CSTLO
MCID: CST001
MIFTS: 68

Costello Syndrome (CSTLO)

Categories: Cardiovascular diseases, Fetal diseases, Genetic diseases, Neuronal diseases, Rare diseases, Skin diseases

Aliases & Classifications for Costello Syndrome

MalaCards integrated aliases for Costello Syndrome:

Name: Costello Syndrome 56 12 74 24 52 25 58 73 36 29 6 43 15 39 71
Faciocutaneoskeletal Syndrome 56 12 52 25 58 73
Fcs Syndrome 56 12 52 25 58 73
Myopathy, Congenital, with Excess of Muscle Spindles 29 6 71
Congenital Myopathy with Excess of Muscle Spindles 56 73 13
Cstlo 56 73
Cmems 73
Fcss 73

Characteristics:

Orphanet epidemiological data:

58
costello syndrome
Inheritance: Autosomal dominant,Not applicable; Prevalence: <1/1000000 (Japan); Age of onset: Antenatal,Neonatal;

OMIM:

56
Miscellaneous:
sudden death
de novo mutation in most cases
associated with advanced paternal age
characteristic facial features become more apparent with age
phenotypic overlap with noonan syndrome 3 or cardiofaciocutaneous syndrome

Inheritance:
autosomal dominant


HPO:

31
costello syndrome:
Clinical modifier sudden death
Inheritance autosomal dominant inheritance sporadic


GeneReviews:

24
Penetrance Penetrance is complete [aoki et al 2005, estep et al 2006, gripp et al 2006a, kerr et al 2006].

Classifications:

Orphanet: 58  
Rare neurological diseases
Rare cardiac malformations
Rare skin diseases
Developmental anomalies during embryogenesis


Summaries for Costello Syndrome

Genetics Home Reference : 25 Costello syndrome is a disorder that affects many parts of the body. This condition is characterized by delayed development and intellectual disability, loose folds of skin (which are especially noticeable on the hands and feet), unusually flexible joints, and distinctive facial features including a large mouth. Heart problems are common, including an abnormal heartbeat (arrhythmia), structural heart defects, and a type of heart disease that enlarges and weakens the heart muscle (hypertrophic cardiomyopathy). Infants with Costello syndrome may be larger than average at birth, but most have difficulty feeding and grow more slowly than other children. People with this condition have relatively short stature and may have reduced growth hormone levels. Other signs and symptoms of Costello syndrome can include tight Achilles tendons (which connect the calf muscles to the heel), weak muscle tone (hypotonia), a structural abnormality of the brain called a Chiari I malformation, skeletal abnormalities, dental problems, and problems with vision. Beginning in early childhood, people with Costello syndrome are at an increased risk of developing certain cancerous and noncancerous tumors. The most common noncancerous tumors associated with this condition are papillomas, which are small, wart-like growths that usually develop around the nose and mouth or near the anus. The most common cancerous tumor associated with Costello syndrome is a childhood cancer called rhabdomyosarcoma, which begins in muscle tissue. Neuroblastoma, a tumor that arises in developing nerve cells, also has been reported in children and adolescents with this syndrome. In addition, some teenagers with Costello syndrome have developed transitional cell carcinoma, a form of bladder cancer that is usually seen in older adults. The signs and symptoms of Costello syndrome overlap significantly with those of two other genetic conditions, cardiofaciocutaneous syndrome (CFC syndrome) and Noonan syndrome. In affected infants, it can be difficult to tell the three conditions apart based on their physical features. However, the conditions can be distinguished by their genetic cause and by specific patterns of signs and symptoms that develop later in childhood.

MalaCards based summary : Costello Syndrome, also known as faciocutaneoskeletal syndrome, is related to cardiofaciocutaneous syndrome 1 and cutis laxa, autosomal dominant 1, and has symptoms including hoarseness and koilonychia. An important gene associated with Costello Syndrome is HRAS (HRas Proto-Oncogene, GTPase), and among its related pathways/superpathways are Ras signaling pathway and Innate Immune System. The drug Anesthetics has been mentioned in the context of this disorder. Affiliated tissues include skin, heart and brain, and related phenotypes are macrocephaly and short neck

Disease Ontology : 12 A syndrome characterized by craniofacial dysmorphology, cardiac defects, mild mental retardation, and high birth weight followed by a failure to thrive and developmental delays.

