HRAS

Summary

HRAS (HRas proto-oncogene, GTPase, HGNC:5173) is a protein-coding gene on chromosome 11p15.5, encoding GTPase HRas (P01112). Involved in the activation of Ras protein signal transduction. 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): 702 total — 23 pathogenic, 22 likely-pathogenic
• Phenotypes (HPO): 210
• Druggable target: yes — 4 molecules with ChEMBL bioactivity
• Precision-oncology evidence (CIViC): 9 curated variant–drug associations
• Cancer driver (intOGen): activating (oncogene-like) across 14 cancer types
• Dosage sensitivity (ClinGen): haploinsufficiency no evidence, triplosensitivity no evidence
• MANE Select transcript: NM_005343

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: 20 — 16 protein_coding, 2 nonsense_mediated_decay, 1 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000311189, ENST00000397594, ENST00000397596, ENST00000417302, ENST00000451590, ENST00000462734, ENST00000468682, ENST00000479482, ENST00000482021, ENST00000493230, ENST00000879220, ENST00000879221, ENST00000879222, ENST00000879223, ENST00000879224, ENST00000932528, ENST00000932529, ENST00000932530, ENST00000932531, ENST00000932532

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.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
117775	27.6164	1811

Top tissues by expression

139 total, 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

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

Regulation

Is transcription factor: no

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

miRNA regulators (miRDB)

23 targeting HRAS, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

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

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

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	hrasb	ENSDARG00000005651
danio_rerio	zgc:55558	ENSDARG00000013161
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)

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): P01112, A0A804HJ06, A0A804HKM6, A0A8C8MQR2, X5D945

UniProt curated annotations — full annotation on UniProt →

Function. Involved in the activation of Ras protein signal transduction. Ras proteins bind GDP/GTP and possess intrinsic GTPase activity.

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.

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), 1 shown:

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

UniProt features (82 total): mutagenesis site 22, sequence variant 19, strand 12, binding site 5, helix 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)

246 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
2CE2	X-RAY DIFFRACTION	1
2EVW	X-RAY DIFFRACTION	1.05
8TBG	X-RAY DIFFRACTION	1.2
2CLD	X-RAY DIFFRACTION	1.22
2CL6	X-RAY DIFFRACTION	1.24
2CL7	X-RAY DIFFRACTION	1.25
5WDQ	X-RAY DIFFRACTION	1.25
1CTQ	X-RAY DIFFRACTION	1.26
2CLC	X-RAY DIFFRACTION	1.3
3K8Y	X-RAY DIFFRACTION	1.3
3OIW	X-RAY DIFFRACTION	1.3
3TGP	X-RAY DIFFRACTION	1.31
4DLR	X-RAY DIFFRACTION	1.32
3OIU	X-RAY DIFFRACTION	1.32
8BWG	X-RAY DIFFRACTION	1.32
2RGB	X-RAY DIFFRACTION	1.35
5P21	X-RAY DIFFRACTION	1.35
5WDP	X-RAY DIFFRACTION	1.35
8CNJ	X-RAY DIFFRACTION	1.35
3I3S	X-RAY DIFFRACTION	1.36
2RGE	X-RAY DIFFRACTION	1.4
3RS0	X-RAY DIFFRACTION	1.4
9PU1	X-RAY DIFFRACTION	1.4
9PU8	X-RAY DIFFRACTION	1.4
5E95	X-RAY DIFFRACTION	1.4
3L8Z	X-RAY DIFFRACTION	1.44
2RGG	X-RAY DIFFRACTION	1.45
8CNN	X-RAY DIFFRACTION	1.48
2QUZ	X-RAY DIFFRACTION	1.49
8FG3	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 — 2UZI, 2VH5

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): 145–147; 13–18; 29–35; 59–60; 116–119

Post-translational modifications (9): 1, 2, 118, 186, 181, 184, 184, 186, 170

Glycosylation sites (1): 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 isofo
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 go

