JPHT
MCID: JVN012
MIFTS: 48

Juvenile Polyposis/hereditary Hemorrhagic Telangiectasia Syndrome (JPHT)

Categories: Genetic diseases

Aliases & Classifications for Juvenile Polyposis/hereditary Hemorrhagic Telangiectasia...

MalaCards integrated aliases for Juvenile Polyposis/hereditary Hemorrhagic Telangiectasia Syndrome:

Name: Juvenile Polyposis/hereditary Hemorrhagic Telangiectasia Syndrome 57 72 29 13 6 70
Juvenile Polyposis-Hereditary Hemorrhagic Telangiectasia Syndrome 12 15
Polyposis, Generalized Juvenile, with Pulmonary Arteriovenous Malformation 57
Telangiectasia, Hereditary Hemorrhagic, with Juvenile Polyposis Coli 57
Polyposis, Juvenile/hereditary Hemorrhagic Telangiectasia Syndrome 39
Juvenile Polyposis with Hereditary Hemorrhagic Telangiectasia 57
Jp/hht Syndrome 57
Jps/hht 57
Jp-Hht 12
Jp/hht 72
Jpht 57

Characteristics:

OMIM®:

57 (Updated 05-Apr-2021)
Inheritance:
autosomal dominant

Miscellaneous:
onset usually in childhood
arteriovenous malformations can occur throughout the body


HPO:

31
juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome:
Inheritance autosomal dominant inheritance


Classifications:



Summaries for Juvenile Polyposis/hereditary Hemorrhagic Telangiectasia...

UniProtKB/Swiss-Prot : 72 Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome: JP/HHT syndrome phenotype consists of the coexistence of juvenile polyposis (JIP) and hereditary hemorrhagic telangiectasia (HHT) [MIM:187300] in a single individual. JIP and HHT are autosomal dominant disorders with distinct and non-overlapping clinical features. The former, an inherited gastrointestinal malignancy predisposition, is caused by mutations in SMAD4 or BMPR1A, and the latter is a vascular malformation disorder caused by mutations in ENG or ACVRL1. All four genes encode proteins involved in the transforming-growth-factor-signaling pathway. Although there are reports of patients and families with phenotypes of both disorders combined, the genetic etiology of this association is unknown.

MalaCards based summary : Juvenile Polyposis/hereditary Hemorrhagic Telangiectasia Syndrome, also known as juvenile polyposis-hereditary hemorrhagic telangiectasia syndrome, is related to generalized juvenile polyposis/juvenile polyposis coli and juvenile polyposis syndrome. An important gene associated with Juvenile Polyposis/hereditary Hemorrhagic Telangiectasia Syndrome is SMAD4 (SMAD Family Member 4), and among its related pathways/superpathways are ERK Signaling and PEDF Induced Signaling. Affiliated tissues include brain, and related phenotypes are mitral valve prolapse and mitral regurgitation

Disease Ontology : 12 A syndrome characterized by hamartomatous polyps in the gastrointestinal tract, telangiectases of the skin, and oral and nasal mucosa, epistaxis, and arteriovenous malformations of the lungs, liver, brain, and gastrointestinal tract that has material basis in heterozygous mutation in SMAD4 on chromosome 18q21.2.

OMIM® : 57 The JPHT syndrome includes the features of both the juvenile polyposis syndrome (JPS; 174900) and hereditary hemorrhagic telangiectasia (HHT; 187300) in a single individual. JPS is characterized by hamartomatous polyps occurring throughout the gastrointestinal tract, resulting in an increased risk of gastrointestinal cancer, and HHT is a vascular dysplasia characterized by telangiectases of the skin, and oral and nasal mucosa, epistaxis, and arteriovenous malformations (AVMs) of the lungs, liver, brain, and gastrointestinal tract (summary by Gallione et al., 2010). (175050) (Updated 05-Apr-2021)

Related Diseases for Juvenile Polyposis/hereditary Hemorrhagic Telangiectasia...

