LDS4
MCID: LYS017
MIFTS: 51

Loeys-Dietz Syndrome 4 (LDS4)

Categories: Bone diseases, Cardiovascular diseases, Eye diseases, Fetal diseases, Genetic diseases, Immune diseases, Rare diseases

Aliases & Classifications for Loeys-Dietz Syndrome 4

MalaCards integrated aliases for Loeys-Dietz Syndrome 4:

Name: Loeys-Dietz Syndrome 4 56 12 52 73 29 6 15 71
Lds4 56 12 73
Aneurysm, Aortic and Cerebral, with Arterial Tortuosity and Skeletal Manifestations 56 12
Aortic and Cerebral Aneurysm with Arterial Tortuosity and Skeletal Manifestations 73
Syndrome, Loeys-Dietz, Type 4 39
Loeys-Dietz Syndrome, Type 4 13
Loeys-Dietz Syndrome Type 4 52

Characteristics:

OMIM:

56
Inheritance:
autosomal dominant

Miscellaneous:
patients do not have ectopia lentis


HPO:

31
loeys-dietz syndrome 4:
Inheritance autosomal dominant inheritance


Classifications:



Summaries for Loeys-Dietz Syndrome 4

UniProtKB/Swiss-Prot : 73 Loeys-Dietz syndrome 4: An aortic aneurysm syndrome with widespread systemic involvement. LDS4 is characterized by arterial tortuosity, aortic dissection, intracranial aneurysm and subarachnoid hemorrhage, hypertelorism, bifid uvula, pectus deformity, bicuspid aortic valve, arachnodactyly, scoliosis, foot deformities, dural ectasia, joint hyperflexibility, and thin skin with easy bruising and striae.

MalaCards based summary : Loeys-Dietz Syndrome 4, also known as lds4, is related to marfan syndrome and loeys-dietz syndrome, and has symptoms including wrist sign and steinberg thumb sign. An important gene associated with Loeys-Dietz Syndrome 4 is TGFB2 (Transforming Growth Factor Beta 2), and among its related pathways/superpathways are PAK Pathway and Toll-like Receptor Signaling Pathway. Affiliated tissues include skin, and related phenotypes are emphysema and bicuspid aortic valve

Disease Ontology : 12 A Loeys-Dietz syndrome that has material basis in heterozygous mutation in the TGFB2 gene on chromosome 1q41.

More information from OMIM: 614816 PS609192

Related Diseases for Loeys-Dietz Syndrome 4

Diseases in the Loeys-Dietz Syndrome family:

Loeys-Dietz Syndrome 1 Loeys-Dietz Syndrome 2
Loeys-Dietz Syndrome 3 Loeys-Dietz Syndrome 4
Loeys-Dietz Syndrome 5

Diseases related to Loeys-Dietz Syndrome 4 via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 63)
# Related Disease Score Top Affiliating Genes
1 marfan syndrome 30.3 TGFBR2 TGFBR1 TGFB2 FBN1
2 loeys-dietz syndrome 29.7 TGFBR2 TGFBR1 TGFB3 TGFB2-OT1 TGFB2-AS1 TGFB2
3 aortic aneurysm 29.7 TGFBR2 TGFBR1 TGFB3 TGFB2 SMAD3 SLC2A10
4 orthostatic intolerance 29.2 TGFBR2 TGFBR1 TGFB3 TGFB2 SMAD3 SLC2A10
5 aortic aneurysm, familial thoracic 1 29.1 TGFBR2 TGFBR1 TGFB3 TGFB2 SMAD3 SMAD2
6 loeys-dietz syndrome 3 28.8 TGFBR2 TGFBR1 TGFB3 TGFB2 SMAD3 SMAD2
7 loeys-dietz syndrome 1 28.8 TGFBR2 TGFBR1 TGFB3 TGFB2 SMAD3 SMAD2
8 scoliosis 10.5
9 hypermobile ehlers-danlos syndrome 10.5
10 transient hypogammaglobulinemia of infancy 10.3 TGFBR2 TGFBR1
11 transient hypogammaglobulinemia 10.3 TGFBR2 TGFBR1
12 eisenmenger syndrome 10.3 TGFBR2 TGFBR1
13 alacrima, achalasia, and mental retardation syndrome 10.3
14 isolated ectopia lentis 10.3
15 blood platelet disease 10.3
16 cerebrovascular disease 10.3
17 retinal degeneration 10.3
18 multiple self-healing squamous epithelioma 10.3 TGFBR2 TGFBR1
19 tendinosis 10.3 TGFBR2 TGFB2
20 juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome 10.2 TGFBR2 TGFBR1
21 ectopia lentis 1, isolated, autosomal dominant 10.2 TGFBR2 FBN1
22 ectopia lentis 2, isolated, autosomal recessive 10.2 TGFBR2 FBN1
23 peyronie's disease 10.2 TGFB3 TGFB2 SMAD3
24 aortic aneurysm, familial thoracic 6 10.2 TGFBR1 SLC2A10
25 bullous keratopathy 10.2 TGFB3 TGFB2 FBN1
26 keratopathy 10.2 TGFB3 TGFB2 FBN1
27 autosomal dominant non-syndromic intellectual disability 19 10.2 SMAD3 SMAD2
28 mitral valve disease 10.2 TGFB3 TGFB2 FBN1
29 intracranial aneurysm 10.2 TGFBR2 TGFBR1 TGFB2
30 aortic aneurysm, familial thoracic 2 10.2 SLC2A10 FBN1
31 hereditary hemorrhagic telangiectasia 10.1 TGFBR2 TGFBR1 TGFB2
32 tracheal stenosis 10.1 TGFB3 FBN1
33 aortic valve insufficiency 10.1 TGFBR2 TGFBR1 FBN1
34 pulsating exophthalmos 10.1 TGFBR2 TGFBR1
35 collagen disease 10.1 TGFBR2 TGFBR1 FBN1
36 albinism, ocular, with late-onset sensorineural deafness 10.1 SMAD3 SMAD2
37 cutis laxa, autosomal recessive, type ia 10.1 SLC2A10 FBN1
38 hypertrophic scars 10.1 TGFB3 SMAD3 SMAD2
39 patent ductus arteriosus 1 10.1 TGFBR2 TGFBR1 FBN1
40 tuberculoid leprosy 10.1 TGFB3 TGFB2
41 spastic paraplegia 3, autosomal dominant 10.1 TGFB2 SMAD3 SMAD2
42 nephrogenic systemic fibrosis 10.1 SMAD3 SMAD2
43 autosomal recessive cutis laxa type i 10.0 SLC2A10 FBN1
44 renal fibrosis 10.0 TGFBR1 SMAD3 SMAD2
45 cleft palate, isolated 9.9 TGFBR2 TGFBR1 TGFB3 TGFB2
46 craniosynostosis 9.8 TGFBR2 TGFBR1 SMAD3 FBN1
47 phacogenic glaucoma 9.8 TGFB2 FBN1
48 cutis laxa, autosomal dominant 1 9.8 TGFBR2 TGFBR1 SLC2A10 FBN1
49 pulmonary fibrosis, idiopathic 9.7 TGFBR1 TGFB3 TGFB2 SMAD3 SMAD2
50 connective tissue disease 9.7 TGFBR2 TGFBR1 TGFB2 SMAD3 FBN1

