RASA2

Summary

RASA2 (RAS p21 protein activator 2, HGNC:9872) is a protein-coding gene on chromosome 3q23, encoding Ras GTPase-activating protein 2 (Q15283). Inhibitory regulator of the Ras-cyclic AMP pathway.

The protein encoded by this gene is member of the GAP1 family of GTPase-activating proteins. The gene product stimulates the GTPase activity of normal RAS p21 but not its oncogenic counterpart. Acting as a suppressor of RAS function, the protein enhances the weak intrinsic GTPase activity of RAS proteins resulting in the inactive GDP-bound form of RAS, thereby allowing control of cellular proliferation and differentiation. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 5922 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Noonan syndrome (Moderate, GenCC)
• GWAS associations: 75
• Clinical variants (ClinVar): 850 total — 1 likely-pathogenic
• Phenotypes (HPO): 70
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 1 cancer types
• MANE Select transcript: NM_006506

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9872
Approved symbol	RASA2
Name	RAS p21 protein activator 2
Location	3q23
Locus type	gene with protein product
Status	Approved
Aliases	GAP1M
Ensembl gene	ENSG00000155903
Ensembl biotype	protein_coding
OMIM	601589
Entrez	5922

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 9 protein_coding, 4 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000286364, ENST00000505833, ENST00000506365, ENST00000509032, ENST00000509118, ENST00000515549, ENST00000884961, ENST00000884962, ENST00000884963, ENST00000884964, ENST00000884965, ENST00000930693, ENST00000950127, ENST00000950128

RefSeq mRNA: 3 — MANE Select: NM_006506 NM_001303245, NM_001303246, NM_006506

CCDS: CCDS3117

Canonical transcript exons

ENST00000286364 — 24 exons

Exon	Start	End
ENSE00001023305	141573944	141574067
ENSE00001023313	141573147	141573221
ENSE00001023332	141609877	141610066
ENSE00001023333	141577000	141577106
ENSE00002035040	141612283	141615344
ENSE00002334495	141570912	141571068
ENSE00002336584	141553857	141553940
ENSE00002378486	141555840	141555912
ENSE00002399062	141540533	141540609
ENSE00002404012	141572609	141572723
ENSE00002415194	141571406	141571554
ENSE00002415458	141559894	141559995
ENSE00002427826	141558886	141558962
ENSE00002701007	141487027	141487216
ENSE00003521046	141529708	141529802
ENSE00003547468	141581100	141581177
ENSE00003565491	141512163	141512280
ENSE00003571870	141586025	141586098
ENSE00003583786	141580368	141580451
ENSE00003594806	141586646	141586752
ENSE00003619180	141607678	141607760
ENSE00003667450	141608489	141608697
ENSE00003677942	141609420	141609523
ENSE00003683393	141516328	141516431

Expression profiles

Bgee: expression breadth ubiquitous, 269 present calls, max score 96.11.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 24.3044 / max 565.2428, expressed in 1801 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
38927	23.0891	1796
38926	1.2152	682

Top tissues by expression

295 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
epithelium of nasopharynx	UBERON:0001951	96.11	gold quality
superficial temporal artery	UBERON:0001614	95.71	gold quality
trabecular bone tissue	UBERON:0002483	95.14	gold quality
nipple	UBERON:0002030	94.91	gold quality
tibia	UBERON:0000979	94.43	gold quality
skin of hip	UBERON:0001554	94.41	gold quality
visceral pleura	UBERON:0002401	93.54	gold quality
Brodmann (1909) area 23	UBERON:0013554	93.48	gold quality
parietal pleura	UBERON:0002400	93.30	gold quality
calcaneal tendon	UBERON:0003701	93.19	gold quality
mucosa of sigmoid colon	UBERON:0004993	93.09	gold quality
mucosa of paranasal sinus	UBERON:0005030	92.27	gold quality
pleura	UBERON:0000977	92.00	gold quality
oral cavity	UBERON:0000167	91.50	gold quality
colonic mucosa	UBERON:0000317	90.99	gold quality
esophagus squamous epithelium	UBERON:0006920	90.74	gold quality
germinal epithelium of ovary	UBERON:0001304	90.27	gold quality
amniotic fluid	UBERON:0000173	90.25	gold quality
pylorus	UBERON:0001166	90.10	gold quality
jejunal mucosa	UBERON:0000399	89.72	gold quality
urethra	UBERON:0000057	89.67	gold quality
seminal vesicle	UBERON:0000998	89.62	gold quality
dorsal root ganglion	UBERON:0000044	89.57	gold quality
bone marrow	UBERON:0002371	89.38	gold quality
upper leg skin	UBERON:0004262	89.38	gold quality
cauda epididymis	UBERON:0004360	89.36	gold quality
blood	UBERON:0000178	89.34	gold quality
bronchial epithelial cell	CL:0002328	89.12	gold quality
tonsil	UBERON:0002372	89.00	gold quality
mammalian vulva	UBERON:0000997	88.95	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	12.91

