC50	15 nM
5-[Bis-(2-chloro-ethyl)-amino]-1-methyl-1H-indole-2-carboxylic acid (5-{5-[5-(2-carbamimidoyl-ethylcarbamoyl)-1-methyl-1H-pyrrol-3-ylcarbamoyl]-1-methyl-1H-pyrrol-3-ylcarbamoyl}-1-methyl-1H-pyrrol-3-yl)-amide; hydrochloride	IC50	20 nM
5-[Bis-(2-chloro-ethyl)-amino]-1H-indole-2-carboxylic acid (5-{5-[5-(2-carbamimidoyl-ethylcarbamoyl)-1-methyl-1H-pyrrol-3-ylcarbamoyl]-1-methyl-1H-pyrrol-3-ylcarbamoyl}-1-methyl-1H-pyrrol-3-yl)-amide; hydrochloride	IC50	20 nM
CHEMBL4456044	KD	51 nM
[(S)-1-((4-Benzyloxy-benzyl)-{[(1-phenyl-cyclobutylmethyl)-carbamoyl]-methyl}-carbamoyl)-2-(3H-imidazol-4-yl)-ethyl]-carbamic acid benzyl ester	IC50	88 nM
CHEMBL5174384	IC50	100 nM
CHEMBL5171806	IC50	100 nM
1-[4-((S)-8-chloro-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-yl)-piperazin-1-yl]-2-pyridin-4-yl-ethanone	IC50	140 nM
[(S)-1-{(4-Benzyloxy-benzyl)-[(2-methyl-2-phenyl-propylcarbamoyl)-methyl]-carbamoyl}-2-(3H-imidazol-4-yl)-ethyl]-carbamic acid benzyl ester	IC50	180 nM
[(S)-1-((4-Benzyloxy-benzyl)-{[(1-phenyl-cyclopropylmethyl)-carbamoyl]-methyl}-carbamoyl)-2-(3H-imidazol-4-yl)-ethyl]-carbamic acid benzyl ester	IC50	180 nM
[(S)-1-{(4-Benzyloxy-benzyl)-[(2-cyano-2-phenyl-ethylcarbamoyl)-methyl]-carbamoyl}-2-(3H-imidazol-4-yl)-ethyl]-carbamic acid benzyl ester	IC50	190 nM
[(S)-1-{(4-Benzyloxy-benzyl)-[((S)-2-phenyl-propylcarbamoyl)-methyl]-carbamoyl}-2-(3H-imidazol-4-yl)-ethyl]-carbamic acid benzyl ester	IC50	300 nM
[(S)-1-{(4-Benzyloxy-benzyl)-[(2-phenyl-propylcarbamoyl)-methyl]-carbamoyl}-2-(3H-imidazol-4-yl)-ethyl]-carbamic acid benzyl ester	IC50	310 nM
[(S)-1-((4-Benzyloxy-benzyl)-{[(1-phenyl-cyclopentylmethyl)-carbamoyl]-methyl}-carbamoyl)-2-(3H-imidazol-4-yl)-ethyl]-carbamic acid benzyl ester	IC50	330 nM
[(S)-1-{(4-Benzyloxy-benzyl)-[(2-phenyl-butylcarbamoyl)-methyl]-carbamoyl}-2-(3H-imidazol-4-yl)-ethyl]-carbamic acid benzyl ester	IC50	400 nM
[(S)-1-{(4-Benzyloxy-benzyl)-[((R)-2-phenyl-propylcarbamoyl)-methyl]-carbamoyl}-2-(3H-imidazol-4-yl)-ethyl]-carbamic acid benzyl ester	IC50	570 nM
[(S)-1-{(4-Benzyloxy-benzyl)-[((R)-1-methyl-2-phenyl-ethylcarbamoyl)-methyl]-carbamoyl}-2-(3H-imidazol-4-yl)-ethyl]-carbamic acid benzyl ester	IC50	710 nM
CHEMBL6172941	IC50	870 nM
1-[(2R,6S)-6-(tert-Butyl-dimethyl-silanyloxymethyl)-4-(2-nitro-benzenesulfonyl)-morpholin-2-yl]-4-chloro-6-methoxy-3-methyl-1H-pyrazolo[3,4-b]quinoline	IC50	1000 nM
(8S)-13-(5-ethyl-6-fluoro-1H-benzo[f]indazol-4-yl)-14-fluoro-17-[[(6Z,8S)-6-(fluoromethylidene)-2,3,5,7-tetrahydro-1H-pyrrolizin-8-yl]methoxy]-6,10-dioxa-2,12,16,18-tetrazatetracyclo[9.7.1.02,8.015,19]nonadeca-1(18),11,13,15(19),16-pentaene	IC50	1280 nM	US-12466840: Small molecule inhibitors of KRAS proteins
3-[(3aS,4R,6R,6aR)-6-(4-Chloro-6-methoxy-3-methyl-pyrazolo[3,4-b]quinolin-1-yl)-2-thioxo-tetrahydro-furo[3,4-d][1,3]dioxol-4-yloxy]-3-hydroxy-1-phenyl-propan-1-one	IC50	1500 nM
CHEMBL6165011	KD	2000 nM
(8S)-13-(5-ethyl-6-fluoro-3-methyl-2H-benzo[f]indazol-4-yl)-14-fluoro-17-[[(6Z,8S)-6-(fluoromethylidene)-2,3,5,7-tetrahydro-1H-pyrrolizin-8-yl]methoxy]-6,10-dioxa-2,12,16,18-tetrazatetracyclo[9.7.1.02,8.015,19]nonadeca-1(18),11,13,15(19),16-pentaene	IC50	2180 nM	US-12466840: Small molecule inhibitors of KRAS proteins
Ophirapstanol Trisulfate	IC50	2550 nM
CHEMBL5592316	EC50	2600 nM
(8S)-13-(5-ethyl-6-fluoro-1H-indazol-4-yl)-14-fluoro-17-[[(2R,8S)-2-fluoro-1,2,3,5,6,7-hexahydropyrrolizin-8-yl]methoxy]-6,10-dioxa-2,12,16,18-tetrazatetracyclo[9.7.1.02,8.015,19]nonadeca-1(18),11,13,15(19),16-pentaene	IC50	2740 nM	US-12466840: Small molecule inhibitors of KRAS proteins
(E)-5-[(2R,6R)-6-(4-Chloro-6-methoxy-3-methyl-pyrazolo[3,4-b]quinolin-1-yl)-4-(4-nitro-phenylsulfanyl)-morpholin-2-yl]-pent-3-en-2-one	IC50	3000 nM
CHEMBL6149416	KD	4100 nM
[(S)-1-[(4-Benzyloxy-benzyl)-(phenethylcarbamoyl-methyl)-carbamoyl]-2-(1H-imidazol-4-yl)-ethyl]-carbamic acid benzyl ester	IC50	4300 nM
(8S)-13-[6-chloro-5-(1-fluorocyclopropyl)-1H-indazol-4-yl]-14-fluoro-17-[[(6Z,8S)-6-(fluoromethylidene)-2,3,5,7-tetrahydro-1H-pyrrolizin-8-yl]methoxy]-6,10-dioxa-2,12,16,18-tetrazatetracyclo[9.7.1.02,8.015,19]nonadeca-1(18),11,13,15(19),16-pentaene	IC50	4680 nM	US-12466840: Small molecule inhibitors of KRAS proteins
