RASA1

Summary

RASA1 (RAS p21 protein activator 1, HGNC:9871) is a protein-coding gene on chromosome 5q14.3, encoding Ras GTPase-activating protein 1 (P20936). GTPase-activating protein (GAP) that stimulates the intrinsic GTPase activity of Ras proteins, such as NRAS, facilitating their transition from the active GTP-bound state to the inactive GDP-bound state, thereby terminating Ras signaling. In precision oncology, RASA1 Loss-of-function confers sensitivity to Trametinib in Lung Non-small Cell Carcinoma (CIViC Level D). It is haploinsufficient (ClinGen: sufficient evidence).

The protein encoded by this gene is located in the cytoplasm and is part 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. Mutations leading to changes in the binding sites of either protein are associated with basal cell carcinomas. Mutations also have been associated with hereditary capillary malformations (CM) with or without arteriovenous malformations (AVM) and Parkes Weber syndrome. Alternative splicing results in two isoforms where the shorter isoform, lacking the N-terminal hydrophobic region but retaining the same activity, appears to be abundantly expressed in placental but not adult tissues.

Source: NCBI Gene 5921 — RefSeq curated summary.

At a glance

• Gene–disease (curated): capillary malformation-arteriovenous malformation 1 (Definitive, GenCC) — +4 more curated relationships
• GWAS associations: 7
• Clinical variants (ClinVar): 400 total — 32 pathogenic, 7 likely-pathogenic
• Phenotypes (HPO): 47
• Precision-oncology evidence (CIViC): 1 curated variant–drug association
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 2 cancer types
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• MANE Select transcript: NM_002890

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9871
Approved symbol	RASA1
Name	RAS p21 protein activator 1
Location	5q14.3
Locus type	gene with protein product
Status	Approved
Aliases	GAP, CM-AVM, p120GAP, p120RASGAP, p120
Ensembl gene	ENSG00000145715
Ensembl biotype	protein_coding
OMIM	139150
Entrez	5921

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 8 protein_coding, 1 retained_intron, 1 nonsense_mediated_decay

ENST00000274376, ENST00000456692, ENST00000506290, ENST00000509953, ENST00000512763, ENST00000515800, ENST00000888488, ENST00000888489, ENST00000888490, ENST00000962098

RefSeq mRNA: 2 — MANE Select: NM_002890 NM_002890, NM_022650

CCDS: CCDS34200, CCDS47243

Canonical transcript exons

ENST00000274376 — 25 exons

Exon	Start	End
ENSE00001082148	87389393	87389527
ENSE00001162572	87331348	87331500
ENSE00001505328	87333267	87333337
ENSE00001505329	87332507	87332642
ENSE00002051467	87390800	87391916
ENSE00002242328	87337974	87338091
ENSE00003467145	87376393	87376565
ENSE00003475407	87363348	87363504
ENSE00003479075	87386826	87386903
ENSE00003483441	87353157	87353235
ENSE00003484839	87349214	87349364
ENSE00003503289	87346672	87346724
ENSE00003505177	87383713	87383780
ENSE00003510021	87369813	87369900
ENSE00003538796	87385301	87385389
ENSE00003563873	87341290	87341321
ENSE00003579086	87378396	87378538
ENSE00003580162	87376881	87377040
ENSE00003593259	87380509	87380595
ENSE00003626345	87372118	87372195
ENSE00003642171	87379735	87379850
ENSE00003644795	87362551	87362671
ENSE00003655477	87374840	87374916
ENSE00003675497	87374163	87374320
ENSE00003889972	87267883	87268990

Expression profiles

Bgee: expression breadth ubiquitous, 298 present calls, max score 98.98.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 25.6003 / max 945.7019, expressed in 1808 samples.

FANTOM5 promoters (12 alternative TSS)

Promoter ID	TPM avg	Samples expressed
57455	17.3940	1800
57464	2.0837	334
57461	1.9258	1072
57458	1.3580	696
57462	0.9450	577
57457	0.5622	335
57454	0.5032	227
57456	0.2991	128
57460	0.2630	116
57459	0.1989	67

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
endothelial cell	CL:0000115	98.98	gold quality
placenta	UBERON:0001987	98.07	gold quality
choroid plexus epithelium	UBERON:0003911	97.69	gold quality
Brodmann (1909) area 23	UBERON:0013554	97.46	gold quality
middle temporal gyrus	UBERON:0002771	96.53	gold quality
pigmented layer of retina	UBERON:0001782	96.32	gold quality
retina	UBERON:0000966	96.29	gold quality
skin of hip	UBERON:0001554	96.02	gold quality
tibia	UBERON:0000979	95.73	gold quality
CA1 field of hippocampus	UBERON:0003881	95.63	gold quality
Brodmann (1909) area 46	UBERON:0006483	95.62	gold quality
parietal pleura	UBERON:0002400	95.61	gold quality
pleura	UBERON:0000977	95.50	gold quality
corpus epididymis	UBERON:0004359	95.40	gold quality
visceral pleura	UBERON:0002401	95.27	gold quality
cervix squamous epithelium	UBERON:0006922	95.08	gold quality
caput epididymis	UBERON:0004358	95.01	gold quality
tongue squamous epithelium	UBERON:0006919	94.90	gold quality
oocyte	CL:0000023	94.57	gold quality
germinal epithelium of ovary	UBERON:0001304	94.49	gold quality
entorhinal cortex	UBERON:0002728	94.46	gold quality
orbitofrontal cortex	UBERON:0004167	94.37	gold quality
periodontal ligament	UBERON:0008266	94.34	gold quality
cauda epididymis	UBERON:0004360	94.23	gold quality
cranial nerve II	UBERON:0000941	94.15	gold quality
mucosa of paranasal sinus	UBERON:0005030	94.09	gold quality
postcentral gyrus	UBERON:0002581	94.01	gold quality
mucosa of sigmoid colon	UBERON:0004993	93.93	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	93.89	gold quality
mammary duct	UBERON:0001765	93.87	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-6701	yes	114.12
E-ANND-3	yes	9.93

