MCID: THR006
MIFTS: 77

Thromboangiitis Obliterans malady

Rare diseases, Cardiovascular diseases, Nephrological diseases, Bone diseases, Blood diseases categories

Summaries for Thromboangiitis Obliterans

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NIH Rare Diseases:43 Buerger disease is a disease that causes obstruction of the blood vessels of the hands and feet. it is caused by vasculitis, which is an inflammation of blood vessels. the blood vessels of the hands and feet are especially affected, becoming constricted or totally blocked. this reduces blood flow to the tissues of hands and feet, resulting in pain and eventually damage. last updated: 11/19/2009

MalaCards based summary: Thromboangiitis Obliterans, also known as buerger disease, is related to arteriosclerosis obliterans and thrombophlebitis, and has symptoms including vasculitis, arterial thrombosis and gangrene. An important gene associated with Thromboangiitis Obliterans is APOH (apolipoprotein H (beta-2-glycoprotein I)), and among its related pathways are Development Leptin signaling via JAK STAT and MAPK cascades and Endothelin. The drugs isoxsuprine and tolazoline and the compounds carvedilol and gliclazide have been mentioned in the context of this disorder. Affiliated tissues include bone, skin and endothelial, and related mouse phenotypes are endocrine/exocrine gland and vision/eye.

Wikipedia:65 Thromboangiitis obliterans (also known as Buerger\'s disease, Buerger disease [English /b?r??r/; German... more...

Aliases & Classifications for Thromboangiitis Obliterans

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Sources:
32LifeMap Discovery®, 10Disease Ontology, 43NIH Rare Diseases, 45Novoseek, 49Orphanet, 62UMLS, 57SNOMED-CT, 35MeSH, 40NCIt, 29ICD9CM, 28ICD10 via Orphanet, 27ICD10
See all sources

Thromboangiitis Obliterans, Aliases & Descriptions:

Name: Thromboangiitis Obliterans 32 10 43 49 62
Buerger Disease 43 45 49
Buerger's Disease 10 43
Inflammatory Occlusive Peripheral Vascular Disease 43
Occlusive Peripheral Vascular Disease 43
 
Thromboangiitis Obliterans Nos 10
Presenile Gangrene 10
Taos 62
Tao 43


Classifications:



Characteristics (Orphanet epidemiological data):

49
thromboangiitis obliterans:
Prevalence: 1-5/10000 (Worldwide); Age of onset: Adult; Age of death: normal life expectancy


External Ids:

Disease Ontology10 DOID:12918
MeSH35 D013919
NCIt40 C35070
ICD9CM29 443.1
Orphanet49 36258
ICD10 via Orphanet28 I73.1
ICD1027 I73.1

Related Diseases for Thromboangiitis Obliterans

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Diseases related to Thromboangiitis Obliterans via text searches within MalaCards or GeneCards/GeneDecks gene sharing:

(show top 50)    (show all 139)
idRelated DiseaseScoreTop Affiliating Genes
1arteriosclerosis obliterans31.0VCAM1, ICAM1
2thrombophlebitis30.9APOH
3arteriosclerosis30.9EDN1, ICAM1, VCAM1, NOS3, SERPINE1
4ischemia30.9NOS3, EDN1, SELE, ICAM1, PLAT
5vascular disease30.9TIMP1, APOH
6atherosclerosis30.6ICAM1, EDN1, APOH, SELE, TIMP1, PLAT
7vasculitis30.5VCAM1, APOH, SELE, ICAM1, SERPINB1
8hyperhomocysteinemia30.5PLAT, NOS3, VCAM1, SERPINE1, APOH, SELE
9impotence30.4NOS3, EDN1
10peripheral vascular disease30.4SELE
11pulmonary embolism30.3APOH, PLAT
12arthritis30.3TIMP1, SELE, MMP9, ICAM1
13thrombophilia30.3PLAT, SELE, SERPINE1, APOH
14obesity30.0SERPINE1, NOS3, HTR2A, SELE
15colorectal cancer30.0ICAM1, SELE, VCAM1, MMP9
16cerebritis10.7
17endotheliitis10.6
18critical limb ischemia10.4
19limb ischemia10.4
20peripheral artery disease10.4
21artery disease10.4
22thyroiditis10.3
23dilated cardiomyopathy10.2
24ischemic heart disease10.2
25cryoglobulinemia10.2
26chronic venous insufficiency10.2
27thrombotic thrombocytopenic purpura10.2
28hypoglycemia10.2
29paronychia10.2
30cellulitis10.2
31diarrhea10.2
32eosinophilia10.2
33purpura10.2
34venous insufficiency10.2
35rheumatic disease10.2
36blindness10.2
37retinal artery occlusion10.1APOH
38retinal vein occlusion10.1APOH
39carotid artery thrombosis10.0SERPINE1
40systemic scleroderma10.0EDN1
41heart valve disease10.0HTR2A, APOH
42compartment syndrome10.0
43malaria10.0ICAM1
44diabetic angiopathy10.0EDN1, SELE
45acute chest syndrome10.0NOS3, VCAM1
46plummer's disease10.0ICAM1, SELE
47cardiac rupture10.0PLAT
48central retinal artery occlusion10.0PLAT
49prinzmetal's variant angina10.0NOS3, EDN1
50protein s deficiency10.0SERPINE1, APOH