(E)-4-[(2R,6R)-6-(4-Chloro-6-methoxy-3-methyl-pyrazolo[3,4-b]quinolin-1-yl)-4-(2-nitro-phenylsulfanyl)-morpholin-2-yl]-1-phenyl-but-2-en-1-one	IC50	4700 nM
CHEMBL1387422	EC50	5000 nM
1-[(2R,6S)-6-(tert-Butyl-dimethyl-silanyloxymethyl)-4-(4-nitro-benzenesulfonyl)-morpholin-2-yl]-4-chloro-6-methoxy-3-methyl-1H-pyrazolo[3,4-b]quinoline	IC50	5000 nM
(8S)-13-(5-ethyl-6-fluoro-3-methyl-2H-benzo[f]indazol-4-yl)-14-fluoro-17-[[(2R,8S)-2-fluoro-1,2,3,5,6,7-hexahydropyrrolizin-8-yl]methoxy]-6,10-dioxa-2,12,16,18-tetrazatetracyclo[9.7.1.02,8.015,19]nonadeca-1(18),11,13,15(19),16-pentaene	IC50	5520 nM	US-12466840: Small molecule inhibitors of KRAS proteins
[(S)-1-{(4-Benzyloxy-benzyl)-[((S)-1-methyl-2-phenyl-ethylcarbamoyl)-methyl]-carbamoyl}-2-(3H-imidazol-4-yl)-ethyl]-carbamic acid benzyl ester	IC50	6300 nM
[(2S,6R)-6-(4-Chloro-6-methoxy-3-methyl-pyrazolo[3,4-b]quinolin-1-yl)-4-(4-nitro-phenylsulfanyl)-morpholin-2-yl]-methanol	IC50	6700 nM
(E)-4-[(2R,6R)-6-(4-Chloro-6-methoxy-3-methyl-pyrazolo[3,4-b]quinolin-1-yl)-4-(4-nitro-benzenesulfonyl)-morpholin-2-yl]-1-phenyl-but-2-en-1-one	IC50	7000 nM
(E)-4-[(2R,6R)-6-(4-Chloro-6-methoxy-3-methyl-pyrazolo[3,4-b]quinolin-1-yl)-4-(4-nitro-phenylsulfanyl)-morpholin-2-yl]-1-phenyl-but-2-en-1-one	IC50	7400 nM
Benzodiazepine-Distamycin Hybrid	IC50	8000 nM
[(2S,6R)-6-(4-Chloro-6-methoxy-3-methyl-pyrazolo[3,4-b]quinolin-1-yl)-4-(4-nitro-benzenesulfonyl)-morpholin-2-yl]-methanol	IC50	8000 nM
(E)-3-[(2S,3S,4R,5R)-5-(4-Chloro-6-methoxy-3-methyl-pyrazolo[3,4-b]quinolin-1-yl)-3,4-dihydroxy-tetrahydro-furan-2-yloxy]-1-phenyl-propenone	IC50	10000 nM
5-(4-chloro-6-methoxy-3-methyl-1H-pyrazolo[3,4-b]quinolin-1-yl)-3,4-di(phenylcarbonyloxy)-2-phenylcarbonyloxymethyl-(2R,3R,4R,5R)-tetrahydrofuran	IC50	10000 nM
5-(4-chloro-6-methoxy-3-methyl-1H-pyrazolo[3,4-b]quinolin-1-yl)-3,4-di(2-furylcarbonyloxy)-2-(2-furylcarbonyloxymethyl)-(2R,3R,4R,5R)-tetrahydrofuran	IC50	10500 nM
[(2S,6R)-4-Benzenesulfonyl-6-(4-chloro-6-methoxy-3-methyl-pyrazolo[3,4-b]quinolin-1-yl)-morpholin-2-yl]-methanol	IC50	12000 nM

ChEMBL bioactivities

50 potent at pChembl≥5 of 71 total, top 49 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.89	IC50	1.3	nM	BMS-214662
8.80	Ki	1.6	nM	L-778123 FREE BASE
8.72	IC50	1.9	nM	CHEMBL66699
7.82	IC50	15	nM	CHEMBL554247
7.82	IC50	15	nM	CHEMBL552690
7.82	IC50	15	nM	CHEMBL554353
7.82	IC50	15	nM	CHEMBL540313
7.82	IC50	15	nM	CHEMBL554189
7.70	IC50	20	nM	CHEMBL552863
7.70	IC50	20	nM	CHEMBL536328
7.29	Kd	51	nM	CHEMBL4456044
7.16	IC50	70	nM	LONAFARNIB
7.06	IC50	88	nM	CHEMBL326352
7.00	IC50	100	nM	CHEMBL5171806
6.75	IC50	180	nM	CHEMBL407445
6.75	IC50	180	nM	CHEMBL431440
6.72	IC50	190	nM	CHEMBL115943
6.70	IC50	200	nM	BAY-293
6.70	IC50	200	nM	STALLIMYCIN
6.52	IC50	300	nM	CHEMBL115669
6.51	IC50	310	nM	CHEMBL324827
6.48	IC50	330	nM	CHEMBL326127
6.40	IC50	400	nM	CHEMBL112512
6.39	IC50	410	nM	BAY-293
6.24	IC50	570	nM	CHEMBL114281
6.15	IC50	710	nM	CHEMBL325073
6.00	IC50	1000	nM	CHEMBL304462
5.82	IC50	1500	nM	CHEMBL304862
5.70	Kd	2000	nM	CHEMBL6165011
5.58	EC50	2600	nM	CHEMBL5592316
5.52	IC50	3000	nM	CHEMBL59515
5.41	Kd	3920	nM	CHEMBL6172941
5.39	Kd	4100	nM	CHEMBL6149416
5.38	IC50	4120	nM	BAY-294
5.37	IC50	4300	nM	CHEMBL102955
5.33	IC50	4700	nM	CHEMBL61161
5.30	EC50	5000	nM	CHEMBL1387422
5.30	IC50	5000	nM	CHEMBL64328
5.26	Kd	5500	nM	CHEMBL3218192
5.20	IC50	6300	nM	CHEMBL324345
5.17	IC50	6700	nM	CHEMBL300769
5.16	IC50	7000	nM	CHEMBL304474
5.13	IC50	7400	nM	CHEMBL294285
5.11	Kd	7800	nM	CHEMBL3218193
5.10	IC50	8000	nM	CHEMBL102341
5.10	IC50	8000	nM	CHEMBL303105
5.02	Kd	9500	nM	CHEMBL3218191
5.00	IC50	1e+04	nM	CHEMBL303512
5.00	IC50	1e+04	nM	CHEMBL304637

PubChem BioAssay actives

33 with measured affinity, of 100 total; 32 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
(3R)-3-benzyl-1-(1H-imidazol-5-ylmethyl)-4-thiophen-2-ylsulfonyl-3,5-dihydro-2H-1,4-benzodiazepine-7-carbonitrile	1893917: Inhibition of HRAS (unknown origin) farnesylation	ic50	0.0013	uM