Function

Pathways and Gene Ontology

Reactome pathways

68 pathways

ID	Pathway
R-HSA-112412	SOS-mediated signalling
R-HSA-1169092	Activation of RAS in B cells
R-HSA-1236382	Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants
R-HSA-1250196	SHC1 events in ERBB2 signaling
R-HSA-1250347	SHC1 events in ERBB4 signaling
R-HSA-1433557	Signaling by SCF-KIT
R-HSA-167044	Signalling to RAS
R-HSA-171007	p38MAPK events
R-HSA-179812	GRB2 events in EGFR signaling
R-HSA-180336	SHC1 events in EGFR signaling
R-HSA-186763	Downstream signal transduction
R-HSA-1963640	GRB2 events in ERBB2 signaling
R-HSA-210993	Tie2 Signaling
R-HSA-2179392	EGFR Transactivation by Gastrin
R-HSA-2424491	DAP12 signaling
R-HSA-2428933	SHC-related events triggered by IGF1R
R-HSA-2871796	FCERI mediated MAPK activation
R-HSA-375165	NCAM signaling for neurite out-growth
R-HSA-3928662	EPHB-mediated forward signaling
R-HSA-442982	Ras activation upon Ca2+ influx through NMDA receptor
R-HSA-5218921	VEGFR2 mediated cell proliferation
R-HSA-5621575	CD209 (DC-SIGN) signaling
R-HSA-5637810	Constitutive Signaling by EGFRvIII
R-HSA-5654688	SHC-mediated cascade:FGFR1
R-HSA-5654693	FRS-mediated FGFR1 signaling
R-HSA-5654699	SHC-mediated cascade:FGFR2
R-HSA-5654700	FRS-mediated FGFR2 signaling
R-HSA-5654704	SHC-mediated cascade:FGFR3
R-HSA-5654706	FRS-mediated FGFR3 signaling
R-HSA-5654712	FRS-mediated FGFR4 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 (44): MAPK cascade (GO:0000165), regulation of transcription by RNA polymerase II (GO:0006357), endocytosis (GO:0006897), 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), positive regulation of type II interferon production (GO:0032729), regulation of actin cytoskeleton organization (GO:0032956), T-helper 1 type immune response (GO:0042088), regulation of cell population proliferation (GO:0042127), myelination (GO:0042552), defense response to protozoan (GO:0042832), positive regulation of MAPK cascade (GO:0043410), negative regulation of neuron apoptotic process (GO:0043524), positive regulation of transcription by RNA polymerase II (GO:0045944), positive regulation of JNK cascade (GO:0046330), fibroblast proliferation (GO:0048144), positive regulation of fibroblast proliferation (GO:0048146), regulation of long-term neuronal synaptic plasticity (GO:0048169), positive regulation of epithelial cell proliferation (GO:0050679), T cell receptor signaling pathway (GO:0050852), neuron apoptotic process (GO:0051402), 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), oncogene-induced cell senescence (GO:0090402), intrinsic apoptotic signaling pathway (GO:0097193), regulation of neurotransmitter receptor localization to postsynaptic specialization membrane (GO:0098696)

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 (14): 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), ciliary basal body (GO:0036064), perinuclear region of cytoplasm (GO:0048471), glutamatergic synapse (GO:0098978), GTPase complex (GO:1905360), nucleus (GO:0005634), endomembrane system (GO:0012505), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-18 pathways:

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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	6
cell population proliferation	3
cytoplasm	3
regulation of cellular process	2
regulation of cell population proliferation	2
guanyl ribonucleotide binding	2
intracellular membrane-bounded organelle	2
intracellular signaling cassette	1
regulation of DNA-templated transcription	1
transcription by RNA polymerase II	1
vesicle budding from membrane	1
membrane invagination	1
vesicle-mediated transport	1
import into cell	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
positive regulation of cytokine production	1
type II interferon production	1
regulation of type II interferon production	1
actin cytoskeleton organization	1

Protein interactions and networks

STRING

6442 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HRAS	TRAF3	Q13114	986
HRAS	RAF1	P04049	986
HRAS	RASA1	P20936	977
HRAS	SOS1	Q07889	977
HRAS	CAV1	Q03135	965
HRAS	BRAF	P15056	953
HRAS	BCL2	P10415	938
HRAS	RASGRF1	Q13972	937
HRAS	EGFR	P00533	931
HRAS	RALGDS	Q12967	920
HRAS	TP53	P04637	894
HRAS	CDKN2A	P42771	893
HRAS	SRC	P12931	891
HRAS	AKT1	P31749	881
HRAS	MYC	P01106	868

IntAct

628 interactions, top by confidence:

A	B	Type	Score
HRAS	RAF1	psi-mi:“MI:0915”(physical association)	0.980
RAF1	HRAS	psi-mi:“MI:0407”(direct interaction)	0.980
HRAS	RAF1	psi-mi:“MI:0407”(direct interaction)	0.980
RAF1	HRAS	psi-mi:“MI:0915”(physical association)	0.980
HRAS	SOS1	psi-mi:“MI:0407”(direct interaction)	0.940
SOS1	HRAS	psi-mi:“MI:0407”(direct interaction)	0.940
HRAS	BRAF	psi-mi:“MI:0407”(direct interaction)	0.940
BRAF	HRAS	psi-mi:“MI:0407”(direct interaction)	0.940
BRAF	HRAS	psi-mi:“MI:0914”(association)	0.940
HRAS	RIN1	psi-mi:“MI:0915”(physical association)	0.930
RIN1	HRAS	psi-mi:“MI:0915”(physical association)	0.930
HRAS	ARAF	psi-mi:“MI:0407”(direct interaction)	0.850
Rassf5	HRAS	psi-mi:“MI:0407”(direct interaction)	0.780

BioGRID (994): ABL2 (Affinity Capture-Western), RIN1 (Affinity Capture-Western), HRAS (Affinity Capture-Western), HRAS (Affinity Capture-Western), LGALS1 (Affinity Capture-Western), HRAS (Affinity Capture-RNA), HRAS (Reconstituted Complex), HRAS (Affinity Capture-MS), HRAS (Affinity Capture-MS), HRAS (Affinity Capture-MS), HRAS (Affinity Capture-MS), HRAS (Affinity Capture-MS), HRAS (Affinity Capture-MS), HRAS (Affinity Capture-MS), HRAS (Affinity Capture-MS)

ESM2 similar proteins: A5A6J7, A6NIZ1, O42277, P01111, P01112, P01116, P03967, P05774, P08556, P08642, P08644, P08645, P12825, P15064, P18262, P18613, P20171, P22123, P22981, P23175, P32883, P34729, P61223, P61224, P62833, P62834, P62835, P62836, P79800, Q04970, Q05147, Q07983, Q18246, Q2MJK3, Q4R9D4, Q5EFX7, Q5F352, Q5RD87, Q5RDM6, Q5ZHX1

Diamond homologs: A5A6J7, A6NIZ1, A8NU18, B3M185, B3NZR4, B4GFJ8, B4HKC7, B4JFU8, B4LY29, B4NJ72, B4PUP5, C4YKT4, G4MZY8, O42277, O42785, O93856, P01111, P01112, P01113, P01115, P01116, P01119, P01120, P03967, P05774, P08556, P08642, P08644, P08645, P08646, P08647, P0CQ42, P0CQ43, P0CY32, P10114, P12825, P13856, P15064, P18613, P20171

SIGNOR signaling

43 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

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 166 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
Endosomal Sorting Complex Required For Transport (ESCRT)	5	18.2×	5e-03

GO biological processes:

GO term	Partners	Fold	FDR
multivesicular body assembly	5	18.7×	3e-03
membrane fission	5	14.6×	6e-03
Ras protein signal transduction	7	10.2×	3e-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).

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	23
Likely pathogenic	22
Uncertain significance	300
Likely benign	274
Benign	39