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

156 targeting RASA2, 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-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-6888-3P	99.97	65.95	1170
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753

Literature-anchored findings (GeneRIF, showing 7)

• GAP1m is a Ras GAP that switches off Ras signalling. GAP1m undergoes a plasma membrane association following growth factor stimulation of PI 3-kinase as a result of its PH domain binding to phosphatidylinositol 3,4,5-trisphosphate. (PMID:10074452)
• Recurrent inactivating RASA2 mutations are associated with melanoma. (PMID:26502337)
• The SNP of ZBTB38-RASA2 was significantly related with the appearance of myoclonus in sporadic Creutzfeldt-Jacob disease patients. (PMID:29216791)
• Authors found that knockdown of RASA2 inhibited MTC cell proliferation. (PMID:31298226)
• Genome-wide association study in the Taiwan Biobank identifies four novel genes for human height: NABP2, RASA2, RNF41 and SLC39A5. (PMID:34270706)
• RASA2 ablation in T cells boosts antigen sensitivity and long-term function. (PMID:36002574)
• [Effect of circRASA2 targeting miR-543/TRAF6 axis on LPS-induced periodontal ligament cell proliferation and osteogenic differentiation]. (PMID:37153995)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	RASA2	ENSDARG00000078775
mus_musculus	Rasa2	ENSMUSG00000032413
rattus_norvegicus	Rasa2	ENSRNOG00000011909
drosophila_melanogaster	RasGAP1	FBGN0004390
drosophila_melanogaster	raskol	FBGN0261570
caenorhabditis_elegans		WBGENE00001515
caenorhabditis_elegans		WBGENE00001516

Paralogs (10): RASAL2 (ENSG00000075391), RASAL3 (ENSG00000105122), RASA4 (ENSG00000105808), RASAL1 (ENSG00000111344), DAB2IP (ENSG00000136848), RASA1 (ENSG00000145715), RASA4B (ENSG00000170667), RASA3 (ENSG00000185989), NF1 (ENSG00000196712), SYNGAP1 (ENSG00000197283)

Protein

Protein identifiers

Ras GTPase-activating protein 2 — Q15283 (reviewed: Q15283)

Alternative names: GTPase-activating protein 1m

All UniProt accessions (2): Q15283, D6RBA9

UniProt curated annotations — full annotation on UniProt →

Function. Inhibitory regulator of the Ras-cyclic AMP pathway. Binds inositol tetrakisphosphate (IP4).

Subcellular location. Cytoplasm. Perinuclear region.

Isoforms (2)

UniProt ID	Names	Canonical?
Q15283-1	1	yes
Q15283-2	2

RefSeq proteins (3): NP_001290174, NP_001290175, NP_006497* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000008	C2_dom	Domain
IPR001562	Znf_Btk_motif	Conserved_site
IPR001849	PH_domain	Domain
IPR001936	RasGAP_dom	Domain
IPR008936	Rho_GTPase_activation_prot	Homologous_superfamily
IPR011993	PH-like_dom_sf	Homologous_superfamily
IPR023152	RasGAP_CS	Conserved_site
IPR035892	C2_domain_sf	Homologous_superfamily
IPR037773	RASA2_PH	Domain
IPR039360	Ras_GTPase	Family