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CIC, GATA4, JUN, MAFB, NR2E1, STAT3, TBP

miRNA regulators (miRDB)

126 targeting RASA1, 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-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-3163	100.00	77.23	8605
HSA-MIR-3134	100.00	66.43	777
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-33A-5P	99.99	68.62	1055
HSA-MIR-33B-5P	99.99	68.58	1062
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-8075	99.97	67.20	962
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-145-5P	99.92	71.13	1836
HSA-MIR-5195-3P	99.92	70.92	1877

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• We show a novel alternative pathway of apoptosis in human primary cells that is mediated by transcriptionally dependent decreases in p53 and c-Myc and decreases in p21. (PMID:11751853)
• N-terminal fragment generated by caspase cleavage protects cells in a Ras/PI3K/Akt-dependent manner that does not rely on NFkappa B activation (PMID:11847220)
• mutual regulation of Ras and NF1-GAP is essential for normal neuronal differentiation (PMID:12730209)
• p21Ras, hSOS1, and p120GAP are not involved in polycystic ovary disease (PMID:15010862)
• The induction of p21 gene expression is mediated by PPARgamma ligands in lung carcinoma. (PMID:15041706)
• ligation of CD40 on EC increased association of Ras with its effector molecules Raf, Rho, and PI3K. But, it was determined that only PI3K was functional for Ras-induced VEGF transcription. (PMID:15187129)
• executioner caspases control the extent of their own activation by a feedback regulatory mechanism initiated by the partial cleavage of RasGAP that is crucial for cell survival under adverse conditions (PMID:15542850)
• p52Shc couples tyrosine kinase receptors to Ras by recruiting Grb2/Sos complexes. (PMID:15688026)
• an uncleavable N-terminal RasGAP fragment in insulin-secreting cells has a role in increasing resistance toward apoptotic stimuli without affecting glucose-induced insulin secretion (PMID:16046410)
• These results demonstrate that integrin signaling through Arg activates p190 by promoting its association with p120, resulting in recruitment of p190 to the cell periphery where it inhibits Rho. (PMID:16971514)
• novel mutation is decribed, which causes capillary malformation and limb enlargement in a patient from a family with vascular malformations (PMID:18327598)
• the spectrum of clinical manifestations due to mutations in RASA1 is wider than previously thought and also includes typical CMs not associated with AVM/AVF. (PMID:18363760)
• 42 novel RASA1 mutations and the associated phenotype in 44 families. (PMID:18446851)
• RasGAP and Capns1 interaction in oncogenic Ras cells is involved in regulating migration and cell survival. (PMID:18761085)
• found a mean Ras activation of 23.1% in cell lines with known constitutively activating ras mutations (PMID:18784923)
• p120Ras-GAP binds the DLC1 Rho-GAP tumor suppressor protein and inhibits its RhoA GTPase and growth-suppressing activities. (PMID:19151751)
• Data show that fibroblast, endothelial and carcinoma polarity during cell migration requires FAK and is associated with a complex between FAK, p120RasGAP and p190RhoGAP (p190A), leading to p190A tyrosine phosphorylation. (PMID:19435801)
• CD200R inhibits the activation of human myeloid cells through direct recruitment of Dok2 and subsequent activation of RAS p21 protein activator 1. (PMID:19786546)
• the monomeric intracellular plexin-B1 binds R-Ras but not H-Ras. These findings suggest that the monomeric form of the intracellular region is primed for GAP activity and extend a model for plexin activation. (PMID:19843518)
• In a collaborative study, 5 index patients (2 females, 3 males) with spinal AVMs or AVFs and cutaneous multifocal capillary lesions were investigated for the RASA1 gene mutation. (PMID:20007727)
• Sema4D/Plexin-B1 promotes the dephosphorylation and activation of PTEN through the R-Ras GAP activity, inducing growth cone collapse. (PMID:20610402)
• miR-132 acts as an angiogenic switch by suppressing endothelial p120RasGAP expression. (PMID:20676106)
• A novel synonymous mutation (c.1229 G > A [p.K420K]) of RASA1 was identified in a Chinese population with sporadic Sturge-Weber syndrome (PMID:20821215)
• Ras mutation cooperates with beta-catenin activation to drive bladder tumourigenesis. (PMID:21368895)
• Ca2+-dependent monomer and dimer formation switches CAPRI Protein between Ras GTPase-activating protein (GAP) and RapGAP activities (PMID:21460216)
• An important role is revealed for p120 RasGAP (RASA1) as a transgenic regulator of CD4+CD8+ double-positive cell survival and positive selection in the thymus as well as naive T cell survival in the periphery. (PMID:21646295)
• Cell adhesion to the substrate is necessary for RasGAP to bind Nck1. Cell detachment makes RasGAP incapable of associating with Nck1 and decreases RasGAP activity. (PMID:21664272)
• Nck1 activates RasGAP by direct binding in the substrate-attached but not in the suspended cells. (PMID:21664272)
• The results assign an unexpected role for p120RasGAP in the regulation of integrin traffic in cancer cells and reveal a new concept of competitive binding of Rab GTPases and GAP proteins to receptors as a regulatory mechanism in trafficking. (PMID:21768288)
• multifocal capillary malformations is the key clinical finding to suggest a RASA1 mutation (PMID:22200646)
• arguments against G3BP1 being a genuine RasGAP-binding partner (PMID:22205990)
• An update of the associated phenotype variability in a family with hereditary capillary malformations caused by a mutation in the RASA1 gene. (PMID:22342634)
• Ras and GTPase-activating protein (GAP) drive GTP into a precatalytic state as revealed by combining FTIR and biomolecular simulations (PMID:22949691)
• capillary malformation-arteriovenous malformation syndrome; study reports a family with a novel mutation in the RASA1 gene - a truncating mutation in exon 11 of RASA1 (Q503X) (PMID:23158644)
• MicroRNA-31 activates the RAS pathway and functions as an oncogenic MicroRNA by repressing RAS p21 GTPase activating protein 1 (RASA1) (PMID:23322774)
• 14-3-3 negatively regulates the RGC downstream of the PI3-kinase/Akt signaling pathway (PMID:23386617)
• The results of the present study indicate that P110, in combination with chemotherapeutics, is likely to represent a potential therapeutic strategy for cancer. (PMID:23447049)
• RASA1 mutation is responsible for the aberrant lymphatic architecture and functional abnormalities, as visualized in the PKWS subject and in the animal model. (PMID:23650393)
• results indicate that, mTOR, Bad, or Survivin are not required for p120 RasGAP fragment N to protect cells from cell death; conclude that downstream targets of Akt other than mTORC1, Bad, or survivin mediate fragment N-induced protection or that several Akt effectors can compensate for each other to induce the pro-survival fragment N-dependent responses (PMID:23826368)
• Multifocal, small, round-to-oval, pinkish-to-red cutaneous capillary malformations are seen in more than 90% of people with RASA1 mutations. (PMID:23829194)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	rasa1a	ENSDARG00000035535
danio_rerio	rasa1b	ENSDARG00000073665
mus_musculus	Rasa1	ENSMUSG00000021549
rattus_norvegicus	Rasa1	ENSRNOG00000029185
drosophila_melanogaster	vap	FBGN0003969

