ACTA2

Summary

ACTA2 (actin alpha 2, smooth muscle, HGNC:130) is a protein-coding gene on chromosome 10q23.31, encoding Actin, aortic smooth muscle (P62736). Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells.

This gene encodes one of six different actin proteins. Actins are highly conserved proteins that are involved in cell motility, structure, integrity, and intercellular signaling. The encoded protein is a smooth muscle actin that is involved in vascular contractility and blood pressure homeostasis. Mutations in this gene cause a variety of vascular diseases, such as thoracic aortic disease, coronary artery disease, stroke, and Moyamoya disease, as well as multisystemic smooth muscle dysfunction syndrome.

Source: NCBI Gene 59 — RefSeq curated summary.

At a glance

• Gene–disease (curated): multisystemic smooth muscle dysfunction syndrome (Definitive, ClinGen) — +4 more curated relationships
• GWAS associations: 8
• Clinical variants (ClinVar): 633 total — 23 pathogenic, 15 likely-pathogenic
• Phenotypes (HPO): 72
• Dosage sensitivity (ClinGen): haploinsufficiency little evidence, triplosensitivity no evidence
• MANE Select transcript: NM_001613

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:130
Approved symbol	ACTA2
Name	actin alpha 2, smooth muscle
Location	10q23.31
Locus type	gene with protein product
Status	Approved
Aliases	ACTSA
Ensembl gene	ENSG00000107796
Ensembl biotype	protein_coding
OMIM	102620
Entrez	59

Gene structure

Transcript identifiers

Ensembl transcripts: 33 — 29 protein_coding, 3 retained_intron, 1 nonsense_mediated_decay

ENST00000224784, ENST00000415557, ENST00000458159, ENST00000480297, ENST00000482085, ENST00000488967, ENST00000713597, ENST00000713598, ENST00000713599, ENST00000713600, ENST00000713601, ENST00000713602, ENST00000713603, ENST00000903375, ENST00000903376, ENST00000903377, ENST00000946937, ENST00000946938, ENST00000946939, ENST00000946940, ENST00000946941, ENST00000946942, ENST00000946943, ENST00000946944, ENST00000946945, ENST00000946946, ENST00000946947, ENST00000946948, ENST00000946949, ENST00000946950, ENST00000946951, ENST00000946952, ENST00000946953

RefSeq mRNA: 11 — MANE Select: NM_001613 NM_001141945, NM_001320855, NM_001406462, NM_001406463, NM_001406464, NM_001406466, NM_001406467, NM_001406468, NM_001406469, NM_001406471, NM_001613

CCDS: CCDS7392

Canonical transcript exons

ENST00000224784 — 9 exons

Exon	Start	End
ENSE00001156216	88952731	88952773
ENSE00001754408	88938061	88938242
ENSE00002430990	88939507	88939698
ENSE00002438133	88941229	88941390
ENSE00003495326	88943797	88943907
ENSE00003558620	88947258	88947386
ENSE00003654552	88948802	88948953
ENSE00003784197	88941785	88941869
ENSE00004011072	88935074	88935366

Expression profiles

Bgee: expression breadth ubiquitous, 289 present calls, max score 99.99.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 123.6629 / max 7873.2060, expressed in 1680 samples.

FANTOM5 promoters (12 alternative TSS)

Promoter ID	TPM avg	Samples expressed
110503	97.7011	955
110513	20.2051	1633
110492	1.1792	411
110507	1.0672	421
110509	0.8834	346
110510	0.8709	461
110499	0.6966	274
110511	0.3203	165
110512	0.2759	164
110500	0.2049	92

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cauda epididymis	UBERON:0004360	99.99	gold quality
blood vessel layer	UBERON:0004797	99.99	gold quality
saphenous vein	UBERON:0007318	99.99	gold quality
aorta	UBERON:0000947	99.98	gold quality
right coronary artery	UBERON:0001625	99.98	gold quality
popliteal artery	UBERON:0002250	99.98	gold quality
tibial artery	UBERON:0007610	99.98	gold quality
urethra	UBERON:0000057	99.97	gold quality
seminal vesicle	UBERON:0000998	99.97	gold quality
ascending aorta	UBERON:0001496	99.97	gold quality
thoracic aorta	UBERON:0001515	99.97	gold quality
myometrium	UBERON:0001296	99.96	gold quality
coronary artery	UBERON:0001621	99.96	gold quality
left coronary artery	UBERON:0001626	99.96	gold quality
descending thoracic aorta	UBERON:0002345	99.96	gold quality
vena cava	UBERON:0004087	99.96	gold quality
body of uterus	UBERON:0009853	99.96	gold quality
superficial temporal artery	UBERON:0001614	99.95	gold quality
mucosa of stomach	UBERON:0001199	99.94	gold quality
adult organism	UBERON:0007023	99.94	gold quality
left uterine tube	UBERON:0001303	99.93	gold quality
lower esophagus	UBERON:0013473	99.93	gold quality
lower esophagus muscularis layer	UBERON:0035833	99.93	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	99.92	gold quality
smooth muscle tissue	UBERON:0001135	99.87	gold quality
mammary duct	UBERON:0001765	99.86	gold quality
nipple	UBERON:0002030	99.86	gold quality
prostate gland	UBERON:0002367	99.85	gold quality
muscle layer of sigmoid colon	UBERON:0035805	99.85	gold quality
urinary bladder	UBERON:0001255	99.83	gold quality

Single-cell (SCXA)

Detected in 35 experiment(s), a significant marker in 34.

Experiment	Marker?	Max mean expression
E-MTAB-8221	yes	12187.41
E-MTAB-10885	yes	10793.76
E-GEOD-124263	yes	10315.58
E-CURD-126	yes	10276.75
E-HCAD-1	yes	9950.97
E-MTAB-10287	yes	9868.18
E-HCAD-11	yes	9568.03
E-MTAB-8322	yes	9284.67
E-MTAB-9906	yes	8134.16
E-MTAB-8410	yes	8060.44
E-MTAB-10662	yes	7955.67
E-GEOD-134144	yes	7699.60
E-MTAB-9841	yes	7495.16
E-GEOD-124472	yes	7365.87
E-CURD-46	yes	6835.67

