CWS1
MCID: CWD006
MIFTS: 78

Cowden Syndrome 1 (CWS1)

Categories: Cancer diseases, Cardiovascular diseases, Eye diseases, Fetal diseases, Gastrointestinal diseases, Genetic diseases, Neuronal diseases, Rare diseases, Reproductive diseases, Skin diseases

Aliases & Classifications for Cowden Syndrome 1

MalaCards integrated aliases for Cowden Syndrome 1:

Name: Cowden Syndrome 1 56 73 29 13 6
Pten Hamartoma Tumor Syndrome 56 12 24 52 58 73 36 29 6 15 71
Bannayan-Riley-Ruvalcaba Syndrome 56 12 52 25 58 73 29 6 15 39
Bannayan-Zonana Syndrome 56 12 74 52 25 73 54
Lhermitte-Duclos Disease 58 73 29 6 71
Riley-Smith Syndrome 56 12 52 25 73
Phts 56 24 52 58 73
Ruvalcaba-Myhre-Smith Syndrome 56 12 25 73
Bzs 56 52 25 73
Rmss 56 52 73
Brrs 52 25 58
Pten Hamartoma Tumor Syndrome with Granular Cell Tumor 56 29
Macrocephaly Multiple Lipomas and Hemangiomata 52 73
Dysplastic Gangliocytoma of the Cerebellum 58 73
Bannayan-Ruvalcaba-Riley Syndrome 25 73
Cerebelloparenchymal Disorder Vi 73 71
Hamartoma Syndrome, Multiple 43 71
Multiple Hamartoma Syndrome 56 73
Myhre-Riley-Smith Syndrome 25 58
Lhermitte-Duclos Syndrome 56 29
Cowden Disease 73 54
Cws1 56 73
Mham 56 73
Ldd 58 73
Cs 56 73
Cd 56 73
Macrocephaly, Pseudopapilledema, and Multiple Hemangiomata 56
Macrocephaly Pseudopapilledema and Multiple Hemangiomata 73
Macrocephaly Pseudopapilledema and Multiple Hemangiomas 52
Cerebellar Granule Cell Hypertrophy and Megalencephaly 73
Macrocephaly, Multiple Lipomas, and Hemangiomata 56
Bannayan-Riley-Ruvalcaba Syndrome; Bbrs 56
Ruvalcaba-Myhre-Smith Syndrome; Rmss 56
Pten Hamartoma Tumor Syndrome; Phts 56
Multiple Hamartoma Syndrome; Mham 56
Ruvalcaba -Myhre-Smith Syndrome 52
Bannayan-Zonana Syndrome; Bzs 56
Ruvalcaba-Myhre Syndrome 25
Proteus-Like Syndrome 58
Cohen-Hayden Syndrome 58
Cs; Cd 56
Bbrs 56
Cpd6 73

Characteristics:

Orphanet epidemiological data:

58
bannayan-riley-ruvalcaba syndrome
Inheritance: Autosomal dominant; Age of onset: Infancy,Neonatal;
proteus-like syndrome
Inheritance: Autosomal dominant; Age of onset: Infancy,Neonatal;
pten hamartoma tumor syndrome
Inheritance: Autosomal dominant; Age of onset: All ages; Age of death: any age;
lhermitte-duclos disease
Prevalence: <1/1000000 (Worldwide); Age of onset: Adult;

OMIM:

56
Inheritance:
autosomal dominant

Miscellaneous:
symptoms usually occur in adults
skin lesions are fully penetrant by second decade
skeletal abnormalities are variable
allelic to bannayan-riley-ruvalcaba syndrome , which has an earlier age at onset
approximately 80% of cs patients have pten mutations


HPO:

31
cowden syndrome 1:
Inheritance autosomal dominant inheritance
Onset and clinical course juvenile onset adult onset


GeneReviews:

24
Penetrance More than 90% of individuals with cs have some clinical manifestation of the disorder by the late 20s [nelen et al 1996, eng 2000, zbuk & eng 2007]. by the third decade, 99% of affected individuals develop the mucocutaneous stigmata, primarily trichilemmomas and papillomatous papules, as well as acral and plantar keratoses. (see also clinical description for age at which specific manifestations are likely to become evident.)

Classifications:

Orphanet: 58  
Rare neurological diseases
Rare eye diseases
Rare circulatory system diseases
Rare gastroenterological diseases
Rare skin diseases
Developmental anomalies during embryogenesis


External Ids:

Disease Ontology 12 DOID:0050657 DOID:0080191
OMIM 56 158350
OMIM Phenotypic Series 56 PS158350
KEGG 36 H00539
MeSH 43 D006223
NCIt 49 C3939
ICD10 32 Q87.89
ICD10 via Orphanet 33 Q04.8 Q87.3 Q87.8
UMLS via Orphanet 72 C0265326 C0391826 C1266181 more
SNOMED-CT via HPO 68 103276001 111266001 112641009 more
UMLS 71 C0018553 C0391826 C1834711 more

Summaries for Cowden Syndrome 1

Genetics Home Reference : 25 Bannayan-Riley-Ruvalcaba syndrome is a genetic condition characterized by a large head size (macrocephaly), multiple noncancerous tumors and tumor-like growths called hamartomas, and dark freckles on the penis in males. The signs and symptoms of Bannayan-Riley-Ruvalcaba syndrome are present from birth or become apparent in early childhood. At least half of affected infants have macrocephaly, and many also have a high birth weight and a large body size (macrosomia). Growth usually slows during childhood, so affected adults are of normal height and body size. About half of all children with Bannayan-Riley-Ruvalcaba syndrome have intellectual disability or delayed development, particularly the development of speech and of motor skills such as sitting, crawling, and walking. These delays may improve with age. About half of all people with Bannayan-Riley-Ruvalcaba syndrome develop hamartomas in their intestines, known as hamartomatous polyps. Other noncancerous growths often associated with Bannayan-Riley-Ruvalcaba syndrome include fatty tumors called lipomas and angiolipomas that develop under the skin. Some affected individuals also develop hemangiomas, which are red or purplish growths that consist of tangles of abnormal blood vessels. People with Bannayan-Riley-Ruvalcaba syndrome may also have an increased risk of developing certain cancers, although researchers are still working to determine the cancer risks associated with this condition. Other signs and symptoms that have been reported in people with Bannayan-Riley-Ruvalcaba syndrome include weak muscle tone (hypotonia) and other muscle abnormalities, thyroid problems, and seizures. Skeletal abnormalities have also been described with this condition, including an unusually large range of joint movement (hyperextensibility), abnormal side-to-side curvature of the spine (scoliosis), and a sunken chest (pectus excavatum). The features of Bannayan-Riley-Ruvalcaba syndrome overlap with those of another disorder called Cowden syndrome. People with Cowden syndrome develop hamartomas and other noncancerous growths; they also have an increased risk of developing certain types of cancer. Both conditions can be caused by mutations in the PTEN gene. Some people with Bannayan-Riley-Ruvalcaba syndrome have had relatives diagnosed with Cowden syndrome, and other individuals have had the characteristic features of both conditions. Based on these similarities, researchers have proposed that Bannayan-Riley-Ruvalcaba syndrome and Cowden syndrome represent a spectrum of overlapping features known as PTEN hamartoma tumor syndrome instead of two distinct conditions. PTEN PTEN

MalaCards based summary : Cowden Syndrome 1, also known as pten hamartoma tumor syndrome, is related to juvenile polyposis syndrome and proteus syndrome, and has symptoms including seizures, action tremor and cerebellar ataxia. An important gene associated with Cowden Syndrome 1 is PTEN (Phosphatase And Tensin Homolog), and among its related pathways/superpathways are ERK Signaling and GAB1 signalosome. The drugs Clotrimazole and Miconazole have been mentioned in the context of this disorder. Affiliated tissues include thyroid, breast and skin, and related phenotypes are macroglossia and macrocephaly

Disease Ontology : 12 A syndrome characterized as a spectrum of disorders (Cowden syndrome, Bannayan-Riley-Ruvalcaba syndrome, PTEN-related Proteus syndrome, and Proteus-like syndrome) caused by germline mutations of the PTEN gene.

NIH Rare Diseases : 52 Bannayan-Riley-Ruvalcaba syndrome (BRRS) is a genetic condition that leads to the growth of both non-cancerous and cancerous tumors . Symptoms of BRRS may include large head size, increased birth weight, developmental delay , and intellectual disability . Other symptoms include the appearance of non-cancerous tumors in the digestive system, fatty tumors under the skin, and freckles on the penis. People with BRRS have an increased risk of developing breast, thyroid, and uterine cancer . This condition is part of a group of conditions known as the PTEN hamartoma tumor syndromes, which all share similar features and are caused by genetic changes (DNA variants ) in the PTEN gene . BRRS is inherited in an autosomal dominant pattern. Diagnosis is based on clinical exam, the symptoms, and genetic testing . Treatment is aimed at managing the symptoms and careful monitoring for signs of cancer.