Pfam: PF00168, PF00169, PF00616, PF00779

UniProt features (21 total): binding site 4, domain 4, sequence conflict 3, modified residue 2, region of interest 2, initiator methionine 1, chain 1, site 1, splice variant 1, zinc finger region 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q15283-F1	83.63	0.48

Functional residue map

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

Catalytic / active sites (1): 397 (arginine finger; crucial for gtp hydrolysis by stabilizing the transition state)

Ligand- & substrate-binding residues (4): 716; 727; 728; 738

Post-translational modifications (2): 2, 555

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-5658442	Regulation of RAS by GAPs

MSigDB gene sets: 393 (showing top): KEGG_MAPK_SIGNALING_PATHWAY, GOBP_REGULATION_OF_SMALL_GTPASE_MEDIATED_SIGNAL_TRANSDUCTION, GOBP_NEGATIVE_REGULATION_OF_SMALL_GTPASE_MEDIATED_SIGNAL_TRANSDUCTION, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, WANG_RESPONSE_TO_BEXAROTENE_UP, BROWNE_HCMV_INFECTION_14HR_DN, GOBP_RAS_PROTEIN_SIGNAL_TRANSDUCTION, LYF1_01, HNF1_C, RYTTCCTG_ETS2_B, IK2_01, CUI_TCF21_TARGETS_2_DN, GOBP_SMALL_GTPASE_MEDIATED_SIGNAL_TRANSDUCTION, AACTGGA_MIR145, TAATTA_CHX10_01

GO Biological Process (5): signal transduction (GO:0007165), intracellular signal transduction (GO:0035556), negative regulation of Ras protein signal transduction (GO:0046580), regulation of intracellular signal transduction (GO:1902531), regulation of GTPase activity (GO:0043087)

GO Molecular Function (5): GTPase activator activity (GO:0005096), phospholipid binding (GO:0005543), zinc ion binding (GO:0008270), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (3): cytosol (GO:0005829), perinuclear region of cytoplasm (GO:0048471), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
RAF/MAP kinase cascade	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
intracellular anatomical structure	2
GTPase activity	2
cytoplasm	2
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
signal transduction	1
Ras protein signal transduction	1
regulation of Ras protein signal transduction	1
negative regulation of small GTPase mediated signal transduction	1
regulation of signal transduction	1
intracellular signal transduction	1
regulation of hydrolase activity	1
enzyme activator activity	1
GTPase regulator activity	1
lipid binding	1
transition metal ion binding	1
binding	1
cation binding	1

Protein interactions and networks

STRING

806 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RASA2	SHOC2	Q9UQ13	636
RASA2	SOS1	Q07889	626
RASA2	A2ML1	A8K2U0	622
RASA2	LZTR1	Q8N653	607
RASA2	SOS2	Q07890	603
RASA2	RRAS	P10301	597
RASA2	RAP1A	P10113	597
RASA2	NRAS	P01111	572
RASA2	PTPN11	Q06124	556
RASA2	RASA1	P20936	545
RASA2	ZBTB38	Q8NAP3	540
RASA2	PLEK2	Q9NYT0	517
RASA2	PLEK	P08567	517
RASA2	SPRED1	Q7Z699	516
RASA2	MAP2K2	P36507	510

IntAct

6 interactions, top by confidence:

A	B	Type	Score
RASA2	NOLC1	psi-mi:“MI:0915”(physical association)	0.500
RASA2	SH3PXD2B	psi-mi:“MI:0915”(physical association)	0.400
HDGFL2	CIBAR1	psi-mi:“MI:0914”(association)	0.350
CD6	CIBAR1	psi-mi:“MI:0914”(association)	0.350
RASA2	DKC1	psi-mi:“MI:0914”(association)	0.350