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ASCL1, BARX2, CEBPB, CILP, CXXC1, EGR1, ELK1, FOXL2, GATA4, GATA6, HEY1, HEY2, HHEX, HMGXB4, HOXB8, JAG1, KLF4, MEF2A, MYB, MYOCD, MYOD1, NFAT5, NFE2L3, NKX2-5, NOTCH1, PDGFB, PPARG, PURA, RBPJ, ROCK1, ROCK2, SMAD1, SMAD2, SMAD3, SMAD7, SNAI1, SP1, SRF, TCF21, TCF3

miRNA regulators (miRDB)

17 targeting ACTA2, 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-513A-5P	100.00	69.77	2465
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-605-3P	99.88	69.22	1833
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-4524A-3P	99.72	66.85	2406
HSA-MIR-3942-3P	99.57	69.03	2854
HSA-MIR-3978	99.24	68.39	2201
HSA-MIR-5000-3P	98.79	65.63	1251
HSA-MIR-4436A	98.05	64.83	1140
HSA-MIR-6818-5P	97.50	67.10	1167
HSA-MIR-6069	97.45	65.88	357

Functional genomics

ClinGen dosage: haploinsufficiency 1 (little evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• Results examine the interactions of wild type and mutant forms of the gp41 helicase with the T4 gp59 helicase loader and gp32 single-stranded DNA binding proteins. (PMID:15740739)
• Bacteriophage T4 helicase loader protein gp59 functions as gatekeeper in origin-dependent replication in vivo (PMID:15781450)
• Gp59 acts as the helicase clamp loader while forming a gp59-gp43 complex at a DNA fork in the presence of the single-stranded DNA binding protein (gp32). (PMID:15909989)
• Gp59-DNA interactions are needed to load Gp41 onto nascent or collapsed replication forks lacking clusters of Gp32 and to coordinate bidirectional replication from T4 origins. (PMID:24338568)
• Smooth muscle alpha-actin is expressed in endothelial cells derived from CD34+ human cord blood cells (PMID:15588509)
• Apha-smooth muscle actin may prove to be a valuable marker in the evaluation fibrosis progression and an early indicator of the development of fibrosis. (PMID:16115228)
• Integrin accelerates the synthesis of alpha-SMA in contracture of hypertrophic scar. (PMID:16573163)
• GATA-6 regulates human alpha-SMA expression via a novel regulatory cis element in the alpha-SMA promoter-enhancer (PMID:17626241)
• Ezrin and alpha-smooth muscle actin are predictive immunohistochemical prognostic markers for patients with an osteosarcoma (PMID:17786474)
• Study shows that missense mutations in ACTA2 are responsible for 14% of inherited ascending thoracic aortic aneurysms and dissections (TAAD). (PMID:17994018)
• TNF-alpha abrogated TGFbeta1-induced SMalphaA gene expression at the level of transcription without disrupting phosphorylation of regulatory Smads. (PMID:19261809)
• These findings indicate the existence of alpha-smooth muscle actin-positive endothelial cells in adult aortic endothelium and the possible association with progression of atherosclerosis. (PMID:19285011)
• heterozygous ACTA2 mutations predispose patients to a variety of diffuse and diverse vascular diseases, including TAAD, premature CAD, ischemic strokes, and MMD (PMID:19409525)
• findings confirm that ACTA2 mutations are important in familial TAAD, while the first sporadic and young-onset TAAD case with an ACTA2 mutation was also identified (PMID:19639654)
• Alpha-SMA metabolism in basal cell carcinoma is associated with a more aggressive behaviour of this tumor. (PMID:19683985)
• Data suggest that ACTA2 is not a major responsible gene for MMD, especially for Japanese MMD patients. (PMID:19745835)
• Mucosal remodeling with alterations of NCAM+ or alpha-SMA+ subepithelial and interstitial cells may play a critical role in UC-associated tumorigenesis. (PMID:19788615)
• The increased gene expressions of bFGF, alpha-SMA and PCNA in atrium during atrial fibrillation may contribute to atrial fibrosis by promoting fibroblast proliferation. (PMID:20128380)
• Data show that the purified hMDCs cultured in SMIM for 4 weeks and expressed significant amount of smooth muscle myosin heavy chain and alpha-smooth muscle actin. (PMID:20132408)
• Alpha-smooth muscle actin was expressed by tumor cells in basal cell carcinoma, but stromal expression of alpha-smooth muscle actin was restricted to the aggressive tumors and highly predictive of aggressive behavior. (PMID:20381122)
• These results suggest that TGF-beta1 plays a pivotal role in synovial fluid from patients with rheumatoid arthritis-induced differentiation of human adipose tissue-derived mesenchymal stem cells to alpha-SMA-positive cells. (PMID:20628268)
• Missense mutation in ACTA2 gene is associated with thoracic aortic aneurysms and dissections. (PMID:20689142)
• De novo mutation in ACTA2 causes a syndrome characterized by dysfunction of smooth muscle cells, leading to aortic and cerebrovascular disease. (PMID:20734336)
• One new mutation (R179H, heterozygous) in exon 6 of ACTA2 is found in one patient with Moyamoya disease. (PMID:20970362)
• The Rho signaling pathway may mediate SiO induced alpha-SMA expression in human bronchial epithelial cells. (PMID:21131735)
• ACTA2 is confirmed to be a major disease gene for autosomal dominant thoracic aortic aneurysms and dissections (12%)and the associated vascular phenotype can be highly malignant. (PMID:21212136)
• Microdeformations produced by the combination of polyurethane foam and suction are associated with increased fibroblast proliferation and up-regulation of gene expressions in fibroblasts (PMID:21233699)
• 3 missense mutations in ACTA2 of German patients of nonsyndromic Thoracic aortic aneurysms leading to type A dissections(TAAD) were identified. (PMID:21248741)
• Allele-specific effects of thoracic aortic aneurysm and dissection alpha-smooth muscle actin mutations on actin function. (PMID:21288906)
• Data show that TGF-beta1 stimulated cell proliferation, enhanced the gene expression of type I and III collagen, and alpha-SMA. (PMID:21343850)
• Plasminogen activator inhibitor-2 (PAI-2) secreted from activated mast cells induces alpha-smooth muscle actin (alpha-SMA) expression in dermal fibroblasts (PMID:21477997)
• Demonstrate increased expression of tenascin-C and alpha-smooth muscle actin positive cells in the large airways in chronic obstructive pulmonary disease. (PMID:21496259)
• With increased tension cytoskeletal stress fibers develop that contain alphaSMA and alphavbeta3 integrin that replaces alpha2beta1 integrin, consistent with cell switching from collagen to non-collagen proteins interactions. (PMID:21530503)
• in our cohort, Renal fibromuscular dysplasia was not caused by ACTA2 (PMID:21553326)
• Report reversal of TGF-beta1 stimulation of alpha-smooth muscle actin and extracellular matrix components by cyclic AMP in Dupuytren’s-derived fibroblasts. (PMID:21612641)
• Report alpha smooth muscle actin levels in varicose veins in relation to apoptosis and cell proliferation. (PMID:21617610)
• TGFBR1, TGFBR2, and ACTA2 mutations were found in 4 families with thoracic aortic aneurysms and dissections and predominantly fusiform intracranial aneurysms. (PMID:21815248)
• ACTA2 mutations are identified in 16% of a cohort presenting with familial thoracic aortic aneurysm/dissection. (PMID:21937134)
• Ultrasound irradiation promotes alpha-SMA and TGF-beta1 expression in human dermal fibroblasts. (PMID:21937873)
• The extracellular matrix of benign myoepithelial cells induces the increase in alpha-smooth muscle actin expression. (PMID:21996542)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Acta2	ENSMUSG00000035783
rattus_norvegicus	Acta2	ENSRNOG00000058039