Diseases related to Juvenile Polyposis/hereditary Hemorrhagic Telangiectasia Syndrome via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 40)
# Related Disease Score Top Affiliating Genes
1 generalized juvenile polyposis/juvenile polyposis coli 30.0 SMAD4 ENG BMPR1A
2 juvenile polyposis syndrome 29.4 SMAD4 BMPR2 BMPR1A ACVRL1
3 hereditary hemorrhagic telangiectasia 29.2 TGFBR1 SMAD4 GDF2 ENG BMPR2 ACVRL1
4 arteriovenous malformation 29.1 TGFBR1 SMAD4 ENG BMPR2 ACVRL1
5 telangiectasis 28.1 TGFBR1 SMAD4 OR2AG1 GDF2 ENG BMPR2
6 leukemia, acute lymphoblastic 10.2
7 alacrima, achalasia, and mental retardation syndrome 10.2
8 complex chromosomal rearrangement 10.2
9 aortic aneurysm, familial thoracic 4 10.1
10 tumor predisposition syndrome 10.1
11 cutaneous telangiectasia and cancer syndrome, familial 10.1
12 juvenile rheumatoid arthritis 10.1
13 arthritis 10.1
14 familial thoracic aortic aneurysm and aortic dissection 10.1
15 inherited cancer-predisposing syndrome 10.1
16 telangiectasia, hereditary hemorrhagic, type 2 10.1 ENG ACVRL1
17 familial colorectal cancer type x 10.1 SMAD4 BMPR1A
18 weber syndrome 10.0 ENG ACVRL1
19 angiodysplasia 10.0 ENG ACVRL1
20 heritable thoracic aortic disease 10.0 TGFBR1 SMAD4
21 arteriovenous malformations of the brain 9.9 OR2AG1 ENG ACVRL1
22 loeys-dietz syndrome 9.9 TGFBR1 SMAD4 ACVRL1
23 brachydactyly, type a1, b 9.9 BMPR1A ACVR1
24 pulmonary valve insufficiency 9.9 BMPR2 ACVRL1
25 proximal symphalangism 9.8 GDF2 ACVR1
26 cardiovascular organ benign neoplasm 9.8 SMAD4 GDF2 ENG ACVRL1
27 hereditary mixed polyposis syndrome 9.8 SMAD4 BMPR1A
28 pulmonary arteriovenous malformation 9.7 ENG BMPR2 ACVRL1
29 persistent mullerian duct syndrome 9.7 BMPR1A ACVR1
30 myositis ossificans 9.7 BMPR2 ACVR1
31 double outlet right ventricle 9.6 BMPR1A BMP10 ACVR1
32 pulmonary arterial hypertension associated with congenital heart disease 9.6 ENG BMPR2 BMPR1A
33 chronic pulmonary heart disease 9.6 BMPR2 ACVRL1 ACVR1
34 pulmonary hypertension, primary, 1 9.5 SMAD4 ENG BMPR2 ACVRL1
35 pulmonary venoocclusive disease 9.5 GDF2 ENG BMPR2 ACVRL1
36 heritable pulmonary arterial hypertension 9.5 GDF2 ENG BMPR2 ACVRL1
37 hepatopulmonary syndrome 9.5 GDF2 ENG BMPR2 ACVRL1
38 fibrodysplasia ossificans progressiva 9.3 GDF2 BMPR2 BMPR1A ACVR1
39 brachydactyly, type a2 9.1 GDF2 BMPR2 BMPR1A ACVRL1 ACVR1
40 pulmonary hypertension 8.5 TGFBR1 SMAD4 GDF2 ENG BMPR2 BMPR1A

Graphical network of the top 20 diseases related to Juvenile Polyposis/hereditary Hemorrhagic Telangiectasia Syndrome:



Diseases related to Juvenile Polyposis/hereditary Hemorrhagic Telangiectasia Syndrome

Symptoms & Phenotypes for Juvenile Polyposis/hereditary Hemorrhagic Telangiectasia...

Human phenotypes related to Juvenile Polyposis/hereditary Hemorrhagic Telangiectasia Syndrome:

31 (show all 16)
# Description HPO Frequency HPO Source Accession
1 mitral valve prolapse 31 occasional (7.5%) HP:0001634
2 mitral regurgitation 31 occasional (7.5%) HP:0001653
3 aortic aneurysm 31 occasional (7.5%) HP:0004942
4 aortic dissection 31 very rare (1%) HP:0002647
5 stroke 31 very rare (1%) HP:0001297
6 epistaxis 31 very rare (1%) HP:0000421
7 gastrointestinal carcinoma 31 very rare (1%) HP:0002672
8 telangiectasia 31 very rare (1%) HP:0001009
9 cerebral arteriovenous malformation 31 very rare (1%) HP:0002408
10 clubbing 31 very rare (1%) HP:0001217
11 pulmonary arteriovenous malformation 31 very rare (1%) HP:0006548
12 juvenile gastrointestinal polyposis 31 very rare (1%) HP:0004784
13 hepatic arteriovenous malformation 31 very rare (1%) HP:0006574
14 anemia 31 HP:0001903
15 hematochezia 31 HP:0002573
16 hamartomatous polyposis 31 HP:0004390

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Hematology:
anemia

Skin Nails Hair Skin:
telangiectasia

Respiratory Lung:
pulmonary arteriovenous malformation

Cardiovascular Heart:
mitral valve prolapse (1 family)
mitral valve regurgitation (1 family)
redundant mitral valve leaflets (1 family)

Abdomen Gastrointestinal:
gastrointestinal hamartomatous polyps
recurrent rectal bleeding

Neoplasia:
increased risk of gastrointestinal cancer

Head And Neck Nose:
epistaxis

Neurologic Central Nervous System:
cerebral arteriovenous malformation

Skeletal Hands:
digital clubbing

Cardiovascular Vascular:
arteriovenous malformations
aortic dilatation (in some patients)
aortic dissection (rare)

Skeletal:
hypertrophic osteoarthropathy

Clinical features from OMIM®:

175050 (Updated 05-Apr-2021)

GenomeRNAi Phenotypes related to Juvenile Polyposis/hereditary Hemorrhagic Telangiectasia Syndrome according to GeneCards Suite gene sharing:

26 (show top 50) (show all 54)
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased viability GR00173-A 10.25 BMPR2
2 Decreased viability GR00221-A-1 10.25 ACVRL1 BMPR1A BMPR2 TGFBR1
3 Decreased viability GR00221-A-2 10.25 ACVRL1 BMPR1A
4 Decreased viability GR00221-A-3 10.25 ACVRL1 BMPR1A BMPR2
5 Decreased viability GR00221-A-4 10.25 ACVRL1 BMPR1A BMPR2 TGFBR1 ACVR1
6 Decreased viability GR00249-S 10.25 BMPR1A BMPR2 TGFBR1
7 Decreased viability GR00301-A 10.25 BMPR2
8 Decreased viability GR00402-S-2 10.25 TGFBR1
9 Decreased substrate adherent cell growth GR00193-A-1 10 ACVR1 ACVRL1 BMPR2
10 Decreased substrate adherent cell growth GR00193-A-2 10 BMPR1A
11 Decreased substrate adherent cell growth GR00193-A-3 10 ACVR1 BMPR1A
12 Decreased substrate adherent cell growth GR00193-A-4 10 ACVR1 ACVRL1 BMPR1A
13 Increased shRNA abundance (Z-score > 2) GR00366-A-11 9.98 TGFBR1
14 Increased shRNA abundance (Z-score > 2) GR00366-A-113 9.98 ACVRL1
15 Increased shRNA abundance (Z-score > 2) GR00366-A-116 9.98 ACVR1
16 Increased shRNA abundance (Z-score > 2) GR00366-A-133 9.98 ACVR1
17 Increased shRNA abundance (Z-score > 2) GR00366-A-145 9.98 ACVRL1
18 Increased shRNA abundance (Z-score > 2) GR00366-A-147 9.98 TGFBR1
19 Increased shRNA abundance (Z-score > 2) GR00366-A-148 9.98 ACVRL1
20 Increased shRNA abundance (Z-score > 2) GR00366-A-153 9.98 ACVRL1
21 Increased shRNA abundance (Z-score > 2) GR00366-A-160 9.98 ACVR1
22 Increased shRNA abundance (Z-score > 2) GR00366-A-166 9.98 BMPR1A
23 Increased shRNA abundance (Z-score > 2) GR00366-A-169 9.98 TGFBR1
24 Increased shRNA abundance (Z-score > 2) GR00366-A-173 9.98 BMPR2
25 Increased shRNA abundance (Z-score > 2) GR00366-A-192 9.98 BMPR1A
26 Increased shRNA abundance (Z-score > 2) GR00366-A-199 9.98 ACVRL1
27 Increased shRNA abundance (Z-score > 2) GR00366-A-200 9.98 TGFBR1
28 Increased shRNA abundance (Z-score > 2) GR00366-A-206 9.98 BMPR2
29 Increased shRNA abundance (Z-score > 2) GR00366-A-213 9.98 BMPR2
30 Increased shRNA abundance (Z-score > 2) GR00366-A-214 9.98 BMPR1A
31 Increased shRNA abundance (Z-score > 2) GR00366-A-22 9.98 TGFBR1
32 Increased shRNA abundance (Z-score > 2) GR00366-A-23 9.98 ACVR1
33 Increased shRNA abundance (Z-score > 2) GR00366-A-24 9.98 BMPR2
34 Increased shRNA abundance (Z-score > 2) GR00366-A-33 9.98 BMPR1A
35 Increased shRNA abundance (Z-score > 2) GR00366-A-37 9.98 TGFBR1
36 Increased shRNA abundance (Z-score > 2) GR00366-A-43 9.98 ACVRL1
37 Increased shRNA abundance (Z-score > 2) GR00366-A-48 9.98 ACVRL1
38 Increased shRNA abundance (Z-score > 2) GR00366-A-60 9.98 ACVR1 ACVRL1 TGFBR1
39 Increased shRNA abundance (Z-score > 2) GR00366-A-63 9.98 ACVRL1
40 Increased shRNA abundance (Z-score > 2) GR00366-A-65 9.98 BMPR2
41 Increased shRNA abundance (Z-score > 2) GR00366-A-66 9.98 ACVR1
42 Increased shRNA abundance (Z-score > 2) GR00366-A-68 9.98 ACVRL1
43 Increased shRNA abundance (Z-score > 2) GR00366-A-73 9.98 ACVRL1
44 Increased shRNA abundance (Z-score > 2) GR00366-A-77 9.98 TGFBR1
45 Increased shRNA abundance (Z-score > 2) GR00366-A-78 9.98 ACVR1
46 Increased shRNA abundance (Z-score > 2) GR00366-A-8 9.98 BMPR1A
47 Increased shRNA abundance (Z-score > 2) GR00366-A-80 9.98 BMPR2
48 Increased shRNA abundance (Z-score > 2) GR00366-A-81 9.98 ACVRL1
49 Increased shRNA abundance (Z-score > 2) GR00366-A-82 9.98 BMPR1A
50 Increased shRNA abundance (Z-score > 2) GR00366-A-85 9.98 ACVR1 ACVRL1 BMPR1A BMPR2 TGFBR1

MGI Mouse Phenotypes related to Juvenile Polyposis/hereditary Hemorrhagic Telangiectasia Syndrome:

46 (show all 12)
# Description MGI Source Accession Score Top Affiliating Genes
1 cardiovascular system MP:0005385 10.16 ACVR1 ACVRL1 BMP10 BMPR1A BMPR2 ENG
2 growth/size/body region MP:0005378 10.09 ACVR1 ACVRL1 BMP10 BMPR1A BMPR2 ENG
3 embryo MP:0005380 10.06 ACVR1 ACVRL1 BMP10 BMPR1A BMPR2 ENG
4 homeostasis/metabolism MP:0005376 10.02 ACVR1 ACVRL1 BMP10 BMPR1A BMPR2 ENG
5 hematopoietic system MP:0005397 10.01 ACVRL1 BMP10 BMPR1A BMPR2 ENG GDF2
6 digestive/alimentary MP:0005381 9.95 ACVR1 ACVRL1 BMPR1A ENG SMAD4 TGFBR1
7 craniofacial MP:0005382 9.89 ACVR1 ACVRL1 BMPR1A ENG SMAD4
8 integument MP:0010771 9.8 BMP10 BMPR1A BMPR2 ENG SMAD4 TGFBR1
9 muscle MP:0005369 9.76 ACVR1 ACVRL1 BMP10 BMPR1A BMPR2 ENG
10 limbs/digits/tail MP:0005371 9.65 ACVR1 BMP10 BMPR1A ENG SMAD4
11 nervous system MP:0003631 9.56 ACVR1 ACVRL1 BMP10 BMPR1A BMPR2 ENG
12 normal MP:0002873 9.17 ACVRL1 BMP10 BMPR1A BMPR2 ENG SMAD4

Drugs & Therapeutics for Juvenile Polyposis/hereditary Hemorrhagic Telangiectasia...