OMIM : 56 Cowden syndrome-1 is a hamartomatous disorder characterized by macrocephaly, facial trichilemmomas, acral keratoses, papillomatous papules, and an increased risk for the development of breast, thyroid, and endometrial carcinoma. Bannayan-Riley-Ruvalcaba syndrome (BRRS), previously thought be distinct, shared clinical characteristics with Cowden syndrome, such as hamartomatous polyps of the gastrointestinal tract, mucocutaneous lesions, and increased risk of developing neoplasms, but had the additional features of developmental delay, macrocephaly, lipomas, hemangiomas, and pigmented speckled macules of the glans penis in males. Because features of BRRS and Cowden syndrome have been found in individuals within the same family with the same PTEN mutation, Cowden syndrome-1 and BRRS are considered to be the same disorder with variable expression and age-related penetrance (summary by Marsh et al., 1999, Lachlan et al., 2007, and Blumenthal and Dennis, 2008). Approximately 80% of patients reported with Cowden syndrome and 60% with BRSS have PTEN mutations (Blumenthal and Dennis, 2008). Some patients with Cowden syndrome may have immune system defects resulting in increased susceptibility to infections (summary by Browning et al., 2015). (158350)

KEGG : 36 PTEN hamartoma tumor syndrome (PHTS) is a spectrum of disorders associated with the formation of hamartomas caused by mutations of the tumor suppressor PTEN. The hamartomas tend to be both benign and malignant tumors, especially in Cowden syndrome.

UniProtKB/Swiss-Prot : 73 Cowden syndrome 1: An autosomal dominant hamartomatous polyposis syndrome with age- related penetrance. Cowden syndrome is characterized by hamartomatous lesions affecting derivatives of ectodermal, mesodermal and endodermal layers, macrocephaly, facial trichilemmomas (benign tumors of the hair follicle infundibulum), acral keratoses, papillomatous papules, and elevated risk for development of several types of malignancy, particularly breast carcinoma in women and thyroid carcinoma in both men and women. Colon cancer and renal cell carcinoma have also been reported. Hamartomas can be found in virtually every organ, but most commonly in the skin, gastrointestinal tract, breast and thyroid.
Lhermitte-Duclos disease: A rare disease characterized by the occurrence of a slowly enlarging mass within the cerebellar cortex corresponding histologically to a cerebellar hamartoma. It manifests, most commonly in the third and fourth decades of life, with increased intracranial pressure, headache, nausea, cerebellar dysfunction, occlusive hydrocephalus, ataxia, visual disturbances and other cranial nerve palsies. Various associated abnormalities may be present such as megalencephaly, microgyria, hydromyelia, polydactyly, partial gigantism, macroglossia. LDD is part of the PTEN hamartoma tumor syndromes spectrum that also includes Cowden syndrome.

Wikipedia : 74 Bannayan-Riley-Ruvalcaba syndrome (BRRS) is a rare overgrowth syndrome and hamartomatous disorder with... more...

GeneReviews: NBK1488

Related Diseases for Cowden Syndrome 1

Diseases in the Cowden Syndrome family:

Cowden Syndrome 1 Cowden Syndrome 4
Cowden Syndrome 5 Cowden Syndrome 6
Cowden Syndrome 7

Diseases related to Cowden Syndrome 1 via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 1132)
# Related Disease Score Top Affiliating Genes
1 juvenile polyposis syndrome 33.0 STK11 SMAD4 PTEN MUTYH LYPD1 BMPR1A
2 proteus syndrome 32.0 TSC2 TSC1 TNS1 PTEN PIK3CA MTOR
3 diabetes mellitus, noninsulin-dependent 31.9 TSC2 TSC1 STK11 SDHB PIK3CA MTOR
4 gastric cancer 31.9 SMAD4 PTEN PIK3CA MUTYH MTOR EGFR
5 juvenile polyposis of infancy 31.7 PTEN BMPR1A
6 congenital heart defects, hamartomas of tongue, and polysyndactyly 31.7 TSC2 TSC1 STK11 PTEN
7 chromosome 10q23 deletion syndrome 31.5 PTEN BMPR1A
8 skin lipoma 31.4 TNS1 RET PTEN LYPD1
9 thyroid tumor 31.2 RET PTEN PIK3CA
10 macrodactyly 31.2 TSC1 PIK3CA
11 lipomatosis 31.1 SDHB PTEN PIK3CA
12 bilateral breast cancer 31.1 SDHB PTEN PIK3CA BRCA2 BRCA1
13 benign ependymoma 31.1 TSC2 TSC1 MTOR EGFR
14 adenoma 30.9 TSC1 SMAD4 RET PIK3CA MUTYH
15 peutz-jeghers syndrome 30.8 TSC2 TSC1 STK11 SMAD4 PTEN EGFR
16 glioma susceptibility 1 30.7 PTEN PIK3CA MTOR EGFR
17 thyroid gland cancer 30.7 SDHB RET PTEN PIK3CA EGFR AKT1
18 carcinosarcoma 30.6 PTEN PIK3CA EGFR
19 tuberous sclerosis 30.6 TSC2 TSC1 STK11 PTEN PIK3CA MTOR
20 hereditary breast ovarian cancer syndrome 30.5 STK11 SMAD4 PTEN MUTYH BRCA2 BRCA1
21 thyroid carcinoma 30.5 RET PTEN PIK3CA KLLN AKT1
22 neurofibromatosis, type ii 30.5 PTEN MTOR EGFR AKT1
23 oropharynx cancer 30.5 PIK3CA EGFR AKT1
24 adenocarcinoma 30.4 STK11 SMAD4 RET PTEN PIK3CA EGFR
25 uterine carcinosarcoma 30.4 PTEN PIK3CA EGFR AKT1
26 cowden syndrome 30.4 USF3 TSC2 TSC1 TNS1 STK11 SMAD4
27 female breast cancer 30.4 EGFR BRCA2 BRCA1
28 squamous cell carcinoma 30.4 STK11 SMAD4 PTEN PIK3CA EGFR AKT1
29 bladder cancer 30.3 TSC1 PTEN PIK3CA EGFR BRCA2 BRCA1
30 mantle cell lymphoma 30.3 PTEN PIK3CA MTOR AKT1
31 breast adenocarcinoma 30.2 PIK3CA MTOR EGFR AKT1
32 melanoma, uveal 30.2 SMAD4 PTEN PIK3CA EGFR BRCA1 AKT1
33 leukemia, acute myeloid 30.2 PTEN PIK3CA MTOR EGFR CDKN3 BRCA2
34 renal cell carcinoma, papillary, 1 30.2 SDHB RET PTEN PIK3CA MTOR KLLN
35 lymphoma, non-hodgkin, familial 30.1 PTEN PIK3CA MTOR CDKN3 AKT1
36 adenoid cystic carcinoma 30.1 PTEN PIK3CA MTOR EGFR BRCA1 AKT1
37 exanthem 30.1 MTOR EGFR AKT1
38 rhabdomyosarcoma 30.1 SMAD4 PTEN MTOR EGFR BRCA1 AKT1
39 nasopharyngeal carcinoma 30.0 SMAD4 PTEN PIK3CA MTOR EGFR AKT1
40 melanoma 30.0 STK11 PTEN PIK3CA MTOR EGFR BRCA2
41 endometrial hyperplasia 30.0 PTEN MTOR CDKN3
42 thymoma 30.0 PIK3CA MTOR EGFR AKT1
43 ovarian disease 29.9 PTEN EGFR BRCA2 BRCA1 AKT1
44 brain cancer 29.9 TSC2 TSC1 PTEN PIK3CA EGFR BRCA2
45 in situ carcinoma 29.9 PTEN PIK3CA EGFR BRCA2 BRCA1 AKT1
46 meningioma, familial 29.9 RET PTEN PIK3CA KLLN EGFR AKT1
47 hemangioma 29.8 TSC2 RET PTEN MTOR AKT1
48 lynch syndrome 29.8 STK11 SMAD4 PTEN PIK3CA MUTYH EGFR
49 cervical cancer 29.8 STK11 SMAD4 PTEN PIK3CA MTOR EGFR
50 suppression of tumorigenicity 12 29.8 SMAD4 PTEN PIK3CA MTOR EGFR BRCA2

Graphical network of the top 20 diseases related to Cowden Syndrome 1:



Diseases related to Cowden Syndrome 1

Symptoms & Phenotypes for Cowden Syndrome 1

Human phenotypes related to Cowden Syndrome 1:

58 31 (show top 50) (show all 165)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 macroglossia 58 31 hallmark (90%) Very frequent (99-80%) HP:0000158
2 macrocephaly 58 31 hallmark (90%) Very frequent (99-80%),Frequent (79-30%),Very frequent (99-80%),Very frequent (99-80%) HP:0000256
3 increased intracranial pressure 58 31 hallmark (90%) Very frequent (99-80%) HP:0002516
4 hydrocephalus 58 31 hallmark (90%) Frequent (79-30%),Very frequent (99-80%) HP:0000238
5 short stature 58 31 hallmark (90%) Very frequent (99-80%) HP:0004322
6 cranial nerve paralysis 58 31 hallmark (90%) Very frequent (99-80%) HP:0006824
7 ataxia 58 31 hallmark (90%) Very frequent (99-80%) HP:0001251
8 papule 58 31 hallmark (90%) Very frequent (99-80%),Frequent (79-30%) HP:0200034
9 arteriovenous malformation 58 31 hallmark (90%) Very frequent (99-80%) HP:0100026
10 nausea and vomiting 58 31 hallmark (90%) Very frequent (99-80%) HP:0002017
11 nevus 58 31 hallmark (90%) Very frequent (99-80%) HP:0003764
12 irregular hyperpigmentation 58 31 hallmark (90%) Very frequent (99-80%),Very frequent (99-80%) HP:0007400
13 hand polydactyly 58 31 hallmark (90%) Very frequent (99-80%) HP:0001161
14 capillary hemangioma 58 31 hallmark (90%) Very frequent (99-80%) HP:0005306
15 headache 58 31 hallmark (90%) Very frequent (99-80%) HP:0002315
16 visceral angiomatosis 58 31 hallmark (90%) Very frequent (99-80%) HP:0100761
17 plantar pits 58 31 hallmark (90%) Very frequent (99-80%) HP:0010612
18 polymicrogyria 58 31 hallmark (90%) Very frequent (99-80%) HP:0002126
19 hamartomatous polyposis 58 31 hallmark (90%) Very frequent (99-80%) HP:0004390
20 lipoma 58 31 hallmark (90%) Very frequent (99-80%),Very frequent (99-80%) HP:0012032
21 papilloma 58 31 hallmark (90%) Very frequent (99-80%) HP:0012740
22 intestinal polyposis 58 31 hallmark (90%) Very frequent (99-80%) HP:0200008
23 abnormal large intestine morphology 58 31 hallmark (90%) Very frequent (99-80%) HP:0002250
24 neoplasm of the breast 58 31 hallmark (90%) Very frequent (99-80%) HP:0100013
25 ganglioneuroma 58 31 hallmark (90%) Very frequent (99-80%) HP:0003005
26 enlarged cerebellum 58 31 hallmark (90%) Very frequent (99-80%) HP:0012081
27 multiple trichilemmomata 58 31 hallmark (90%) Very frequent (99-80%) HP:0012846
28 seizure 31 occasional (7.5%) HP:0001250
29 scoliosis 58 31 frequent (33%) Frequent (79-30%) HP:0002650
30 subcutaneous nodule 58 31 frequent (33%) Frequent (79-30%) HP:0001482
31 pectus excavatum 58 31 frequent (33%) Frequent (79-30%) HP:0000767
32 hemangioma 58 31 frequent (33%) Very frequent (99-80%),Frequent (79-30%) HP:0001028
33 freckling 58 31 frequent (33%) Frequent (79-30%) HP:0001480
34 subcutaneous hemorrhage 58 31 frequent (33%) Frequent (79-30%) HP:0001933
35 breast carcinoma 58 31 frequent (33%) Frequent (79-30%) HP:0003002
36 renal cell carcinoma 58 31 frequent (33%) Frequent (79-30%) HP:0005584
37 endometrial carcinoma 58 31 frequent (33%) Frequent (79-30%) HP:0012114
38 neoplasm of the thyroid gland 58 31 frequent (33%) Frequent (79-30%) HP:0100031
39 ovarian neoplasm 58 31 frequent (33%) Frequent (79-30%) HP:0100615
40 acrokeratosis 58 31 frequent (33%) Frequent (79-30%) HP:0200016
41 autistic behavior 58 31 frequent (33%) Frequent (79-30%) HP:0000729
42 thyroid carcinoma 58 31 occasional (7.5%) Occasional (29-5%),Frequent (79-30%) HP:0002890
43 fibroadenoma of the breast 58 31 frequent (33%) Frequent (79-30%) HP:0010619
44 trichilemmoma 58 31 frequent (33%) Frequent (79-30%) HP:0012844
45 hyperkeratotic papule 58 31 frequent (33%) Frequent (79-30%) HP:0045059
46 intellectual disability 58 31 occasional (7.5%) Occasional (29-5%),Very frequent (99-80%),Occasional (29-5%) HP:0001249
47 delayed skeletal maturation 58 31 occasional (7.5%) Occasional (29-5%) HP:0002750
48 narrow palate 58 31 occasional (7.5%) Occasional (29-5%) HP:0000189
49 macrotia 58 31 occasional (7.5%) Occasional (29-5%) HP:0000400
50 muscular hypotonia 58 31 occasional (7.5%) Occasional (29-5%) HP:0001252

Symptoms via clinical synopsis from OMIM:

56
Head And Neck Eyes:
cataract
myopia
angioid streaks

Endocrine Features:
hypothyroidism
thyroiditis
hyperthyroidism
goiter
thyroid adenoma
more
Abdomen Gastrointestinal:
colonic diverticula
hamartomatous polyps

Neurologic Central Nervous System:
intention tremor
seizure
lhermitte-duclos disease
mental retardation, mild to moderate (in 12%)
psychomotor delay, mild to moderate
more
Head And Neck Head:
progressive macrocephaly

Head And Neck Mouth:
high-arched palate
microstomia
scrotal tongue
oral papillomas

Skin Nails Hair Skin:
subcutaneous lipomas
multiple facial papules
acral keratoses
palmoplantar keratoses
multiple skin tags
more
Head And Neck Face:
'birdlike' facies (uncommon)
hypoplastic mandible (uncommon)
hypoplastic maxilla (uncommon)

Chest Breasts:
virginal hyperplasia
fibrocystic breast disease
gynecomastia in males
breast fibroadenomas

Genitourinary Internal Genitalia Female:
ovarian cysts
leiomyomas

Skeletal Spine:
scoliosis
kyphosis

Chest Ribs Sternum Clavicles And Scapulae:
pectus excavatum

Neoplasia:
meningioma
transitional cell carcinoma of the bladder
ovarian carcinoma
breast cancer
cervical carcinoma
more
Genitourinary External Genitalia Male:
varicocele
hydrocele

Head And Neck Ears:
hearing loss

Immunology:
recurrent infections (in some patients)
primary immunodeficiency (in some patients)
opportunistic infections (in some patients)
hypogammaglobulinemia (in some patients)
lymphopenia (in some patients)
more
Growth Weight:
obesity, increased risk of

Cardiovascular Vascular:
vascular anomalies (50% of patients)
intracranial developmental venous anomalies

Genitourinary External Genitalia Female:
vaginal cysts
vulvar cysts

Clinical features from OMIM:

158350

UMLS symptoms related to Cowden Syndrome 1:


seizures, action tremor, cerebellar ataxia

GenomeRNAi Phenotypes related to Cowden Syndrome 1 according to GeneCards Suite gene sharing:

26 (show all 45)
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased viability GR00055-A-1 10.8 PIK3CA EGFR MTOR
2 Decreased viability GR00055-A-2 10.8 PIK3CA EGFR MTOR
3 Decreased viability GR00221-A-1 10.8 AKT1 BMPR1A PIK3CA RET EGFR MTOR
4 Decreased viability GR00221-A-2 10.8 AKT1 BMPR1A BRCA1 PIK3CA RET TSC1
5 Decreased viability GR00221-A-3 10.8 AKT1 BMPR1A BRCA1 TSC1
6 Decreased viability GR00221-A-4 10.8 AKT1 BMPR1A PIK3CA RET EGFR MTOR
7 Decreased viability GR00249-S 10.8 AKT1 BMPR1A
8 Decreased viability GR00301-A 10.8 BRCA1 RET TSC1
9 Decreased viability GR00342-S-1 10.8 MTOR
10 Decreased viability GR00342-S-2 10.8 MTOR
11 Decreased viability GR00402-S-2 10.8 PIK3CA RET
12 Decreased shRNA abundance (Z-score < -2) GR00366-A-11 10.49 MTOR
13 Decreased shRNA abundance (Z-score < -2) GR00366-A-116 10.49 PIK3CA
14 Decreased shRNA abundance (Z-score < -2) GR00366-A-117 10.49 TSC1
15 Decreased shRNA abundance (Z-score < -2) GR00366-A-152 10.49 PTEN
16 Decreased shRNA abundance (Z-score < -2) GR00366-A-157 10.49 PIK3CA
17 Decreased shRNA abundance (Z-score < -2) GR00366-A-16 10.49 AKT1 MTOR PIK3CA
18 Decreased shRNA abundance (Z-score < -2) GR00366-A-166 10.49 PIK3CA
19 Decreased shRNA abundance (Z-score < -2) GR00366-A-173 10.49 MTOR
20 Decreased shRNA abundance (Z-score < -2) GR00366-A-177 10.49 AKT1 PIK3CA
21 Decreased shRNA abundance (Z-score < -2) GR00366-A-190 10.49 PIK3CA
22 Decreased shRNA abundance (Z-score < -2) GR00366-A-203 10.49 TSC1
23 Decreased shRNA abundance (Z-score < -2) GR00366-A-206 10.49 TSC1
24 Decreased shRNA abundance (Z-score < -2) GR00366-A-21 10.49 SMAD4
25 Decreased shRNA abundance (Z-score < -2) GR00366-A-216 10.49 PIK3CA
26 Decreased shRNA abundance (Z-score < -2) GR00366-A-33 10.49 TSC1
27 Decreased shRNA abundance (Z-score < -2) GR00366-A-42 10.49 AKT1 MTOR PIK3CA SMAD4
28 Decreased shRNA abundance (Z-score < -2) GR00366-A-46 10.49 SMAD4
29 Decreased shRNA abundance (Z-score < -2) GR00366-A-49 10.49 PIK3CA
30 Decreased shRNA abundance (Z-score < -2) GR00366-A-50 10.49 AKT1
31 Decreased shRNA abundance (Z-score < -2) GR00366-A-53 10.49 MTOR PIK3CA
32 Decreased shRNA abundance (Z-score < -2) GR00366-A-54 10.49 SMAD4
33 Decreased shRNA abundance (Z-score < -2) GR00366-A-73 10.49 MTOR SMAD4
34 Decreased shRNA abundance (Z-score < -2) GR00366-A-74 10.49 SMAD4
35 Decreased shRNA abundance (Z-score < -2) GR00366-A-79 10.49 AKT1
36 Decreased shRNA abundance (Z-score < -2) GR00366-A-81 10.49 SMAD4
37 Decreased shRNA abundance (Z-score < -2) GR00366-A-82 10.49 TSC1
38 Decreased cell migration GR00055-A-1 9.88 AKT1 TNS1 TSC1
39 Decreased cell migration GR00055-A-3 9.88 EGFR MTOR PIK3CA
40 Decreased viability with paclitaxel GR00179-A-1 9.35 EGFR MTOR
41 Decreased viability with paclitaxel GR00179-A-2 9.35 MTOR
42 Decreased viability with paclitaxel GR00179-A-3 9.35 EGFR MTOR
43 Decreased cell viability after pRB stimulation GR00230-A-1 9.07 BMPR1A
44 Decreased sensitivity to paclitaxel GR00112-A-0 9.02 PTEN
45 Upregulation of Wnt/beta-catenin pathway after WNT3A stimulation GR00016-A 9.02 BRCA1 BRCA2 SMAD4 TSC1 TSC2

MGI Mouse Phenotypes related to Cowden Syndrome 1:

45 (show all 22)
# Description MGI Source Accession Score Top Affiliating Genes
1 behavior/neurological MP:0005386 10.48 AKT1 BMPR1A BRCA1 BRCA2 CDKN3 LYPD1
2 cellular MP:0005384 10.47 AKT1 BMPR1A BRCA1 BRCA2 EGFR MTOR
3 cardiovascular system MP:0005385 10.41 AKT1 BMPR1A BRCA1 EGFR MTOR PIK3CA
4 endocrine/exocrine gland MP:0005379 10.41 AKT1 BMPR1A BRCA1 BRCA2 EGFR MTOR
5 homeostasis/metabolism MP:0005376 10.41 AKT1 BMPR1A BRCA1 BRCA2 EGFR MTOR
6 embryo MP:0005380 10.39 AKT1 BMPR1A BRCA1 BRCA2 EGFR MTOR
7 mortality/aging MP:0010768 10.38 AKT1 BMPR1A BRCA1 BRCA2 EGFR MTOR
8 growth/size/body region MP:0005378 10.37 AKT1 BMPR1A BRCA1 BRCA2 EGFR MTOR
9 hematopoietic system MP:0005397 10.33 AKT1 BMPR1A BRCA1 BRCA2 EGFR MTOR
10 immune system MP:0005387 10.3 AKT1 BMPR1A BRCA1 BRCA2 EGFR MTOR
11 neoplasm MP:0002006 10.28 AKT1 BMPR1A BRCA1 BRCA2 EGFR MUTYH
12 nervous system MP:0003631 10.28 AKT1 BMPR1A BRCA1 BRCA2 EGFR LYPD1
13 integument MP:0010771 10.25 AKT1 BMPR1A BRCA1 BRCA2 EGFR PIK3CA
14 muscle MP:0005369 10.2 AKT1 BMPR1A BRCA1 EGFR MTOR PIK3CA
15 digestive/alimentary MP:0005381 10.19 BMPR1A BRCA1 BRCA2 EGFR PTEN RET
16 normal MP:0002873 10.1 AKT1 BMPR1A BRCA1 BRCA2 EGFR MTOR
17 limbs/digits/tail MP:0005371 10.04 BMPR1A BRCA1 BRCA2 EGFR PTEN RET
18 renal/urinary system MP:0005367 10 BRCA1 EGFR MTOR PTEN RET SDHB
19 reproductive system MP:0005389 9.97 AKT1 BMPR1A BRCA1 BRCA2 EGFR PIK3CA
20 no phenotypic analysis MP:0003012 9.91 EGFR LYPD1 MTOR PIK3CA RET SDHB
21 respiratory system MP:0005388 9.61 AKT1 BMPR1A BRCA1 EGFR MTOR PTEN
22 skeleton MP:0005390 9.32 AKT1 BMPR1A BRCA1 BRCA2 EGFR MTOR

Drugs & Therapeutics for Cowden Syndrome 1

Drugs for Cowden Syndrome 1 (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 15)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Clotrimazole Approved, Vet_approved Phase 2 23593-75-1 2812
2
Miconazole Approved, Investigational, Vet_approved Phase 2 22916-47-8 4189
3
Sirolimus Approved, Investigational Phase 2 53123-88-9 5284616 6436030 46835353
4 Fluorodeoxyglucose F18 Phase 2
5 Radiopharmaceuticals Phase 2
6 Anti-Infective Agents Phase 2
7 Anti-Bacterial Agents Phase 2
8 Antifungal Agents Phase 2
9 Cola Phase 2
10 Antibiotics, Antitubercular Phase 2
11
Trastuzumab Approved, Investigational Phase 1 180288-69-1 9903
12 Dactolisib Investigational Phase 1 915019-65-7
13 Vaccines
14 Chelating Agents Early Phase 1
15 Gadolinium 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetate Early Phase 1

Interventional clinical trials:

(show all 16)
# Name Status NCT ID Phase Drugs
1 A Pilot Study of Sirolimus (Rapamycin, Rapamune[Registered Trademark]) in Subjects With Cowden Syndrome or Other Syndromes Characterized by Germline Mutations in PTEN Completed NCT00971789 Phase 2 sirolimus
2 A Phase I/II, Multi-center, Open-label Study of BGT226, Administered Orally in Adult Patients With Advanced Solid Malignancies Including Patients With Advanced Breast Cancer Completed NCT00600275 Phase 1, Phase 2 BGT226
3 Sirolimus for Cowden Syndrome With Colon Polyposis Recruiting NCT04094675 Phase 2 Sirolimus
4 A Randomized Double-Blind Controlled Trial of Everolimus in Individuals With PTEN Mutations (RAD001XUS257T) Active, not recruiting NCT02991807 Phase 1, Phase 2 RAD001;Placebo
5 Open Label Phase II Study of Everolimus (RAD001) in Patients With Segmental Overgrowth Syndrome Withdrawn NCT02569125 Phase 2 Everolimus
6 A Phase I/II, Multi-center, Open-label Study of BEZ235, Administered Orally on a Continuous Daily Dosing Schedule in Adult Patients With Advanced Solid Malignancies Including Patients With Advanced Breast Cancer Completed NCT00620594 Phase 1 BEZ235
7 Eculizumab in HELLP Syndrome Not yet recruiting NCT04103489 Phase 1 Eculizumab
8 Access to Resources for Patients With PTEN Hamartoma Tumor Syndrome Completed NCT03680924
9 Natural History Study of Individuals With Autism and Germline Heterozygous PTEN Mutations Recruiting NCT02461446
10 French Digestive Polyposis Cohorte Recruiting NCT01987518
11 Liquid Biopsy Evaluation and Repository Development at Princess Margaret Recruiting NCT03702309
12 Familial Investigations of Childhood Cancer Predisposition Recruiting NCT03050268
13 Evaluating Cardiorespiratory Development in Premature Babies Recruiting NCT03655639
14 Registering the Immune Response to a Flu Vaccination Challenge in PTEN Hamartoma Tumour Syndrome Not yet recruiting NCT03630523
15 Abbreviated MRI Protocol: Initial Experience With Dotarem® (Gadoterate Meglumine) Not yet recruiting NCT04341129 Early Phase 1 Abbreviated MRI protocol: initial experience with Dotarem® (Gadoterate Meglumine)
16 Network-based Epigenome-Wide associaTion Study in Obesity precisioN Medicine: NEWTON Clinical Trial Not yet recruiting NCT03903757