Paralogs (26): ACTR6 (ENSG00000075089), ACTB (ENSG00000075624), ACTL6B (ENSG00000077080), ACTR5 (ENSG00000101442), ACTR3C (ENSG00000106526), ACTR8 (ENSG00000113812), ACTR1B (ENSG00000115073), ACTR3 (ENSG00000115091), ACTL8 (ENSG00000117148), ACTRT1 (ENSG00000123165), ACTR10 (ENSG00000131966), ACTR3B (ENSG00000133627), ACTL6A (ENSG00000136518), ACTR2 (ENSG00000138071), ACTR1A (ENSG00000138107), ACTA1 (ENSG00000143632), ACTL7B (ENSG00000148156), ACTC1 (ENSG00000159251), ACTG2 (ENSG00000163017), ACTBL2 (ENSG00000169067), ACTRT2 (ENSG00000169717), ACTL9 (ENSG00000181786), ACTG1 (ENSG00000184009), ACTRT3 (ENSG00000184378), ACTL7A (ENSG00000187003), ACTL10 (ENSG00000288649)

Protein

Protein identifiers

Actin, aortic smooth muscle — P62736 (reviewed: P62736)

Alternative names: Alpha-actin-2, Cell growth-inhibiting gene 46 protein

All UniProt accessions (8): P62736, A0AAQ5BGG5, A0AAQ5BGG7, A0AAQ5BGH2, A0AAQ5BGI6, D2JYH4, F6QUT6, F6UVQ4

UniProt curated annotations — full annotation on UniProt →

Function. Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells.

Subunit / interactions. Polymerization of globular actin (G-actin) leads to a structural filament (F-actin) in the form of a two-stranded helix. Each actin can bind to 4 others.

Subcellular location. Cytoplasm. Cytoskeleton.

Post-translational modifications. Oxidation of Met-46 and Met-49 by MICALs (MICAL1, MICAL2 or MICAL3) to form methionine sulfoxide promotes actin filament depolymerization. MICAL1 and MICAL2 produce the (R)-S-oxide form. The (R)-S-oxide form is reverted by MSRB1 and MSRB2, which promotes actin repolymerization. Monomethylation at Lys-86 (K84me1) regulates actin-myosin interaction and actomyosin-dependent processes. Demethylation by ALKBH4 is required for maintaining actomyosin dynamics supporting normal cleavage furrow ingression during cytokinesis and cell migration. Methylated at His-75 by SETD3. N-terminal cleavage of acetylated cysteine of intermediate muscle actin by ACTMAP. (Microbial infection) Monomeric actin is cross-linked by V.cholerae toxins RtxA and VgrG1 in case of infection: bacterial toxins mediate the cross-link between Lys-52 of one monomer and Glu-272 of another actin monomer, resulting in formation of highly toxic actin oligomers that cause cell rounding. The toxin can be highly efficient at very low concentrations by acting on formin homology family proteins: toxic actin oligomers bind with high affinity to formins and adversely affect both nucleation and elongation abilities of formins, causing their potent inhibition in both profilin-dependent and independent manners.

Disease relevance. ACTA2 mutations predispose patients to a variety of diffuse and diverse vascular diseases, premature onset coronary artery disease (CAD), premature ischemic strokes and Moyamoya disease. Aortic aneurysm, familial thoracic 6 (AAT6) [MIM:611788] A disease characterized by permanent dilation of the thoracic aorta usually due to degenerative changes in the aortic wall. It is primarily associated with a characteristic histologic appearance known as ‘medial necrosis’ or ‘Erdheim cystic medial necrosis’ in which there is degeneration and fragmentation of elastic fibers, loss of smooth muscle cells, and an accumulation of basophilic ground substance. The disease is caused by variants affecting the gene represented in this entry. Moyamoya disease 5 (MYMY5) [MIM:614042] A progressive cerebral angiopathy characterized by bilateral intracranial carotid artery stenosis and telangiectatic vessels in the region of the basal ganglia. The abnormal vessels resemble a ‘puff of smoke’ (moyamoya) on cerebral angiogram. Affected individuals can develop transient ischemic attacks and/or cerebral infarction, and rupture of the collateral vessels can cause intracranial hemorrhage. Hemiplegia of sudden onset and epileptic seizures constitute the prevailing presentation in childhood, while subarachnoid bleeding occurs more frequently in adults. The disease is caused by variants affecting the gene represented in this entry. Smooth muscle dysfunction syndrome (SMDYS) [MIM:613834] An autosomal dominant syndrome characterized by dysfunction of smooth muscle cells throughout the body, leading to aortic and cerebrovascular disease, fixed dilated pupils, hypotonic bladder, malrotation, and hypoperistalsis of the gut and pulmonary hypertension. The disease is caused by variants affecting the gene represented in this entry.

Induction. Up-regulated in response to enterovirus 71 (EV71) infection.

Miscellaneous. In vertebrates 3 main groups of actin isoforms, alpha, beta and gamma have been identified. The alpha actins are found in muscle tissues and are a major constituent of the contractile apparatus. The beta and gamma actins coexist in most cell types as components of the cytoskeleton and as mediators of internal cell motility.

Similarity. Belongs to the actin family.