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1209208	NM_005343.4(HRAS):c.35_36delinsTT (p.Gly12Val)	Pathogenic
12600	NM_005343.4(HRAS):c.35G>T (p.Gly12Val)	Pathogenic
12602	NM_005343.4(HRAS):c.34G>A (p.Gly12Ser)	Pathogenic
12603	NM_005343.4(HRAS):c.35G>C (p.Gly12Ala)	Pathogenic
12604	NM_005343.4(HRAS):c.38G>A (p.Gly13Asp)	Pathogenic
12605	NM_005343.4(HRAS):c.350A>G (p.Lys117Arg)	Pathogenic
12606	NM_005343.4(HRAS):c.37G>T (p.Gly13Cys)	Pathogenic
12607	NM_005343.4(HRAS):c.436G>A (p.Ala146Thr)	Pathogenic
12608	NM_005343.4(HRAS):c.187G>A (p.Glu63Lys)	Pathogenic
12610	NM_005343.4(HRAS):c.173C>T (p.Thr58Ile)	Pathogenic
12613	NM_005343.4(HRAS):c.34G>T (p.Gly12Cys)	Pathogenic
1327492	NM_005343.4(HRAS):c.466T>C (p.Phe156Leu)	Pathogenic
180854	NM_005343.4(HRAS):c.35_36delinsAT (p.Gly12Asp)	Pathogenic
1810343	NM_005343.4(HRAS):c.176C>G (p.Ala59Gly)	Pathogenic
279921	NM_005343.4(HRAS):c.35_36delinsTA (p.Gly12Val)	Pathogenic
29911	NM_005343.4(HRAS):c.110_111+1dup	Pathogenic
29912	NM_005343.4(HRAS):c.108_110dup (p.Glu37dup)	Pathogenic
3340440	NM_005343.4(HRAS):c.203_232dup (p.Gly77_Phe78insTrpAspGlnTyrMetArgThrGlyGluGly)	Pathogenic
391700	NM_005343.4(HRAS):c.179G>T (p.Gly60Val)	Pathogenic
40430	NM_005343.4(HRAS):c.35_36delinsCT (p.Gly12Ala)	Pathogenic
40436	NM_005343.4(HRAS):c.179G>A (p.Gly60Asp)	Pathogenic
462149	NM_005343.4(HRAS):c.186_206dup (p.Glu62_Arg68dup)	Pathogenic
690298	NM_005343.4(HRAS):c.172_177delinsGTCCTGGATGTT (p.Thr58_Ala59delinsValLeuAspVal)	Pathogenic
120223	NM_005343.4(HRAS):c.187_207dup (p.Glu63_Asp69dup)	Likely pathogenic
12609	NM_005343.4(HRAS):c.64C>A (p.Gln22Lys)	Likely pathogenic
12611	NM_005343.4(HRAS):c.437C>T (p.Ala146Val)	Likely pathogenic
1478514	NM_005343.4(HRAS):c.171_185dup (p.Asp57_Gln61dup)	Likely pathogenic
160364	NM_005343.4(HRAS):c.182A>G (p.Gln61Arg)	Likely pathogenic
1691375	NM_005343.4(HRAS):c.191_217dup (p.Met72_Arg73insHisSerAlaMetArgAspGlnTyrMet)	Likely pathogenic
1691376	NM_005343.4(HRAS):c.191_220dup (p.Arg73_Thr74insAsnSerAlaMetArgAspGlnTyrMetArg)	Likely pathogenic

SpliceAI

812 predictions. Top by Δscore:

Variant	Effect	Δscore
11:532751:ACTCC:A	acceptor_gain	1.0000
11:532752:CTCC:C	acceptor_gain	1.0000
11:532752:CTCCC:C	acceptor_gain	1.0000
11:532753:TCC:T	acceptor_gain	1.0000
11:532753:TCCCT:T	acceptor_gain	1.0000
11:532754:CC:C	acceptor_gain	1.0000
11:532754:CCC:C	acceptor_gain	1.0000
11:532755:CC:C	acceptor_gain	1.0000
11:532756:C:CA	acceptor_loss	1.0000
11:532756:C:CC	acceptor_gain	1.0000
11:532756:C:T	acceptor_gain	1.0000
11:533275:A:AC	donor_gain	1.0000
11:533276:C:CC	donor_gain	1.0000
11:533276:CAG:C	donor_gain	1.0000
11:533276:CAGCG:C	donor_gain	1.0000
11:533448:CTCA:C	donor_loss	1.0000
11:533449:TCA:T	donor_loss	1.0000
11:533450:CAC:C	donor_loss	1.0000
11:533451:A:AC	donor_gain	1.0000
11:533451:ACCT:A	donor_loss	1.0000
11:533452:C:CA	donor_loss	1.0000
11:533452:C:CC	donor_gain	1.0000
11:533452:CCTG:C	donor_gain	1.0000
11:533609:CTCC:C	acceptor_gain	1.0000
11:533610:TCC:T	acceptor_gain	1.0000
11:533611:CC:C	acceptor_gain	1.0000
11:533611:CCC:C	acceptor_gain	1.0000
11:533612:CC:C	acceptor_gain	1.0000
11:533612:CCTG:C	acceptor_loss	1.0000
11:533613:C:CC	acceptor_gain	1.0000