4-[[5-[[4-(3-chlorophenyl)-3-oxopiperazin-1-yl]methyl]imidazol-1-yl]methyl]benzonitrile	1893894: Binding affinity to HRAS (unknown origin) assessed as inhibition constant	ki	0.0016	uM
1-[4-[(2S)-13-chloro-4-azatricyclo[9.4.0.03,8]pentadeca-1(11),3(8),4,6,12,14-hexaen-2-yl]piperazin-1-yl]-2-pyridin-4-ylethanone	1979346: Inhibition of H-Ras (unknown origin)	ic50	0.0019	uM
N-[5-[[5-[[5-[(3-amino-3-iminopropyl)carbamoyl]-1-methylpyrrol-3-yl]carbamoyl]-1-methylpyrrol-3-yl]carbamoyl]-1-methylpyrrol-3-yl]-5-[[4-[bis(2-chloroethyl)amino]benzoyl]amino]-1H-benzimidazole-2-carboxamide;hydrochloride	85480: Tested for 50% inhibition of generation of Human Ha-ras polymerase chain reaction(PCR) products	ic50	0.0150	uM
N-[5-[[5-[[5-[(3-amino-3-iminopropyl)carbamoyl]-1-methylpyrrol-3-yl]carbamoyl]-1-methylpyrrol-3-yl]carbamoyl]-1-methylpyrrol-3-yl]-5-[[4-[bis(2-chloroethyl)amino]benzoyl]amino]-1-methylindole-2-carboxamide;hydrochloride	85480: Tested for 50% inhibition of generation of Human Ha-ras polymerase chain reaction(PCR) products	ic50	0.0150	uM
N-(3-amino-3-iminopropyl)-4-[[4-[[4-[[5-[[4-[bis(2-chloroethyl)amino]benzoyl]amino]-1-benzofuran-2-carbonyl]amino]-1-methylpyrrole-2-carbonyl]amino]-1-methylpyrrole-2-carbonyl]amino]-1-methylpyrrole-2-carboxamide;hydrochloride	85480: Tested for 50% inhibition of generation of Human Ha-ras polymerase chain reaction(PCR) products	ic50	0.0150	uM
N-[5-[[5-[[5-[(3-amino-3-iminopropyl)carbamoyl]-1-methylpyrrol-3-yl]carbamoyl]-1-methylpyrrol-3-yl]carbamoyl]-1-methylpyrrol-3-yl]-5-[[4-[bis(2-chloroethyl)amino]benzoyl]amino]-1H-indole-2-carboxamide;hydrochloride	85480: Tested for 50% inhibition of generation of Human Ha-ras polymerase chain reaction(PCR) products	ic50	0.0150	uM
N-(3-amino-3-iminopropyl)-4-[[4-[[4-[[5-[bis(2-chloroethyl)amino]-1-benzofuran-2-carbonyl]amino]-1-methylpyrrole-2-carbonyl]amino]-1-methylpyrrole-2-carbonyl]amino]-1-methylpyrrole-2-carboxamide;hydrochloride	85480: Tested for 50% inhibition of generation of Human Ha-ras polymerase chain reaction(PCR) products	ic50	0.0150	uM
N-[5-[[5-[[5-[(3-amino-3-iminopropyl)carbamoyl]-1-methylpyrrol-3-yl]carbamoyl]-1-methylpyrrol-3-yl]carbamoyl]-1-methylpyrrol-3-yl]-5-[bis(2-chloroethyl)amino]-1-methylindole-2-carboxamide;hydrochloride	85480: Tested for 50% inhibition of generation of Human Ha-ras polymerase chain reaction(PCR) products	ic50	0.0200	uM
N-[5-[[5-[[5-[(3-amino-3-iminopropyl)carbamoyl]-1-methylpyrrol-3-yl]carbamoyl]-1-methylpyrrol-3-yl]carbamoyl]-1-methylpyrrol-3-yl]-5-[bis(2-chloroethyl)amino]-1H-indole-2-carboxamide;hydrochloride	85480: Tested for 50% inhibition of generation of Human Ha-ras polymerase chain reaction(PCR) products	ic50	0.0200	uM
6-(2,3-dihydro-1,4-benzodioxin-5-yl)-N-[4-[(dimethylamino)methyl]phenyl]-2-methoxypyridin-3-amine	1582666: Inhibition GST-tagged recombinant HRAS G12V mutant (1 to 166 amino acids) (unknown origin) expressed in Escherichia coli C41(DE3) by SPR assay	kd	0.0510	uM
Lonafarnib	79248: Compound was measured for inhibition of H-ras NIH tumor cell line under soft agar assay.	ic50	0.0700	uM
benzyl N-[(2S)-3-(1H-imidazol-5-yl)-1-oxo-1-[[2-oxo-2-[(1-phenylcyclobutyl)methylamino]ethyl]-[(4-phenylmethoxyphenyl)methyl]amino]propan-2-yl]carbamate	79247: Concentration required to inhibit 50% of the cultured colonies of H-Ras-Fcells.	ic50	0.0880	uM
methyl (2S)-4-[5-[[[(2R)-2-amino-3-sulfanylpropyl]amino]methyl]-2-phenylphenyl]-2-(2-methylsulfanylethyl)-4-oxobutanoate	1893906: Inhibition of HRAS (unknown origin) transfected in BALB/c nude mouse incubated for 3 days measured by immunoblot analysis	ic50	0.1000	uM
benzyl N-[(2S)-3-(1H-imidazol-5-yl)-1-oxo-1-[[2-oxo-2-[(1-phenylcyclopropyl)methylamino]ethyl]-[(4-phenylmethoxyphenyl)methyl]amino]propan-2-yl]carbamate	79247: Concentration required to inhibit 50% of the cultured colonies of H-Ras-Fcells.	ic50	0.1800	uM