RefSeq proteins (11): NP_001135417, NP_001307784, NP_001393391, NP_001393392, NP_001393393, NP_001393395, NP_001393396, NP_001393397, NP_001393398, NP_001393400, NP_001604* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004000	Actin	Family
IPR004001	Actin_CS	Conserved_site
IPR020902	Actin/actin-like_CS	Conserved_site
IPR043129	ATPase_NBD	Homologous_superfamily

Pfam: PF00022

Catalyzed reactions (Rhea), 1 shown:

• ATP + H2O = ADP + phosphate + H(+) (RHEA:13065)

UniProt features (31 total): sequence variant 19, modified residue 6, chain 2, cross-link 2, initiator methionine 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P62736-F1	95.43	0.93

Functional residue map

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

Post-translational modifications (8): 272, 2, 3, 46, 49, 75, 86, 52

Function

Pathways and Gene Ontology

Reactome pathways

12 pathways

ID	Pathway
R-HSA-445355	Smooth Muscle Contraction
R-HSA-9013695	NOTCH4 Intracellular Domain Regulates Transcription
R-HSA-9764561	Regulation of CDH1 Function
R-HSA-9913351	Formation of the dystrophin-glycoprotein complex (DGC)
R-HSA-9927432	Developmental Lineage of Mammary Gland Myoepithelial Cells
R-HSA-9958825	Activation of STAT3 by cadherin engagement
R-HSA-1474244	Extracellular matrix organization
R-HSA-157118	Signaling by NOTCH
R-HSA-162582	Signal Transduction
R-HSA-3000171	Non-integrin membrane-ECM interactions
R-HSA-397014	Muscle contraction
R-HSA-9013694	Signaling by NOTCH4

MSigDB gene sets: 457 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_DN, GOBP_REGULATION_OF_CELL_ACTIVATION, REACTOME_SIGNALING_BY_NOTCH, BERENJENO_ROCK_SIGNALING_NOT_VIA_RHOA_DN, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_REGULATION_OF_BLOOD_PRESSURE, GOBP_CIRCULATORY_SYSTEM_PROCESS, BERTUCCI_MEDULLARY_VS_DUCTAL_BREAST_CANCER_DN, GOBP_EPITHELIAL_CELL_DEVELOPMENT, KAAB_HEART_ATRIUM_VS_VENTRICLE_UP, GOBP_POSITIVE_REGULATION_OF_MAPK_CASCADE, IVANOVA_HEMATOPOIESIS_MATURE_CELL, MCBRYAN_PUBERTAL_TGFB1_TARGETS_UP, DARWICHE_SKIN_TUMOR_PROMOTER_UP, GOBP_REGULATION_OF_FIBROBLAST_MIGRATION

GO Biological Process (13): regulation of blood pressure (GO:0008217), response to virus (GO:0009615), positive regulation of gene expression (GO:0010628), vascular associated smooth muscle contraction (GO:0014829), positive regulation of hepatic stellate cell migration (GO:0061870), positive regulation of hepatic stellate cell contraction (GO:0061874), positive regulation of ERK1 and ERK2 cascade (GO:0070374), cellular response to transforming growth factor beta stimulus (GO:0071560), juxtaglomerular apparatus development (GO:0072051), glomerular mesangial cell development (GO:0072144), mesenchyme migration (GO:0090131), positive regulation of hepatic stellate cell activation (GO:2000491), muscle contraction (GO:0006936)

GO Molecular Function (5): ATP binding (GO:0005524), hydrolase activity (GO:0016787), protein kinase binding (GO:0019901), nucleotide binding (GO:0000166), protein binding (GO:0005515)

GO Cellular Component (14): stress fiber (GO:0001725), basement membrane (GO:0005604), obsolete extracellular space (GO:0005615), cytoplasm (GO:0005737), cytosol (GO:0005829), actin cytoskeleton (GO:0015629), lamellipodium (GO:0030027), filopodium (GO:0030175), smooth muscle contractile fiber (GO:0030485), motile cilium (GO:0031514), protein-containing complex (GO:0032991), cell body (GO:0044297), extracellular exosome (GO:0070062), cytoskeleton (GO:0005856)

Reactome top-level categories

Rollup of top-9 pathways:

Category	Pathways
Muscle contraction	1
Signaling by NOTCH4	1
Regulation of CDH1 Expression and Function	1
Non-integrin membrane-ECM interactions	1
Developmental Lineages of the Mammary Gland	1
Adherens junctions interactions	1
Signal Transduction	1
Extracellular matrix organization	1
Signaling by NOTCH	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
blood circulation	1
regulation of biological quality	1
response to other organism	1
gene expression	1
regulation of gene expression	1
positive regulation of macromolecule biosynthetic process	1
smooth muscle contraction	1
vasoconstriction	1
positive regulation of fibroblast migration	1
hepatic stellate cell migration	1
regulation of hepatic stellate cell migration	1
hepatic stellate cell contraction	1
regulation of hepatic stellate cell contraction	1
positive regulation of actin filament-based movement	1
positive regulation of MAPK cascade	1
ERK1 and ERK2 cascade	1
regulation of ERK1 and ERK2 cascade	1
cellular response to growth factor stimulus	1
response to transforming growth factor beta	1
kidney development	1
anatomical structure development	1
epithelial cell development	1
glomerular mesangial cell differentiation	1
mesangial cell development	1
mesenchyme morphogenesis	1
tissue migration	1
hepatic stellate cell activation	1
positive regulation of cell activation	1
regulation of hepatic stellate cell activation	1
muscle system process	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
catalytic activity	1
kinase binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
actomyosin	1
contractile actin filament bundle	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

304 interactions, top by confidence:

A	B	Type	Score
FNTB	FNTA	psi-mi:“MI:0914”(association)	0.960
SAMD4B	YWHAQ	psi-mi:“MI:0914”(association)	0.850
RBM17	U2SURP	psi-mi:“MI:0914”(association)	0.740
JADE1	KAT7	psi-mi:“MI:0914”(association)	0.720
CGN	YWHAQ	psi-mi:“MI:0914”(association)	0.710
CGN	YWHAE	psi-mi:“MI:0914”(association)	0.710
BUB3	ZNF207	psi-mi:“MI:0914”(association)	0.690
USE1	NBAS	psi-mi:“MI:0914”(association)	0.640
RNASE3	GGPS1	psi-mi:“MI:0914”(association)	0.640
TWF2	CAP2	psi-mi:“MI:0914”(association)	0.640
GM2A	ACTA2	psi-mi:“MI:0915”(physical association)	0.590
YIPF2	ACTA2	psi-mi:“MI:0915”(physical association)	0.590
MAP1LC3C	ACTA2	psi-mi:“MI:0915”(physical association)	0.590
TCP11L2	ACTA2	psi-mi:“MI:0915”(physical association)	0.560
FAM53B	SFN	psi-mi:“MI:0914”(association)	0.560
SCGB1A1	ACTA2	psi-mi:“MI:0915”(physical association)	0.560
HTR2C	KLRG2	psi-mi:“MI:0914”(association)	0.530
GC	POTEF	psi-mi:“MI:0914”(association)	0.530
MAS1	POTEF	psi-mi:“MI:0914”(association)	0.530
ACTBL2	POTEF	psi-mi:“MI:0914”(association)	0.530
CENPC	NDC80	psi-mi:“MI:0914”(association)	0.530
DUSP19	NARS1	psi-mi:“MI:0914”(association)	0.530
ZMAT5	DENND4B	psi-mi:“MI:0914”(association)	0.530
PLEKHG6	CST4	psi-mi:“MI:0914”(association)	0.530
CAPNS2	CAPNS1	psi-mi:“MI:0914”(association)	0.530
PHACTR2	POTEI	psi-mi:“MI:0914”(association)	0.530

BioGRID (470): ALOX12 (Affinity Capture-Western), ACTA2 (Affinity Capture-MS), ACTA2 (Affinity Capture-MS), ACTA2 (Affinity Capture-MS), ACTA2 (Affinity Capture-MS), ACTA2 (Affinity Capture-MS), ACTA2 (Affinity Capture-MS), ACTA2 (Affinity Capture-MS), ACTA2 (Affinity Capture-MS), ACTA2 (Affinity Capture-MS), ACTA2 (Affinity Capture-MS), ACTA2 (Affinity Capture-MS), ACTA2 (Affinity Capture-MS), ACTA2 (Affinity Capture-MS), ACTA2 (Affinity Capture-MS)

ESM2 similar proteins: A5DQP9, O13419, O17502, O17503, O74258, P04751, P10365, P10989, P11426, P12717, P14235, P17128, P18499, P20359, P26183, P30161, P30164, P30165, P43239, P53455, P53457, P53459, P53465, P53466, P53467, P53474, P53491, P60009, P60010, P60011, P62736, P62737, P62738, P62739, P78711, P84856, Q00214, Q00215, Q25472, Q55EU6

Diamond homologs: A2WKK5, A2XLF2, A2XNS1, A2ZP58, A3C6D7, D0LWX4, O16808, O18499, O65314, O65315, O65316, O81221, P02576, P04751, P07828, P07830, P07836, P07837, P08023, P0C539, P0C540, P0C542, P0CJ46, P0CJ47, P10981, P12716, P12717, P17126, P17304, P18601, P23343, P24902, P30162, P30164, P30165, P30167, P30168, P30169, P30171, P30172

SIGNOR signaling

6 interactions.

A	Effect	B	Mechanism
SRF	“up-regulates quantity by expression”	ACTA2	“transcriptional regulation”
TGFB1	“up-regulates quantity by expression”	ACTA2	“transcriptional regulation”
“Activated PSC”	“up-regulates quantity”	ACTA2
ACTA2	up-regulates	ECM_synthesis
HOXB8	“down-regulates quantity by repression”	ACTA2	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 250 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
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	6	24.1×	8e-05
Activation of BAD and translocation to mitochondria	5	22.8×	3e-04
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	5	20.1×	5e-04
Activation of BH3-only proteins	5	14.9×	2e-03
Signaling by high-kinase activity BRAF mutants	6	11.4×	1e-03
MAP2K and MAPK activation	6	10.3×	2e-03
RAF activation	5	10.1×	6e-03
Signaling by RAF1 mutants	6	10.0×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	23
Likely pathogenic	15
Uncertain significance	299
Likely benign	213
Benign	24

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1459384	NC_000010.10:g.(?90749963)(90750683_?)del	Pathogenic
1693278	NM_001613.4(ACTA2):c.454+1del	Pathogenic
1708188	GRCh37/hg19 10q23.1-23.31(chr10:83533660-91913077)x1	Pathogenic
1807623	GRCh37/hg19 10q23.1-23.32(chr10:82595472-93542416)x1	Pathogenic
1807839	GRCh37/hg19 10q23.31-23.33(chr10:89823147-96056941)x1	Pathogenic
18276	NM_001613.4(ACTA2):c.445C>T (p.Arg149Cys)	Pathogenic
18278	NM_001613.4(ACTA2):c.772C>T (p.Arg258Cys)	Pathogenic
2032218	NM_001613.4(ACTA2):c.369+1G>C	Pathogenic
239036	NM_001613.4(ACTA2):c.138G>A (p.Met46Ile)	Pathogenic
265026	NM_001613.4(ACTA2):c.535C>T (p.Arg179Cys)	Pathogenic
29598	NM_001613.4(ACTA2):c.536G>A (p.Arg179His)	Pathogenic
3572951	NC_000010.10:g.90533969_90911342del	Pathogenic
3720953	NM_001613.4(ACTA2):c.133G>T (p.Val45Leu)	Pathogenic
4279100	NM_001613.4(ACTA2):c.79G>T (p.Asp27Tyr)	Pathogenic
4802635	NM_001613.4(ACTA2):c.133G>C (p.Val45Leu)	Pathogenic
563795	GRCh37/hg19 10q23.1-23.32(chr10:83379241-93219169)x1	Pathogenic
563800	GRCh37/hg19 10q21.3-23.32(chr10:69040366-93194993)x3	Pathogenic
577891	NM_001613.4(ACTA2):c.941G>A (p.Arg314Gln)	Pathogenic
65450	NM_001613.4(ACTA2):c.145A>G (p.Met49Val)	Pathogenic
831277	NC_000010.11:g.(?88989499)(89247668_?)del	Pathogenic
911956	NM_001613.4(ACTA2):c.535C>A (p.Arg179Ser)	Pathogenic
979281	GRCh37/hg19 10q23.2-23.31(chr10:88685387-92144296)x1	Pathogenic
986791	NM_001613.4(ACTA2):c.536G>T (p.Arg179Leu)	Pathogenic
1054067	NM_001613.4(ACTA2):c.55T>C (p.Cys19Arg)	Likely pathogenic
1066384	NM_001613.4(ACTA2):c.115C>A (p.Arg39Ser)	Likely pathogenic
1213255	NM_000043.6(FAS):c.20T>C (p.Leu7Pro)	Likely pathogenic
1328396	NM_001613.4(ACTA2):c.340_343del (p.Pro114fs)	Likely pathogenic
1421069	NM_001613.4(ACTA2):c.136A>G (p.Met46Val)	Likely pathogenic
1700983	NM_001613.4(ACTA2):c.1076T>G (p.Ile359Ser)	Likely pathogenic
199678	NM_001613.4(ACTA2):c.991-1G>C	Likely pathogenic