Graphical network of the top 20 diseases related to Loeys-Dietz Syndrome 4:



Diseases related to Loeys-Dietz Syndrome 4

Symptoms & Phenotypes for Loeys-Dietz Syndrome 4

Human phenotypes related to Loeys-Dietz Syndrome 4:

31 (show all 30)
# Description HPO Frequency HPO Source Accession
1 emphysema 31 occasional (7.5%) HP:0002097
2 bicuspid aortic valve 31 occasional (7.5%) HP:0001647
3 pneumothorax 31 occasional (7.5%) HP:0002107
4 hypertelorism 31 very rare (1%) HP:0000316
5 scoliosis 31 very rare (1%) HP:0002650
6 pes planus 31 very rare (1%) HP:0001763
7 retrognathia 31 very rare (1%) HP:0000278
8 high, narrow palate 31 very rare (1%) HP:0002705
9 ptosis 31 very rare (1%) HP:0000508
10 aortic dissection 31 very rare (1%) HP:0002647
11 talipes equinovarus 31 very rare (1%) HP:0001762
12 striae distensae 31 very rare (1%) HP:0001065
13 arachnodactyly 31 very rare (1%) HP:0001166
14 dural ectasia 31 very rare (1%) HP:0100775
15 downslanted palpebral fissures 31 very rare (1%) HP:0000494
16 spondylolisthesis 31 very rare (1%) HP:0003302
17 joint hyperflexibility 31 very rare (1%) HP:0005692
18 bruising susceptibility 31 very rare (1%) HP:0000978
19 tall stature 31 very rare (1%) HP:0000098
20 hyperextensible skin 31 very rare (1%) HP:0000974
21 bifid uvula 31 very rare (1%) HP:0000193
22 torticollis 31 very rare (1%) HP:0000473
23 arterial tortuosity 31 very rare (1%) HP:0005116
24 chronic pain 31 very rare (1%) HP:0012532
25 broad uvula 31 very rare (1%) HP:0010809
26 inguinal hernia 31 HP:0000023
27 mitral valve prolapse 31 HP:0001634
28 abnormality of the sternum 31 HP:0000766
29 aortic root aneurysm 31 HP:0002616
30 eosinophilic infiltration of the esophagus 31 HP:0410151

Symptoms via clinical synopsis from OMIM:

56
Genitourinary External Genitalia Male:
inguinal hernia

Skeletal Spine:
scoliosis
spondylolisthesis (rare)

Cardiovascular Vascular:
aortic dissection
aortic root aneurysm
arterial tortuosity
cerebrovascular aneurysm (in some patients)
fusiform dilation and tortuosity of cerebrovascular arteries

Skeletal Hands:
arachnodactyly
steinberg thumb sign

Skeletal:
joint hyperflexibility
tall stature

Skin Nails Hair Skin:
easy bruising
skin striae

Head And Neck Mouth:
high-arched palate
broad or bifid uvula (in some patients)