benzyl N-[(2S)-3-(1H-imidazol-5-yl)-1-[[2-[(2-methyl-2-phenylpropyl)amino]-2-oxoethyl]-[(4-phenylmethoxyphenyl)methyl]amino]-1-oxopropan-2-yl]carbamate	79247: Concentration required to inhibit 50% of the cultured colonies of H-Ras-Fcells.	ic50	0.1800	uM
benzyl N-[(2S)-1-[[2-[(2-cyano-2-phenylethyl)amino]-2-oxoethyl]-[(4-phenylmethoxyphenyl)methyl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]carbamate	79247: Concentration required to inhibit 50% of the cultured colonies of H-Ras-Fcells.	ic50	0.1900	uM
N-[5-[[5-[(3-amino-3-iminopropyl)carbamoyl]-1-methylpyrrol-3-yl]carbamoyl]-1-methylpyrrol-3-yl]-4-formamido-1-methylpyrrole-2-carboxamide	85480: Tested for 50% inhibition of generation of Human Ha-ras polymerase chain reaction(PCR) products	ic50	0.2000	uM
benzyl N-[(2S)-3-(1H-imidazol-5-yl)-1-oxo-1-[[2-oxo-2-[[(2S)-2-phenylpropyl]amino]ethyl]-[(4-phenylmethoxyphenyl)methyl]amino]propan-2-yl]carbamate	79247: Concentration required to inhibit 50% of the cultured colonies of H-Ras-Fcells.	ic50	0.3000	uM
benzyl N-[(2S)-3-(1H-imidazol-5-yl)-1-oxo-1-[[2-oxo-2-(2-phenylpropylamino)ethyl]-[(4-phenylmethoxyphenyl)methyl]amino]propan-2-yl]carbamate	79247: Concentration required to inhibit 50% of the cultured colonies of H-Ras-Fcells.	ic50	0.3100	uM
benzyl N-[(2S)-3-(1H-imidazol-5-yl)-1-oxo-1-[[2-oxo-2-[(1-phenylcyclopentyl)methylamino]ethyl]-[(4-phenylmethoxyphenyl)methyl]amino]propan-2-yl]carbamate	79247: Concentration required to inhibit 50% of the cultured colonies of H-Ras-Fcells.	ic50	0.3300	uM
benzyl N-[(2S)-3-(1H-imidazol-5-yl)-1-oxo-1-[[2-oxo-2-(2-phenylbutylamino)ethyl]-[(4-phenylmethoxyphenyl)methyl]amino]propan-2-yl]carbamate	79247: Concentration required to inhibit 50% of the cultured colonies of H-Ras-Fcells.	ic50	0.4000	uM
benzyl N-[(2S)-3-(1H-imidazol-5-yl)-1-oxo-1-[[2-oxo-2-[[(2R)-2-phenylpropyl]amino]ethyl]-[(4-phenylmethoxyphenyl)methyl]amino]propan-2-yl]carbamate	79247: Concentration required to inhibit 50% of the cultured colonies of H-Ras-Fcells.	ic50	0.5700	uM
benzyl N-[(2S)-3-(1H-imidazol-5-yl)-1-oxo-1-[[2-oxo-2-[[(2R)-1-phenylpropan-2-yl]amino]ethyl]-[(4-phenylmethoxyphenyl)methyl]amino]propan-2-yl]carbamate	79247: Concentration required to inhibit 50% of the cultured colonies of H-Ras-Fcells.	ic50	0.7100	uM
(4S)-5-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2R)-3-[[4-[[4-[[(2R)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S,3S)-2-[[(2S)-2-acetamido-3-(1H-indol-3-yl)propanoyl]amino]-3-methylpentanoyl]amino]acetyl]amino]-5-carbamimidamidopentanoyl]amino]-4-methylpentanoyl]amino]-3-[[(2S,3R)-1-[[(2S)-1-[[(2S,3S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-4-amino-1-[[2-[[(2S)-1,4-diamino-1,4-dioxobutan-2-yl]amino]-2-oxoethyl]amino]-1,4-dioxobutan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-6-carbamimidamido-1-oxohexan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-4-carboxy-1-oxobutan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-3-oxopropyl]sulfanylmethyl]phenyl]methoxymethyl]phenyl]methylsulfanyl]-1-amino-1-oxopropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-1-oxopropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-4-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-acetamido-4-methylpentanoyl]amino]propanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-5-carbamimidamidopentanoyl]amino]-4-methylpentanoyl]amino]-5-carbamimidamidopentanoyl]amino]-4-carboxybutanoyl]amino]-4-methylpentanoyl]amino]-4-carboxybutanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-oxopentanoic acid	2255380: Binding affinity to HRas (unknown origin) assessed as dissociation constant	kd	2.0000	uM
methyl 3-amino-4-[4-[[ethyl-[7-[(4-fluorobenzoyl)-propan-2-ylamino]heptanoyl]amino]methyl]piperidin-1-yl]benzoate	2115760: Induction of Rluc8-tagged and GFP2-tagged H-Ras G12V mutant (unknown origin) disruption extracted from HEK293-EBNA cells assessed as intracellular H-Ras G12V membrane anchorage disruption by measuring effective concentration measured after 24 hrs by BRET assay	ec50	2.6000	uM