NIH Rare Diseases : 52 Costello syndrome is a rare condition that affects many different parts of the body. Signs and symptoms generally include developmental delay , intellectual disability , distinctive facial features, loose folds of extra skin (especially on the hands and feet), and unusually flexible joints. Affected people may also have heart abnormalities such as tachycardia , structural heart defects, and hypertrophic cardiomyopathy . Beginning in early childhood, people with Costello syndrome additionally have an increased risk to develop certain cancerous and noncancerous tumors . Costello syndrome is caused by changes (mutations ) in the HRAS gene . It is considered an autosomal dominant condition, but almost all cases are the result of de novo gene mutations and occur in people with no family history of the condition. Treatment is based on the signs and symptoms present in each person. Costello syndrome belongs to a group of related conditions called the RASopathies . These conditions have some overlapping features and are all caused by genetic changes that disrupt the body's RAS pathway, affecting growth and development. The features of Costello syndrome overlap significantly with two of the RASopathies, cardiofaciocutaneous (CFC) syndrome and Noonan syndrome .

OMIM : 56 Costello syndrome is a rare multiple congenital anomaly syndrome associated in all cases with a characteristic coarse facies, short stature, distinctive hand posture and appearance, severe feeding difficulty, and failure to thrive. Other features include cardiac anomalies and developmental disability. Facial warts, particularly nasolabial, are often present in childhood (Kerr et al., 2006). In patients with a clinical diagnosis of Costello syndrome, Zenker et al. (2007) identified mutations in the KRAS gene, but noted that these patients may later develop features of CFC syndrome. In either case, the findings underscore the central role of Ras in the pathogenesis of these phenotypically related disorders (Zenker et al., 2007). However, Kerr et al. (2008) commented that the diagnosis of Costello syndrome should only be used to refer to patients with mutations in the HRAS gene. (218040)

KEGG : 36 Costello syndrome (CS) is a rare multiple congenital abnormality syndrome. Patients present with the typical coarse face, deep palmar and plantar creases, redundant and loose skin, severe failure to thrive, congenital heart defect, and mild to severe mental retardation. Hyperpigmentation and papillomas can also be present. They have an increased risk of malignancy. The majority of patients show a mutation in HRAS.

UniProtKB/Swiss-Prot : 73 Congenital myopathy with excess of muscle spindles: Variant of Costello syndrome.
Costello syndrome: A rare condition characterized by prenatally increased growth, postnatal growth deficiency, mental retardation, distinctive facial appearance, cardiovascular abnormalities (typically pulmonic stenosis, hypertrophic cardiomyopathy and/or atrial tachycardia), tumor predisposition, skin and musculoskeletal abnormalities.

Wikipedia : 74 Costello syndrome, also called faciocutaneoskeletal syndrome or FCS syndrome, is a rare genetic disorder... more...