Chest Ribs Sternum Clavicles And Scapulae:
pectus deformity

Skeletal Pelvis:
protrusio acetabularis

Genitourinary External Genitalia Female:
inguinal hernia

Head And Neck Face:
retrognathia

Cardiovascular Heart:
mitral valve prolapse
bicuspid aortic valve (rare)

Neurologic Central Nervous System:
dural ectasia

Skeletal Limbs:
wrist sign

Skeletal Feet:
flat feet
club feet (in some patients)

Head And Neck Eyes:
hypertelorism (in some patients)
downslanting palpebral fissures (in some patients)

Respiratory Lung:
emphysema (rare)
pneumothorax (rare)

Clinical features from OMIM:

614816

UMLS symptoms related to Loeys-Dietz Syndrome 4:


wrist sign, steinberg thumb sign

GenomeRNAi Phenotypes related to Loeys-Dietz Syndrome 4 according to GeneCards Suite gene sharing:

26 (show all 34)
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Increased shRNA abundance (Z-score > 2) GR00366-A-100 9.92 SMAD2
2 Increased shRNA abundance (Z-score > 2) GR00366-A-11 9.92 SMAD2 TGFB2 TGFBR1 TGFBR2
3 Increased shRNA abundance (Z-score > 2) GR00366-A-115 9.92 TGFB2
4 Increased shRNA abundance (Z-score > 2) GR00366-A-12 9.92 TGFBR2
5 Increased shRNA abundance (Z-score > 2) GR00366-A-132 9.92 TGFBR2
6 Increased shRNA abundance (Z-score > 2) GR00366-A-138 9.92 TGFB2
7 Increased shRNA abundance (Z-score > 2) GR00366-A-14 9.92 TGFB2
8 Increased shRNA abundance (Z-score > 2) GR00366-A-147 9.92 TGFBR1 TGFBR2
9 Increased shRNA abundance (Z-score > 2) GR00366-A-162 9.92 TGFBR2
10 Increased shRNA abundance (Z-score > 2) GR00366-A-165 9.92 TGFBR2
11 Increased shRNA abundance (Z-score > 2) GR00366-A-169 9.92 TGFBR1
12 Increased shRNA abundance (Z-score > 2) GR00366-A-172 9.92 SMAD2
13 Increased shRNA abundance (Z-score > 2) GR00366-A-174 9.92 SMAD2
14 Increased shRNA abundance (Z-score > 2) GR00366-A-186 9.92 TGFBR2
15 Increased shRNA abundance (Z-score > 2) GR00366-A-188 9.92 TGFBR2
16 Increased shRNA abundance (Z-score > 2) GR00366-A-196 9.92 TGFB2
17 Increased shRNA abundance (Z-score > 2) GR00366-A-200 9.92 TGFBR1
18 Increased shRNA abundance (Z-score > 2) GR00366-A-203 9.92 SMAD2
19 Increased shRNA abundance (Z-score > 2) GR00366-A-205 9.92 SMAD2
20 Increased shRNA abundance (Z-score > 2) GR00366-A-215 9.92 TGFB2
21 Increased shRNA abundance (Z-score > 2) GR00366-A-22 9.92 TGFBR1
22 Increased shRNA abundance (Z-score > 2) GR00366-A-25 9.92 SMAD2
23 Increased shRNA abundance (Z-score > 2) GR00366-A-37 9.92 TGFBR1
24 Increased shRNA abundance (Z-score > 2) GR00366-A-39 9.92 TGFBR2
25 Increased shRNA abundance (Z-score > 2) GR00366-A-42 9.92 TGFB2
26 Increased shRNA abundance (Z-score > 2) GR00366-A-48 9.92 TGFBR2
27 Increased shRNA abundance (Z-score > 2) GR00366-A-59 9.92 TGFB2
28 Increased shRNA abundance (Z-score > 2) GR00366-A-60 9.92 TGFB2 TGFBR1 TGFBR2
29 Increased shRNA abundance (Z-score > 2) GR00366-A-7 9.92 TGFBR2
30 Increased shRNA abundance (Z-score > 2) GR00366-A-72 9.92 TGFB2
31 Increased shRNA abundance (Z-score > 2) GR00366-A-73 9.92 TGFB2
32 Increased shRNA abundance (Z-score > 2) GR00366-A-77 9.92 TGFBR1
33 Increased shRNA abundance (Z-score > 2) GR00366-A-85 9.92 TGFBR1
34 Increased shRNA abundance (Z-score > 2) GR00366-A-88 9.92 TGFBR1

MGI Mouse Phenotypes related to Loeys-Dietz Syndrome 4:

45
# Description MGI Source Accession Score Top Affiliating Genes
1 cardiovascular system MP:0005385 10.06 FBN1 SLC2A10 SMAD2 SMAD3 TGFB2 TGFB3
2 craniofacial MP:0005382 9.91 FBN1 SMAD2 SMAD3 TGFB2 TGFB3 TGFBR2
3 digestive/alimentary MP:0005381 9.87 SMAD2 SMAD3 TGFB2 TGFB3 TGFBR1 TGFBR2
4 embryo MP:0005380 9.86 FBN1 NDUFA9 SMAD2 SMAD3 TGFB2 TGFB3
5 growth/size/body region MP:0005378 9.85 FBN1 NDUFA9 NEURL2 SMAD2 SMAD3 TGFB2
6 respiratory system MP:0005388 9.56 FBN1 SLC2A10 SMAD2 TGFB2 TGFB3 TGFBR1
7 skeleton MP:0005390 9.23 FBN1 SMAD2 SMAD3 TGFB2 TGFB3 TGFBR1