(2S)-2-[[2-[[(2S)-2-[[(2S)-2-[[(2S,5S,8S,11S,15Z,20S)-20-[[(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S,3S)-2-[[(2S)-2-acetamido-3-(1H-indol-3-yl)propanoyl]amino]-3-methylpentanoyl]amino]acetyl]amino]-5-carbamimidamidopentanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]-3-hydroxybutanoyl]amino]-5-(4-carbamimidamidobutyl)-2-(3-carbamimidamidopropyl)-11,20-dimethyl-8-(2-methylpropyl)-3,6,9,21-tetraoxo-1,4,7,10-tetrazacyclohenicos-15-ene-11-carbonyl]amino]-5-carbamimidamidopentanoyl]amino]-4-amino-4-oxobutanoyl]amino]acetyl]amino]butanediamide	2255380: Binding affinity to HRas (unknown origin) assessed as dissociation constant	kd	3.9200	uM
(4S)-4-[3-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(3S)-3-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[3-[[2-[(3S,6S,12Z)-6-benzyl-3-(2-carboxyethyl)-2,5,8-trioxo-1,4,7-triazacyclotetradec-12-en-1-yl]acetyl]amino]-3-methylpentanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-5-carbamimidamidopentanoyl]amino]-4-methylpentanoyl]amino]-4-carboxybutanoyl]amino]-4-methylpentanoyl]amino]-6-[4-(ethenylsulfonylamino)butanoylamino]hexanoyl]amino]hexanoyl]amino]propanoylamino]-5-[[(2S)-4-carboxy-1-[[(2S)-1-[[(2S)-1,4-diamino-1,4-dioxobutan-2-yl]amino]-1-oxopropan-2-yl]amino]-1-oxobutan-2-yl]amino]-5-oxopentanoic acid	2255367: Binding affinity to wild-type H-Ras (unknown origin) assessed as dissociation constant by fluorescence polarization assay	kd	4.1000	uM
benzyl N-[(2S)-3-(1H-imidazol-5-yl)-1-oxo-1-[[2-oxo-2-(2-phenylethylamino)ethyl]-[(4-phenylmethoxyphenyl)methyl]amino]propan-2-yl]carbamate	79247: Concentration required to inhibit 50% of the cultured colonies of H-Ras-Fcells.	ic50	4.3000	uM
4-[3,4-dimethyl-2-(4-methylphenyl)-7-oxopyrazolo[3,4-d]pyridazin-6-yl]-N-(2-phenylpropyl)butanamide	2115760: Induction of Rluc8-tagged and GFP2-tagged H-Ras G12V mutant (unknown origin) disruption extracted from HEK293-EBNA cells assessed as intracellular H-Ras G12V membrane anchorage disruption by measuring effective concentration measured after 24 hrs by BRET assay	ec50	5.0000	uM
benzyl N-[(2S)-3-(1H-imidazol-5-yl)-1-oxo-1-[[2-oxo-2-[[(2S)-1-phenylpropan-2-yl]amino]ethyl]-[(4-phenylmethoxyphenyl)methyl]amino]propan-2-yl]carbamate	79247: Concentration required to inhibit 50% of the cultured colonies of H-Ras-Fcells.	ic50	6.3000	uM
4-[3-[[(6aS)-2-methoxy-11-oxo-6a,7,8,9-tetrahydropyrrolo[2,1-c][1,4]benzodiazepin-3-yl]oxy]propanoylamino]-N-[5-[[5-[(3-amino-3-iminopropyl)carbamoyl]-1-methylpyrrol-3-yl]carbamoyl]-1-methylpyrrol-3-yl]-1-methylpyrrole-2-carboxamide	85481: Inhibition of Ha-ras polymerase-chain reaction product	ic50	8.0000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression, decreases reaction, increases response to substance, increases activity, decreases expression	5
Benzo(a)pyrene	affects methylation, increases expression, decreases methylation, increases response to substance	4
Estradiol	decreases reaction, increases expression, affects expression, affects reaction, increases response to substance	4
Methylnitrosourea	increases response to substance, decreases reaction	4
Urethane	increases reaction, increases response to substance, increases mutagenesis, increases expression	4
Aflatoxin B1	affects expression, increases expression	4
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one	decreases reaction, increases activity, increases expression	3
Cisplatin	affects splicing, increases expression, increases reaction, decreases response to substance	3
Doxorubicin	decreases expression, decreases reaction, increases expression	3
Valproic Acid	affects expression, increases expression, increases methylation	3
Simvastatin	increases localization, decreases prenylation, affects localization, decreases farnesylation, increases activity (+4 more)	3
perfluorooctanoic acid	decreases expression, affects cotreatment, affects expression	2
2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine	affects response to substance, increases expression, increases mutagenesis, affects reaction, increases abundance (+1 more)	2
perfluorooctane sulfonic acid	affects expression, affects cotreatment, decreases expression	2