Paralogs (10): RASAL2 (ENSG00000075391), RASAL3 (ENSG00000105122), RASA4 (ENSG00000105808), RASAL1 (ENSG00000111344), DAB2IP (ENSG00000136848), RASA2 (ENSG00000155903), RASA4B (ENSG00000170667), RASA3 (ENSG00000185989), NF1 (ENSG00000196712), SYNGAP1 (ENSG00000197283)

Protein

Protein identifiers

Ras GTPase-activating protein 1 — P20936 (reviewed: P20936)

Alternative names: Ras p21 protein activator, p120GAP

All UniProt accessions (2): E9PGC0, P20936

UniProt curated annotations — full annotation on UniProt →

Function. GTPase-activating protein (GAP) that stimulates the intrinsic GTPase activity of Ras proteins, such as NRAS, facilitating their transition from the active GTP-bound state to the inactive GDP-bound state, thereby terminating Ras signaling.

Subunit / interactions. Interacts with SQSTM1. Interacts with SPSB1; the interaction does not promote degradation. Interacts with CAV2 (tyrosine phosphorylated form). Directly interacts with NCK1. Interacts with PDGFRB (tyrosine phosphorylated). Interacts (via SH2 domain) with the ‘Tyr-9’ phosphorylated form of PDPK1. Interacts with tyrosine-phosphorylated EPHB4.

Subcellular location. Cytoplasm.

Tissue specificity. In placental villi, detected only in the trophoblast layer (cytotrophoblast and syncytiotrophoblast). Not detected in stromal, endothelial or Hofbauer cells (at protein level).

Post-translational modifications. The N-terminus is blocked. Phosphorylated by SRC and LCK. The phosphorylation SRC inhibits its ability to stimulate the Ras-GTPase activity, whereas phosphorylation by LCK does not display any effect on stimulation activity.

Disease relevance. Mutations in the SH2 domain of RASA seem to be oncogenic and cause basal cell carcinomas. Capillary malformation-arteriovenous malformation 1 (CMAVM1) [MIM:608354] A disorder characterized by atypical capillary malformations that are multiple, small, round to oval in shape and pinkish red in color. These capillary malformations are associated with either arteriovenous malformation, arteriovenous fistula, or Parkes Weber syndrome. CMAVM1 inheritance is autosomal dominant. The disease is caused by variants affecting the gene represented in this entry.