Search NIH Clinical Center for Cowden Syndrome 1

Cochrane evidence based reviews: hamartoma syndrome, multiple

Genetic Tests for Cowden Syndrome 1

Genetic tests related to Cowden Syndrome 1:

# Genetic test Affiliating Genes
1 Pten Hamartoma Tumor Syndrome 29 PTEN
2 Cowden Syndrome 1 29 PTEN
3 Bannayan-Riley-Ruvalcaba Syndrome 29
4 Pten Hamartoma Tumor Syndrome with Granular Cell Tumor 29
5 Lhermitte-Duclos Disease 29
6 Lhermitte-Duclos Syndrome 29

Anatomical Context for Cowden Syndrome 1

MalaCards organs/tissues related to Cowden Syndrome 1:

40
Thyroid, Breast, Skin, Colon, Cerebellum, Testes, Cortex

Publications for Cowden Syndrome 1

Articles related to Cowden Syndrome 1:

(show top 50) (show all 381)
# Title Authors PMID Year
1
Male breast cancer in Cowden syndrome patients with germline PTEN mutations. 54 56 6 24
11238682 2001
2
Germline mutations and variants in the succinate dehydrogenase genes in Cowden and Cowden-like syndromes. 6 24 56
18678321 2008
3
Segmental overgrowth, lipomatosis, arteriovenous malformation and epidermal nevus (SOLAMEN) syndrome is related to mosaic PTEN nullizygosity. 56 24 6
17392703 2007
4
Germline mutation of the tumour suppressor PTEN in Proteus syndrome. 56 6 24
12471211 2002
5
Germline and germline mosaic PTEN mutations associated with a Proteus-like syndrome of hemihypertrophy, lower limb asymmetry, arteriovenous malformations and lipomatosis. 24 56 6
10749983 2000
6
Localization of the gene for Cowden disease to chromosome 10q22-23. 24 6 56
8673088 1996
7
Protean PTEN: form and function. 56 6 61
11875759 2002
8
Phenotypic findings of Cowden syndrome and Bannayan-Zonana syndrome in a family associated with a single germline mutation in PTEN. 54 56 6
10353779 1999
9
Variant manifestation of Cowden disease in Japan: hamartomatous polyposis of the digestive tract with mutation of the PTEN gene. 54 56 6
9915974 1999
10
Mutations of PTEN in patients with Bannayan-Riley-Ruvalcaba phenotype. 54 56 6
9832032 1998
11
Germline mutations in PTEN are present in Bannayan-Zonana syndrome. 56 6 54
9241266 1997
12
Germline mutations in the PTEN/MMAC1 gene in patients with Cowden disease. 54 56 6
9259288 1997
13
Germline mutations of the PTEN gene in Cowden disease, an inherited breast and thyroid cancer syndrome. 54 6 56
9140396 1997
14
A clinical scoring system for selection of patients for PTEN mutation testing is proposed on the basis of a prospective study of 3042 probands. 56 24 61
21194675 2011
15
Epidermal naevus in Proteus syndrome showing loss of heterozygosity for an inherited PTEN mutation. 24 56 54
16704655 2006
16
Proteus syndrome: misdiagnosis with PTEN mutations. 56 6
14518070 2003
17
Novel PTEN mutations in patients with Cowden disease: absence of clear genotype-phenotype correlations. 24 56 54
10234502 1999
18
Germline PTEN mutations in Cowden syndrome-like families. 56 6
9832031 1998
19
Mutation spectrum and genotype-phenotype analyses in Cowden disease and Bannayan-Zonana syndrome, two hamartoma syndromes with germline PTEN mutation. 24 6 54
9467011 1998
20
PTEN germ-line mutations in juvenile polyposis coli. 56 6
9425889 1998
21
Germline PIK3CA and AKT1 mutations in Cowden and Cowden-like syndromes. 56 24
23246288 2013
22
Increasing knowledge of PTEN germline mutations: Two additional patients with autism and macrocephaly. 24 6
17286265 2007
23
Distinct expression profiles for PTEN transcript and its splice variants in Cowden syndrome and Bannayan-Riley-Ruvalcaba syndrome. 56 61 54
16773562 2006
24
PTEN: one gene, many syndromes. 6 24
12938083 2003
25
Germline PTEN promoter mutations and deletions in Cowden/Bannayan-Riley-Ruvalcaba syndrome result in aberrant PTEN protein and dysregulation of the phosphoinositol-3-kinase/Akt pathway. 24 6
12844284 2003
26
Association of germline mutation in the PTEN tumour suppressor gene and Proteus and Proteus-like syndromes. 24 56
11476841 2001
27
PTEN coordinates G(1) arrest by down-regulating cyclin D1 via its protein phosphatase activity and up-regulating p27 via its lipid phosphatase activity in a breast cancer model. 6 24
11230179 2001
28
PTEN mutation spectrum and genotype-phenotype correlations in Bannayan-Riley-Ruvalcaba syndrome suggest a single entity with Cowden syndrome. 24 56
10400993 1999
29
Bannayan-Riley-Ruvalcaba syndrome. 24 56
1336932 1992
30
Genetic/familial high-risk assessment: breast and ovarian, version 1.2014. 61 6
25190698 2014
31
Estimate of de novo mutation frequency in probands with PTEN hamartoma tumor syndrome. 61 56
22595938 2012
32
Cowden syndrome-affected patients with PTEN promoter mutations demonstrate abnormal protein translation. 54 6
17847000 2007
33
Cowden syndrome and Bannayan Riley Ruvalcaba syndrome represent one condition with variable expression and age-related penetrance: results of a clinical study of PTEN mutation carriers. 56 54
17526800 2007
34
The spectrum of vascular anomalies in patients with PTEN mutations: implications for diagnosis and management. 54 56
17526801 2007
35
Differential expression of novel naturally occurring splice variants of PTEN and their functional consequences in Cowden syndrome and sporadic breast cancer. 56 54
16436456 2006
36
PTEN Hamartoma Tumor Syndrome 61 6
20301661 2001
37
Regulation of G1 progression by the PTEN tumor suppressor protein is linked to inhibition of the phosphatidylinositol 3-kinase/Akt pathway. 54 6
10051603 1999
38
Severe Lhermitte-Duclos disease with unique germline mutation of PTEN. 6 54
10051160 1999
39
Germline PTEN mutation in a family with Cowden syndrome and Bannayan-Riley-Ruvalcaba syndrome. 54 6
9856571 1998
40
Absence of PTEN/MMAC1 germ-line mutations in sporadic Bannayan-Riley-Ruvalcaba syndrome. 54 56
9661881 1998
41
Deletion 10q23.2-q23.33 in a patient with gastrointestinal juvenile polyposis and other features of a Cowden-like syndrome. 54 56
9491322 1998
42
Inherited mutations in PTEN that are associated with breast cancer, cowden disease, and juvenile polyposis. 56 54
9399897 1997
43
Deletion of PTEN in a patient with Bannayan-Riley-Ruvalcaba syndrome suggests allelism with Cowden disease. 54 56
9286463 1997
44
PTEN Hamartoma Tumor Syndrome: A Clinical Overview. 52 61
31216739 2019
45
Recommendations for reporting of secondary findings in clinical exome and genome sequencing, 2016 update (ACMG SF v2.0): a policy statement of the American College of Medical Genetics and Genomics. 6
27854360 2017
46
Phosphatase and tensin homolog (PTEN) mutation can cause activated phosphatidylinositol 3-kinase δ syndrome-like immunodeficiency. 6
27426521 2016
47
Increased PI3K/Akt activity and deregulated humoral immune response in human PTEN deficiency. 56
27531073 2016
48
Cowden's syndrome with immunodeficiency. 56
26246517 2015
49
ACG clinical guideline: Genetic testing and management of hereditary gastrointestinal cancer syndromes. 6
25645574 2015
50
A practice guideline from the American College of Medical Genetics and Genomics and the National Society of Genetic Counselors: referral indications for cancer predisposition assessment. 6
25394175 2015

Variations for Cowden Syndrome 1

ClinVar genetic disease variations for Cowden Syndrome 1:

6 (show top 50) (show all 891) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 PTEN NM_000314.7(PTEN):c.445C>T (p.Gln149Ter)SNV Pathogenic 404164 rs1060500122 10:89692961-89692961 10:87933204-87933204
2 PTEN NC_000010.11:g.(?_87894025)_(87894109_?)deldeletion Pathogenic 417326 10:89653782-89653866 10:87894025-87894109
3 PTEN NM_001304718.2(PTEN):c.-541-5498dupduplication Pathogenic 404145 rs1060500113 10:89685304-89685305 10:87925547-87925548
4 PTEN NM_000314.7(PTEN):c.945T>G (p.Tyr315Ter)SNV Pathogenic 404157 rs876661058 10:89720794-89720794 10:87961037-87961037
5 PTEN NM_000314.7(PTEN):c.723dup (p.Glu242Ter)duplication Pathogenic 404149 rs1060500115 10:89717695-89717696 10:87957938-87957939
6 PTEN NM_000314.8(PTEN):c.801+1deldeletion Pathogenic 404140 rs1060500110 10:89717776-89717776 10:87958019-87958019
7 PTEN NM_000314.7(PTEN):c.176C>G (p.Ser59Ter)SNV Pathogenic 404151 rs1060500116 10:89685281-89685281 10:87925524-87925524
8 PTEN NM_001304718.2(PTEN):c.-405_-393dupduplication Pathogenic 404150 rs1064792910 10:89692861-89692862 10:87933104-87933105
9 PTEN NM_000314.7(PTEN):c.675T>G (p.Tyr225Ter)SNV Pathogenic 404162 rs1057520900 10:89717650-89717650 10:87957893-87957893
10 PTEN NM_000314.7(PTEN):c.744_745TG[3] (p.Cys250fs)short repeat Pathogenic 404156 rs780264945 10:89717719-89717720 10:87957962-87957963
11 PTEN NM_000314.8(PTEN):c.464A>G (p.Tyr155Cys)SNV Pathogenic 404168 rs1060500126 10:89692980-89692980 10:87933223-87933223
12 PTEN NM_000314.7(PTEN):c.629del (p.Thr210fs)deletion Pathogenic 404148 rs1060500114 10:89712011-89712011 10:87952254-87952254
13 PTEN NM_000314.7(PTEN):c.875del (p.Asn292fs)deletion Pathogenic 419505 rs786204905 10:89720721-89720721 10:87960964-87960964
14 PTEN NM_000314.7(PTEN):c.35A>C (p.Asn12Thr)SNV Pathogenic 427586 rs1085308044 10:89624261-89624261 10:87864504-87864504
15 PTEN NM_000314.7(PTEN):c.40A>G (p.Arg14Gly)SNV Pathogenic 427589 rs1085308047 10:89624266-89624266 10:87864509-87864509
16 PTEN NM_000314.7(PTEN):c.131G>A (p.Gly44Asp)SNV Pathogenic 427582 rs1085308042 10:89653833-89653833 10:87894076-87894076
17 PTEN NM_000314.7(PTEN):c.164+1G>CSNV Pathogenic 427583 rs1554893835 10:89653867-89653867 10:87894110-87894110
18 PTEN NM_000314.7(PTEN):c.165-2A>GSNV Pathogenic 427584 rs1085308043 10:89685268-89685268 10:87925511-87925511
19 PTEN NM_000314.7(PTEN):c.253+1G>CSNV Pathogenic 427585 rs587776667 10:89690847-89690847 10:87931090-87931090
20 PTEN NM_000314.7(PTEN):c.316G>T (p.Glu106Ter)SNV Pathogenic 427579 rs1085308039 10:89692832-89692832 10:87933075-87933075
21 PTEN NM_000314.7(PTEN):c.369C>G (p.His123Gln)SNV Pathogenic 427587 rs1085308045 10:89692885-89692885 10:87933128-87933128
22 PTEN NM_000314.7(PTEN):c.401T>C (p.Met134Thr)SNV Pathogenic 427588 rs1085308046 10:89692917-89692917 10:87933160-87933160
23 PTEN NM_000314.7(PTEN):c.416T>G (p.Leu139Ter)SNV Pathogenic 427590 rs1085308048 10:89692932-89692932 10:87933175-87933175
24 PTEN NM_001304718.2(PTEN):c.-331dupduplication Pathogenic 427592 rs1085308050 10:89692935-89692936 10:87933178-87933179
25 PTEN NM_000314.7(PTEN):c.520dup (p.Tyr174fs)duplication Pathogenic 427594 rs1085308052 10:89711901-89711902 10:87952144-87952145
26 PTEN NM_000314.7(PTEN):c.605C>T (p.Thr202Ile)SNV Pathogenic 427595 rs1085308053 10:89711987-89711987 10:87952230-87952230
27 PTEN NM_000314.7(PTEN):c.607_608del (p.Ile203fs)deletion Pathogenic 427596 rs1085308054 10:89711988-89711989 10:87952231-87952232
28 PTEN NM_000314.7(PTEN):c.617_621del (p.Phe206fs)deletion Pathogenic 427597 rs1085308055 10:89711997-89712001 10:87952240-87952244
29 PTEN NM_000314.7(PTEN):c.635-1G>ASNV Pathogenic 427598 rs876661024 10:89717609-89717609 10:87957852-87957852
30 PTEN NM_000314.7(PTEN):c.667A>T (p.Lys223Ter)SNV Pathogenic 427591 rs1085308049 10:89717642-89717642 10:87957885-87957885
31 PTEN NM_000314.7(PTEN):c.821G>T (p.Trp274Leu)SNV Pathogenic 427600 rs786204875 10:89720670-89720670 10:87960913-87960913
32 PTEN NM_000314.7(PTEN):c.1004G>A (p.Arg335Gln)SNV Pathogenic 427580 rs1085308040 10:89720853-89720853 10:87961096-87961096
33 PTEN NM_000314.7(PTEN):c.1027-2A>GSNV Pathogenic 427581 rs1085308041 10:89725042-89725042 10:87965285-87965285
34 PTEN duplication Pathogenic 427601 10:89589557-89642550
35 PTEN NM_000314.7(PTEN):c.165-1G>CSNV Pathogenic 427613 rs786203847 10:89685269-89685269 10:87925512-87925512
36 PTEN NM_000314.7(PTEN):c.209+5G>ASNV Pathogenic 427614 rs1114167650 10:89685319-89685319 10:87925562-87925562
37 PTEN NM_000314.8(PTEN):c.210-2_211deldeletion Pathogenic 427615 rs1554897854 10:89690799-89690802 10:87931042-87931045
38 PTEN NM_000314.7(PTEN):c.210-1G>ASNV Pathogenic 427616 rs1114167621 10:89690802-89690802 10:87931045-87931045
39 PTEN NM_000314.7(PTEN):c.253+5G>TSNV Pathogenic 427617 rs1554897889 10:89690851-89690851 10:87931094-87931094
40 PTEN NM_000314.7(PTEN):c.634+1G>CSNV Pathogenic 427620 rs1114167622 10:89712017-89712017 10:87952260-87952260
41 PTEN NM_000314.7(PTEN):c.634+2T>CSNV Pathogenic 427621 rs727504114 10:89712018-89712018 10:87952261-87952261
42 PTEN NM_000314.7(PTEN):c.634+4A>TSNV Pathogenic 427622 rs1554900675 10:89712020-89712020 10:87952263-87952263
43 PTEN NM_000314.7(PTEN):c.1027-2A>CSNV Pathogenic 427624 rs1085308041 10:89725042-89725042 10:87965285-87965285
44 PTEN NM_000314.7(PTEN):c.367C>G (p.His123Asp)SNV Pathogenic 428277 rs786204931 10:89692883-89692883 10:87933126-87933126
45 PTEN NM_000314.7(PTEN):c.493G>A (p.Gly165Arg)SNV Pathogenic 428256 rs587782603 10:89711875-89711875 10:87952118-87952118
46 PTEN NM_001304718.2(PTEN):c.-80dupduplication Pathogenic 428206 rs1114167632 10:89711893-89711894 10:87952136-87952137
47 PTEN NM_000314.7(PTEN):c.545T>G (p.Leu182Ter)SNV Pathogenic 428241 rs794729664 10:89711927-89711927 10:87952170-87952170
48 PTEN NM_000314.7(PTEN):c.328C>T (p.Gln110Ter)SNV Pathogenic 428203 rs1114167629 10:89692844-89692844 10:87933087-87933087
49 PTEN NM_000314.7(PTEN):c.959del (p.Thr319_Leu320insTer)deletion Pathogenic 428276 rs1114167682 10:89720806-89720806 10:87961049-87961049
50 PTEN NM_000314.7(PTEN):c.1016del (p.Pro339fs)deletion Pathogenic 436443 rs1554825643 10:89720864-89720864 10:87961107-87961107

UniProtKB/Swiss-Prot genetic disease variations for Cowden Syndrome 1:

73 (show all 31)
# Symbol AA change Variation ID SNP ID
1 PTEN p.Ile67Arg VAR_007461
2 PTEN p.Tyr68His VAR_007462 rs398123317
3 PTEN p.His123Arg VAR_007463 rs121909222
4 PTEN p.Cys124Arg VAR_007464 rs121909223
5 PTEN p.Gly129Glu VAR_007465 rs121909218
6 PTEN p.Arg130Leu VAR_007467 rs121909229
7 PTEN p.Arg130Gln VAR_007468 rs121909229
8 PTEN p.Ser170Arg VAR_007470 rs121909221
9 PTEN p.Leu112Pro VAR_007807 rs121909230
10 PTEN p.Cys136Tyr VAR_007808 rs786204859
11 PTEN p.Met35Arg VAR_008036 rs121909225
12 PTEN p.Ala34Asp VAR_008734
13 PTEN p.Cys105Tyr VAR_008735 rs587782343
14 PTEN p.Ile135Val VAR_008736 rs587782360
15 PTEN p.Gly165Val VAR_008738 rs786204863
16 PTEN p.Gly165Glu VAR_008739
17 PTEN p.Pro246Leu VAR_008740 rs587782350
18 PTEN p.Lys289Glu VAR_008741 rs562015640
19 PTEN p.Val343Glu VAR_008742
20 PTEN p.Phe347Leu VAR_008743
21 PTEN p.Arg47Gly VAR_011587 rs786204855
22 PTEN p.Leu70Pro VAR_018102 rs121909226
23 PTEN p.Cys124Ser VAR_018104
24 PTEN p.Cys71Tyr VAR_026254
25 PTEN p.His93Tyr VAR_026255
26 PTEN p.Cys105Phe VAR_026256
27 PTEN p.Asp107Tyr VAR_026257
28 PTEN p.Tyr155Cys VAR_026263 rs106050012
29 PTEN p.Asp331Gly VAR_026275
30 PTEN p.Phe341Val VAR_026276 rs155482565
31 PTEN p.Lys342Asn VAR_026277 rs398123314

Cosmic variations for Cowden Syndrome 1:

9 (show top 50) (show all 273)
# Cosmic Mut ID Gene Symbol COSMIC Disease Classification
(Primary site, Site subtype, Primary histology, Histology subtype)
Mutation CDS Mutation AA GRCh38 Location Conf
1 COSM88644633 TP63 skin,penis,carcinoma,NS c.1922C>T p.A641V 3:189894381-189894381 9
2 COSM87910495 TP53 skin,chest,carcinoma,NS c.832C>T p.P278S 17:7673788-7673788 9
3 COSM87906968 TP53 skin,chest,carcinoma,NS c.833C>T p.P278L 17:7673787-7673787 9
4 COSM87899377 TP53 skin,chest,carcinoma,NS c.375+1G>A p.? 17:7675993-7675993 9
5 COSM87906137 TP53 skin,chest,carcinoma,NS c.260C>A p.P87Q 17:7676109-7676109 9
6 COSM87898458 TP53 skin,chest,carcinoma,NS c.853G>A p.E285K 17:7673767-7673767 9
7 COSM87898709 TP53 skin,chest,carcinoma,NS c.742C>T p.R248W 17:7674221-7674221 9
8 COSM87901765 TP53 skin,chest,carcinoma,NS c.734G>A p.G245D 17:7674229-7674229 9
9 COSM87900604 TP53 skin,chest,carcinoma,NS c.637C>T p.R213* 17:7674894-7674894 9
10 COSM87897745 TP53 skin,penis,carcinoma,NS c.524G>A p.R175H 17:7675088-7675088 9
11 COSM87898578 TP53 skin,chest,carcinoma,NS c.733G>A p.G245S 17:7674230-7674230 9
12 COSM90836184 PTCH1 skin,chest,carcinoma,NS c.707G>A p.W236* 9:95481988-95481988 9
13 COSM90830850 PTCH1 skin,chest,carcinoma,NS c.1249C>T p.Q417* 9:95478153-95478153 9
14 COSM90854275 PTCH1 skin,chest,carcinoma,NS c.3487G>A p.G1163S 9:95449903-95449903 9
15 COSM90855041 PTCH1 skin,chest,carcinoma,NS c.1292T>A p.L431Q 9:95478110-95478110 9
16 COSM90827053 PTCH1 skin,chest,carcinoma,NS c.2062C>T p.Q688* 9:95468939-95468939 9
17 COSM90826920 PTCH1 skin,chest,carcinoma,NS c.2042C>T p.P681L 9:95468959-95468959 9
18 COSM87133066 PIK3CA skin,penis,carcinoma,NS c.317G>T p.G106V 3:179199142-179199142 9
19 COSM97107379 NRAS skin,chest,carcinoma,NS c.35G>A p.G12D 1:114716126-114716126 9
20 COSM97133186 NRAS skin,chest,carcinoma,NS c.70A>T p.I24F 1:114716091-114716091 9
21 COSM97132910 NRAS skin,chest,carcinoma,NS c.295C>T p.Q99* 1:114709724-114709724 9
22 COSM88406249 NOTCH2 skin,chest,carcinoma,NS c.500C>T p.S167F 1:119997248-119997248 9
23 COSM88401219 NOTCH2 skin,chest,carcinoma,NS c.5104C>T p.R1702* 1:119922345-119922345 9
24 COSM88406240 NOTCH2 skin,chest,carcinoma,NS c.3194A>G p.N1065S 1:119938000-119938000 9
25 COSM88395159 NOTCH2 skin,chest,carcinoma,NS c.3008T>C p.V1003A 1:119940730-119940730 9
26 COSM88406243 NOTCH2 skin,chest,carcinoma,NS c.995G>T p.G332V 1:119969624-119969624 9
27 COSM88398088 NOTCH2 skin,chest,carcinoma,NS c.6761T>C p.M2254T 1:119915961-119915961 9
28 COSM88388711 NOTCH2 skin,chest,carcinoma,NS c.337C>T p.R113* 1:120005407-120005407 9
29 COSM87662462 NOTCH1 skin,chest,carcinoma,NS c.1753G>A p.A585T 9:136515633-136515633 9
30 COSM87652841 NOTCH1 skin,chest,carcinoma,NS c.3556G>A p.E1186K 9:136507392-136507392 9
31 COSM87657852 NOTCH1 skin,chest,carcinoma,NS c.4093T>C p.S1365P 9:136505803-136505803 9
32 COSM87665486 NOTCH1 skin,chest,carcinoma,NS c.4070G>A p.C1357Y 9:136505826-136505826 9
33 COSM87692105 NOTCH1 skin,chest,carcinoma,NS c.3709A>G p.K1237E 9:136506908-136506908 9
34 COSM87641820 NOTCH1 skin,chest,carcinoma,NS c.5026G>A p.V1676I 9:136503323-136503323 9
35 COSM87657831 NOTCH1 skin,chest,carcinoma,NS c.6832G>A p.V2278M 9:136496907-136496907 9
36 COSM87692708 NOTCH1 skin,chest,carcinoma,NS c.4772A>G p.H1591R 9:136504919-136504919 9
37 COSM87692661 NOTCH1 skin,chest,carcinoma,NS c.6808C>T p.P2270S 9:136496931-136496931 9
38 COSM87657872 NOTCH1 skin,chest,carcinoma,NS c.3716T>C p.F1239S 9:136506901-136506901 9
39 COSM87643994 NOTCH1 skin,chest,carcinoma,NS c.1348G>A p.E450K 9:136517845-136517845 9
40 COSM87665732 NOTCH1 skin,chest,carcinoma,NS c.5526G>T p.Q1842H 9:136501860-136501860 9
41 COSM87692671 NOTCH1 skin,chest,carcinoma,NS c.6634G>A p.D2212N 9:136497105-136497105 9
42 COSM89197987 MYCN skin,penis,carcinoma,NS c.131C>T p.P44L 2:15942195-15942195 9
43 COSM87995251 KRAS skin,chest,carcinoma,NS c.544A>G p.K182E 12:25215467-25215467 9
44 COSM112990966 HRAS skin,chest,carcinoma,NS c.10T>C p.Y4H 11:534313-534313 9
45 COSM112992405 HRAS skin,chest,carcinoma,NS c.95A>G p.Y32C 11:534228-534228 9
46 COSM112989160 HRAS skin,chest,carcinoma,NS c.38G>T p.G13V 11:534285-534285 9
47 COSM112988917 HRAS skin,chest,carcinoma,NS c.35G>T p.G12V 11:534288-534288 9
48 COSM103913221 DOT1L skin,penis,carcinoma,NS c.4292C>T p.A1431V 19:2226813-2226813 9
49 COSM119230289 CDKN2A skin,chest,carcinoma,NS c.242C>T p.P81L 9:21971117-21971117 9
50 COSM119230203 CDKN2A skin,chest,carcinoma,NS c.148C>T p.Q50* 9:21974680-21974680 9

Copy number variations for Cowden Syndrome 1 from CNVD:

7
# CNVD ID Chromosome Start End Type Gene Symbol CNVD Disease
1 47170 10 89675267 89701622 Deletion PTEN Bannayan-Riley-Ruvalcaba syndrome

Expression for Cowden Syndrome 1

Search GEO for disease gene expression data for Cowden Syndrome 1.