Resveratrol	increases response to substance, affects expression, increases activity, increases reaction, increases expression (+2 more)	2
Zoledronic Acid	decreases localization, increases expression	2
Arsenic Trioxide	increases expression, affects cotreatment	2
Copper	affects cotreatment, increases mutagenesis, decreases reaction	2
Dactinomycin	increases cleavage, increases reaction, affects cotreatment, increases expression	2
Lipopolysaccharides	decreases reaction, increases activity, increases localization, increases expression, increases prenylation	2
Lovastatin	decreases prenylation, decreases localization	2
Malathion	affects cotreatment, increases expression	2
Parathion	affects cotreatment, increases expression	2
Quercetin	decreases expression, increases expression	2
Tetradecanoylphorbol Acetate	affects reaction, increases phosphorylation, affects cotreatment, increases expression	2
9,10-Dimethyl-1,2-benzanthracene	affects reaction, increases response to substance	2
aristolochic acid I	increases expression	1
ammonium 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)-propanoate	affects cotreatment, affects expression	1
BI-2852	affects binding	1
bathocuproine	affects cotreatment, decreases reaction, increases mutagenesis	1

ChEMBL screening assays

48 unique, capped per target: 45 binding, 3 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1009538	Binding	Inhibition of human recombinant p21RAS by GDPX assay	Ophirapstanol trisulfate, a new biologically active steroid sulfate from the deep water marine sponge Topsentia ophiraphidites. — *J Nat Prod*
CHEMBL685869	Functional	Concentration required to inhibit 50% of the cultured colonies of H-Ras-Fcells.	C-terminal modifications of histidyl-N-benzylglycinamides to give improved inhibition of Ras farnesyltransferase, cellular activity, and anticancer activity in mice. — *J Med Chem*

Cellosaurus cell lines

505 cell lines: 310 cancer cell line, 149 transformed cell line, 29 spontaneously immortalized cell line, 8 telomerase immortalized cell line, 5 hybrid cell line, 4 induced pluripotent stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_0046	HTh83	Cancer cell line	Male
CVCL_0309	HO-23	Transformed cell line	Female
CVCL_0332	Hs 578T	Cancer cell line	Female
CVCL_0505	RL95-2	Cancer cell line	Female
CVCL_0554	T24	Cancer cell line	Female
CVCL_0562	TRM-6/PDX-1	Transformed cell line	Sex unspecified
CVCL_0586	YMB-A	Cancer cell line	Female
CVCL_0588	ZR-75-1	Cancer cell line	Female
CVCL_0590	Kasumi-2	Cancer cell line	Male
CVCL_0U15	BRN-1	Transformed cell line	Sex unspecified

Clinical trials (associated diseases)

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

showing 60 of 452 trials:

NCT	Phase	Status	Title
NCT00339118	Phase 4	UNKNOWN	EpSSG (European Soft Tissue Sarcoma Study Group) Protocol for Non-Metastatic Rhabdomyosarcoma in Children
NCT04854018	Phase 4	COMPLETED	Indo-cyanine Green (ICG) in Paediatric Oncology MIS
NCT01418118	Phase 4	COMPLETED	Assessment of the Effects of Pressors on Graft Blood Flow After Free Tissue Transfer Surgery
NCT03017053	Phase 4	UNKNOWN	The Optimal Neck Treatments Strategy of Early Oral Cancer Based on Adverse Pathological Factor
NCT03684707	Phase 4	UNKNOWN	Cancer Chemoprevention by Metformin Hydrochloride Compared to Placebo in Oral Potentially Malignant Lesions
NCT00162695	Phase 3	TERMINATED	Rhabdomyosarcoma and Malignant Soft Tissue Tumours of Childhood
NCT00354835	Phase 3	COMPLETED	Combination Chemotherapy and Radiation Therapy in Treating Patients With Newly Diagnosed Rhabdomyosarcoma
NCT02567435	Phase 3	ACTIVE_NOT_RECRUITING	Combination Chemotherapy With or Without Temsirolimus in Treating Patients With Intermediate Risk Rhabdomyosarcoma
NCT04994132	Phase 3	ACTIVE_NOT_RECRUITING	A Study to Compare Early Use of Vinorelbine and Maintenance Therapy for Patients With High Risk Rhabdomyosarcoma
NCT06836492	Phase 3	RECRUITING	A Prospective Clinical Cohort Study on Stratified Treatment of Rhabdomyosarcoma Based on Risk Factors.