Isoforms (4)

UniProt ID	Names	Canonical?
P20936-1	1, Long	yes
P20936-2	2, Short
P20936-3	3
P20936-4	4

RefSeq proteins (2): NP_002881, NP_072179 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000008	C2_dom	Domain
IPR000980	SH2	Domain
IPR001452	SH3_domain	Domain
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
IPR035652	RasGAP_SH3	Domain
IPR035841	RasGAP_N_SH2	Domain
IPR035842	RasGAP_C_SH2	Domain
IPR035892	C2_domain_sf	Homologous_superfamily
IPR036028	SH3-like_dom_sf	Homologous_superfamily
IPR036860	SH2_dom_sf	Homologous_superfamily
IPR039360	Ras_GTPase	Family

Pfam: PF00017, PF00018, PF00168, PF00169, PF00616

UniProt features (94 total): strand 33, helix 28, sequence variant 8, turn 7, domain 6, splice variant 6, modified residue 3, chain 1, sequence conflict 1, site 1

Structure

Experimental structures (PDB)

15 structures.

PDB	Method	Resolution (Å)
2J05	X-RAY DIFFRACTION	1.5
6WAX	X-RAY DIFFRACTION	1.5
6WAY	X-RAY DIFFRACTION	1.5
1WER	X-RAY DIFFRACTION	1.6
6PXC	X-RAY DIFFRACTION	1.6
6PXB	X-RAY DIFFRACTION	1.75
2J06	X-RAY DIFFRACTION	1.8
8DGQ	X-RAY DIFFRACTION	1.95
8BOS	X-RAY DIFFRACTION	2.1
4FSS	X-RAY DIFFRACTION	2.25
9BZ4	X-RAY DIFFRACTION	2.45
1WQ1	X-RAY DIFFRACTION	2.5
2GQI	SOLUTION NMR
2GSB	SOLUTION NMR
2M51	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P20936-F1	77.37	0.34

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): 789 (arginine finger; crucial for gtp hydrolysis by stabilizing the transition state)

Post-translational modifications (3): 831, 1, 615

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-186763	Downstream signal transduction
R-HSA-3928662	EPHB-mediated forward signaling
R-HSA-5218921	VEGFR2 mediated cell proliferation
R-HSA-5658442	Regulation of RAS by GAPs
R-HSA-8849471	PTK6 Regulates RHO GTPases, RAS GTPase and MAP kinases

MSigDB gene sets: 453 (showing top): PID_BCR_5PATHWAY, GOBP_MITOTIC_CYTOKINESIS, GOBP_NEGATIVE_REGULATION_OF_NEURON_APOPTOTIC_PROCESS, BORCZUK_MALIGNANT_MESOTHELIOMA_UP, GOBP_REGULATION_OF_PROTEIN_POLYMERIZATION, GOBP_REGULATION_OF_CELL_MORPHOGENESIS, TGCGCANK_UNKNOWN, PAL_PRMT5_TARGETS_UP, KEGG_MAPK_SIGNALING_PATHWAY, THEILGAARD_NEUTROPHIL_AT_SKIN_WOUND_DN, GOCC_RUFFLE, GOMF_GTPASE_BINDING, BIOCARTA_TPO_PATHWAY, CTATGCA_MIR153, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS

GO Biological Process (17): mitotic cytokinesis (GO:0000281), angiogenesis (GO:0001525), vasculogenesis (GO:0001570), negative regulation of cell-matrix adhesion (GO:0001953), negative regulation of cell adhesion (GO:0007162), signal transduction (GO:0007165), regulation of cell shape (GO:0008360), regulation of actin filament polymerization (GO:0030833), intracellular signal transduction (GO:0035556), negative regulation of apoptotic process (GO:0043066), negative regulation of neuron apoptotic process (GO:0043524), ephrin receptor signaling pathway (GO:0048013), blood vessel morphogenesis (GO:0048514), regulation of RNA metabolic process (GO:0051252), regulation of intracellular signal transduction (GO:1902531), regulation of GTPase activity (GO:0043087), system development (GO:0048731)

GO Molecular Function (8): phosphotyrosine residue binding (GO:0001784), GTPase activity (GO:0003924), GTPase activator activity (GO:0005096), signaling receptor binding (GO:0005102), potassium channel inhibitor activity (GO:0019870), GTPase binding (GO:0051020), protein binding (GO:0005515), enzyme binding (GO:0019899)