AlphaMissense

1238 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:532730:A:C	L159W	1.000
11:533466:G:T	A146D	1.000
11:533552:C:A	K117N	1.000
11:533552:C:G	K117N	1.000
11:533554:T:C	K117E	1.000
11:533555:G:C	N116K	1.000
11:533555:G:T	N116K	1.000
11:533559:C:T	G115E	1.000
11:533560:C:A	G115W	1.000
11:533598:C:G	R102P	1.000
11:533820:A:G	L79P	1.000
11:533822:G:C	F78L	1.000
11:533822:G:T	F78L	1.000
11:533823:A:G	F78S	1.000
11:533824:A:G	F78L	1.000
11:533826:C:T	G77D	1.000
11:533827:C:G	G77R	1.000
11:533832:C:T	G75E	1.000
11:533833:C:A	G75W	1.000
11:533856:A:T	M67K	1.000
11:533866:A:G	Y64H	1.000
11:533877:C:A	G60V	1.000
11:533877:C:T	G60D	1.000
11:533878:C:A	G60C	1.000
11:533878:C:G	G60R	1.000
11:533880:G:T	A59D	1.000
11:533883:G:A	T58I	1.000
11:533885:A:C	D57E	1.000
11:533885:A:T	D57E	1.000
11:533886:T:A	D57V	1.000

dbSNP variants (sampled 300 via entrez): RS1000052897 (11:532216 G>C), RS1001207172 (11:537242 C>A,T), RS1001334619 (11:533125 G>A,C), RS1001590700 (11:537432 C>G,T), RS1002023266 (11:534720 A>G), RS1002344219 (11:534102 G>A), RS1002849852 (11:536663 C>T), RS1002996949 (11:537523 G>A), RS1003078505 (11:532265 G>T), RS1004355475 (11:536446 T>A), RS1004790966 (11:536231 C>G), RS1005954332 (11:532906 G>C,T), RS1006436095 (11:534987 G>A), RS1006886079 (11:534715 C>A,T), RS1007033029 (11:532185 C>G,T)

Disease associations

OMIM: gene MIM:190020 | disease phenotypes: MIM:218040, MIM:167000, MIM:109800, MIM:162900, MIM:188470, MIM:609942, MIM:163950, MIM:163200, MIM:137550, MIM:236750, MIM:601518, MIM:185500, MIM:265500, MIM:135700

GenCC curated gene-disease

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

ClinGen Gene-Disease Validity (2)

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

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

Mondo (33): Costello syndrome (MONDO:0009026), hereditary neoplastic syndrome (MONDO:0015356), ovarian cancer (MONDO:0008170), Noonan syndrome and Noonan-related syndrome (MONDO:0020297), 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), RASopathy (MONDO:0021060)

Orphanet (20): Costello syndrome (Orphanet:3071), Inherited cancer-predisposing syndrome (Orphanet:140162), Rare ovarian cancer (Orphanet:213500), Noonan syndrome and Noonan-related syndrome (Orphanet:98733), Woolly hair nevus (Orphanet:79414), Noonan syndrome (Orphanet:648), Spermatocytic seminoma (Orphanet:99865), RASopathy (Orphanet:536391), Rhabdomyosarcoma (Orphanet:780), Linear nevus sebaceus syndrome (Orphanet:2612), Large/giant congenital melanocytic nevus (Orphanet:626), Non-immune hydrops fetalis (Orphanet:363999), Familial prostate cancer (Orphanet:1331), Epidermolytic nevus (Orphanet:497737), Congenital pulmonary valvar stenosis (Orphanet:3189)

HPO phenotypes

210 total (30 of 210 shown, 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

GWAS associations

0 associations (top):

MeSH disease descriptors (15)

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
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D009386	Neoplastic Syndromes, Hereditary	C04.700; C16.320.700
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
D010051	Ovarian Neoplasms	C04.588.322.455; C12.050.351.500.056.630.705; C12.050.351.937.418.685; C12.100.250.056.630.705; C12.900.418.685; C19.344.410; C19.391.630.705
D012208	Rhabdomyosarcoma	C04.557.450.590.550.660; C04.557.450.795.550.660
D063730	Rickets, Hypophosphatemic	C05.116.198.816.875; C18.452.104.816.875; C18.452.174.845.875; C18.452.750.400.750; C18.654.521.500.133.770.734.875
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.)
C580012	congenital fibrosis of the extraocular muscles (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)

Molecules with ChEMBL bioactivity

4 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 15,434 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL298734	LONAFARNIB	4	12,801
CHEMBL11252	STALLIMYCIN	2	1,910
CHEMBL279433	L-778123 FREE BASE	1	324
CHEMBL351706	BMS-214662	1	399

Clinical evidence (CIViC)

Drug × variant × indication: 9 predictive associations from 9 curated evidence items; also 1 functional, 1 oncogenic, 1 prognostic.