BioGRID (32): RASA2 (Co-fractionation), RASA2 (Affinity Capture-RNA), RASA2 (Affinity Capture-MS), RASA2 (Affinity Capture-MS), RASA2 (Reconstituted Complex), RASA2 (Proximity Label-MS), TOE1 (Affinity Capture-MS), MLLT3 (Affinity Capture-MS), NBN (Affinity Capture-MS), DKC1 (Affinity Capture-MS), WDR70 (Affinity Capture-MS), RASA2 (Affinity Capture-MS), RASA2 (Affinity Capture-MS), RASA2 (Affinity Capture-MS), TCOF1 (Affinity Capture-MS)

ESM2 similar proteins: A0A1B0GW35, A6QNM3, B0R034, B1ANS9, B9EK06, D2KC46, D3ZY60, F1MS15, F1P065, F1REV3, O00522, O15091, O75747, P10911, P58069, Q008S8, Q14449, Q14D04, Q15283, Q32NR9, Q45GW3, Q4R366, Q4R6T7, Q5H9U9, Q5K651, Q5PQS3, Q5XGX5, Q5XIZ9, Q5ZLD2, Q60862, Q63713, Q69Z37, Q6DCF6, Q6S5J6, Q6TNJ1, Q75PQ8, Q80W71, Q86VD1, Q86YR7, Q8C5W4

Diamond homologs: A6QQ91, F6SEU4, P48423, P97526, Q14644, Q15283, Q28013, Q3UHC7, Q54Y08, Q5VWQ8, Q60790, Q6P730, Q86YV0, Q8C2K5, Q8MLZ5, Q8T498, Q96PV0, Q9QUH6, Q9QYJ2, Q9UJF2, Q9Z268, P58069, Q63713, P18963, P19158, P33277, O95294, P09851, P20936, P50904, P21359, P41823, P42680, Q04690, Q5M7N9, Q5T7P8, Q62746, Q99N80, P35608, C9J798

SIGNOR signaling

0 interactions.

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: loss-of-function (tumor-suppressor-like) across 1 cancer types — DLBCLNOS.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	456
Likely benign	299
Benign	42

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
2674586	NM_006506.5(RASA2):c.716C>T (p.Ser239Phe)	Likely pathogenic

SpliceAI

4125 predictions. Top by Δscore:

Variant	Effect	Δscore
3:141487212:GATCT:G	donor_gain	1.0000
3:141487213:A:G	donor_gain	1.0000
3:141487217:G:GG	donor_gain	1.0000
3:141509671:A:T	donor_gain	1.0000
3:141509674:G:GG	donor_gain	1.0000
3:141512276:TTAAG:T	donor_loss	1.0000
3:141512278:AAG:A	donor_loss	1.0000
3:141512280:GGTT:G	donor_loss	1.0000
3:141512281:G:GC	donor_loss	1.0000
3:141516326:A:AG	acceptor_gain	1.0000
3:141516327:G:GG	acceptor_gain	1.0000
3:141516327:GC:G	acceptor_gain	1.0000
3:141516327:GCC:G	acceptor_gain	1.0000
3:141516327:GCCC:G	acceptor_gain	1.0000
3:141516327:GCCCA:G	acceptor_gain	1.0000
3:141540610:G:GG	donor_gain	1.0000
3:141558883:CA:C	acceptor_loss	1.0000
3:141558884:A:AG	acceptor_gain	1.0000
3:141558884:A:G	acceptor_loss	1.0000
3:141558885:G:GT	acceptor_gain	1.0000
3:141558885:GGT:G	acceptor_gain	1.0000
3:141558885:GGTA:G	acceptor_gain	1.0000
3:141558959:TCAGG:T	donor_loss	1.0000
3:141558960:CAGG:C	donor_loss	1.0000
3:141558961:AGGTA:A	donor_loss	1.0000
3:141558962:GGTA:G	donor_loss	1.0000
3:141558963:G:GA	donor_loss	1.0000
3:141558964:T:G	donor_loss	1.0000
3:141559991:GCCTG:G	donor_gain	1.0000
3:141571018:GA:G	donor_gain	1.0000