Graphical network of the top 20 diseases related to Thromboangiitis Obliterans:



Diseases related to thromboangiitis obliterans

Symptoms for Thromboangiitis Obliterans

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Symptoms:

 49 (show all 12)
  • chronic skin infection/ulcerations/ulcers/cancrum
  • arterial embolism/thrombosis
  • arterial pulse abolition
  • vascularitis/vasculitides/arteritis
  • gangrena/necrosis
  • sensitive trouble/deficit
  • acrocyanosis/raynaud's phenomenon/vasomotor disorders
  • acute ischemia of the lower limbs
  • paresthesia/dysesthesia/hypoesthesia/anesthesia/numbness
  • articular/joint pain/arthralgia
  • hyperhidrosis/increased sweating
  • insomnia

HPO human phenotypes related to Thromboangiitis Obliterans:

(show all 9)
id Description Frequency HPO Source Accession
1 vasculitis hallmark (90%) HP:0002633
2 arterial thrombosis hallmark (90%) HP:0004420
3 gangrene hallmark (90%) HP:0100758
4 skin ulcer hallmark (90%) HP:0200042
5 acrocyanosis typical (50%) HP:0001063
6 arthralgia typical (50%) HP:0002829
7 paresthesia typical (50%) HP:0003401
8 hyperhidrosis occasional (7.5%) HP:0000975
9 insomnia occasional (7.5%) HP:0100785

Drugs & Therapeutics for Thromboangiitis Obliterans

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Drug clinical trials:

Search ClinicalTrials for Thromboangiitis Obliterans

Search NIH Clinical Center for Thromboangiitis Obliterans

Inferred drug relations via UMLS62/NDF-RT41:

Cell-based therapeutics:


LifeMap Discovery
The database of embryonic development, stem cell research and regenerative medicine
Read about Thromboangiitis Obliterans cell therapies at LifeMap Discovery.

Genetic Tests for Thromboangiitis Obliterans

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Anatomical Context for Thromboangiitis Obliterans

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MalaCards organs/tissues related to Thromboangiitis Obliterans:

33
Bone, Skin, Endothelial, Bone marrow, Colon, Spinal cord, Heart, Neutrophil, Kidney

LifeMap Discovery
The database of embryonic development, stem cell research and regenerative medicine

Cells/anatomical compartments in embryo or adult related to Thromboangiitis Obliterans:
id TissueAnatomical CompartmentCell Relevance
1 AdiposeSubcutaneous White AdiposeMesenchymal Stem Cells Potential therapeutic candidate
2 AdiposeSubcutaneous White AdiposeStromal Cells Potential therapeutic candidate

Animal Models for Thromboangiitis Obliterans or affiliated genes

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Publications for Thromboangiitis Obliterans

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Articles related to Thromboangiitis Obliterans:

(show top 50)    (show all 309)
idTitleAuthorsYear
1
Integrated treatment for lower-limb stage II thromboangiitis obliterans by interventional therapy and oral administration of Chinese medicine: a randomized controlled clinical trial. (25842727)
2015
2
Buerger Disease (Thromboangiitis Obliterans). (25770636)
2014
3
The value of FDG-PET in the diagnosis of thromboangiitis obliterans-a case series. (24794493)
2014
4
Noninvasive Transcutaneous Monitoring in Long-Term Follow-Up of Patients With Thromboangiitis Obliterans Treated With Intravenous Iloprost. (25005765)
2014
5
Temporal artery involvement as the presenting sign of thromboangiitis obliterans. (23519182)
2013
6
Imbalanced matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 activities in patients with thromboangiitis obliterans. (22402936)
2012
7
Buerger's disease (Thromboangiitis obliterans): a diagnostic challenge. (22679237)
2011
8
Buerger's Disease (Thromboangiitis Obliterans)- Management by Ilizarov's Technique of Horizontal Distraction. A Retrospective Study of 60 Cases. (22211037)
2011
9
Effectiveness of bosentan in the treatment of ischemic lesions in a case of thromboangiitis obliterans (Buerger disease): a case report. (21810389)
2011
10
Protective effect of Shenfu injection on thromboangiitis obliterans model rats. (21982791)
2011
11
Color doppler flows of corkscrew collaterals in Thromboangiitis obliterans (Buerger's disease) using color duplex ultrasonography. (21679855)
2011
12
Classification of corkscrew collaterals in thromboangiitis obliterans (Buerger's disease): relationship between corkscrew type and prevalence of ischemic ulcers. (20534945)
2010
13
Thromboangiitis obliterans and endothelial function. (20584171)
2010
14
Treatment of Buerger disease (thromboangiitis obliterans) with bosentan: a case report. (21686681)
2009
15
Thromboangiitis obliterans in the 21st century--a new face of disease. (19269635)
2009
16
A prospective, case-control study of tobacco dependence in thromboangiitis obliterans (Buerger's Disease). (16444459)
2006
17
One of the most frequent vascular diseases in northeastern of Turkey: Thromboangiitis obliterans or Buerger's disease (experience with 344 cases). (16580754)
2006
18
Inflammatory joint disease and severe ischemia of the extremities revealing thromboangiitis obliterans in a female. (15681252)
2005
19
Thromboangiitis obliterans associated with peripheral blood and eosinophilic cellulitis-like skin lesions. (15985040)
2005
20
Involvement of the coronary artery in a patient with thromboangiitis obliterans. A case report. (12181595)
2002
21
Distribution of arterial involvement in thromboangiitis obliterans (Buerger's disease): results of a study conducted by the Intractable Vasculitis Syndromes Research Group in Japan. (10930225)
2000
22
Current status of thromboangiitis obliterans (Buerger's disease) in Japan. (10980360)
2000
23
Implantable spinal cord stimulator to treat the ischemic manifestations of thromboangiitis obliterans (Buerger's disease). (10231644)
1999
24
Study of anti-neutrophil cytoplasmic antibodies in patients with thromboangiitis obliterans (Buerger's disease). (9822265)
1998
25
Is the capillary microscopic determination of the visible capillary length a diagnostic criterion in thromboangiitis obliterans? (9612111)
1998
26
Inpatient treatment of severe nicotine dependence in a patient with thromboangiitis obliterans (Buerger's disease). (9621859)
1998
27
Thromboangiitis obliterans (Buerger's disease) in visceral vessels confirmed by angiographic and histological findings. (9854560)
1998
28
Thromboangiitis obliterans (Buerger's disease). (9189999)
1997
29
Pharmacokinetics and tolerability of oral iloprost in thromboangiitis obliterans patients. (9349930)
1997
30
Thromboangiitis obliterans (Buerger's disease) (9119522)
1996
31
Case of thromboangiitis obliterans (Buerger's disease) of the upper lip. (7573750)
1995
32
Impotence as a cardinal sign in the thromboangiitis obliterans diagnosis. (8608695)
1995
33
Cerebral thromboangiitis obliterans: clinical and MRI findings in a case. (7671993)
1995
34
Thromboangiitis obliterans. (7518238)
1994
35
Buerger's disease (thromboangiitis obliterans). (2189162)
1990
36
Serum zinc and copper in patients with atherosclerosis and thromboangiitis obliterans. (2484753)
1989
37
CAT scan and immunohistochemical findings in a case of cerebral thromboangiitis obliterans (Buerger's disease). (6714279)
1984
38
Cellular sensitivity to collagen in thromboangiitis obliterans. (6835334)
1983
39
Buerger's disease (thromboangiitis obliterans): an analysis of the arteriograms of 119 cases. (7067357)
1982
40
Autoantibodies in thromboangiitis obliterans (Buerger's disease). (6751163)
1982
41
Factors influenced on prognosis of reconstructive surgery for peripheral arterial occlusion: comparative study between arteriosclerosis obliterans and thromboangiitis obliterans. (599159)
1977
42
Traditional chinese medicine in the treatment of thromboangiitis obliterans. Report of 136 cases. (5678364)
1968
43
Coexistence of thromboangiitis obliterans and arteriosclerosis: relationship to smoking. (5914684)
1966
44
Thromboangiitis obliterans and arteriosclerosis obliterans. (5833515)
1965
45
THROMBOANGIITIS OBLITERANS AND ARTERIOSCLEROSIS OBLITERANS. CLINICAL AND PROGNOSTIC DIFFERENCES. (14065946)
1963
46
Cogan's syndrome and systemic vascular disease. Analysis of pathologic features with reference to its relationship to thromboangiitis obliterans (Buerger). (13893233)
1961
47
Thromboangiitis obliterans: a 30-year study. (13502019)
1958
48
A follow-up study of patient with thromboangiitis obliterans (Buerger's disease). (15395864)
1949
49
Cerebral thromboangiitis obliterans. (20289123)
1947
50
Treatment of thromboangiitis obliterans. (21006071)
1945