SpliceAI

961 predictions. Top by Δscore:

Variant	Effect	Δscore
10:88938055:CAGTA:C	donor_loss	1.0000
10:88938056:AGTAC:A	donor_loss	1.0000
10:88938057:GTACC:G	donor_loss	1.0000
10:88938058:TA:T	donor_loss	1.0000
10:88938059:A:C	donor_loss	1.0000
10:88938060:C:G	donor_loss	1.0000
10:88938240:TCC:T	acceptor_gain	1.0000
10:88938241:CCC:C	acceptor_gain	1.0000
10:88938243:C:CC	acceptor_gain	1.0000
10:88938243:CTGG:C	acceptor_loss	1.0000
10:88939694:CTCAG:C	acceptor_gain	1.0000
10:88939696:CAG:C	acceptor_gain	1.0000
10:88939699:C:CC	acceptor_gain	1.0000
10:88939706:CCAGA:C	acceptor_gain	1.0000
10:88939707:C:CT	acceptor_gain	1.0000
10:88939707:C:T	acceptor_gain	1.0000
10:88939708:A:T	acceptor_gain	1.0000
10:88939710:A:C	acceptor_gain	1.0000
10:88941223:CCTCA:C	donor_loss	1.0000
10:88941224:CTCA:C	donor_loss	1.0000
10:88941225:TCA:T	donor_loss	1.0000
10:88941226:CA:C	donor_loss	1.0000
10:88941227:A:AC	donor_gain	1.0000
10:88941228:C:CC	donor_gain	1.0000
10:88941388:TGC:T	acceptor_gain	1.0000
10:88941391:C:CC	acceptor_gain	1.0000
10:88941866:TAAT:T	acceptor_gain	1.0000
10:88943793:TTA:T	donor_loss	1.0000
10:88943794:TACTT:T	donor_loss	1.0000
10:88943795:A:AC	donor_gain	1.0000

AlphaMissense

2492 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:88935242:A:T	V372D	1.000
10:88935254:C:T	G368E	1.000
10:88935255:C:A	G368W	1.000
10:88935255:C:G	G368R	1.000
10:88935255:C:T	G368R	1.000
10:88935285:A:G	W358R	1.000
10:88935285:A:T	W358R	1.000
10:88935295:G:C	F354L	1.000
10:88935295:G:T	F354L	1.000
10:88935297:A:G	F354L	1.000
10:88935305:A:G	L351P	1.000
10:88935305:A:T	L351Q	1.000
10:88935309:A:G	S350P	1.000
10:88935311:G:T	A349D	1.000
10:88935312:C:G	A349P	1.000
10:88935314:A:G	L348P	1.000
10:88935314:A:T	L348Q	1.000
10:88935317:A:T	I347N	1.000
10:88935320:G:A	S346F	1.000
10:88935320:G:T	S346Y	1.000
10:88935321:A:G	S346P	1.000
10:88935323:C:A	G345V	1.000
10:88935323:C:T	G345D	1.000
10:88935324:C:A	G345C	1.000
10:88935324:C:G	G345R	1.000
10:88935326:C:A	G344V	1.000
10:88935326:C:T	G344D	1.000
10:88935327:C:A	G344C	1.000
10:88935327:C:G	G344R	1.000
10:88935327:C:T	G344S	1.000

dbSNP variants (sampled 300 via entrez): RS1000075584 (10:88985458 CTA>C), RS1000133026 (10:88957602 A>T), RS1000156040 (10:88966603 A>G), RS1000314216 (10:88943945 T>G), RS1000346992 (10:88943605 G>C), RS1000483868 (10:88937449 C>G,T), RS1000580835 (10:88983730 G>A,C), RS1000617218 (10:88965227 T>C), RS1000624870 (10:88974112 G>GT), RS1000684472 (10:88976490 T>C), RS1000701669 (10:88963711 G>T), RS1000713502 (10:88976250 C>T), RS1000845346 (10:88969702 T>A), RS1000870931 (10:88940742 T>C), RS1000902254 (10:88963080 G>C)

Disease associations

OMIM: gene MIM:102620 | disease phenotypes: MIM:611788, MIM:607086, MIM:601859, MIM:613834, MIM:607087, MIM:614042, MIM:154700, MIM:252350

GenCC curated gene-disease

Disease	Classification	Inheritance
multisystemic smooth muscle dysfunction syndrome	Definitive	Autosomal dominant
Moyamoya disease 5	Strong	Autosomal dominant
aortic aneurysm, familial thoracic 6	Strong	Autosomal dominant
connective tissue disorder	Moderate	Autosomal dominant
familial thoracic aortic aneurysm and aortic dissection	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
multisystemic smooth muscle dysfunction syndrome	Definitive	AD

Mondo (13): aortic aneurysm, familial thoracic 6 (MONDO:0012730), familial thoracic aortic aneurysm and aortic dissection (MONDO:0019625), autoimmune lymphoproliferative syndrome type 1 (MONDO:0011158), multisystemic smooth muscle dysfunction syndrome (MONDO:0013452), thoracic aortic aneurysm (MONDO:0005396), aortic aneurysm, familial thoracic 2 (MONDO:0011770), Moyamoya disease 5 (MONDO:0013542), connective tissue disorder (MONDO:0003900), autoimmune lymphoproliferative syndrome (MONDO:0017979), Marfan syndrome (MONDO:0007947), lung adenocarcinoma (MONDO:0005061), Moyamoya disease (MONDO:0016820), aortic aneurysm, familial thoracic 1 (MONDO:0024559)

Orphanet (8): Familial thoracic aortic aneurysm and aortic dissection (Orphanet:91387), Autoimmune lymphoproliferative syndrome (Orphanet:3261), Multisystemic smooth muscle dysfunction syndrome (Orphanet:404463), Moyamoya disease (Orphanet:2573), Marfan syndrome type 1 (Orphanet:284963), Marfan syndrome (Orphanet:558), Familial aortic dissection (Orphanet:229), NON RARE IN EUROPE: Adenocarcinoma of the lung (Orphanet:415268)