AlphaMissense

5629 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000011787 (3:141515253 TA>T,TAA), RS1000022896 (3:141502227 G>C), RS1000089060 (3:141546399 T>C,G), RS1000096542 (3:141595873 C>T), RS1000115014 (3:141495120 T>G), RS1000116653 (3:141508370 T>G), RS1000172179 (3:141508448 G>C), RS1000189056 (3:141491114 C>G,T), RS1000203587 (3:141508751 T>A), RS1000269362 (3:141553138 G>T), RS1000278050 (3:141615152 A>C), RS1000318557 (3:141540062 A>G), RS1000326101 (3:141598133 G>A), RS1000335709 (3:141571303 C>T), RS1000339578 (3:141566756 G>T)

Disease associations

OMIM: gene MIM:601589 | disease phenotypes: MIM:163950

GenCC curated gene-disease

Disease	Classification	Inheritance
Noonan syndrome	Moderate	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
Noonan syndrome	Limited	AD

Mondo (3): Noonan syndrome 1 (MONDO:0008104), Noonan syndrome (MONDO:0018997), hereditary neoplastic syndrome (MONDO:0015356)

Orphanet (2): Noonan syndrome (Orphanet:648), Inherited cancer-predisposing syndrome (Orphanet:140162)

HPO phenotypes

70 total (30 of 70 shown, HPO-id order):

HPO	Term
HP:0000028	Cryptorchidism
HP:0000044	Hypogonadotropic hypogonadism
HP:0000078	Abnormality of the genital system
HP:0000179	Thick lower lip vermilion
HP:0000218	High palate
HP:0000316	Hypertelorism
HP:0000325	Triangular face
HP:0000347	Micrognathia
HP:0000348	High forehead
HP:0000358	Posteriorly rotated ears
HP:0000391	Thickened helices
HP:0000407	Sensorineural hearing impairment
HP:0000465	Webbed neck
HP:0000474	Thickened nuchal skin fold
HP:0000476	Cystic hygroma
HP:0000486	Strabismus
HP:0000494	Downslanted palpebral fissures
HP:0000508	Ptosis
HP:0000520	Proptosis
HP:0000635	Blue irides
HP:0000639	Nystagmus
HP:0000767	Pectus excavatum
HP:0000768	Pectus carinatum
HP:0000938	Osteopenia
HP:0000978	Bruising susceptibility
HP:0000995	Melanocytic nevus
HP:0001004	Lymphedema
HP:0001156	Brachydactyly
HP:0001249	Intellectual disability
HP:0001252	Hypotonia

GWAS associations

75 associations (top):

Study	Trait	p-value
GCST001366_2	Prion diseases	2.000000e-06
GCST001765_41	Red blood cell traits	4.000000e-11
GCST002783_26	Body mass index	5.000000e-08
GCST002783_290	Body mass index	2.000000e-10
GCST002783_546	Body mass index	4.000000e-10
GCST004495_92	BMI (adjusted for smoking behaviour)	2.000000e-06
GCST004495_93	BMI (adjusted for smoking behaviour)	3.000000e-12
GCST004495_94	BMI (adjusted for smoking behaviour)	9.000000e-08
GCST004497_34	Body mass index (joint analysis main effects and smoking interaction)	2.000000e-11
GCST004497_35	Body mass index (joint analysis main effects and smoking interaction)	3.000000e-07
GCST004497_36	Body mass index (joint analysis main effects and smoking interaction)	1.000000e-06
GCST004499_97	BMI in non-smokers	2.000000e-11
GCST004499_98	BMI in non-smokers	5.000000e-08
GCST004557_162	Body mass index	7.000000e-09
GCST004557_181	Body mass index	1.000000e-07
GCST004557_266	Body mass index	7.000000e-06
GCST004557_46	Body mass index	8.000000e-11
GCST004557_88	Body mass index	6.000000e-06
GCST004558_194	Body mass index (joint analysis main effects and physical activity interaction)	6.000000e-07
GCST004558_212	Body mass index (joint analysis main effects and physical activity interaction)	8.000000e-06
GCST004558_230	Body mass index (joint analysis main effects and physical activity interaction)	3.000000e-10
GCST004558_81	Body mass index (joint analysis main effects and physical activity interaction)	8.000000e-09
GCST004559_120	Body mass index in physically active individuals	6.000000e-06
GCST004559_159	Body mass index in physically active individuals	6.000000e-09
GCST004559_76	Body mass index in physically active individuals	5.000000e-07
GCST004602_135	Mean corpuscular volume	5.000000e-30
GCST004602_136	Mean corpuscular volume	2.000000e-16
GCST004608_80	Granulocyte percentage of myeloid white cells	2.000000e-10
GCST004609_117	Monocyte percentage of white cells	3.000000e-18
GCST004610_62	White blood cell count	9.000000e-10