Variations for Thromboangiitis Obliterans

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Expression for genes affiliated with Thromboangiitis Obliterans

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Search GEO for disease gene expression data for Thromboangiitis Obliterans.

Pathways for genes affiliated with Thromboangiitis Obliterans

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Pathways related to Thromboangiitis Obliterans according to GeneCards/GeneDecks:

(show all 27)
idSuper pathways (with members indented)ScoreTop Affiliating Genes
1
Show member pathways
9.8TIMP1, EDN1
29.7NOS3, EDN1
39.7VCAM1, ICAM1
49.7ICAM1, VCAM1
59.7MMP9, SELE
6
Show member pathways
Angiogenesis38
9.5MMP9, NOS3
79.5MMP9, NOS3
89.5MMP9, NOS3
99.4SELE, VCAM1, ICAM1
109.4ICAM1, VCAM1, SELE
119.4ICAM1, VCAM1, SELE
129.3MMP9, PLAT
139.2NOS3, MMP9, TIMP1
149.2VCAM1, MMP9, ICAM1
159.0PLAT, SERPINE1
169.0SELE, VCAM1, ICAM1, NOS3
17
Show member pathways
Development VEGF signaling via VEGFR2 generic cascades60
9.0SELE, VCAM1, ICAM1, NOS3
18
Show member pathways
Cytoskeleton remodeling FAK signaling60
Development Endothelin 1 EDNRA transactivation of EGFR60
8.9EDN1, MMP9, HTR2A, NOS3
198.9PLAT, ICAM1, MMP9
208.9ICAM1, VCAM1, SERPINE1
21
Show member pathways
thioredoxin pathway38
8.6SERPINE1, ICAM1, PLAT
228.5EDN1, TIMP1, SERPINE1, NOS3
238.5ICAM1, MMP9, VCAM1, SELE, EDN1
24
Show member pathways
8.3ICAM1, MMP9, VCAM1, SERPINE1
25
Show member pathways
8.2TIMP1, SERPINE1, MMP9, PLAT
26
Show member pathways
8.0ICAM1, MMP9, VCAM1, SERPINE1, TIMP1
27
Show member pathways
8.0TIMP1, SERPINE1, SELE, PLAT, NOS3

Compounds for genes affiliated with Thromboangiitis Obliterans

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Compounds related to Thromboangiitis Obliterans according to GeneCards/GeneDecks:

(show top 50)    (show all 213)
idCompoundScoreTop Affiliating Genes
1carvedilol45 51 30 1312.3VCAM1, EDN1, SELE, NOS3
2gliclazide45 51 1311.1PLAT, SELE, VCAM1, ICAM1
3iloprost61 30 45 1312.1PLAT, VCAM1, SELE, EDN1
4apocynin45 6110.0VCAM1, SELE, EDN1, ICAM1, NOS3
5polymyxin b458.9ICAM1, SERPINE1, SELE, VCAM1
6l-nmma458.8NOS3, EDN1, VCAM1, MMP9
7cytochalasin d45 619.8SELE, VCAM1, MMP9, ICAM1, TIMP1
8nebivolol45 139.8NOS3, SERPINE1, EDN1
9quinapril45 51 1310.7EDN1, SERPINE1, SELE, PLAT
10folate458.7NOS3, TIMP1, MMP9, VCAM1, SELE, APOH
11norepinephrine45 26 1310.7SELE, HTR2A, MMP9, VCAM1, TIMP1, EDN1
12hirudin458.6PLAT, SELE, SERPINE1, TIMP1
13herbimycin a45 619.6MMP9, SELE, TIMP1, ICAM1, VCAM1, EDN1
14ciglitazone45 309.5SERPINE1, MMP9, ICAM1, NOS3
15endotoxin458.5ICAM1, APOH, SERPINE1, SELE, VCAM1
16pravastatin45 51 30 26 1312.5NOS3, ICAM1, VCAM1, SELE, SERPINE1
17nifedipine45 30 51 1311.4TIMP1, MMP9, SELE, SERPINE1, EDN1
18histamine45 30 2610.4PLAT, VCAM1, EDN1, TIMP1, SELE, ICAM1
19losartan45 51 30 1311.4PLAT, VCAM1, SERPINE1, SELE, EDN1
20pge2458.3VCAM1, EDN1, TIMP1, SELE, MMP9, ICAM1
21lactate458.3TIMP1, APOH, ICAM1, SELE, VCAM1, MMP9
22sodium nitroprusside458.2VCAM1, PLAT, NOS3, SERPINE1, EDN1
23methotrexate51 45 1310.2TIMP1, APOH, MMP9, SELE, NOS3, SERPINE1
24cyclophosphamide45 51 1310.2APOH, NOS3, MMP9, VCAM1, SELE, SERPINE1
25rosiglitazone30 45 51 26 1312.2SELE, NOS3, MMP9, VCAM1, SERPINE1, TIMP1
26isoproterenol45 139.2SERPINE1, PLAT, SELE, EDN1, VCAM1
27homocysteine45 269.1APOH, VCAM1, PLAT, NOS3, SERPINE1, SELE
28aspirin45 51 30 2611.1SELE, NOS3, SERPINE1, TIMP1, APOH, PLAT
29fenofibrate45 51 1310.1SERPINE1, NOS3, SELE, VCAM1, MMP9, ICAM1
30phosphatidylinositol458.0MMP9, VCAM1, TIMP1, APOH, NOS3, EDN1
31nicotine45 30 51 1310.9SERPINE1, SELE, MMP9, ICAM1, PLAT
32troglitazone45 30 61 1310.8MMP9, VCAM1, SELE, PLAT, ICAM1, SERPINE1
33ly294002457.7MMP9, SELE, TIMP1, VCAM1, NOS3, ICAM1
34heparin45 30 26 1310.6APOH, SELE, PLAT, VCAM1, SERPINB1, TIMP1
35pd 98,059457.6VCAM1, SERPINE1, TIMP1, EDN1, ICAM1, NOS3
36nitric oxide45 26 139.6APOH, EDN1, ICAM1, TIMP1, SERPINE1, SELE
37fibrinogen457.6SELE, VCAM1, SERPINE1, ICAM1, PLAT, APOH
38aspartate457.5TIMP1, PLAT, VCAM1, SELE, SERPINE1, MMP9
39fluvastatin45 51 30 1310.5SELE, NOS3, VCAM1, MMP9, ICAM1, PLAT
40simvastatin45 51 61 30 26 1312.4SELE, PLAT, MMP9, ICAM1, VCAM1, SERPINE1
418-isoprostane457.4EDN1, VCAM1, NOS3, SELE, SERPINE1, MMP9
42cycloheximide457.4SERPINE1, SELE, PLAT, ICAM1, EDN1, TIMP1
43sb 20358045 618.4EDN1, SELE, VCAM1, MMP9, ICAM1, NOS3
44genistein45 30 61 3 26 1312.4MMP9, ICAM1, VCAM1, SELE, SERPINE1, TIMP1
45creatinine457.3SELE, EDN1, APOH, PLAT, MMP9, SERPINE1
46matrigel457.1SERPINE1, TIMP1, VCAM1, SELE, NOS3, MMP9
47vegf457.1TIMP1, APOH, SERPINE1, MMP9, SELE, NOS3
48actinomycin d457.1SELE, MMP9, EDN1, NOS3, TIMP1, ICAM1
49prostacyclin457.0ICAM1, VCAM1, SELE, SERPINE1, TIMP1, APOH
50atorvastatin45 51 30 26 1310.8TIMP1, SERPINE1, SELE, NOS3, PLAT, ICAM1