GO Cellular Component (4): ruffle (GO:0001726), cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Signaling by PDGF	1
EPH-Ephrin signaling	1
VEGFA-VEGFR2 Pathway	1
RAF/MAP kinase cascade	1
Signaling by PTK6	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
blood vessel morphogenesis	2
intracellular anatomical structure	2
GTPase activity	2
protein binding	2
cellular anatomical structure	2
mitotic cell cycle	1
cytoskeleton-dependent cytokinesis	1
mitotic cell cycle process	1
anatomical structure formation involved in morphogenesis	1
cell differentiation	1
regulation of cell-matrix adhesion	1
cell-matrix adhesion	1
negative regulation of cell-substrate adhesion	1
cell adhesion	1
regulation of cell adhesion	1
negative regulation of cellular process	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
regulation of cell morphogenesis	1
regulation of biological quality	1
regulation of actin polymerization or depolymerization	1
actin filament polymerization	1
regulation of protein polymerization	1
signal transduction	1
apoptotic process	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
negative regulation of apoptotic process	1
regulation of neuron apoptotic process	1
neuron apoptotic process	1
cell surface receptor protein tyrosine kinase signaling pathway	1
blood vessel development	1
tube morphogenesis	1
RNA metabolic process	1
regulation of nucleobase-containing compound metabolic process	1
regulation of macromolecule metabolic process	1
regulation of signal transduction	1

Protein interactions and networks

STRING

4002 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RASA1	G3BP1	Q13283	993
RASA1	ARHGAP35	Q9NRY4	993
RASA1	RALA	P11233	987
RASA1	DOK1	Q99704	983
RASA1	HRAS	P01112	977
RASA1	DOK2	O60496	963
RASA1	PXN	P49023	943
RASA1	RABIF	P47224	930
RASA1	TSC2	P49815	928
RASA1	CDC42	P21181	928
RASA1	ARHGAP1	Q07960	913
RASA1	TSC1	Q92574	913
RASA1	EGFR	P00533	902
RASA1	AKT1	P31749	901
RASA1	SOS1	Q07889	891

IntAct

197 interactions, top by confidence:

A	B	Type	Score
DLC1	RASA1	psi-mi:“MI:0915”(physical association)	0.710
RASA1	DLC1	psi-mi:“MI:0915”(physical association)	0.710
RASA1	NCK1	psi-mi:“MI:0915”(physical association)	0.670
NCK1	RASA1	psi-mi:“MI:0915”(physical association)	0.670
RASA1	NCK1	psi-mi:“MI:0407”(direct interaction)	0.670
RASA1	PDGFRB	psi-mi:“MI:0914”(association)	0.640
FYB1	NCK2	psi-mi:“MI:0914”(association)	0.620
CAV1	RASA1	psi-mi:“MI:0407”(direct interaction)	0.590
RASA1	CAV1	psi-mi:“MI:0914”(association)	0.590
RASA1	GAB1	psi-mi:“MI:0914”(association)	0.590
RASA1	ERBB2	psi-mi:“MI:0407”(direct interaction)	0.590
RASA1	ERBB2	psi-mi:“MI:0915”(physical association)	0.590
RASA1	GAB1	psi-mi:“MI:0407”(direct interaction)	0.590

BioGRID (208): RASA1 (Affinity Capture-Western), RASA1 (Affinity Capture-MS), OLIG1 (Two-hybrid), RASA1 (Affinity Capture-Western), HRAS (Reconstituted Complex), HRAS (Affinity Capture-Western), RASA1 (Affinity Capture-MS), RASA1 (Affinity Capture-Western), RASA1 (Affinity Capture-RNA), RASA1 (Reconstituted Complex), DOK1 (Affinity Capture-Western), DOK2 (Affinity Capture-Western), RASA1 (Affinity Capture-MS), RASA1 (Affinity Capture-MS), RASA1 (Two-hybrid)

ESM2 similar proteins: A0A0G2JTR4, A1A4S6, A2AWA9, A4FUD6, A4II46, A6H6A9, A6QNS3, A6QQZ7, O60890, P09851, P0CAX5, P20936, P23727, P26450, P27986, P50904, Q08DP6, Q12979, Q5R372, Q5R5M3, Q5R685, Q5R6F2, Q5R8I6, Q5RCC1, Q5RCW6, Q5SSL4, Q5T2T1, Q5U2Y3, Q5ZJ17, Q5ZLX4, Q5ZMW5, Q62696, Q63787, Q6Y5D8, Q6ZQ82, Q7YQL5, Q7YQL6, Q8AVG0, Q8BPU7, Q8K0F1

Diamond homologs: A0A8I3NFE2, A0FI79, A0JNB0, A1Y2K1, A6QLK6, B2RZ59, B5KFD7, D3ZGS3, D7PF45, F1RDG9, G5ECJ6, O14306, O14796, O15357, O35324, O60880, O88890, O88900, P00519, P00520, P00521, P00522, P03949, P06239, P06241, P09851, P0CE43, P10447, P17713, P20936, P29350, P29351, P32019, P34370, P39688, P42684, P42685, P42686, P50904, P53356

SIGNOR signaling

7 interactions.