Drugs & Therapeutics for Loeys-Dietz Syndrome 4

Search Clinical Trials , NIH Clinical Center for Loeys-Dietz Syndrome 4

Genetic Tests for Loeys-Dietz Syndrome 4

Genetic tests related to Loeys-Dietz Syndrome 4:

# Genetic test Affiliating Genes
1 Loeys-Dietz Syndrome 4 29 TGFB2

Anatomical Context for Loeys-Dietz Syndrome 4

MalaCards organs/tissues related to Loeys-Dietz Syndrome 4:

40
Skin

Publications for Loeys-Dietz Syndrome 4

Articles related to Loeys-Dietz Syndrome 4:

(show all 11)
# Title Authors PMID Year
1
Whole exome sequencing for the identification of a new mutation in TGFB2 involved in a familial case of non-syndromic aortic disease. 56 6
25046559 2014
2
Loss-of-function mutations in TGFB2 cause a syndromic presentation of thoracic aortic aneurysm. 56 6
22772368 2012
3
TGFB2 mutations cause familial thoracic aortic aneurysms and dissections associated with mild systemic features of Marfan syndrome. 6 56
22772371 2012
4
2014 ESC Guidelines on the diagnosis and treatment of aortic diseases: Document covering acute and chronic aortic diseases of the thoracic and abdominal aorta of the adult. The Task Force for the Diagnosis and Treatment of Aortic Diseases of the European Society of Cardiology (ESC). 6
25173340 2014
5
Canadian Cardiovascular Society position statement on the management of thoracic aortic disease. 6
24882528 2014
6
Identification of 23 TGFBR2 and 6 TGFBR1 gene mutations and genotype-phenotype investigations in 457 patients with Marfan syndrome type I and II, Loeys-Dietz syndrome and related disorders. 6
18781618 2008
7
Loeys-Dietz Syndrome 6
20301312 2008
8
TGFBR1 and TGFBR2 mutations in patients with features of Marfan syndrome and Loeys-Dietz syndrome. 6
16799921 2006
9
Phenotypic variability and diffuse arterial lesions in a family with Loeys-Dietz syndrome type 4. 61
27440102 2017
10
Further delineation of Loeys-Dietz syndrome type 4 in a family with mild vascular involvement and a TGFB2 splicing mutation. 61
25163805 2014
11
Diagnostic yield in adults screened at the Marfan outpatient clinic using the 1996 and 2010 Ghent nosologies. 61
22461464 2012

Variations for Loeys-Dietz Syndrome 4

ClinVar genetic disease variations for Loeys-Dietz Syndrome 4:

6 (show top 50) (show all 251) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 TGFB3 NM_003239.4(TGFB3):c.883_884del (p.Gly295fs)deletion Pathogenic 410268 rs1060502826 14:76429701-76429702 14:75963358-75963359
2 TGFB3 NM_003239.4(TGFB3):c.989G>A (p.Trp330Ter)SNV Pathogenic 477652 rs1555360222 14:76427357-76427357 14:75961014-75961014
3 TGFB2 NM_001135599.2:c.595_1245deldeletion Pathogenic 620591
4 TGFB3 NC_000014.9:g.(?_75958692)_(75980923_?)deldeletion Pathogenic 832288 14:76425035-76447266
5 TGFB3 NM_003239.5(TGFB3):c.109A>T (p.Lys37Ter)SNV Pathogenic 862476 14:76447128-76447128 14:75980785-75980785
6 TGFB2 NM_001135599.3(TGFB2):c.1097C>A (p.Pro366His)SNV Pathogenic 37085 rs387907278 1:218610765-218610765 1:218437423-218437423
7 TGFB2 NM_001135599.3(TGFB2):c.771C>A (p.Cys257Ter)SNV Pathogenic 37088 rs398122885 1:218607723-218607723 1:218434381-218434381
8 TGFB2 NM_001135599.3(TGFB2):c.297C>A (p.Tyr99Ter)SNV Pathogenic 224874 rs760759052 1:218520340-218520340 1:218346998-218346998
9 TGFB2 NM_001135599.3(TGFB2):c.1106_1110del (p.Tyr369fs)deletion Pathogenic 224873 rs398122884 1:218610773-218610777 1:218437431-218437435
10 covers 21 genes, none of which curated to show dosage sensitivity deletion Pathogenic 224870 1:215588712-222145072
11 TGFB2 deletion Pathogenic 224871 1:216672181-220202575
12 TGFB2 NM_001135599.3(TGFB2):c.980G>A (p.Arg327Gln)SNV Pathogenic/Likely pathogenic 381708 rs1057521150 1:218609453-218609453 1:218436111-218436111
13 TGFB2 NM_001135599.3(TGFB2):c.988C>T (p.Arg330Cys)SNV Pathogenic/Likely pathogenic 224872 rs869312903 1:218609461-218609461 1:218436119-218436119
14 TGFB2 NM_001135599.3(TGFB2):c.979C>T (p.Arg327Trp)SNV Pathogenic/Likely pathogenic 213845 rs863223792 1:218609452-218609452 1:218436110-218436110
15 TGFB3 NM_003239.4(TGFB3):c.899G>A (p.Arg300Gln)SNV Pathogenic/Likely pathogenic 143945 rs587777617 14:76429686-76429686 14:75963343-75963343
16 TGFB3 NM_003239.4(TGFB3):c.898C>T (p.Arg300Trp)SNV Pathogenic/Likely pathogenic 203490 rs796051885 14:76429687-76429687 14:75963344-75963344
17 TGFB3 NM_003239.4(TGFB3):c.1034C>G (p.Ser345Ter)SNV Pathogenic/Likely pathogenic 410269 rs1060502827 14:76427312-76427312 14:75960969-75960969
18 TGFB3 NM_003239.4(TGFB3):c.353-1G>CSNV Likely pathogenic 477636 rs1555360883 14:76438062-76438062 14:75971719-75971719
19 TGFB2 NM_001135599.3(TGFB2):c.631C>T (p.Arg211Cys)SNV Likely pathogenic 547806 rs1436552875 1:218607460-218607460 1:218434118-218434118
20 TGFB3 NM_003239.4(TGFB3):c.927-1G>CSNV Likely pathogenic 487471 rs767548724 14:76427420-76427420 14:75961077-75961077
21 TGFB2 NM_001135599.3(TGFB2):c.1042C>T (p.Arg348Cys)SNV Likely pathogenic 495213 rs1553303352 1:218610710-218610710 1:218437368-218437368
22 TGFB3 NM_003239.4(TGFB3):c.916del (p.Tyr306fs)deletion Likely pathogenic 543951 rs1555360362 14:76429669-76429669 14:75963326-75963326
23 TGFB3 NM_003239.5(TGFB3):c.1219A>T (p.Lys407Ter)SNV Likely pathogenic 857481 14:76425550-76425550 14:75959207-75959207
24 TGFB3 NM_003239.4(TGFB3):c.517-1G>CSNV Likely pathogenic 569027 rs1566682530 14:76437599-76437599 14:75971256-75971256
25 TGFB3 NC_000014.9:g.(?_75958692)_(75965705_?)deldeletion Likely pathogenic 665632 14:76425035-76432048 14:75958692-75965705
26 TGFB3 NC_000014.9:g.(?_75958692)_(75971728_?)deldeletion Likely pathogenic 663430 14:76425035-76438071 14:75958692-75971728
27 TGFB3 NM_003239.5(TGFB3):c.926+1G>ASNV Likely pathogenic 858860 14:76429658-76429658 14:75963315-75963315