GO Terms for genes affiliated with Thromboangiitis Obliterans

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Cellular components related to Thromboangiitis Obliterans according to GeneCards/GeneDecks:

idNameGO IDScoreTop Affiliating Genes
1caveolaGO:00059019.4SELE, HTR2A, NOS3
2extracellular matrixGO:00310128.5PLAT, SERPINE1, APOH
3extracellular regionGO:00055767.8PLAT, MMP9, SERPINE1, TIMP1, EDN1
4extracellular spaceGO:00056156.2PLAT, EDN1, APOH, SERPINE1, SELE, SERPINB1

Biological processes related to Thromboangiitis Obliterans according to GeneCards/GeneDecks:

(show all 30)
idNameGO IDScoreTop Affiliating Genes
1negative regulation of smooth muscle cell apoptotic processGO:003439210.2APOH, EDN1
2artery smooth muscle contractionGO:001482410.1HTR2A, EDN1
3leukocyte tethering or rollingGO:005090110.1SELE, VCAM1
4regulation of systemic arterial blood pressure by endothelinGO:000310010.1NOS3, EDN1
5negative regulation of potassium ion transportGO:004326710.1HTR2A, NOS3
6membrane to membrane dockingGO:002261410.0ICAM1, VCAM1
7phosphatidylinositol 3-kinase signalingGO:001406510.0HTR2A, EDN1
8plasminogen activationGO:00316399.9APOH, PLAT
9negative regulation of calcium ion transportGO:00519269.9ICAM1, NOS3
10positive regulation of vasoconstrictionGO:00459079.9HTR2A, ICAM1
11agingGO:00075689.8TIMP1, VCAM1, HTR2A
12response to nicotineGO:00350949.8EDN1, VCAM1
13leukocyte cell-cell adhesionGO:00071599.8SELE, VCAM1, ICAM1
14heterophilic cell-cell adhesionGO:00071579.8ICAM1, VCAM1, SELE
15response to amino acidGO:00432009.7EDN1, ICAM1
16response to lipopolysaccharideGO:00324969.7VCAM1, SELE, EDN1
17negative regulation of fibrinolysisGO:00519189.7SERPINE1, APOH
18cellular response to glucose stimulusGO:00713339.7ICAM1, VCAM1
19cellular response to tumor necrosis factorGO:00713569.7EDN1, VCAM1, ICAM1
20positive regulation of blood coagulationGO:00301949.6APOH, SERPINE1
21positive regulation of nitric oxide biosynthetic processGO:00454299.5ICAM1, EDN1
22leukocyte migrationGO:00509009.5ICAM1, MMP9, SELE
23negative regulation of extrinsic apoptotic signaling pathway via death domain receptorsGO:019020429.4NOS3, SERPINE1
24negative regulation of blood coagulationGO:00301959.4SERPINE1, APOH, EDN1
25response to hypoxiaGO:00016669.4PLAT, VCAM1, EDN1
26cellular response to interleukin-1GO:00713479.3ICAM1, EDN1
27fibrinolysisGO:00427309.2SERPINE1, PLAT
28negative regulation of endopeptidase activityGO:00109519.1SERPINB1, SERPINE1, TIMP1
29extracellular matrix organizationGO:00301988.4ICAM1, MMP9, VCAM1, SERPINE1, TIMP1
30blood coagulationGO:00075968.4TIMP1, SERPINE1, SELE, PLAT, NOS3

Molecular functions related to Thromboangiitis Obliterans according to GeneCards/GeneDecks:

idNameGO IDScoreTop Affiliating Genes
1protein bindingGO:00055156.4NOS3, PLAT, ICAM1, MMP9, SELE, SERPINE1

Products for genes affiliated with Thromboangiitis Obliterans

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Sources for Thromboangiitis Obliterans

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4CDC
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27ICD10
28ICD10 via Orphanet
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