HPO phenotypes

72 total (30 of 72 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000023	Inguinal hernia
HP:0000028	Cryptorchidism
HP:0000098	Tall stature
HP:0000278	Retrognathia
HP:0000316	Hypertelorism
HP:0000525	Abnormality iris morphology
HP:0000766	Abnormal sternum morphology
HP:0000822	Hypertension
HP:0000965	Cutis marmorata
HP:0000978	Bruising susceptibility
HP:0001009	Telangiectasia
HP:0001166	Arachnodactyly
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001297	Stroke
HP:0001631	Atrial septal defect
HP:0001640	Cardiomegaly
HP:0001643	Patent ductus arteriosus
HP:0001647	Bicuspid aortic valve
HP:0001659	Aortic regurgitation
HP:0001677	Coronary artery atherosclerosis
HP:0001763	Pes planus
HP:0002092	Pulmonary arterial hypertension
HP:0002105	Hemoptysis
HP:0002107	Pneumothorax
HP:0002119	Ventriculomegaly
HP:0002138	Subarachnoid hemorrhage
HP:0002140	Ischemic stroke
HP:0002326	Transient ischemic attack

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST000763_3	Immunoglobulin A	6.000000e-06
GCST002073_3	Chronic lymphocytic leukemia	1.000000e-14
GCST003468_11	Chronic lymphocytic leukemia	9.000000e-14
GCST003814_2	Selective IgA deficiency	7.000000e-08
GCST005537_192	Chronic inflammatory diseases (ankylosing spondylitis, Crohn’s disease, psoriasis, primary sclerosing cholangitis, ulcerative colitis) (pleiotropy)	4.000000e-09
GCST007269_113	Pulse pressure	4.000000e-09
GCST90002389_449	Lymphocyte percentage of white cells	6.000000e-14
GCST90010715_13	Arthritis (juvenile idiopathic)	1.000000e-07

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004747	protein measurement
EFO:0005763	pulse pressure measurement
EFO:0007993	lymphocyte percentage of leukocytes

MeSH disease descriptors (8)

Descriptor	Name	Tree numbers
D017545	Aortic Aneurysm, Thoracic	C14.907.055.239.125; C14.907.109.139.125
D056735	Autoimmune Lymphoproliferative Syndrome	C15.604.515.138; C16.320.089; C20.111.288; C20.683.515.124
D003240	Connective Tissue Diseases	C17.300
D008382	Marfan Syndrome	C05.116.099.674; C14.240.400.725; C14.280.400.725; C16.131.077.550; C16.131.240.400.720; C16.320.540; C17.300.500
D009072	Moyamoya Disease	C10.228.140.300.200.600; C10.228.140.300.510.200.737; C14.907.137.615; C14.907.253.123.620; C14.907.253.560.200.737
C562834	Aortic Aneurysm, Familial Thoracic 1 (supp.)
C564627	Aortic Aneurysm, Familial Thoracic 2 (supp.)
C567085	Aortic Aneurysm, Familial Thoracic 6 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs2234767	ACTA2, FAS		0.00	0

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases abundance, increases reaction, decreases reaction, decreases expression, increases expression (+5 more)	14
Silicon Dioxide	decreases reaction, increases expression, increases reaction, decreases expression, increases secretion (+3 more)	11
bisphenol A	increases expression, increases methylation, affects expression, decreases expression	7
Valproic Acid	affects expression, decreases expression, increases expression	7
Arsenic Trioxide	affects reaction, increases reaction, decreases reaction, increases expression, decreases expression	6
Benzo(a)pyrene	affects methylation, decreases expression, increases expression	6
Paraquat	increases expression, increases reaction, affects reaction, decreases reaction, decreases expression	6
Tretinoin	decreases expression, affects cotreatment, increases expression, decreases reaction	6
SB 203580	decreases reaction, increases expression, decreases expression	5
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases expression, affects reaction, decreases reaction, increases expression, affects cotreatment	5
Glucose	affects cotreatment, affects expression, affects reaction, increases reaction, decreases reaction (+1 more)	5
aristolochic acid I	decreases reaction, affects cotreatment, increases expression	4
Resveratrol	decreases expression, decreases reaction, increases reaction, increases expression	4
Bleomycin	decreases expression, increases expression, decreases reaction	4
Niclosamide	increases phosphorylation, decreases expression, decreases reaction, decreases response to substance, increases expression	4
Cyclosporine	increases expression, decreases reaction, affects cotreatment, decreases expression	4
Aflatoxin B1	affects expression, decreases methylation, increases expression	4
Asbestos, Serpentine	decreases expression, increases expression, affects reaction	4
N-(1,2,3,5,6,7-hexahydro-S-indacen-4-ylcarbamoyl)-4-(2-hydroxy-2-propanyl)-2-furansulfonamide	decreases reaction, increases expression	3
methylmercuric chloride	decreases expression, increases expression, affects cotreatment	3
ochratoxin A	decreases reaction, increases expression, affects cotreatment, affects reaction	3
nickel monoxide	increases expression, decreases reaction	3
U 0126	decreases reaction, increases expression, decreases expression	3
Air Pollutants	increases abundance, increases expression, decreases expression	3
Ascorbic Acid	affects cotreatment, increases expression, increases reaction	3
Folic Acid	affects expression, decreases expression, increases expression	3
Nickel	affects binding, decreases activity, decreases reaction, increases expression, decreases expression	3
Oxygen	decreases reaction, increases expression, affects cotreatment, decreases expression, affects reaction (+2 more)	3
Progesterone	decreases expression, increases expression	3
Quartz	increases expression, increases reaction, decreases expression, affects binding, decreases reaction	3