EFO canonical traits (18, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0004318	smoking behavior
EFO:0008002	physical activity measurement
EFO:0007997	granulocyte percentage of myeloid white cells
EFO:0007989	monocyte percentage of leukocytes
EFO:0004833	neutrophil count
EFO:0004842	eosinophil count
EFO:0007987	granulocyte count
EFO:0005090	basophil count
EFO:0005091	monocyte count
EFO:0004527	mean corpuscular hemoglobin
EFO:0004341	body fat distribution
EFO:0004338	body weight
EFO:0009819	comparative body size at age 10, self-reported
EFO:0007789	BMI-adjusted waist circumference
EFO:0008039	BMI-adjusted hip circumference
EFO:0010701	mean reticulocyte volume
EFO:0004305	erythrocyte count

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
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

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression	7
trichostatin A	affects cotreatment, decreases expression	3
entinostat	decreases expression, affects cotreatment	2
Resveratrol	affects cotreatment, increases expression	2
Vorinostat	affects cotreatment, decreases expression	2
Panobinostat	affects cotreatment, decreases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Cyclosporine	increases expression	2
aristolochic acid I	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects cotreatment, increases methylation	1
sodium arsenite	decreases expression	1
1-nitropyrene	increases expression	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
jinfukang	decreases expression	1
Sunitinib	increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Acetaminophen	increases expression	1
Air Pollutants	affects expression, increases abundance	1
Arsenic	affects methylation	1
Chelating Agents	affects binding, increases expression	1
Copper	affects binding, increases expression	1
Succimer	affects cotreatment, increases expression	1
Doxorubicin	decreases expression	1
Formaldehyde	decreases expression	1
Ozone	affects expression, increases abundance	1
Plant Extracts	affects cotreatment, increases expression	1