Pathways for Cowden Syndrome 1

Pathways related to Cowden Syndrome 1 according to GeneCards Suite gene sharing:

(show top 50) (show all 88)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
13.88 TSC2 TSC1 STK11 SMAD4 PTEN MTOR
2
Show member pathways
13.17 TSC2 PTEN PIK3CA MTOR EGFR AKT1
3
Show member pathways
13.1 TSC2 TSC1 STK11 MTOR EGFR AKT1
4
Show member pathways
13.03 TSC2 TSC1 STK11 PTEN MTOR BRCA1
5
Show member pathways
12.99 TSC2 TSC1 PIK3CA MTOR EGFR AKT1
6
Show member pathways
12.97 TSC2 TSC1 PTEN PIK3CA MTOR EGFR
7
Show member pathways
12.97 TSC2 TSC1 STK11 PTEN PIK3CA MTOR
8 12.87 SMAD4 RET PTEN PIK3CA MTOR EGFR
9 12.85 TSC2 TSC1 PIK3CA MTOR AKT1
10
Show member pathways
12.8 TSC2 SMAD4 RET PTEN PIK3CA MTOR
11
Show member pathways
12.79 TSC2 PTEN PIK3CA MTOR EGFR AKT1
12
Show member pathways
12.78 SMAD4 PTEN PIK3CA MTOR EGFR BRCA2
13
Show member pathways
12.7 TSC2 PIK3CA MTOR EGFR AKT1
14
Show member pathways
12.68 PTEN PIK3CA MTOR EGFR AKT1
15
Show member pathways
12.66 PTEN PIK3CA MTOR EGFR AKT1
16
Show member pathways
12.6 TSC2 TSC1 PTEN PIK3CA MTOR AKT1
17 12.59 PTEN PIK3CA MTOR EGFR BRCA1
18
Show member pathways
12.58 SMAD4 PTEN PIK3CA MTOR EGFR AKT1
19
Show member pathways
12.56 TSC2 TSC1 STK11 PIK3CA MTOR AKT1
20
Show member pathways
12.5 PIK3CA MTOR EGFR BMPR1A AKT1
21
Show member pathways
12.5 TSC2 TSC1 STK11 PIK3CA MTOR AKT1
22
Show member pathways
12.49 PTEN PIK3CA MTOR AKT1
23
Show member pathways
12.49 TSC2 TSC1 PIK3CA MTOR EGFR AKT1
24
Show member pathways
12.47 TSC2 TSC1 PTEN PIK3CA MTOR AKT1
25 12.45 PIK3CA MTOR EGFR AKT1
26
Show member pathways
12.4 TSC2 PTEN PIK3CA MTOR EGFR AKT1
27 12.39 SMAD4 PTEN PIK3CA AKT1
28
Show member pathways
12.39 TSC2 TSC1 STK11 PTEN PIK3CA MTOR
29 12.36 PIK3CA MTOR EGFR AKT1
30
Show member pathways
12.29 TSC2 TSC1 PTEN PIK3CA MTOR EGFR
31
Show member pathways
12.28 TSC2 TSC1 STK11 MTOR AKT1
32 12.25 PTEN MTOR EGFR AKT1
33
Show member pathways
12.23 PIK3CA MTOR BMPR1A AKT1
34 12.21 TSC2 TSC1 PTEN PIK3CA MTOR AKT1
35
Show member pathways
12.21 TSC2 TSC1 PTEN PIK3CA MTOR EGFR
36
Show member pathways
12.2 PTEN PIK3CA EGFR AKT1
37
Show member pathways
12.18 TSC2 TSC1 STK11 PIK3CA MTOR AKT1
38 12.17 SMAD4 PIK3CA BMPR1A AKT1
39
Show member pathways
12.16 PIK3CA MTOR AKT1
40
Show member pathways
12.11 STK11 SMAD4 PTEN PIK3CA EGFR AKT1
41 12.08 TSC2 PIK3CA MTOR AKT1
42 12.05 SMAD4 PTEN PIK3CA AKT1
43
Show member pathways
12.03 PTEN PIK3CA MTOR AKT1
44 12.02 PIK3CA MTOR EGFR AKT1
45 11.99 PIK3CA MTOR EGFR AKT1
46 11.98 TSC2 TSC1 PTEN MTOR EGFR AKT1
47 11.95 TSC2 TSC1 PTEN PIK3CA AKT1
48 11.93 SMAD4 PTEN EGFR BRCA1 AKT1
49 11.91 PTEN PIK3CA AKT1
50
Show member pathways
11.9 PIK3CA MTOR AKT1

GO Terms for Cowden Syndrome 1

Cellular components related to Cowden Syndrome 1 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 protein-containing complex GO:0032991 9.43 TSC1 MTOR EGFR BRCA2 BRCA1 AKT1
2 TSC1-TSC2 complex GO:0033596 8.62 TSC2 TSC1

Biological processes related to Cowden Syndrome 1 according to GeneCards Suite gene sharing:

(show all 27)
# Name GO ID Score Top Affiliating Genes
1 cellular response to DNA damage stimulus GO:0006974 10.02 STK11 MUTYH BRCA2 BRCA1 AKT1
2 positive regulation of gene expression GO:0010628 10.02 RET PTEN MTOR BRCA1 AKT1
3 phosphorylation GO:0016310 9.98 STK11 RET PIK3CA MTOR EGFR BMPR1A
4 negative regulation of cell proliferation GO:0008285 9.93 TSC2 TSC1 STK11 SMAD4 PTEN CDKN3
5 positive regulation of transcription, DNA-templated GO:0045893 9.91 SMAD4 RET EGFR BRCA2 BRCA1 BMPR1A
6 positive regulation of protein kinase B signaling GO:0051897 9.88 RET PIK3CA MTOR EGFR
7 protein autophosphorylation GO:0046777 9.87 STK11 MTOR EGFR AKT1
8 protein phosphorylation GO:0006468 9.87 STK11 RET PIK3CA MTOR EGFR BMPR1A
9 positive regulation of peptidyl-serine phosphorylation GO:0033138 9.81 PIK3CA EGFR AKT1
10 cell cycle arrest GO:0007050 9.8 STK11 MTOR KLLN CDKN3
11 cellular response to growth factor stimulus GO:0071363 9.79 EGFR BMPR1A AKT1
12 negative regulation of protein kinase B signaling GO:0051898 9.77 TSC2 PTEN AKT1
13 positive regulation of smooth muscle cell proliferation GO:0048661 9.76 MTOR EGFR AKT1
14 epidermal growth factor receptor signaling pathway GO:0007173 9.73 PIK3CA EGFR AKT1
15 phosphatidylinositol 3-kinase signaling GO:0014065 9.69 PTEN PIK3CA AKT1
16 regulation of glycogen biosynthetic process GO:0005979 9.63 MTOR AKT1
17 positive regulation of histone H3-K9 acetylation GO:2000617 9.61 SMAD4 BRCA1
18 mesendoderm development GO:0048382 9.6 SMAD4 BMPR1A
19 regulation of protein kinase B signaling GO:0051896 9.58 STK11 PTEN MTOR
20 protein kinase B signaling GO:0043491 9.56 TSC2 PTEN PIK3CA AKT1
21 chordate embryonic development GO:0043009 9.55 BRCA2 BRCA1
22 positive regulation of neuron maturation GO:0014042 9.54 RET MTOR
23 cellular response to decreased oxygen levels GO:0036294 9.52 PTEN AKT1
24 response to UV-A GO:0070141 9.48 EGFR AKT1
25 negative regulation of macroautophagy GO:0016242 9.46 TSC1 PIK3CA MTOR AKT1
26 negative regulation of cell size GO:0045792 9.26 TSC1 PTEN MTOR AKT1
27 anoikis GO:0043276 9.02 TSC2 STK11 PIK3CA MTOR AKT1

Molecular functions related to Cowden Syndrome 1 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 transferase activity GO:0016740 9.92 STK11 RET PIK3CA MTOR EGFR BRCA1
2 identical protein binding GO:0042802 9.91 SMAD4 PTEN MTOR EGFR BRCA2 BRCA1
3 protein serine/threonine kinase activity GO:0004674 9.55 STK11 PIK3CA MTOR BMPR1A AKT1
4 protein kinase activity GO:0004672 9.43 STK11 RET MTOR EGFR BMPR1A AKT1
5 nitric-oxide synthase regulator activity GO:0030235 9.26 EGFR AKT1
6 kinase activity GO:0016301 9.17 STK11 RET PIK3CA MTOR EGFR BMPR1A

Sources for Cowden Syndrome 1

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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