GeneReviews: NBK1507

Related Diseases for Costello Syndrome

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

(show top 50) (show all 312)
# Related Disease Score Top Affiliating Genes
1 cardiofaciocutaneous syndrome 1 32.6 SOS1 PTPN11 MAP2K2 MAP2K1 KRAS HRAS
2 cutis laxa, autosomal dominant 1 32.4 FBN1 FBLN5 ELN
3 autosomal recessive cutis laxa type i 32.3 FBN1 FBLN5 ELN
4 noonan syndrome 1 31.7 SOS1 PTPN11 MIR1304 MAP2K2 MAP2K1 KRAS
5 leopard syndrome 31.4 SOS1 PTPN11 PIK3CA MIR1304 MAP2K2 MAP2K1
6 embryonal rhabdomyosarcoma 31.0 SOS1 PTPN11 HRAS
7 heart septal defect 31.0 SOS1 PTPN11 ELN
8 nevus, epidermal 30.8 PIK3CA KRAS HRAS
9 hypertrophic cardiomyopathy 30.7 SOS1 PTPN11 MAP2K2 MAP2K1 KRAS HRAS
10 pulmonic stenosis 30.7 SOS1 KRAS HRAS BRAF
11 cutis laxa 30.6 LOX FBN1 FBLN5 ELN
12 neurofibromatosis, type iv, of riccardi 30.5 PTPN11 PDGFRA KRAS HRAS
13 atrial heart septal defect 30.5 SOS1 PTPN11 HRAS FBN1 ELN
14 noonan syndrome 3 30.4 SOS1 PTPN11 KRAS HRAS
15 rasopathy 30.4 SOS1 PTPN11 MAP2K2 MAP2K1 KRAS HRAS
16 cryptorchidism, unilateral or bilateral 30.3 SOS1 PTPN11 INS HRAS
17 rhabdomyosarcoma 30.1 PTPN11 PDGFRB PDGFRA MAP2K1 KRAS HRAS
18 inguinal hernia 29.8 LOX FBN1 FBLN5 ELN
19 scoliosis 29.8 PTPN11 LOX FBN1 FBLN5 ELN CHST11
20 bladder urothelial carcinoma 29.7 PIK3CA PDGFRA MAP2K1 KRAS HRAS BRAF
21 neuroblastoma 29.0 SOS1 PTPN11 PIK3CA PDGFRB MAP2K1 INS
22 chaotic atrial tachycardia 11.2
23 spitzoid melanoma 10.6 HRAS BRAF
24 signet ring basal cell carcinoma 10.6 KRAS HRAS
25 selection of therapeutic option in colorectal cancer 10.6 KRAS BRAF
26 trachea carcinoma in situ 10.6 KRAS HRAS
27 nasal cavity adenocarcinoma 10.6 KRAS HRAS
28 urachal adenocarcinoma 10.5 KRAS BRAF
29 spitz nevus 10.5 HRAS BRAF
30 hyperplastic polyposis syndrome 10.5 KRAS BRAF
31 apocrine adenoma 10.5 KRAS BRAF
32 ampulla of vater neoplasm 10.5 KRAS HRAS
33 periampullary adenoma 10.5 KRAS HRAS
34 late-onset focal dermal elastosis 10.5 FBN1 ELN
35 pseudoxanthoma elasticum-like papillary dermal elastolysis 10.5 FBN1 ELN
36 ovarian clear cell adenofibroma 10.5 PIK3CA KRAS
37 breast squamous cell carcinoma 10.5 PIK3CA HRAS
38 acquired cutis laxa 10.5 FBLN5 ELN
39 fbln5-related cutis laxa 10.5 FBLN5 ELN
40 alacrima, achalasia, and mental retardation syndrome 10.5
41 pseudo-turner syndrome 10.5
42 acneiform dermatitis 10.5 MAP2K1 KRAS HRAS
43 myh-associated polyposis 10.5 KRAS HRAS
44 chronic actinic dermatitis 10.5 FBN1 ELN
45 appendix adenocarcinoma 10.5 KRAS HRAS
46 mucinous lung adenocarcinoma 10.5 KRAS HRAS
47 cystadenocarcinoma 10.5 PIK3CA HRAS BRAF
48 familial abdominal aortic aneurysm 10.5 FBN1 ELN
49 testicular spermatocytic seminoma 10.5 PTPN11 HRAS
50 rare adenocarcinoma of the breast 10.5 PIK3CA KRAS

Graphical network of the top 20 diseases related to Costello Syndrome:



Diseases related to Costello Syndrome

Symptoms & Phenotypes for Costello Syndrome

Human phenotypes related to Costello Syndrome:

58 31 (show top 50) (show all 100)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 macrocephaly 58 31 hallmark (90%) Very frequent (99-80%) HP:0000256
2 short neck 58 31 hallmark (90%) Very frequent (99-80%) HP:0000470
3 narrow palate 58 31 hallmark (90%) Very frequent (99-80%) HP:0000189
4 delayed skeletal maturation 58 31 hallmark (90%) Very frequent (99-80%) HP:0002750
5 depressed nasal bridge 58 31 hallmark (90%) Very frequent (99-80%) HP:0005280
6 short stature 58 31 hallmark (90%) Very frequent (99-80%) HP:0004322
7 ventricular septal defect 58 31 hallmark (90%) Very frequent (99-80%) HP:0001629
8 hyperkeratosis 58 31 hallmark (90%) Very frequent (99-80%) HP:0000962
9 acanthosis nigricans 58 31 hallmark (90%) Very frequent (99-80%) HP:0000956
10 lack of skin elasticity 58 31 hallmark (90%) Very frequent (99-80%) HP:0100679
11 failure to thrive in infancy 58 31 hallmark (90%) Very frequent (99-80%) HP:0001531
12 redundant skin 58 31 hallmark (90%) Very frequent (99-80%) HP:0001582
13 pulmonic stenosis 58 31 hallmark (90%) Very frequent (99-80%) HP:0001642
14 woolly hair 58 31 hallmark (90%) Very frequent (99-80%) HP:0002224
15 concave nail 58 31 hallmark (90%) Very frequent (99-80%) HP:0001598
16 deep-set nails 58 31 hallmark (90%) Very frequent (99-80%) HP:0001814
17 abnormal fingernail morphology 31 hallmark (90%) HP:0001231
18 intellectual disability 58 31 frequent (33%) Frequent (79-30%) HP:0001249
19 macroglossia 58 31 frequent (33%) Frequent (79-30%) HP:0000158
20 cryptorchidism 58 31 frequent (33%) Frequent (79-30%) HP:0000028
21 cerebral cortical atrophy 58 31 frequent (33%) Frequent (79-30%) HP:0002120
22 gastroesophageal reflux 58 31 frequent (33%) Frequent (79-30%) HP:0002020
23 polyhydramnios 58 31 frequent (33%) Frequent (79-30%) HP:0001561
24 hypertrophic cardiomyopathy 58 31 frequent (33%) Frequent (79-30%) HP:0001639
25 full cheeks 58 31 frequent (33%) Frequent (79-30%) HP:0000293
26 thick lower lip vermilion 58 31 frequent (33%) Frequent (79-30%) HP:0000179
27 strabismus 58 31 frequent (33%) Frequent (79-30%) HP:0000486
28 joint hyperflexibility 58 31 frequent (33%) Frequent (79-30%) HP:0005692
29 epicanthus 58 31 frequent (33%) Frequent (79-30%) HP:0000286
30 thickened nuchal skin fold 58 31 frequent (33%) Frequent (79-30%) HP:0000474
31 hypoplastic toenails 58 31 frequent (33%) Frequent (79-30%) HP:0001800
32 abnormal dermatoglyphics 58 31 frequent (33%) Frequent (79-30%) HP:0007477
33 mitral valve prolapse 58 31 frequent (33%) Frequent (79-30%) HP:0001634
34 abnormality of dental enamel 58 31 frequent (33%) Frequent (79-30%) HP:0000682
35 ulnar deviation of finger 58 31 frequent (33%) Frequent (79-30%) HP:0009465
36 keratoconus 58 31 frequent (33%) Frequent (79-30%) HP:0000563
37 papilloma 58 31 frequent (33%) Frequent (79-30%) HP:0012740
38 thickened achilles tendon 58 31 frequent (33%) Frequent (79-30%) HP:0004690
39 large face 58 31 occasional (7.5%) Occasional (29-5%) HP:0100729
40 coarse facial features 58 31 occasional (7.5%) Occasional (29-5%) HP:0000280
41 poor suck 58 31 occasional (7.5%) Occasional (29-5%) HP:0002033
42 low-set, posteriorly rotated ears 58 31 occasional (7.5%) Occasional (29-5%) HP:0000368
43 generalized hyperpigmentation 58 31 occasional (7.5%) Occasional (29-5%) HP:0007440
44 large earlobe 58 31 occasional (7.5%) Occasional (29-5%) HP:0009748
45 renal insufficiency 31 occasional (7.5%) HP:0000083
46 hypertelorism 31 HP:0000316
47 low-set ears 31 HP:0000369
48 high palate 31 HP:0000218
49 hydrocephalus 31 HP:0000238
50 ptosis 31 HP:0000508

Symptoms via clinical synopsis from OMIM:

56
Head And Neck Head:
macrocephaly
large anterior fontanel

Head And Neck Ears:
low-set ears
posteriorly rotated ears
thickened lobes

Neurologic Central Nervous System:
hydrocephalus
ventriculomegaly
cerebral atrophy
enlarged cerebellum
chiari i malformation
more
Head And Neck Mouth:
macroglossia
high-arched palate
thick lips