28 TGFB3 NM_003239.5(TGFB3):c.517-2A>GSNV Likely pathogenic 862608 14:76437600-76437600 14:75971257-75971257
29 TGFB2 NM_001135599.3(TGFB2):c.542G>A (p.Arg181His)SNV Likely pathogenic 374302 rs1057518684 1:218578622-218578622 1:218405280-218405280
30 TGFB2 NM_001135599.3(TGFB2):c.303G>A (p.Lys101=)SNV Conflicting interpretations of pathogenicity 380608 rs147052890 1:218520346-218520346 1:218347004-218347004
31 TGFB3 NM_003239.4(TGFB3):c.1230A>G (p.Lys410=)SNV Conflicting interpretations of pathogenicity 314447 rs373100223 14:76425539-76425539 14:75959196-75959196
32 TGFB3 NM_003239.4(TGFB3):c.294G>A (p.Ser98=)SNV Conflicting interpretations of pathogenicity 314454 rs778214495 14:76446943-76446943 14:75980600-75980600
33 TGFB3 NM_003239.4(TGFB3):c.517-6C>GSNV Conflicting interpretations of pathogenicity 314450 rs45586636 14:76437604-76437604 14:75971261-75971261
34 TGFB3 NM_003239.4(TGFB3):c.339G>A (p.Gly113=)SNV Conflicting interpretations of pathogenicity 314453 rs886050798 14:76446898-76446898 14:75980555-75980555
35 TGFB3 NM_003239.4(TGFB3):c.442C>T (p.Arg148Ter)SNV Conflicting interpretations of pathogenicity 390113 rs1057523647 14:76437972-76437972 14:75971629-75971629
36 TGFB2 NM_001135599.3(TGFB2):c.594+12TTG[12]short repeat Conflicting interpretations of pathogenicity 228320 rs10482769 1:218578685-218578686 1:218405343-218405344
37 TGFB3 NM_003239.4(TGFB3):c.873G>A (p.Pro291=)SNV Conflicting interpretations of pathogenicity 239524 rs370006165 14:76429712-76429712 14:75963369-75963369
38 TGFB3 NM_003239.4(TGFB3):c.744C>A (p.Ile248=)SNV Conflicting interpretations of pathogenicity 239522 rs45477900 14:76431941-76431941 14:75965598-75965598
39 TGFB3 NM_003239.4(TGFB3):c.293C>T (p.Ser98Leu)SNV Conflicting interpretations of pathogenicity 192131 rs142047577 14:76446944-76446944 14:75980601-75980601
40 TGFB2 NM_001135599.3(TGFB2):c.37C>A (p.His13Asn)SNV Conflicting interpretations of pathogenicity 295485 rs763918203 1:218520080-218520080 1:218346738-218346738
41 TGFB2 NM_001135599.3(TGFB2):c.272G>A (p.Arg91His)SNV Conflicting interpretations of pathogenicity 213835 rs10482721 1:218520315-218520315 1:218346973-218346973
42 TGFB2 NM_001135599.3(TGFB2):c.440C>T (p.Pro147Leu)SNV Conflicting interpretations of pathogenicity 213840 rs149533093 1:218578520-218578520 1:218405178-218405178
43 TGFB2 NM_001135599.3(TGFB2):c.294_308del (p.Ala100_Tyr104del)deletion Conflicting interpretations of pathogenicity 37086 rs398122883 1:218520337-218520351 1:218346995-218347009
44 TGFB3 NM_003239.4(TGFB3):c.973C>T (p.Arg325Ter)SNV Conflicting interpretations of pathogenicity 477651 rs1555360229 14:76427373-76427373 14:75961030-75961030
45 TGFB3 NM_003239.4(TGFB3):c.164G>A (p.Ser55Asn)SNV Conflicting interpretations of pathogenicity 416061 rs143229915 14:76447073-76447073 14:75980730-75980730
46 TGFB3 NM_003239.4(TGFB3):c.97G>A (p.Gly33Ser)SNV Uncertain significance 410270 rs781353815 14:76447140-76447140 14:75980797-75980797
47 TGFB3 NM_003239.4(TGFB3):c.516+4A>TSNV Uncertain significance 477638 rs1252391096 14:76437894-76437894 14:75971551-75971551
48 TGFB3 NM_003239.4(TGFB3):c.1186C>T (p.Pro396Ser)SNV Uncertain significance 477633 rs899613458 14:76425583-76425583 14:75959240-75959240
49 TGFB3 NM_003239.4(TGFB3):c.813G>C (p.Lys271Asn)SNV Uncertain significance 477645 rs147601018 14:76429772-76429772 14:75963429-75963429
50 TGFB3 NM_003239.4(TGFB3):c.754+5C>TSNV Uncertain significance 477641 rs754211381 14:76431926-76431926 14:75965583-75965583