NCT07466316	Phase 3	RECRUITING	A Study Comparing Higher Dose Chemotherapy Over a Shorter Amount of Time to Lower Dose Chemotherapy Plus Maintenance Over a Longer Amount of Time in Patients With Newly Diagnosed Intermediate-Risk Rhabdomyosarcoma (IR RMS)
NCT00384891	Phase 3	TERMINATED	Hyperthermia Treatment in Conjunction With Mitomycin C Versus Bacillus Calmette-Guérin Immunotherapy (BCG) for Superficial Bladder Cancer
NCT03335059	Phase 3	TERMINATED	Mitomycin C Intravesical Chemotherapy in Conjunction With Synergo® Radiofrequency-Induced Hyperthermia for Treatment of Carcinoma in Situ Non-Muscle Invasive Bladder Cancer Patients Unresponsive to Bacillus Calmette-Guérin, With or Without Papillary Tumors.
NCT04534075	Phase 3	COMPLETED	Dietary Fiber During Radiotherapy - a Placebo-controlled Randomized Trial
NCT05822934	Phase 3	UNKNOWN	Carboplatin-gemcitabine Versus Cisplatin- Gemcitabine as Neoadjuvant Chemotherapy for Treatment of Muscle Invasive Urinary Bladder Cancer
NCT00158652	Phase 3	COMPLETED	Accelerated Radiotherapy and Concomitant Chemo-radiotherapy in HNSCC
NCT00158678	Phase 3	COMPLETED	IMRT Plus Cisplatin Versus Conventional Radiotherapy Plus Cisplatin in Stage III-IV HNSCC
NCT00402779	Phase 3	COMPLETED	Erlotinib Prevention of Oral Cancer (EPOC)
NCT00655421	Phase 3	UNKNOWN	Oral Cancer Screening in Mumbai, India by Primary Health Care Workers
NCT00750503	Phase 3	COMPLETED	Workplace Tobacco Cessation And Oral Cancer Screening Study
NCT00964977	Phase 3	COMPLETED	Effectiveness of Adjuvant Radiotherapy in Small Oropharyngeal Squamous Cell Cancer and Single Lymph Node Metastasis.
NCT01039298	Phase 3	UNKNOWN	Efficacy of Optically-guided Surgery in the Management of Early-staged Oral Cancer - COOLS TRIAL
NCT03685409	Phase 3	UNKNOWN	Cancer Chemoprevention by Metformin Hydrochloride in Oral Potentially Malignant Lesions
NCT05721755	Phase 3	ACTIVE_NOT_RECRUITING	Combining Radiation Therapy With Immunotherapy for the Treatment of Metastatic Squamous Cell Carcinoma of the Head and Neck
NCT06589804	Phase 3	RECRUITING	Testing the Addition of Anti-Cancer Drug, Cetuximab, to Standard of Care Treatment (Pembrolizumab) for Returning or Spreading Head and Neck Cancer After Previous Treatment
NCT06737822	Phase 3	RECRUITING	Upfront Surgery Vs Induction Chemotherapy Followed By Surgery In Oral Cancers:
NCT07402538	Phase 3	NOT_YET_RECRUITING	Surgery With or Without Neoadjuvant Treatment of SBRT Plus Chemoimmunotherapy in Resectable Locally Advanced Oral and HPV-unrelated Oropharyngeal Squamous Cell Carcinoma
NCT07441681	Phase 3	RECRUITING	Comparing Radiation Plus Cetuximab to Radiation Plus Chemotherapy in People With Head and Neck Cancer Who Cannot Receive Cisplatin
NCT07827872	Phase 3	NOT_YET_RECRUITING	Neoadjuvant Sintilimab Plus Chemotherapy for cT2N0M0 Oral Squamous Cell Carcinoma
NCT00001335	Phase 2	COMPLETED	New Therapeutic Strategies for Patients With Ewing’s Sarcoma Family of Tumors, High Risk Rhabdomyosarcoma, and Neuroblastoma
NCT00001564	Phase 2	COMPLETED	A Pilot Study of Tumor-Specific Peptide Vaccination and IL-2 With or Without Autologous T Cell Transplantation in Recurrent Pediatric Sarcomas
NCT00001566	Phase 2	COMPLETED	A Pilot Study of Autologous T-Cell Transplantation With Vaccine Driven Expansion of Anti-Tumor Effectors After Cytoreductive Therapy in Metastatic Pediatric Sarcomas
NCT00180947	Phase 2	UNKNOWN	Study of Vinorelbine and Cyclofosfamide Among Patients With Refractory Tumours or in Relapse
NCT00186992	Phase 2	ACTIVE_NOT_RECRUITING	Radiation Therapy to Treat Musculoskeletal Tumors
NCT00464620	Phase 2	COMPLETED	Trial of Dasatinib in Advanced Sarcomas
NCT00520936	Phase 2	COMPLETED	A Study of Pemetrexed in Children With Recurrent Cancer