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 Mutation	Selumetinib + Mirdametinib + MTOR Kinase Inhibitor AZD8055 + Everolimus + Binimetinib	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

PharmGKB: 1 entry (VIP=true, CPIC=false)

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

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

30 with measured affinity, of 89 total; 29 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
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
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	decreases reaction, increases response to substance, increases activity, decreases expression, increases expression	5
Benzo(a)pyrene	affects methylation, increases expression, decreases methylation, increases response to substance	4
Estradiol	increases response to substance, decreases reaction, increases expression, affects expression, affects reaction	4
Methylnitrosourea	decreases reaction, increases response to substance	4
Urethane	increases expression, increases reaction, increases response to substance, increases mutagenesis	4
Aflatoxin B1	affects expression, increases expression	4
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one	increases expression, decreases reaction, increases activity	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 prenylation, decreases prenylation, decreases farnesylation, increases reaction, decreases localization (+4 more)	3
perfluorooctanoic acid	affects cotreatment, affects expression, decreases expression	2
2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine	increases expression, increases mutagenesis, affects reaction, increases abundance, increases phosphorylation (+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 expression, increases cleavage, increases reaction, affects cotreatment	2
Lipopolysaccharides	decreases reaction, increases activity, increases localization, increases expression, increases prenylation	2
Lovastatin	decreases localization, decreases prenylation	2
Malathion	affects cotreatment, increases expression	2
Parathion	affects cotreatment, increases expression	2
Quercetin	decreases expression, increases expression	2
Tetradecanoylphorbol Acetate	affects cotreatment, increases expression, affects reaction, increases phosphorylation	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	increases mutagenesis, affects cotreatment, decreases reaction	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

496 cell lines: 301 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)