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D9QA	Ubigene HEK293 RASA2 KO	Transformed cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00452725	PHASE3	COMPLETED	Effect of MAXOMAT ® on the Growth of Small Children to NOONAN’s Syndrome
NCT01529840	PHASE3	COMPLETED	Somatropin Effect on Linear Growth and Final Height in Subjects With Noonan Syndrome
NCT01529944	PHASE3	COMPLETED	Genetic Testing of Noonan Subjects Previously Treated With Norditropin®. An Extension to Trial GHNOO-1658
NCT01927861	PHASE3	COMPLETED	Investigating the Long-term Efficacy and Safety of Two Doses of NN-220 (Somatropin) in Short Stature Due to Noonan Syndrome
NCT02713945	PHASE3	COMPLETED	Treatment With HMG-COA Reductase Inhibitor of Growth and Bone Abnormalities in Children With Noonan Syndrome
NCT05723835	PHASE3	ACTIVE_NOT_RECRUITING	A Research Study Looking at How Safe Somapacitan is and How Well it Works in Children Who Need Help to Grow - REAL 9
NCT00351221	PHASE2	TERMINATED	Research Study Using Recombinant Human Insulin-Like Growth Factor-1/Recombinant Human Insulin-Like Growth Factor Binding Protein-3 for Children With Noonan Syndrome
NCT06555237	PHASE2	RECRUITING	MEK Inhibitors for the Treatment of Hypertrophic Cardiomyopathy in Patients With RASopathies
NCT06668805	PHASE2	RECRUITING	A Study of Vosoritide in Children With Noonan Syndrome With Inadequate Growth During or After Human Growth Hormone Treatment
NCT00960128	Not specified	COMPLETED	Observational Prospective Study on Patients Treated With Norditropin®
NCT02486731	Not specified	COMPLETED	Hormonal Sensitivity in Patients With Noonan and LEOPARD Syndromes
NCT03435627	Not specified	COMPLETED	Post Marketing Surveillance on Long-term Use With Norditropin® (Short Stature Due to Noonan Syndrome)
NCT04395495	Not specified	RECRUITING	RASopathy Biorepository
NCT04463316	Not specified	RECRUITING	GROWing Up With Rare GENEtic Syndromes
NCT04888936	Not specified	RECRUITING	Clinical, Genetic, and Epidemiologic Study of Children and Adults With RASopathies
NCT05202210	Not specified	RECRUITING	Constitution of a Biological Collection to Study the Pathophysiology in Noonan Syndrome
NCT05308927	Not specified	ENROLLING_BY_INVITATION	French Registry of Children Treated With Norditropin® for Short Stature Associated With Noonan Syndrome
NCT05361811	Not specified	RECRUITING	Acceptance and Commitment Therapy for Caregivers of Children With a RASopathy: An Internal Pilot Feasibility Study and Follow-up Randomized Controlled Trial
NCT05761314	Not specified	RECRUITING	Solid Tumors in RASopathies
NCT06267807	Not specified	COMPLETED	Lymphatic Phenotype in Noonan Syndrome Spectrum Disorders
NCT06331117	Not specified	UNKNOWN	Effect of RAS/MAPK Pathway Hyperactivation on Growth’ and Bone’ Profile of the RASopathies
NCT06355622	Not specified	UNKNOWN	Prevalence and Characterization of Pain in RASopathies
NCT06550635	Not specified	COMPLETED	Joint and Hematologic Disorders of Noonan Syndrome: French Descriptive Cross-sectional Study
NCT06938542	Not specified	ENROLLING_BY_INVITATION	Palliative Care Needs of Children With Rare Diseases and Their Families
NCT07259135	Not specified	NOT_YET_RECRUITING	Link Between Abnormal Bleeding and Coagulation Disorders in Noonan Syndromes
NCT07336394	Not specified	RECRUITING	Precision Diagnosis and Risk Stratification of Rare Cardiomyopathies Based on Novel Cardiac Magnetic Resonance Techniques
NCT07464821	Not specified	RECRUITING	National Multicentre Study on Lipid Profile in Noonan Syndrome and Related Disorders: Trends by Age, Gender and Genotype
NCT00001496	Not specified	COMPLETED	Establishment of Normal Breast Epithelial Cell Lines From Patients at High Risk for Breast Cancer
NCT00001898	Not specified	COMPLETED	Microarray Analysis for Human Genetic Disease
NCT00026884	Not specified	RECRUITING	Collection of Serum and Tissue Samples From Patients With Biopsy-Proved or Suspected Malignant Disease
NCT02289326	Not specified	COMPLETED	Biomarker Monitoring in TP53 Mutation Carriers
NCT02958462	Not specified	RECRUITING	Pre-myeloid Cancer and Bone Marrow Failure Clinic Study
NCT03160274	Not specified	RECRUITING	Genetic Analysis of Pheochromocytomas, Paragangliomas and Associated Conditions
NCT03426878	Not specified	COMPLETED	Cancer Health Assessments Reaching Many
NCT03857594	Not specified	ACTIVE_NOT_RECRUITING	Integrative Sequencing In Germline and Hereditary Tumours
NCT03973450	Not specified	UNKNOWN	Epidemiology of Pituitary Tumours: Prevalence of Associated Neoplasia
NCT03979612	Not specified	UNKNOWN	Evaluation of the Adhesion to the GENEPY Network
NCT04261972	Not specified	ACTIVE_NOT_RECRUITING	Cell-free DNA in Hereditary And High-Risk Malignancies 1
NCT04494945	Not specified	RECRUITING	Identifying and Caring for Individuals With Inherited Cancer Syndrome
NCT04541654	Not specified	RECRUITING	Li-Fraumeni & TP53 (LiFT UP): Understanding and Progress