A	Effect	B	Mechanism
PDGFRB	up-regulates	RASA1	binding
EGFR	unknown	RASA1	phosphorylation
hsa-miR-31-5p	“down-regulates quantity by repression”	RASA1	“post transcriptional regulation”
RASA1	down-regulates	HRAS	binding
EPHB2	up-regulates	RASA1	binding
SRC	down-regulates	RASA1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 72 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
Signaling by ERBB2 ECD mutants	6	69.5×	1e-08
Constitutive Signaling by EGFRvIII	5	61.5×	8e-07
Signaling by ERBB2 KD Mutants	8	58.3×	1e-10
PI3K events in ERBB2 signaling	5	57.9×	1e-06
Signaling by ERBB2 TMD/JMD mutants	7	57.4×	3e-09
GRB2 events in ERBB2 signaling	5	54.7×	1e-06
SHC1 events in ERBB2 signaling	6	49.2×	1e-07
Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants	5	49.2×	2e-06

GO biological processes:

GO term	Partners	Fold	FDR
epidermal growth factor receptor signaling pathway	8	31.5×	7e-08
cell surface receptor protein tyrosine kinase signaling pathway	10	27.6×	3e-09
ephrin receptor signaling pathway	5	27.3×	8e-05
cellular response to epidermal growth factor stimulus	5	25.2×	1e-04
epithelial cell proliferation	5	24.8×	1e-04
positive regulation of epithelial cell proliferation	6	23.3×	2e-05
insulin receptor signaling pathway	6	21.1×	3e-05
protein autophosphorylation	9	20.8×	7e-08

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: loss-of-function (tumor-suppressor-like) across 2 cancer types — HNSC, LUSC.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	32
Likely pathogenic	7
Uncertain significance	207
Likely benign	113
Benign	4

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1075206	NM_002890.3(RASA1):c.172_173del (p.Ala58fs)	Pathogenic
1075680	NM_002890.3(RASA1):c.442dup (p.Ala148fs)	Pathogenic
1354503	NM_002890.3(RASA1):c.538del (p.Gln180fs)	Pathogenic
1451377	NC_000005.9:g.(?86564269)(86686700_?)del	Pathogenic
1457368	NC_000005.9:g.(?86564269)(86659341_?)del	Pathogenic
1477458	NC_000005.9:g.(?86633771)(86659341_?)del	Pathogenic
1527177	GRCh37/hg19 5q14.3(chr5:86426877-86614352)	Pathogenic
15999	NM_002890.3(RASA1):c.475_476del (p.Leu159fs)	Pathogenic
1992410	NM_002890.2:c.540-406_692+21735del	Pathogenic
2001480	NM_002890.3(RASA1):c.474dup (p.Leu159fs)	Pathogenic
2001727	NM_002890.3(RASA1):c.132_152delinsACAGCGAAACTCCATCTCTCAAAAAAAAAAAAAAAAAAAAAGAAGTCTACTAAAAACAGTTTTTTTTAACTACAATATCCTAAATATACCTAATTTAGTTATAAACTAGCATAAGACTAGATTCTTTCAGTATGAAAAGTT (p.Ala45_Gly51delinsGlnArgAsnSerIleSerGlnLysLysLysLysLysLysArgSerLeuLeuLysThrValPhePheAsnTyrAsnIleLeuAsnIleProAsnLeuValIleAsnTer)	Pathogenic
2042873	NM_002890.3(RASA1):c.78del (p.Ser27fs)	Pathogenic
2051636	NM_002890.3(RASA1):c.539+4A>G	Pathogenic
2115938	NM_002890.3(RASA1):c.539+4dup	Pathogenic
2195273	NM_002890.3(RASA1):c.383_384del (p.Leu128fs)	Pathogenic
2424564	NC_000005.9:g.(?86564269)(86564827_?)del	Pathogenic
2732232	NM_002890.3(RASA1):c.496G>T (p.Glu166Ter)	Pathogenic
2746283	NM_002890.3(RASA1):c.426C>G (p.Tyr142Ter)	Pathogenic
2877034	NM_002890.3(RASA1):c.434_451delinsA (p.Pro145fs)	Pathogenic
2893369	NM_002890.3(RASA1):c.402del (p.Pro136fs)	Pathogenic
3246331	NC_000005.9:g.(?86669960)(86670753_?)del	Pathogenic
3391888	GRCh37/hg19 5q14.3(chr5:86011540-86616649)x1	Pathogenic
3659038	NM_002890.3(RASA1):c.231_232del (p.Ala78fs)	Pathogenic
3660323	NM_002890.3(RASA1):c.217G>T (p.Gly73Ter)	Pathogenic
4279976	NM_002890.3(RASA1):c.463G>T (p.Glu155Ter)	Pathogenic
452663	NM_002890.3(RASA1):c.297del (p.Ala100fs)	Pathogenic
4724217	NM_002890.3(RASA1):c.117dup (p.Ala40fs)	Pathogenic
503721	NM_002890.3(RASA1):c.261_262del (p.Gly89fs)	Pathogenic
811221	NM_002890.3(RASA1):c.431_438del (p.Pro144fs)	Pathogenic
952905	NM_002890.3(RASA1):c.365C>A (p.Ser122Ter)	Pathogenic

SpliceAI

4926 predictions. Top by Δscore:

Variant	Effect	Δscore
5:87268991:G:GG	donor_gain	1.0000
5:87331344:CTAG:C	acceptor_loss	1.0000
5:87331345:TAGG:T	acceptor_loss	1.0000
5:87331346:A:AG	acceptor_gain	1.0000
5:87331346:AG:A	acceptor_gain	1.0000
5:87331346:AGGT:A	acceptor_gain	1.0000
5:87331346:AGGTG:A	acceptor_gain	1.0000
5:87331347:G:A	acceptor_gain	1.0000
5:87331347:G:GT	acceptor_gain	1.0000
5:87331347:GGT:G	acceptor_gain	1.0000
5:87331347:GGTG:G	acceptor_gain	1.0000
5:87331347:GGTGG:G	acceptor_gain	1.0000
5:87331405:G:T	donor_gain	1.0000
5:87331499:AGG:A	donor_loss	1.0000
5:87331501:G:GG	donor_gain	1.0000
5:87331501:GTA:G	donor_loss	1.0000
5:87331502:T:A	donor_loss	1.0000
5:87332505:A:AG	acceptor_gain	1.0000
5:87332506:G:GG	acceptor_gain	1.0000
5:87333256:AT:A	acceptor_gain	1.0000
5:87333257:T:TA	acceptor_gain	1.0000
5:87333265:A:AG	acceptor_gain	1.0000
5:87333266:G:GG	acceptor_gain	1.0000
5:87333266:GCCA:G	acceptor_gain	1.0000
5:87337972:A:AG	acceptor_gain	1.0000
5:87337973:G:GG	acceptor_gain	1.0000
5:87337973:GTTT:G	acceptor_gain	1.0000
5:87338092:G:GA	donor_loss	1.0000
5:87338093:TAAGT:T	donor_loss	1.0000
5:87341322:G:GG	donor_gain	1.0000

AlphaMissense

6849 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:87331349:T:A	W181R	1.000
5:87331349:T:C	W181R	1.000
5:87331359:G:A	G184E	1.000
5:87331365:T:C	L186P	1.000
5:87331371:G:C	R188T	1.000
5:87331372:A:C	R188S	1.000
5:87331372:A:T	R188S	1.000
5:87331389:G:C	R194P	1.000
5:87331392:T:A	L195H	1.000
5:87331392:T:C	L195P	1.000
5:87331418:T:G	Y204D	1.000
5:87331422:T:A	L205H	1.000
5:87331422:T:C	L205P	1.000
5:87331425:T:A	I206K	1.000
5:87331428:G:C	R207T	1.000
5:87331428:G:T	R207I	1.000
5:87331429:A:C	R207S	1.000
5:87331429:A:T	R207S	1.000
5:87331461:T:A	L218H	1.000
5:87331461:T:C	L218P	1.000
5:87331461:T:G	L218R	1.000
5:87331463:T:C	S219P	1.000
5:87331493:C:G	H229D	1.000
5:87331495:T:A	H229Q	1.000
5:87331495:T:G	H229Q	1.000
5:87331496:T:C	F230L	1.000
5:87331497:T:C	F230S	1.000
5:87331498:T:A	F230L	1.000
5:87331498:T:G	F230L	1.000
5:87331500:G:T	R231M	1.000

dbSNP variants (sampled 300 via entrez): RS1000035296 (5:87332782 A>G,T), RS1000081869 (5:87267702 A>C,G), RS1000119777 (5:87347379 G>A,T), RS1000123902 (5:87314405 G>A,C), RS1000125560 (5:87378098 T>G), RS1000128628 (5:87302530 T>C,G), RS1000139410 (5:87331770 A>C,T), RS1000158306 (5:87323455 G>A,C), RS1000192507 (5:87351682 CCTGA>C), RS1000224192 (5:87374351 T>C), RS1000324352 (5:87357887 T>C), RS1000359888 (5:87333855 C>G), RS1000359906 (5:87271216 C>T), RS1000386220 (5:87285158 C>T), RS1000412441 (5:87318675 C>G,T)

Disease associations

OMIM: gene MIM:139150 | disease phenotypes: MIM:605462, MIM:608354, MIM:608355, MIM:123880

GenCC curated gene-disease

Disease	Classification	Inheritance
capillary malformation-arteriovenous malformation 1	Definitive	Autosomal dominant
capillary malformation-arteriovenous malformation syndrome	Supportive	Autosomal dominant
Parkes Weber syndrome	Supportive	Autosomal dominant
Noonan syndrome	Disputed Evidence	Autosomal dominant
telangiectasia, hereditary hemorrhagic, type 1	No Known Disease Relationship	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
Noonan syndrome	Disputed	AD

Mondo (7): basal cell carcinoma, susceptibility to, 1 (MONDO:0011556), capillary malformation-arteriovenous malformation syndrome (MONDO:0012016), capillary malformation-arteriovenous malformation 1 (MONDO:0020783), Gorham-Stout disease (MONDO:0007414), Noonan syndrome (MONDO:0018997), telangiectasia, hereditary hemorrhagic, type 1 (MONDO:0008535), (MONDO:0012017)

Orphanet (4): Capillary malformation-arteriovenous malformation (Orphanet:137667), RASA1-related capillary malformation-arteriovenous malformation (Orphanet:693907), Gorham-Stout disease (Orphanet:73), Parkes Weber syndrome (Orphanet:90307)