UniProtKB/Swiss-Prot genetic disease variations for Loeys-Dietz Syndrome 4:

73
# Symbol AA change Variation ID SNP ID
1 TGFB2 p.Arg299Trp VAR_068932 rs863223792
2 TGFB2 p.Arg302Cys VAR_068933 rs869312903
3 TGFB2 p.Pro338His VAR_068934 rs387907278

Expression for Loeys-Dietz Syndrome 4

Search GEO for disease gene expression data for Loeys-Dietz Syndrome 4.

Pathways for Loeys-Dietz Syndrome 4

Pathways related to Loeys-Dietz Syndrome 4 according to GeneCards Suite gene sharing:

(show all 47)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
13.23 TGFBR2 TGFBR1 TGFB3 TGFB2 SMAD3 SLC2A10
2
Show member pathways
13.02 TGFBR2 TGFBR1 TGFB3 TGFB2 SMAD3 SMAD2
3
Show member pathways
12.87 TGFBR2 TGFBR1 TGFB3 TGFB2 SMAD3 SMAD2
4 12.84 TGFBR2 TGFBR1 TGFB3 TGFB2 SMAD3 SMAD2
5
Show member pathways
12.77 TGFBR2 TGFBR1 TGFB3 TGFB2 SMAD3 SMAD2
6
Show member pathways
12.59 TGFBR2 TGFBR1 TGFB3 TGFB2 SMAD3 SMAD2
7
Show member pathways
12.48 TGFBR2 TGFBR1 TGFB3 TGFB2 SMAD3 SMAD2
8 12.37 TGFBR2 TGFBR1 SMAD3 SMAD2
9 12.37 TGFBR2 TGFBR1 TGFB3 TGFB2 SMAD3 SMAD2
10 12.33 TGFB3 TGFB2 SMAD3 SMAD2
11
Show member pathways
12.27 TGFBR2 TGFBR1 SMAD3 SMAD2
12 12.26 TGFBR1 TGFB3 TGFB2 SMAD3 SMAD2
13
Show member pathways
12.23 TGFBR2 TGFBR1 TGFB2 SMAD3 SMAD2
14 12.2 TGFBR2 TGFBR1 TGFB3 TGFB2 SMAD3 SMAD2
15 12.17 TGFBR2 TGFBR1 TGFB3 TGFB2 SMAD3 SMAD2
16 12.15 TGFBR2 TGFBR1 TGFB3 TGFB2 SMAD3 SMAD2
17
Show member pathways
12.1 TGFBR2 TGFBR1 TGFB3 TGFB2 SMAD3
18 12.08 TGFBR2 TGFBR1 SMAD3 SMAD2
19 12.06 TGFBR2 TGFBR1 SMAD2
20 12.04 TGFBR2 TGFB2 SLC2A10
21 12.01 TGFBR1 SMAD3 SMAD2
22 11.97 TGFBR2 TGFBR1 TGFB2
23
Show member pathways
11.9 TGFBR2 TGFBR1 SMAD3 SMAD2
24 11.85 TGFBR2 TGFBR1 TGFB3 TGFB2 SMAD3 SMAD2
25 11.8 TGFBR1 TGFB3 TGFB2
26
Show member pathways
11.8 TGFBR2 TGFBR1 SMAD3 SMAD2
27 11.78 TGFBR2 TGFBR1 TGFB3 TGFB2 SMAD3 SMAD2
28 11.77 TGFBR2 TGFBR1 SMAD3 SMAD2
29
Show member pathways
11.75 TGFBR2 TGFBR1 SMAD3 SMAD2
30 11.73 TGFBR2 TGFBR1 TGFB3 TGFB2 SMAD3 SMAD2
31
Show member pathways
11.71 TGFB3 TGFB2 FBN1
32 11.7 TGFBR2 TGFBR1 SMAD3
33
Show member pathways
11.69 TGFBR2 TGFBR1 TGFB3 TGFB2 SMAD3 SMAD2
34 11.65 TGFBR2 TGFBR1 SMAD3 SMAD2
35
Show member pathways
11.57 TGFBR2 TGFBR1 TGFB3 TGFB2 SMAD3 SMAD2
36 11.54 TGFBR2 TGFBR1 TGFB3 SMAD3 SMAD2
37 11.52 TGFBR2 TGFBR1 TGFB2
38 11.47 TGFBR2 TGFBR1 TGFB3 TGFB2 SMAD3 SMAD2
39
Show member pathways
11.25 TGFBR2 TGFBR1 TGFB3
40 11.25 TGFBR2 TGFBR1 TGFB3 SMAD2
41 11.13 TGFBR2 TGFBR1 SMAD3
42 10.99 TGFBR2 TGFBR1 TGFB3 TGFB2
43 10.97 SMAD3 SMAD2
44 10.95 TGFBR2 TGFBR1 SMAD3 SMAD2 FBN1
45 10.94 SMAD3 SMAD2
46 10.76 TGFB3 TGFB2
47 10.58 TGFBR2 TGFBR1 TGFB3 TGFB2 SMAD3 SMAD2

GO Terms for Loeys-Dietz Syndrome 4

Cellular components related to Loeys-Dietz Syndrome 4 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cell surface GO:0009986 9.55 TGFBR2 TGFBR1 TGFB3 PPFIA4 PPFIA2
2 SMAD protein complex GO:0071141 8.96 SMAD3 SMAD2
3 heteromeric SMAD protein complex GO:0071144 8.62 SMAD3 SMAD2

Biological processes related to Loeys-Dietz Syndrome 4 according to GeneCards Suite gene sharing:

(show all 49)
# Name GO ID Score Top Affiliating Genes
1 protein phosphorylation GO:0006468 10.08 ULK4 TGFBR2 TGFBR1 TGFB2 SMAD2
2 negative regulation of cell proliferation GO:0008285 10.04 TGFBR2 TGFB3 TGFB2 SMAD3 SMAD2
3 response to hypoxia GO:0001666 9.92 TGFBR2 TGFB3 TGFB2 SMAD3
4 heart development GO:0007507 9.92 TGFBR2 TGFBR1 TGFB2 SMAD2 FBN1
5 in utero embryonic development GO:0001701 9.91 TGFBR2 TGFBR1 TGFB3 SMAD3 SMAD2
6 skeletal system development GO:0001501 9.89 TGFBR1 TGFB2 SMAD3 FBN1
7 cell cycle arrest GO:0007050 9.88 TGFBR1 TGFB2 SMAD3
8 kidney development GO:0001822 9.87 TGFBR1 TGFB2 FBN1
9 response to glucose GO:0009749 9.83 TGFBR2 SMAD2 NDUFA9
10 cellular response to transforming growth factor beta stimulus GO:0071560 9.82 TGFBR1 SMAD3 FBN1
11 positive regulation of stress fiber assembly GO:0051496 9.81 TGFBR1 TGFB3 SMAD3
12 positive regulation of pathway-restricted SMAD protein phosphorylation GO:0010862 9.8 TGFBR1 TGFB3 TGFB2
13 SMAD protein signal transduction GO:0060395 9.78 TGFB3 TGFB2 SMAD3 SMAD2
14 ventricular septum morphogenesis GO:0060412 9.76 TGFBR2 TGFBR1 TGFB2
15 gastrulation GO:0007369 9.74 TGFBR2 SMAD3 SMAD2
16 embryonic cranial skeleton morphogenesis GO:0048701 9.73 TGFBR2 TGFBR1 SMAD3 SMAD2
17 transforming growth factor beta receptor signaling pathway GO:0007179 9.73 TGFBR2 TGFBR1 TGFB3 TGFB2 SMAD3 SMAD2
18 regulation of transforming growth factor beta receptor signaling pathway GO:0017015 9.71 SMAD3 SMAD2
19 cell-cell junction organization GO:0045216 9.71 TGFB3 TGFB2 SMAD3
20 adrenal gland development GO:0030325 9.7 SMAD3 SMAD2
21 signal transduction involved in regulation of gene expression GO:0023019 9.7 SMAD3 SMAD2
22 transmembrane receptor protein serine/threonine kinase signaling pathway GO:0007178 9.7 TGFBR2 TGFBR1
23 ventricular trabecula myocardium morphogenesis GO:0003222 9.69 TGFBR1 TGFB2
24 positive regulation of SMAD protein signal transduction GO:0060391 9.69 TGFBR1 TGFB3
25 cardiac epithelial to mesenchymal transition GO:0060317 9.68 TGFBR1 TGFB2
26 atrioventricular valve morphogenesis GO:0003181 9.68 TGFBR2 TGFB2
27 nodal signaling pathway GO:0038092 9.68 SMAD3 SMAD2
28 primary miRNA processing GO:0031053 9.67 SMAD3 SMAD2
29 salivary gland morphogenesis GO:0007435 9.67 TGFB3 TGFB2
30 membranous septum morphogenesis GO:0003149 9.67 TGFBR2 TGFB2
31 pathway-restricted SMAD protein phosphorylation GO:0060389 9.67 TGFBR2 TGFBR1 TGFB2
32 activin receptor signaling pathway GO:0032924 9.67 TGFBR2 TGFBR1 SMAD3 SMAD2
33 pericardium development GO:0060039 9.66 SMAD3 SMAD2
34 embryonic foregut morphogenesis GO:0048617 9.66 SMAD3 SMAD2
35 SMAD protein complex assembly GO:0007183 9.65 SMAD3 SMAD2
36 common-partner SMAD protein phosphorylation GO:0007182 9.64 TGFBR2 SMAD2
37 negative regulation of macrophage cytokine production GO:0010936 9.63 TGFB3 TGFB2
38 response to cholesterol GO:0070723 9.63 TGFBR2 TGFBR1 SMAD2
39 wound healing GO:0042060 9.63 TGFBR2 TGFBR1 TGFB3 TGFB2 SMAD3 SMAD2
40 secondary palate development GO:0062009 9.62 TGFBR2 TGFB3 TGFB2 SMAD2
41 regulation of binding GO:0051098 9.61 SMAD3 SMAD2
42 regulation of transforming growth factor beta2 production GO:0032909 9.61 TGFB2 SMAD3
43 endocardial cushion fusion GO:0003274 9.6 TGFBR2 TGFB2
44 positive regulation of tight junction disassembly GO:1905075 9.58 TGFBR1 TGFB3
45 positive regulation of epithelial to mesenchymal transition involved in endocardial cushion formation GO:1905007 9.58 TGFBR2 TGFBR1 TGFB2
46 paraxial mesoderm morphogenesis GO:0048340 9.56 SMAD3 SMAD2
47 uterine wall breakdown GO:0042704 9.55 TGFB3 TGFB2
48 negative regulation of transforming growth factor beta receptor signaling pathway GO:0030512 9.43 TGFBR2 TGFBR1 TGFB3 SMAD3 SMAD2 SLC2A10
49 positive regulation of epithelial to mesenchymal transition GO:0010718 9.1 TGFBR2 TGFBR1 TGFB3 TGFB2 SMAD3 SMAD2

Molecular functions related to Loeys-Dietz Syndrome 4 according to GeneCards Suite gene sharing:

(show all 15)
# Name GO ID Score Top Affiliating Genes
1 R-SMAD binding GO:0070412 9.55 SMAD3 SMAD2
2 activin binding GO:0048185 9.54 TGFBR2 TGFBR1
3 enhancer binding GO:0035326 9.52 SMAD3 SMAD2
4 co-SMAD binding GO:0070410 9.51 SMAD3 SMAD2
5 transforming growth factor beta binding GO:0050431 9.5 TGFBR2 TGFBR1 TGFB3
6 transmembrane receptor protein serine/threonine kinase activity GO:0004675 9.49 TGFBR2 TGFBR1
7 I-SMAD binding GO:0070411 9.48 TGFBR1 SMAD2
8 primary miRNA binding GO:0070878 9.46 SMAD3 SMAD2
9 SMAD binding GO:0046332 9.46 TGFBR2 TGFBR1 SMAD3 SMAD2
10 transforming growth factor beta-activated receptor activity GO:0005024 9.43 TGFBR2 TGFBR1
11 type I transforming growth factor beta receptor binding GO:0034713 9.43 TGFBR2 TGFB3 SMAD2
12 transforming growth factor beta receptor, pathway-specific cytoplasmic mediator activity GO:0030618 9.4 SMAD3 SMAD2
13 type III transforming growth factor beta receptor binding GO:0034714 9.37 TGFB3 TGFB2
14 type II transforming growth factor beta receptor binding GO:0005114 9.13 TGFBR1 TGFB3 TGFB2
15 transforming growth factor beta receptor binding GO:0005160 8.92 TGFB3 TGFB2 SMAD3 SMAD2

Sources for Loeys-Dietz Syndrome 4

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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