449 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00339118	PHASE4	UNKNOWN	EpSSG (European Soft Tissue Sarcoma Study Group) Protocol for Non-Metastatic Rhabdomyosarcoma in Children
NCT04854018	PHASE4	COMPLETED	Indo-cyanine Green (ICG) in Paediatric Oncology MIS
NCT00190697	PHASE4	COMPLETED	A Study of LY353381 (Arzoxifene) for Patients Who Benefitted From This Drug in Other Oncology Trials and Wished to Continue Treatment
NCT00277160	PHASE4	COMPLETED	A Study of Primary Prophylaxis With Neulasta (Pegfilgrastim) Versus Secondary Prophylaxis After Chemotherapy in Elderly Subjects (>/= 65 Years Old) With Cancer
NCT00727961	PHASE4	COMPLETED	A Study to Evaluate Efficacy and Tolerance of Caelyx in Patients With Epithelial Ovarian Cancer. (Study P04072)(COMPLETED)
NCT00740116	PHASE4	COMPLETED	Tranexamic Acid in Surgery of Advanced Ovarian Cancer
NCT00817479	PHASE4	COMPLETED	Tumor Gene Expression in Women With Ovarian Cancer
NCT01432015	PHASE4	COMPLETED	Fosaprepitant Versus Aprepitant in the Prevention of Chemotherapy Induced Nausea and Vomiting
NCT01706120	PHASE4	UNKNOWN	Study of Clinical and Biological Prognostic Factors in Patients With Ovarian Cancer Receiving Carboplatin +Paclitaxel With Bevacizumab
NCT01932125	PHASE4	COMPLETED	An Interventional Study of Avastin (Bevacizumab) in Patients With Advanced/Metastatic Epithelial Ovarian Cancer, Fallopian Tube Cancer or Primary Peritoneal Cancer
NCT01953107	PHASE4	COMPLETED	Oral Iron vs. Placebo in Newly Diagnosed Gynecologic Oncology Patients Who Are Surgical Candidates.
NCT02035345	PHASE4	TERMINATED	Slowed Carboplatin Infusion for Ovarian Cancer Patients Receiving Carboplatin Re-Treatment
NCT02243059	PHASE4	WITHDRAWN	Magnetic Resonance Imaging for Lymph Node Staging in Ovarian Cancer
NCT03164980	PHASE4	TERMINATED	QoL-Comparison Between Trabectedin/PLD and Pt-based Therapy in Patients With Pt-sensitive Recurrent Ovarian Cancer
NCT03384511	PHASE4	COMPLETED	The Use of 18F-ALF-NOTA-PRGD2 PET/CT Scan to Predict the Efficacy and Adverse Events of Apatinib in Malignancies.
NCT03543462	PHASE4	COMPLETED	Diaphragmatic Resection And Gynecological Ovarian Neoplasm
NCT03752216	PHASE4	COMPLETED	NIraparib and Quality of LifE is a Longitudinal Study Evaluating in Real Life the Tolerability of Niraparib.
NCT03858166	PHASE4	TERMINATED	Efficacy and Safety of PEG-rhG-CSF Secondary Prophylaxis vs. Therapeutic Administration in Patients With Ovarian Cancer
NCT04024254	PHASE4	COMPLETED	A Study of Serum Folate Levels in Patients Treated With Olaparib
NCT04330040	PHASE4	COMPLETED	Prospective Multicentre Phase-IV Clinical Trial of Olaparib in Indian Patients With Ovarian and Metastatic Breast Cancer
NCT04352439	PHASE4	COMPLETED	Aspirin for Prevention of Venous Thromboembolism Among Ovarian Cancer Patients Receiving Neoadjuvant Chemotherapy
NCT05187208	PHASE4	UNKNOWN	PARP Inhibitor Oral Maintenance in Low-Risk Ovarian Cancer
NCT05606692	PHASE4	RECRUITING	Influences of Propofol and Sevoflurane Anesthesia in Ovarian Cancer (Anesthetics)
NCT05926336	PHASE4	RECRUITING	The Effects of Using Different Anesthetics on the Prognosis of Primary Tumors and Its Mechanism of Action
NCT06412120	PHASE4	RECRUITING	Study Evaluating Safety, Tolerability, and Metabolism of Niraparib
NCT06871787	PHASE4	NOT_YET_RECRUITING	Near-Infrared Fluorescence Imaging With Indocyanine Green to Evaluate Bowel Anastomoses in Gynecologic Oncology Surgery
NCT06887933	PHASE4	NOT_YET_RECRUITING	A Trial to Evaluate the Safety of Niraparib Tablets in Adult Female Participants With Advanced or Relapsed Epithelial Ovarian Cancer
NCT07469202	PHASE4	NOT_YET_RECRUITING	CYTALUX Dose Extension Study
NCT00162695	PHASE3	TERMINATED	Rhabdomyosarcoma and Malignant Soft Tissue Tumours of Childhood
NCT00354835	PHASE3	COMPLETED	Combination Chemotherapy and Radiation Therapy in Treating Patients With Newly Diagnosed Rhabdomyosarcoma
NCT02567435	PHASE3	ACTIVE_NOT_RECRUITING	Combination Chemotherapy With or Without Temsirolimus in Treating Patients With Intermediate Risk Rhabdomyosarcoma
NCT04994132	PHASE3	ACTIVE_NOT_RECRUITING	A Study to Compare Early Use of Vinorelbine and Maintenance Therapy for Patients With High Risk Rhabdomyosarcoma
NCT06836492	PHASE3	RECRUITING	A Prospective Clinical Cohort Study on Stratified Treatment of Rhabdomyosarcoma Based on Risk Factors.
NCT07466316	PHASE3	NOT_YET_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)
NCT00001806	PHASE3	COMPLETED	Methods in Education for Breast Cancer Genetics
NCT00002477	PHASE3	UNKNOWN	Adjuvant Chemotherapy Compared With Observation in Treating Patients With Resected Early Stage Ovarian Epithelial Cancer
NCT00002568	PHASE3	COMPLETED	Combination Chemotherapy With or Without Surgery in Treating Patients With Stage III Ovarian Epithelial Cancer
NCT00002641	PHASE3	COMPLETED	Surgery With or Without Chemotherapy in Treating Patients With Soft Tissue Sarcoma
NCT00002717	PHASE3	COMPLETED	Paclitaxel and Cisplatin in Treating Patients With Stage III or Stage IV Ovarian Cancer or Primary Peritoneal Cancer
NCT00002764	PHASE3	COMPLETED	Surgery With or Without Combination Chemotherapy in Treating Patients With Lung Metastases From Soft Tissue Sarcoma