HPO phenotypes

47 total (30 of 47 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000016	Urinary retention
HP:0000079	Abnormality of the urinary system
HP:0000100	Nephrotic syndrome
HP:0001722	High-output congestive heart failure
HP:0001892	Abnormal bleeding
HP:0002138	Subarachnoid hemorrhage
HP:0002196	Myelopathy
HP:0002315	Headache
HP:0002390	Spinal arteriovenous malformation
HP:0002408	Cerebral arteriovenous malformation
HP:0002617	Vascular dilatation
HP:0002619	Varicose veins
HP:0002671	Basal cell carcinoma
HP:0002814	Abnormality of the lower limb
HP:0002817	Abnormality of the upper limb
HP:0002936	Distal sensory impairment
HP:0003418	Back pain
HP:0003474	Somatic sensory dysfunction
HP:0004947	Arteriovenous fistula
HP:0004948	Vascular tortuosity
HP:0005306	Capillary hemangioma
HP:0005521	Disseminated intravascular coagulation
HP:0006489	Abnormal femoral metaphysis morphology
HP:0007340	Lower limb muscle weakness
HP:0007394	Prominent superficial blood vessels
HP:0007461	Hemangiomatosis
HP:0008968	Muscle hypertrophy of the lower extremities
HP:0010484	Hypertrophy of the upper limb
HP:0010550	Paraplegia

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST000922_1	Openness	2.000000e-06
GCST001850_35	Major depressive disorder	4.000000e-06
GCST002886_1	Prostate cancer aggressiveness	6.000000e-09
GCST006976_58	Macular thickness	4.000000e-10
GCST007576_417	Chronotype	5.000000e-10
GCST007576_47	Chronotype	4.000000e-11
GCST009379_40	Type 2 diabetes	2.000000e-08

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0007914	openness measurement
EFO:0006999	cancer aggressiveness measurement
EFO:0007000	Gleason score measurement
EFO:0008328	chronotype measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
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
C564254	Capillary Malformation-Arteriovenous Malformation (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

Clinical evidence (CIViC)

Drug × variant × indication: 1 predictive associations from 1 curated evidence items.

Variant	Therapy	Indication	Effect	Level	CIViC
RASA1 Loss-of-function	Trametinib	Lung Non-small Cell Carcinoma	Sensitivity/Response	CIViC D	EID5994

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol F	affects cotreatment, decreases expression, increases expression	2
bisphenol A	affects cotreatment, decreases methylation, increases expression	2
Benzo(a)pyrene	decreases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
Cadmium Chloride	decreases expression, increases abundance, increases expression	2
aristolochic acid I	decreases expression	1
taxifolin	decreases expression	1
triphenyl phosphate	affects expression	1
pyrogallol 1,3-dimethyl ether	increases expression, affects cotreatment, affects localization, decreases expression	1
arsenite	affects binding, decreases reaction	1
sodium arsenite	increases expression	1
cobaltous chloride	decreases expression	1
potassium chromate(VI)	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	decreases expression, affects response to substance, increases expression, affects cotreatment	1
di-n-butylphosphoric acid	affects expression	1
rofecoxib	affects expression	1
CP 31398	increases expression	1
bisphenol B	increases expression	1
abrine	decreases expression	1
asparanin A	decreases expression	1
jinfukang	decreases expression, increases reaction	1
7-(benzylamino)-1,3,4,8-tetrahydropyrrolo(4,3,2-de)quinolin-8(1H)-one	decreases expression	1
Irinotecan	decreases expression	1
Temozolomide	decreases expression	1
Sunitinib	increases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Acetaminophen	decreases expression	1
Aerosols	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	increases methylation	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_E2II	HAP1 RASA1 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02389959	PHASE4	COMPLETED	Intranasal Bevacizumab for HHT-Related Epistaxis
NCT04999618	PHASE4	COMPLETED	A New Approach in Laser Surgery Using the Regenerative Solution in Children Diagnosed With Vascular Pathology
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
NCT01314274	PHASE2	COMPLETED	Intranasal Submucosal Bevacizumab for Epistaxis in Hereditary Hemorrhagic Telangiectasia (HHT)
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
NCT03850964	PHASE2/PHASE3	ACTIVE_NOT_RECRUITING	Effects of Pazopanib on Hereditary Hemorrhagic Telangiectasia Related Epistaxis and Anemia (Paz)
NCT04150822	Not specified	ACTIVE_NOT_RECRUITING	CHORUS - Comprehensive HHT Outcomes Registry of the United States (Formerly OUR HHT Registry)
NCT05550376	Not specified	COMPLETED	Genotype-phenotype Association in Hereditary Hemorrhagic Telangiectasia
NCT06039124	Not specified	COMPLETED	Subsequent Bevacizumab Treatment in Patients With HHT. Follow up BABH
NCT06266624	Not specified	ACTIVE_NOT_RECRUITING	Tourniquet-Test in HHT
NCT06573723	Not specified	RECRUITING	Institutional Registry of Rare Diseases
NCT02399527	Not specified	RECRUITING	Lymphatic Anomalies Registry for the Assessment of Outcome Data
NCT02744027	Not specified	COMPLETED	Imaging of Lymphatic Anomalies
NCT03001180	Not specified	RECRUITING	Identification of Biomarkers for Patients with Vascular Anomalies