Search Clinical Trials , NIH Clinical Center for Juvenile Polyposis/hereditary Hemorrhagic Telangiectasia Syndrome

Genetic Tests for Juvenile Polyposis/hereditary Hemorrhagic Telangiectasia...

Genetic tests related to Juvenile Polyposis/hereditary Hemorrhagic Telangiectasia Syndrome:

# Genetic test Affiliating Genes
1 Juvenile Polyposis/hereditary Hemorrhagic Telangiectasia Syndrome 29 SMAD4

Anatomical Context for Juvenile Polyposis/hereditary Hemorrhagic Telangiectasia...

MalaCards organs/tissues related to Juvenile Polyposis/hereditary Hemorrhagic Telangiectasia Syndrome:

40
Brain

Publications for Juvenile Polyposis/hereditary Hemorrhagic Telangiectasia...

Articles related to Juvenile Polyposis/hereditary Hemorrhagic Telangiectasia Syndrome:

(show all 23)
# Title Authors PMID Year
1
SMAD4 mutation segregating in a family with juvenile polyposis, aortopathy, and mitral valve dysfunction. 6 57
21465659 2011
2
SMAD4 mutations found in unselected HHT patients. 6 57
16613914 2006
3
A combined syndrome of juvenile polyposis and hereditary haemorrhagic telangiectasia associated with mutations in MADH4 (SMAD4). 57 6
15031030 2004
4
Novel de novo mutation of MADH4/SMAD4 in a patient with juvenile polyposis. 6 57
12116240 2002
5
Generalized juvenile polyposis with pulmonary arteriovenous malformations and hypertrophic osteoarthropathy. 6 57
6604412 1983
6
Mutational and phenotypic characterization of hereditary hemorrhagic telangiectasia. 6
32573726 2020
7
Prevalence of thoracic aortopathy in patients with juvenile Polyposis Syndrome-Hereditary Hemorrhagic Telangiectasia due to SMAD4. 57
25931195 2015
8
Overlapping spectra of SMAD4 mutations in juvenile polyposis (JP) and JP-HHT syndrome. 57
20101697 2010
9
Hypermanganesemia, hereditary hemorrhagic telangiectasia, brain abscess: the hepatic connection. 57
18824676 2008
10
Gastric juvenile polyposis associated with germline SMAD4 mutation. 6
15754356 2005
11
Mutations in DPC4 (SMAD4) cause juvenile polyposis syndrome, but only account for a minority of cases. 6
9811934 1998
12
Mutations in the SMAD4/DPC4 gene in juvenile polyposis. 6
9582123 1998
13
Comparative mutational analysis of DPC4 (Smad4) in prostatic and colorectal carcinomas. 6
9285566 1997
14
Somatic alterations of the DPC4 gene in human colorectal cancers in vivo. 6
8898652 1996
15
Colonic hamartomatous polyposis associated with hypertrophic osteoarthropathy. 57
8078721 1994
16
Association of juvenile and adenomatous polyposis with pulmonary arteriovenous malformation and hypertrophic osteoarthropathy. 57
2388124 1990
17
Association of hypertrophic osteoarthropathy with gastrointestinal polyposis. 57
3872584 1985
18
Hereditary generalized juvenile polyposis associated with pulmonary arteriovenous malformation. 57
7372073 1980
19
Processed Pseudogene Confounding Deletion/Duplication Assays for SMAD4. 61
26165824 2015
20
Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome in an adolescent with complex chromosomal rearrangement and intellectual disability. 61
25081192 2014
21
Appreciating the broad clinical features of SMAD4 mutation carriers: a multicenter chart review. 61
24525918 2014
22
Recurrent Gastrointestinal Hemorrhage in Treatment with Dasatinib in a Patient Showing SMAD4 Mutation with Acute Lymphoblastic Leukemia Philadelphia Positive and Juvenile Polyposis Hereditary Hemorrhagic Telangiectasia Syndrome. 61
23888243 2013
23
SMAD4 haploinsufficiency associates with augmented colonic inflammation in select humans and mice. 61
23090737 2012

Variations for Juvenile Polyposis/hereditary Hemorrhagic Telangiectasia...

ClinVar genetic disease variations for Juvenile Polyposis/hereditary Hemorrhagic Telangiectasia Syndrome:

6 (show top 50) (show all 215)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 SMAD4 SMAD4, 14-BP DEL, NT1612 Deletion Pathogenic 8547 GRCh37:
GRCh38:
2 SMAD4 SMAD4, 2-BP DEL/1-BP INS, 1596CC/T Indel Pathogenic 8548 GRCh37:
GRCh38:
3 SMAD4 NM_005359.6(SMAD4):c.302G>A (p.Trp101Ter) SNV Pathogenic 24798 rs377767323 GRCh37: 18:48575108-48575108
GRCh38: 18:51048738-51048738
4 SMAD4 NM_005359.6(SMAD4):c.1055G>A (p.Gly352Glu) SNV Pathogenic 24828 rs377767345 GRCh37: 18:48591892-48591892
GRCh38: 18:51065522-51065522
5 SMAD4 NM_005359.6(SMAD4):c.1082G>T (p.Arg361Leu) SNV Pathogenic 24833 rs377767347 GRCh37: 18:48591919-48591919
GRCh38: 18:51065549-51065549
6 SMAD4 NM_005359.6(SMAD4):c.1088_1090del (p.Cys363del) Deletion Pathogenic 24835 rs377767349 GRCh37: 18:48591923-48591925
GRCh38: 18:51065553-51065555
7 SMAD4 NM_005359.5(SMAD4):c.1102_1103delTC (p.Ser368Glnfs) Microsatellite Pathogenic 24837 rs377767351 GRCh37: 18:48591936-48591937
GRCh38: 18:51065566-51065567
8 SMAD4 NM_005359.6(SMAD4):c.1148T>A (p.Ile383Lys) SNV Pathogenic 24840 rs377767355 GRCh37: 18:48593397-48593397
GRCh38: 18:51067027-51067027
9 SMAD4 NM_005359.6(SMAD4):c.1586_1587dup (p.His530fs) Duplication Pathogenic 24869 rs1555687599 GRCh37: 18:48604763-48604764
GRCh38: 18:51078393-51078394
10 SMAD4 NM_005359.6(SMAD4):c.1594del (p.Ala532fs) Deletion Pathogenic 24870 rs377767378 GRCh37: 18:48604770-48604770
GRCh38: 18:51078400-51078400
11 SMAD4 NM_005359.6(SMAD4):c.1596_1597delinsT (p.Leu533fs) Indel Pathogenic 24871 rs377767379 GRCh37: 18:48604774-48604775
GRCh38: 18:51078404-51078405
12 SMAD4 NM_005359.6(SMAD4):c.1597del (p.Leu533fs) Deletion Pathogenic 24872 rs377767380 GRCh37: 18:48604773-48604773
GRCh38: 18:51078403-51078403
13 SMAD4 NM_005359.6(SMAD4):c.1598T>G (p.Leu533Arg) SNV Pathogenic 24874 rs377767382 GRCh37: 18:48604776-48604776
GRCh38: 18:51078406-51078406
14 SMAD4 NM_005359.6(SMAD4):c.1600C>T (p.Gln534Ter) SNV Pathogenic 24875 rs377767383 GRCh37: 18:48604778-48604778
GRCh38: 18:51078408-51078408
15 SMAD4 NM_005359.6(SMAD4):c.1598T>C (p.Leu533Pro) SNV Pathogenic 24876 rs377767382 GRCh37: 18:48604776-48604776
GRCh38: 18:51078406-51078406
16 SMAD4 NM_005359.6(SMAD4):c.1612_1625del (p.Glu538fs) Deletion Pathogenic 24878 rs377767385 GRCh37: 18:48604788-48604801
GRCh38: 18:51078418-51078431
17 SMAD4 NM_005359.6(SMAD4):c.1139+274del Deletion Pathogenic 24879 rs483352871 GRCh37: 18:48592247-48592247
GRCh38: 18:51065877-51065877
18 SMAD4 NM_005359.6(SMAD4):c.1447+1G>A SNV Pathogenic 38740 rs377767387 GRCh37: 18:48603147-48603147
GRCh38: 18:51076777-51076777
19 SMAD4 SMAD4, 1-BP INS Insertion Pathogenic 8542 GRCh37:
GRCh38:
20 SMAD4 NM_005359.6(SMAD4):c.692dup (p.Ser232fs) Duplication Pathogenic 24811 rs377767334 GRCh37: 18:48584513-48584514
GRCh38: 18:51058143-51058144
21 SMAD4 NM_005359.6(SMAD4):c.303G>A (p.Trp101Ter) SNV Pathogenic 982455 GRCh37: 18:48575109-48575109
GRCh38: 18:51048739-51048739
22 SMAD4 NM_005359.6(SMAD4):c.1308+2T>C SNV Pathogenic 548563 rs1555686624 GRCh37: 18:48593559-48593559
GRCh38: 18:51067189-51067189
23 SMAD4 NM_005359.5(SMAD4):c.1245_1248delCAGA (p.Asp415Glufs) Deletion Pathogenic 142253 rs80338965 GRCh37: 18:48593491-48593494
GRCh38: 18:51067121-51067124
24 SMAD4 NM_005359.6(SMAD4):c.1333C>T (p.Arg445Ter) SNV Pathogenic 24850 rs377767360 GRCh37: 18:48603032-48603032
GRCh38: 18:51076662-51076662
25 SMAD4 NM_005359.5(SMAD4):c.1245_1248delCAGA (p.Asp415Glufs) Deletion Pathogenic 142253 rs80338965 GRCh37: 18:48593491-48593494
GRCh38: 18:51067121-51067124
26 SMAD4 NM_005359.6(SMAD4):c.1081C>T (p.Arg361Cys) SNV Pathogenic 8543 rs80338963 GRCh37: 18:48591918-48591918