NCT00668148	Phase 2	COMPLETED	A Five-Tier, Open-Label Study of IMC-A12 in Advanced Sarcoma
NCT00840047	Phase 2	ACTIVE_NOT_RECRUITING	Methionine PET/CT Studies In Patients With Cancer
NCT01336803	Phase 2	COMPLETED	Differentiation of Bone Sarcomas and Osteomyelitis With Ferumoxytol-Enhanced MRI
NCT01355445	Phase 2	COMPLETED	Vincristine and Irinotecan With or Without Temozolomide in Children and Adults With Refractory/Relapsed Rhabdomyosarcoma
NCT01614795	Phase 2	COMPLETED	Cixutumumab and Temsirolimus in Treating Younger Patients With Recurrent or Refractory Sarcoma
NCT01807468	Phase 2	UNKNOWN	Haploidentical Stem Cell Transplantation and NK Cell Therapy in Patients With High-risk Solid Tumors
NCT01871766	Phase 2	ACTIVE_NOT_RECRUITING	Risk-Adapted Focal Proton Beam Radiation and/or Surgery in Patients With Low, Intermediate and High Risk Rhabdomyosarcoma Receiving Standard or Intensified Chemotherapy
NCT02011126	Phase 2	WITHDRAWN	Imetelstat Sodium in Treating Younger Patients With Relapsed or Refractory Solid Tumors
NCT02048371	Phase 2	COMPLETED	SARC024: A Blanket Protocol to Study Oral Regorafenib in Patients With Selected Sarcoma Subtypes
NCT02100891	Phase 2	TERMINATED	Phase 2 STIR Trial: Haploidentical Transplant and Donor Natural Killer Cells for Solid Tumors
NCT02452554	Phase 2	COMPLETED	Lorvotuzumab Mertansine in Treating Younger Patients With Relapsed or Refractory Wilms Tumor, Rhabdomyosarcoma, Neuroblastoma, Pleuropulmonary Blastoma, Malignant Peripheral Nerve Sheath Tumor, or Synovial Sarcoma
NCT02509598	Phase 2	COMPLETED	A Study of Lymphoseek® as a Lymphoid Tissue Targeting Agent in Pediatric Patients With Melanoma, Rhabdomyosarcoma, or Other Solid Tumors Who Are Undergoing Lymph Node Mapping
NCT02624388	Phase 2	TERMINATED	Study of Genistein in Pediatric Oncology Patients (UVA-Gen001)
NCT02689336	Phase 2	WITHDRAWN	Erlotinib in Combination With Temozolomide in Treating Relapsed/Recurrent/Refractory Pediatric Solid Tumors
NCT02867592	Phase 2	ACTIVE_NOT_RECRUITING	Cabozantinib-S-Malate in Treating Younger Patients With Recurrent, Refractory, or Newly Diagnosed Sarcomas, Wilms Tumor, or Other Rare Tumors
NCT02945800	Phase 2	COMPLETED	Nab-Paclitaxel and Gemcitabine for Recurrent/Refractory Sarcoma
NCT03155620	Phase 2	ACTIVE_NOT_RECRUITING	Targeted Therapy Directed by Genetic Testing in Treating Pediatric Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphomas, or Histiocytic Disorders (The Pediatric MATCH Screening Trial)
NCT03213652	Phase 2	ACTIVE_NOT_RECRUITING	Ensartinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With ALK or ROS1 Genomic Alterations (A Pediatric MATCH Treatment Trial)
NCT03213665	Phase 2	COMPLETED	Tazemetostat in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With EZH2, SMARCB1, or SMARCA4 Gene Mutations (A Pediatric MATCH Treatment Trial)
NCT03213678	Phase 2	COMPLETED	Samotolisib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With TSC or PI3K/MTOR Mutations (A Pediatric MATCH Treatment Trial)
NCT03213704	Phase 2	ACTIVE_NOT_RECRUITING	Larotrectinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With NTRK Fusions (A Pediatric MATCH Treatment Trial)
NCT03220035	Phase 2	COMPLETED	Vemurafenib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With BRAF V600 Mutations (A Pediatric MATCH Treatment Trial)
NCT03233204	Phase 2	COMPLETED	Olaparib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With Defects in DNA Damage Repair Genes (A Pediatric MATCH Treatment Trial)
NCT03526250	Phase 2	COMPLETED	Palbociclib in Treating Patients With Relapsed or Refractory Rb Positive Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With Activating Alterations in Cell Cycle Genes (A Pediatric MATCH Treatment Trial)

Predicted chemistry — Sugi Predict

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