Cellosaurus cell lines

5 cell lines: 5 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1IX	Abcam HeLa ACTA2 KO	Cancer cell line	Female
CVCL_B8AT	Abcam HCT 116 ACTA2 KO	Cancer cell line	Male
CVCL_B8S4	Abcam MCF-7 ACTA2 KO	Cancer cell line	Female
CVCL_B9CV	Abcam A-549 ACTA2 KO	Cancer cell line	Male
CVCL_D7JF	Ubigene A-549 ACTA2 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01042158	PHASE4	COMPLETED	A Clinical Trial of Ambrisentan and Tadalafil in Pulmonary Arterial Hypertension Associated With Systemic Sclerosis
NCT03688191	PHASE4	UNKNOWN	Study of Sirolimus in CTD-TP in China
NCT04169100	PHASE4	UNKNOWN	Novel Form of Acquired Long QT Syndrome
NCT04197050	PHASE4	UNKNOWN	Effect of Sacubitril/Valsartan on Reduced Right Ventricular Ejection Fraction in Patients With CTD
NCT04928586	PHASE4	UNKNOWN	Immunosuppressant Combined With Pirfenidone in CTD-ILD
NCT05440240	PHASE4	RECRUITING	Percutaneous Needle Fasciotomy +/- Corticosteroid Injection for Dupuytren’s Contracture
NCT05505409	PHASE4	UNKNOWN	Efficacy and Safety of Pirfenidone in CTD-ILD
NCT06499233	PHASE4	RECRUITING	Efficacy and Safety of Prophylactic Treatment for Pneumocystis Jirovecii Pneumonia in Patients With Autoimmune Inflammatory Rheumatic Disease
NCT00339053	PHASE4	UNKNOWN	Immunonutrition and Thoracoabdominal Aorta Aneurysm Repair
NCT02291718	PHASE4	COMPLETED	Thoracoabdominal Arortic CTA Study
NCT01295047	PHASE4	COMPLETED	Comparison of Medical Therapies in Marfan Syndrome.
NCT02399566	PHASE4	UNKNOWN	Clinical Trial of Erlotinib and Pemetrexed for Maintenance Treatment in Lung Adenocarcinoma
NCT02804646	PHASE4	UNKNOWN	Endostar Durative Transfusion Combined With Chemotherapy in the Treatment of Advanced Lung Adenocarcinoma
NCT00864201	PHASE3	UNKNOWN	A Study to Evaluate the Use of Bosentan in Patients With Exercise Induced Pulmonary Arterial Hypertension Associated With Connective Tissue Disease
NCT01196091	PHASE3	COMPLETED	A Study of LY2127399 in Participants With Systemic Lupus Erythematosus
NCT01205438	PHASE3	COMPLETED	A Study of LY2127399 in Participants With Systemic Lupus Erythematosus
NCT01488708	PHASE3	TERMINATED	On Open-Label Study in Participants With Systemic Lupus Erythematosus
NCT03626688	PHASE3	COMPLETED	A Study Evaluating the Efficacy and Safety of Ralinepag to Improve Treatment Outcomes in PAH Patients
NCT03683186	PHASE3	ENROLLING_BY_INVITATION	A Study Evaluating the Long-Term Efficacy and Safety of Ralinepag in Subjects With PAH Via an Open-Label Extension
NCT04084678	PHASE3	TERMINATED	A Study of Ralinepag to Evaluate Effects on Exercise Capacity by CPET in Subjects With WHO Group 1 PH
NCT06716606	PHASE3	RECRUITING	A Study to Investigate the Long-term Safety and Efficacy of Belimumab in Adults With Interstitial Lung Disease (ILD) Associated With Systemic Sclerosis (SSc) and Other Connective Tissue Diseases (CTD) (BLISSconneCTD-OLE)
NCT06917690	PHASE3	RECRUITING	A Study to Learn About the Safety and Efficacy of the Drug Oleogel-S10 in Japanese Patients With Epidermolysis Bullosa
NCT00429364	PHASE3	COMPLETED	Comparison of Two Medications Aimed at Slowing Aortic Root Enlargement in Individuals With Marfan Syndrome
NCT00485368	PHASE3	COMPLETED	Angiotensin Converting Enzyme Inhibitors in Marfan Syndrome
NCT00683124	PHASE3	UNKNOWN	Nebivolol Versus Losartan Versus Nebivolol+Losartan Against Aortic Root Dilation in Genotyped Marfan Patients
NCT00723801	PHASE3	COMPLETED	Effects of Losartan Versus Atenolol on Aortic and Cardiac Muscle Stiffness in Adults With Marfan Syndrome
NCT00763893	PHASE3	TERMINATED	Study of the Efficacy of Losartan on Aortic Dilatation in Patients With Marfan Syndrome
NCT00782327	PHASE3	COMPLETED	Randomized, Double-blind Study for the Evaluation of the Effect of Losartan Versus Placebo on Aortic Root Dilatation in Patients With Marfan Syndrome Under Treatment With Beta-blockers
NCT01145612	PHASE3	UNKNOWN	Atenolol Versus Losartan in the Prevention of Progressive Dilation of the Aorta in Marfan Syndrome
NCT01361087	PHASE3	WITHDRAWN	Circulating Transforming Growth Factor Beta (TGF-β) in Individuals With Marfan Syndrome
NCT01715207	PHASE3	COMPLETED	Comparison of Aliskiren vs Negative Controls on Aortic Stiffness in Patients With MFS
NCT00002852	PHASE3	COMPLETED	Surgery With or Without Chemotherapy in Treating Patients With Stage I Non-small Cell Lung Cancer
NCT00005838	PHASE3	COMPLETED	Combination Chemotherapy Plus Radiation Therapy With or Without AE-941 in Treating Patients With Stage III Non-small Cell Lung Cancer That Cannot Be Removed By Surgery
NCT00020709	PHASE3	COMPLETED	Combination Chemotherapy and Radiation Therapy With or Without Gefitinib in Treating Patients With Stage III Non-Small Cell Lung Cancer That Cannot Be Removed By Surgery
NCT00049543	PHASE3	COMPLETED	Gefitinib in Treating Patients With Stage IB, II, or IIIA Non-small Cell Lung Cancer That Was Completely Removed by Surgery
NCT00946712	PHASE3	TERMINATED	S0819: Carboplatin and Paclitaxel With or Without Bevacizumab and/or Cetuximab in Treating Patients With Stage IV or Recurrent Non-Small Cell Lung Cancer
NCT01798485	PHASE3	TERMINATED	A Phase 3 Study of Ganetespib in Combination With Docetaxel Versus Docetaxel Alone in Patients With Advanced NSCLC
NCT02011997	PHASE3	UNKNOWN	Comparison of cVATS Segmentectomy Versus Lobectomy for Lung Adenocarcinoma in Situ and With Microinvasion
NCT03391869	PHASE3	ACTIVE_NOT_RECRUITING	Nivolumab and Ipilimumab With or Without Local Consolidation Therapy in Treating Patients With Stage IV Non-Small Cell Lung Cancer
NCT03676192	PHASE3	COMPLETED	To Compare Efficacy and Safety of CT-P16 and European Union-Approved Avastin as First-Line Treatment for Metastatic or Recurrent Non-Squamous Non-Small Cell Lung Cancer