GRCh38: 18:51065548-51065548
27 SMAD4 NM_005359.6(SMAD4):c.1157G>A (p.Gly386Asp) SNV Pathogenic 8545 rs121912580 GRCh37: 18:48593406-48593406
GRCh38: 18:51067036-51067036
28 SMAD4 NM_005359.6(SMAD4):c.1054G>A (p.Gly352Arg) SNV Pathogenic 24827 rs121912581 GRCh37: 18:48591891-48591891
GRCh38: 18:51065521-51065521
29 SMAD4 NM_005359.6(SMAD4):c.1082G>A (p.Arg361His) SNV Pathogenic 24832 rs377767347 GRCh37: 18:48591919-48591919
GRCh38: 18:51065549-51065549
30 SMAD4 NM_005359.6(SMAD4):c.533C>G (p.Ser178Ter) SNV Pathogenic 24807 rs377767331 GRCh37: 18:48581229-48581229
GRCh38: 18:51054859-51054859
31 SMAD4 NM_005359.6(SMAD4):c.1498A>G (p.Ile500Val) SNV Pathogenic 30150 rs281875322 GRCh37: 18:48604676-48604676
GRCh38: 18:51078306-51078306
32 SMAD4 NM_005359.6(SMAD4):c.1498A>G (p.Ile500Val) SNV Pathogenic 30150 rs281875322 GRCh37: 18:48604676-48604676
GRCh38: 18:51078306-51078306
33 SMAD4 NM_005359.6(SMAD4):c.803_804insCTAAGTGGTAGTA (p.Trp268delinsCysTer) Insertion Likely pathogenic 1032991 GRCh37: 18:48584725-48584726
GRCh38: 18:51058355-51058356
34 SMAD4 NM_005359.6(SMAD4):c.1309G>A (p.Val437Ile) SNV Likely pathogenic 630855 rs1568211172 GRCh37: 18:48603008-48603008
GRCh38: 18:51076638-51076638
35 SMAD4 NM_005359.6(SMAD4):c.1058A>G (p.Tyr353Cys) SNV Likely pathogenic 597824 rs377767346 GRCh37: 18:48591895-48591895
GRCh38: 18:51065525-51065525
36 SMAD4 NM_005359.6(SMAD4):c.87T>G (p.Gly29=) SNV Uncertain significance 327109 rs886053893 GRCh37: 18:48573503-48573503
GRCh38: 18:51047133-51047133
37 SMAD4 NM_005359.6(SMAD4):c.*1067G>A SNV Uncertain significance 327122 rs542839921 GRCh37: 18:48605904-48605904
GRCh38: 18:51079534-51079534
38 SMAD4 NM_005359.6(SMAD4):c.*3286A>T SNV Uncertain significance 327155 rs886053912 GRCh37: 18:48608123-48608123
GRCh38: 18:51081753-51081753
39 SMAD4 NM_005359.6(SMAD4):c.*4987T>C SNV Uncertain significance 327170 rs188228460 GRCh37: 18:48609824-48609824
GRCh38: 18:51083454-51083454
40 SMAD4 NM_005359.6(SMAD4):c.*2962C>T SNV Uncertain significance 327150 rs543699844 GRCh37: 18:48607799-48607799
GRCh38: 18:51081429-51081429
41 SMAD4 NM_005359.6(SMAD4):c.*1801A>G SNV Uncertain significance 327131 rs886053904 GRCh37: 18:48606638-48606638
GRCh38: 18:51080268-51080268
42 SMAD4 NM_005359.6(SMAD4):c.*5551A>G SNV Uncertain significance 327199 rs202140561 GRCh37: 18:48610388-48610388
GRCh38: 18:51084018-51084018
43 SMAD4 NM_005359.6(SMAD4):c.*2693A>G SNV Uncertain significance 327145 rs778780100 GRCh37: 18:48607530-48607530
GRCh38: 18:51081160-51081160
44 SMAD4 NM_005359.6(SMAD4):c.*5530T>C SNV Uncertain significance 327180 rs886053921 GRCh37: 18:48610367-48610367
GRCh38: 18:51083997-51083997
45 SMAD4 NM_005359.6(SMAD4):c.*5791C>T SNV Uncertain significance 327206 rs886053932 GRCh37: 18:48610628-48610628
GRCh38: 18:51084258-51084258
46 SMAD4 NM_005359.6(SMAD4):c.*2674A>G SNV Uncertain significance 327143 rs886053907 GRCh37: 18:48607511-48607511
GRCh38: 18:51081141-51081141
47 SMAD4 NM_005359.6(SMAD4):c.*2682T>C SNV Uncertain significance 327144 rs557955183 GRCh37: 18:48607519-48607519
GRCh38: 18:51081149-51081149
48 SMAD4 NM_005359.6(SMAD4):c.*1277G>T SNV Uncertain significance 327127 rs886053900 GRCh37: 18:48606114-48606114
GRCh38: 18:51079744-51079744
49 SMAD4 NM_005359.6(SMAD4):c.*2793T>G SNV Uncertain significance 327147 rs886053909 GRCh37: 18:48607630-48607630
GRCh38: 18:51081260-51081260
50 SMAD4 NM_005359.6(SMAD4):c.*1812T>G SNV Uncertain significance 327132 rs557065270 GRCh37: 18:48606649-48606649
GRCh38: 18:51080279-51080279

UniProtKB/Swiss-Prot genetic disease variations for Juvenile Polyposis/hereditary Hemorrhagic Telangiectasia Syndrome:

72
# Symbol AA change Variation ID SNP ID
1 SMAD4 p.Gly352Arg VAR_019571 rs121912581
2 SMAD4 p.Gly386Asp VAR_019573 rs121912580

Expression for Juvenile Polyposis/hereditary Hemorrhagic Telangiectasia...

Search GEO for disease gene expression data for Juvenile Polyposis/hereditary Hemorrhagic Telangiectasia Syndrome.

Pathways for Juvenile Polyposis/hereditary Hemorrhagic Telangiectasia...

Pathways related to Juvenile Polyposis/hereditary Hemorrhagic Telangiectasia Syndrome according to GeneCards Suite gene sharing:

(show all 27)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
13.63 TGFBR1 SMAD4 GDF2 BMPR2 BMPR1A BMP10
2
Show member pathways
13.44 TGFBR1 SMAD4 GDF2 BMPR2 BMPR1A BMP10
3
Show member pathways
13.22 TGFBR1 GDF2 BMPR2 BMPR1A BMP10 ACVRL1
4
Show member pathways
12.99 TGFBR1 SMAD4 GDF2 BMPR2 BMPR1A BMP10
5
Show member pathways
12.54 SMAD4 BMPR2 BMPR1A ACVRL1 ACVR1
6
Show member pathways
12.38 SMAD4 BMPR2 BMPR1A ACVR1
7
Show member pathways
12.23 TGFBR1 BMPR1A ACVR1
8
Show member pathways
12.18 TGFBR1 SMAD4 BMPR2 BMPR1A BMP10 ACVR1
9 12.07 TGFBR1 SMAD4 BMPR2 BMPR1A
10 12.06 TGFBR1 SMAD4 BMPR2 BMPR1A
11 12.06 TGFBR1 SMAD4 ENG BMPR2 ACVR1
12
Show member pathways
11.99 TGFBR1 BMPR1A ACVR1
13 11.99 SMAD4 BMPR2 BMPR1A ACVR1
14 11.92 BMPR2 BMPR1A ACVR1
15 11.76 TGFBR1 SMAD4 ENG ACVRL1
16
Show member pathways
11.64 TGFBR1 SMAD4 BMPR2 BMPR1A
17
Show member pathways
11.62 SMAD4 BMPR2 BMPR1A
18 11.53 TGFBR1 SMAD4 BMP10
19 11.53 TGFBR1 SMAD4 BMPR2 BMPR1A ACVR1
20 11.52 TGFBR1 SMAD4 ENG
21 11.33 SMAD4 BMPR2 BMPR1A BMP10
22 11.1 TGFBR1 SMAD4
23 11.08 TGFBR1 SMAD4 ENG
24 10.94 TGFBR1 SMAD4
25 10.65 SMAD4 BMPR2 ACVR1
26 10.6 SMAD4 BMPR2 BMPR1A BMP10
27
Show member pathways
10.53 TGFBR1 SMAD4 GDF2 BMPR2 ACVRL1 ACVR1

GO Terms for Juvenile Polyposis/hereditary Hemorrhagic Telangiectasia...

Cellular components related to Juvenile Polyposis/hereditary Hemorrhagic Telangiectasia Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cell surface GO:0009986 9.43 TGFBR1 ENG BMPR2 BMPR1A BMP10 ACVRL1
2 activin receptor complex GO:0048179 9.26 TGFBR1 ACVR1
3 BMP receptor complex GO:0070724 9.16 ACVRL1 ACVR1
4 receptor complex GO:0043235 9.1 TGFBR1 ENG BMPR2 BMPR1A ACVRL1 ACVR1

Biological processes related to Juvenile Polyposis/hereditary Hemorrhagic Telangiectasia Syndrome according to GeneCards Suite gene sharing:

(show top 50) (show all 80)
# Name GO ID Score Top Affiliating Genes
1 positive regulation of transcription by RNA polymerase II GO:0045944 10.17 SMAD4 GDF2 ENG BMPR2 BMPR1A ACVRL1
2 positive regulation of transcription, DNA-templated GO:0045893 10.11 TGFBR1 SMAD4 GDF2 BMP10 ACVRL1 ACVR1
3 phosphorylation GO:0016310 10.09 TGFBR1 BMPR2 BMPR1A ACVRL1 ACVR1
4 protein phosphorylation GO:0006468 10.07 TGFBR1 BMPR2 BMPR1A ACVRL1 ACVR1
5 positive regulation of gene expression GO:0010628 10.03 TGFBR1 GDF2 ENG BMP10
6 angiogenesis GO:0001525 10.01 TGFBR1 GDF2 ENG ACVRL1 ACVR1
7 heart development GO:0007507 9.99 TGFBR1 ENG BMPR1A BMP10 ACVRL1 ACVR1
8 in utero embryonic development GO:0001701 9.98 TGFBR1 SMAD4 BMPR1A ACVRL1 ACVR1
9 anterior/posterior pattern specification GO:0009952 9.93 TGFBR1 SMAD4 BMPR2 BMPR1A
10 negative regulation of cell growth GO:0030308 9.93 SMAD4 GDF2 BMPR2 BMP10 ACVRL1
11 regulation of cell proliferation GO:0042127 9.92 SMAD4 ENG BMPR2
12 response to hypoxia GO:0001666 9.91 SMAD4 ENG ACVRL1
13 positive regulation of angiogenesis GO:0045766 9.9 GDF2 ENG ACVRL1
14 negative regulation of cell migration GO:0030336 9.9 ENG BMP10 ACVRL1
15 kidney development GO:0001822 9.9 TGFBR1 SMAD4 BMP10
16 positive regulation of endothelial cell proliferation GO:0001938 9.89 TGFBR1 GDF2 BMPR2 ACVRL1
17 cellular response to growth factor stimulus GO:0071363 9.88 TGFBR1 BMPR2 BMPR1A ACVRL1 ACVR1
18 transforming growth factor beta receptor signaling pathway GO:0007179 9.88 TGFBR1 SMAD4 ENG BMPR1A ACVRL1 ACVR1
19 positive regulation of osteoblast differentiation GO:0045669 9.86 BMPR2 BMPR1A ACVR1
20 negative regulation of endothelial cell proliferation GO:0001937 9.86 TGFBR1 GDF2 ENG ACVRL1
21 SMAD protein signal transduction GO:0060395 9.85 SMAD4 GDF2 BMP10
22 dorsal/ventral pattern formation GO:0009953 9.84 BMPR1A ACVRL1 ACVR1
23 positive regulation of bone mineralization GO:0030501 9.83 BMPR2 BMPR1A ACVR1
24 mesoderm formation GO:0001707 9.83 BMPR2 BMPR1A ACVR1
25 ventricular septum morphogenesis GO:0060412 9.83 TGFBR1 SMAD4 BMPR2 ACVR1
26 positive regulation of BMP signaling pathway GO:0030513 9.83 SMAD4 GDF2 ENG BMPR2 ACVRL1
27 branching involved in blood vessel morphogenesis GO:0001569 9.82 GDF2 ENG ACVR1
28 negative regulation of endothelial cell migration GO:0010596 9.82 GDF2 BMP10 ACVRL1
29 positive regulation of cartilage development GO:0061036 9.8 GDF2 BMPR2 BMP10
30 endocardial cushion morphogenesis GO:0003203 9.8 ENG BMPR1A ACVRL1 ACVR1
31 positive regulation of SMAD protein signal transduction GO:0060391 9.79 TGFBR1 SMAD4 BMPR1A
32 negative regulation of DNA biosynthetic process GO:2000279 9.78 GDF2 BMPR2 ACVRL1
33 ventricular trabecula myocardium morphogenesis GO:0003222 9.77 TGFBR1 ENG BMPR1A
34 outflow tract septum morphogenesis GO:0003148 9.77 SMAD4 ENG BMPR2 BMPR1A ACVR1
35 negative regulation of blood vessel endothelial cell migration GO:0043537 9.76 GDF2 ACVRL1
36 epithelial to mesenchymal transition GO:0001837 9.76 TGFBR1 ENG
37 pathway-restricted SMAD protein phosphorylation GO:0060389 9.76 TGFBR1 GDF2 BMP10 ACVR1
38 positive regulation of pri-miRNA transcription by RNA polymerase II GO:1902895 9.75 SMAD4 BMPR1A
39 negative regulation of extrinsic apoptotic signaling pathway GO:2001237 9.75 TGFBR1 ACVR1
40 positive regulation of cardiac muscle cell proliferation GO:0060045 9.75 BMPR1A BMP10
41 cell motility GO:0048870 9.75 TGFBR1 ENG
42 gastrulation GO:0007369 9.75 SMAD4 ACVR1
43 blood vessel remodeling GO:0001974 9.75 BMPR2 ACVRL1
44 mesoderm development GO:0007498 9.75 SMAD4 ACVR1
45 dorsal aorta morphogenesis GO:0035912 9.75 ENG BMPR1A ACVRL1
46 neuron fate commitment GO:0048663 9.74 TGFBR1 SMAD4
47 blood vessel morphogenesis GO:0048514 9.74 GDF2 ACVRL1
48 endoderm development GO:0007492 9.74 SMAD4 BMPR1A
49 developmental growth GO:0048589 9.74 SMAD4 BMPR1A
50 regulation of transforming growth factor beta receptor signaling pathway GO:0017015 9.74 SMAD4 ENG

Molecular functions related to Juvenile Polyposis/hereditary Hemorrhagic Telangiectasia Syndrome according to GeneCards Suite gene sharing:

(show all 18)
# Name GO ID Score Top Affiliating Genes
1 ATP binding GO:0005524 9.97 TGFBR1 BMPR2 BMPR1A ACVRL1 ACVR1
2 kinase activity GO:0016301 9.91 TGFBR1 BMPR2 BMPR1A ACVRL1 ACVR1
3 protein kinase activity GO:0004672 9.89 TGFBR1 BMPR2 BMPR1A ACVRL1 ACVR1
4 protein homodimerization activity GO:0042803 9.87 SMAD4 ENG BMPR1A ACVR1
5 protein serine/threonine kinase activity GO:0004674 9.85 TGFBR1 BMPR2 BMPR1A ACVRL1 ACVR1
6 SMAD binding GO:0046332 9.73 TGFBR1 BMPR1A ACVRL1 ACVR1
7 growth factor binding GO:0019838 9.65 TGFBR1 BMPR2 ACVR1
8 transforming growth factor beta binding GO:0050431 9.62 TGFBR1 ENG ACVRL1 ACVR1
9 BMP receptor activity GO:0098821 9.58 BMPR2 BMPR1A ACVRL1
10 protein tyrosine kinase binding GO:1990782 9.56 BMPR2 ACVR1
11 activin binding GO:0048185 9.56 TGFBR1 ENG ACVRL1 ACVR1
12 I-SMAD binding GO:0070411 9.55 TGFBR1 SMAD4
13 BMP binding GO:0036122 9.54 ENG BMPR2
14 activin receptor activity, type I GO:0016361 9.54 TGFBR1 ACVRL1 ACVR1
15 type II transforming growth factor beta receptor binding GO:0005114 9.52 TGFBR1 ENG
16 transforming growth factor beta-activated receptor activity GO:0005024 9.46 TGFBR1 ENG BMPR2 ACVRL1
17 transforming growth factor beta receptor activity, type I GO:0005025 9.26 TGFBR1 BMPR1A ACVRL1 ACVR1
18 transmembrane receptor protein serine/threonine kinase activity GO:0004675 9.02 TGFBR1 BMPR2 BMPR1A ACVRL1 ACVR1

Sources for Juvenile Polyposis/hereditary Hemorrhagic Telangiectasia...

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
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
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Apr-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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