Chest External Features:
pectus carinatum
barrel chest

Head And Neck Face:
micrognathia
full cheeks
pointed chin
coarse facies

Prenatal Manifestations Amniotic Fluid:
polyhydramnios

Skin Nails Hair Skin:
acanthosis nigricans
deep palmar creases
palmar nevi
cutis laxa (especially hands and feet)
loose, redundant skin
more
Neoplasia:
rhabdomyosarcoma
bladder carcinoma
vestibular schwannoma
epithelioma

Respiratory:
obstructive sleep apnea

Respiratory Airways:
tracheomalacia
bronchomalacia

Skin Nails Hair Nails:
koilonychia
brittle nails
thin, deep-set nails

Genitourinary Kidneys:
renal failure (in some patients)
dilated calyces (in some patients)
echogenic kidneys with thick-walled pelvises (in some patients)

Head And Neck Teeth:
defective enamel formation

Skeletal Limbs:
restricted elbow motion
tight achilles tendon

Head And Neck Eyes:
hypertelorism
ptosis
strabismus
downslanting palpebral fissures
epicanthal folds

Head And Neck Neck:
short neck
webbed neck
loose, redundant neck skin

Growth Other:
failure to thrive
fetal overgrowth
postnatal onset growth deficiency

Head And Neck Nose:
depressed nasal bridge
anteverted nostrils

Growth Height:
short stature
increased birth length

Cardiovascular Heart:
ventricular septal defect
hypertrophic cardiomyopathy
atrial septal defect
mitral valve prolapse
pulmonic stenosis
more
Laboratory Abnormalities:
hypoglycemia

Respiratory Lung:
respiratory failure
pneumothorax, recurrent
lymphangiectasia
alveolar/capillary dysplasia
small lungs

Voice:
hoarse voice

Skin Nails Hair Hair:
curly hair
sparse hair
thin anterior head hair

Skeletal Feet:
deep plantar creases
clubfeet

Growth Weight:
increased birth weight

Prenatal Manifestations Delivery:
preterm delivery

Abdomen Gastrointestinal:
poor suck in infancy
pyloric stenosis, hypertrophic

Skeletal Hands:
deep palmar creases
hyperextensible finger
wide distal phalanges
palmar nevi

Clinical features from OMIM:

218040

UMLS symptoms related to Costello Syndrome:


hoarseness, koilonychia

GenomeRNAi Phenotypes related to Costello Syndrome according to GeneCards Suite gene sharing:

26 (show all 13)
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased viability GR00055-A-2 10.34 HRAS KRAS PIK3CA BRAF
2 Decreased viability GR00106-A-0 10.34 KRAS
3 Decreased viability GR00173-A 10.34 PDGFRA
4 Decreased viability GR00221-A-1 10.34 HRAS KRAS PDGFRA PDGFRB PIK3CA
5 Decreased viability GR00221-A-2 10.34 HRAS KRAS PIK3CA
6 Decreased viability GR00221-A-3 10.34 HRAS PDGFRA PDGFRB
7 Decreased viability GR00221-A-4 10.34 PDGFRA PDGFRB PIK3CA BRAF
8 Decreased viability GR00301-A 10.34 KRAS BRAF
9 Decreased viability GR00342-S-1 10.34 PDGFRB
10 Decreased viability GR00381-A-1 10.34 KRAS BRAF
11 Decreased viability GR00402-S-2 10.34 HRAS KRAS PDGFRA PDGFRB PIK3CA BRAF
12 Decreased cell migration GR00055-A-1 9.7 BRAF HRAS KRAS MAP2K2 PDGFRB PIK3CA
13 Increased cell migration GR00055-A-3 9.02 BRAF HRAS KRAS PIK3CA SOS1

MGI Mouse Phenotypes related to Costello Syndrome:

45 (show all 24)
# Description MGI Source Accession Score Top Affiliating Genes
1 cardiovascular system MP:0005385 10.54 BRAF CHST11 FBLN5 FBN1 HRAS INS
2 growth/size/body region MP:0005378 10.5 BRAF CHST11 EGF FBLN5 FBN1 HRAS
3 homeostasis/metabolism MP:0005376 10.46 BRAF FBLN5 FBN1 HRAS INS KRAS
4 endocrine/exocrine gland MP:0005379 10.42 BRAF CHST11 EGF FBN1 HRAS INS
5 integument MP:0010771 10.41 BRAF EGF FBLN5 FBN1 HRAS INS
6 mortality/aging MP:0010768 10.39 BRAF CHST11 FBN1 HRAS INS KRAS
7 cellular MP:0005384 10.38 BRAF FBLN5 FBN1 INS KRAS MAP2K1
8 craniofacial MP:0005382 10.38 BRAF CHST11 FBLN5 FBN1 HRAS KRAS
9 digestive/alimentary MP:0005381 10.37 BRAF CHST11 EGF HRAS INS KRAS
10 embryo MP:0005380 10.36 BRAF CHST11 FBN1 INS KRAS MAP2K1
11 immune system MP:0005387 10.33 BRAF CHST11 EGF FBN1 INS KRAS
12 muscle MP:0005369 10.27 BRAF CHST11 FBLN5 FBN1 INS KRAS
13 nervous system MP:0003631 10.27 BRAF CHST11 FBN1 HRAS INS KRAS
14 adipose tissue MP:0005375 10.22 BRAF FBN1 INS MAP2K2 MFAP2 PDGFRB
15 normal MP:0002873 10.14 BRAF EGF HRAS INS KRAS MAP2K1
16 limbs/digits/tail MP:0005371 10.13 BRAF CHST11 FBN1 KRAS PDGFRA PDGFRB
17 neoplasm MP:0002006 10.13 BRAF FBLN5 HRAS KRAS MAP2K1 MAP2K2
18 no phenotypic analysis MP:0003012 9.98 FBN1 HRAS INS KRAS PDGFRA PIK3CA
19 reproductive system MP:0005389 9.96 BRAF EGF FBN1 INS KRAS MAP2K1
20 renal/urinary system MP:0005367 9.92 BRAF CHST11 FBN1 HRAS INS KRAS
21 skeleton MP:0005390 9.86 BRAF CHST11 FBN1 HRAS INS KRAS
22 respiratory system MP:0005388 9.81 BRAF CHST11 FBLN5 FBN1 HRAS KRAS
23 pigmentation MP:0001186 9.77 BRAF FBN1 KRAS PDGFRA PTPN11
24 vision/eye MP:0005391 9.36 BRAF CHST11 EGF INS KRAS MAP2K1

Drugs & Therapeutics for Costello Syndrome

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


# Name Status Phase Clinical Trials Cas Number PubChem Id
1 Anesthetics

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Pathophysiology Analysis of "Costello Syndrome" on Cellular Models Completed NCT02812511
2 Effects of Physical Training on Bone and Muscle Quality, Muscle Strength, and Motor Coordination in Children With Neurofibromatosis Type 1 Completed NCT01058330

Search NIH Clinical Center for Costello Syndrome

Cochrane evidence based reviews: costello syndrome

Genetic Tests for Costello Syndrome

Genetic tests related to Costello Syndrome:

# Genetic test Affiliating Genes
1 Costello Syndrome 29 HRAS
2 Myopathy, Congenital, with Excess of Muscle Spindles 29

Anatomical Context for Costello Syndrome

MalaCards organs/tissues related to Costello Syndrome:

40
Skin, Heart, Brain, Bone, Cerebellum, Kidney, Lung

Publications for Costello Syndrome

Articles related to Costello Syndrome:

(show top 50) (show all 424)
# Title Authors PMID Year
1
Phenotypic analysis of individuals with Costello syndrome due to HRAS p.G13C. 56 6 24 61
21438134 2011
2
Severe neonatal manifestations of Costello syndrome. 61 6 24 56
18039947 2008
3
Costello syndrome associated with novel germline HRAS mutations: an attenuated phenotype? 6 56 24 61
18247425 2008
4
Myopathy caused by HRAS germline mutations: implications for disturbed myogenic differentiation in the presence of constitutive HRas activation. 61 24 56 6
17412879 2007
5
Diversity, parental germline origin, and phenotypic spectrum of de novo HRAS missense changes in Costello syndrome. 56 24 61 6
17054105 2007
6
Genotype-phenotype correlation in Costello syndrome: HRAS mutation analysis in 43 cases. 56 24 6 61
16443854 2006
7
Germline mutations in HRAS proto-oncogene cause Costello syndrome. 61 6 56 24
16170316 2005
8
Functional analysis of a duplication (p.E63_D69dup) in the switch II region of HRAS: new aspects of the molecular pathogenesis underlying Costello syndrome. 56 6 61
23335589 2013
9
A premature infant with Costello syndrome due to a rare G13C HRAS mutation. 61 56 6
19213030 2009
10
Assessing genotype-phenotype correlation in Costello syndrome using a severity score. 61 56 24
23429430 2013
11
Clinical, pathological, and molecular analyses of cardiovascular abnormalities in Costello syndrome: a Ras/MAPK pathway syndrome. 61 24 56
21344638 2011
12
High incidence of progressive postnatal cerebellar enlargement in Costello syndrome: brain overgrowth associated with HRAS mutations as the likely cause of structural brain and spinal cord abnormalities. 61 56 24
20425820 2010
13
Duplication of Glu37 in the switch I region of HRAS impairs effector/GAP binding and underlies Costello syndrome by promoting enhanced growth factor-dependent MAPK and AKT activation. 61 6 24
19995790 2010
14
Male-to-male transmission of Costello syndrome: G12S HRAS germline mutation inherited from a father with somatic mosaicism. 61 24 56
19206176 2009
15
The diagnosis of Costello syndrome: nomenclature in Ras/MAPK pathway disorders. 24 56 61
18386799 2008
16
Further delineation of the phenotype resulting from BRAF or MEK1 germline mutations helps differentiate cardio-facio-cutaneous syndrome from Costello syndrome. 56 24 61
17551924 2007
17
Somatic mosaicism for an HRAS mutation causes Costello syndrome. 24 56 61
16969868 2006
18
Paternal bias in parental origin of HRAS mutations in Costello syndrome. 61 6 24
16835863 2006
19
Obstructive sleep apnea in Costello syndrome. 56 61 24
16419102 2006
20
HRAS mutation analysis in Costello syndrome: genotype and phenotype correlation. 24 61 56
16329078 2006
21
HRAS mutations in Costello syndrome: detection of constitutional activating mutations in codon 12 and 13 and loss of wild-type allele in malignancy. 61 56 24
16372351 2006
22
The adult phenotype in Costello syndrome. 61 24 56
15940703 2005
23
A new syndrome of myopathy with muscle spindle excess. 56 6
15843272 2005
24
Adaptive skills, cognitive, and behavioral characteristics of Costello syndrome. 61 24 56
15264285 2004
25
Elevated catecholamine metabolites in patients with Costello syndrome. 61 24 56
15211656 2004
26
Further delineation of the behavioral and neurologic features in Costello syndrome. 24 56 61
12605434 2003
27
Costello syndrome: an overview. 56 24 61
12561057 2003
28
Further delineation of cardiac abnormalities in Costello syndrome. 24 56 61
12210337 2002
29
Five additional Costello syndrome patients with rhabdomyosarcoma: proposal for a tumor screening protocol. 24 56 61
11857556 2002
30
Myopathy with muscle spindle excess: A new congenital neuromuscular syndrome? 6 56
11150980 2001
31
Second case of bladder carcinoma in a patient with Costello syndrome. 61 24 56
10678668 2000
32
Costello syndrome: phenotype, natural history, differential diagnosis, and possible cause. 56 24 61
9738731 1998
33
Myopathology in patients with a Noonan phenotype. 6 56
8960317 1996
34
Costello syndrome: update on the original cases and commentary. 56 24 61
8882404 1996
35
Costello syndrome: further clinical delineation, natural history, genetic definition, and nosology. 61 24 56
8213903 1993
36
New multiple congenital anomalies: mental retardation syndrome (MCA/MR) with facio-cutaneous-skeletal involvement. 56 61 24
1621757 1992
37
Costello syndrome. 24 56 61
1951465 1991
38
Distinguishing Costello versus cardio-facio-cutaneous syndrome: BRAF mutations in patients with a Costello phenotype. 56 24
16804887 2006
39
A new syndrome: mental subnormality and nasal papillomata. 24 56
907573 1977
40
Abnormal Ras signaling in Costello syndrome (CS) negatively regulates enamel formation. 61 56
24057668 2014
41
Keratinocytic epidermal nevi are associated with mosaic RAS mutations. 6 61
22499344 2012
42
Polyhydramnios, fetal overgrowth, and macrocephaly: prenatal ultrasound findings of Costello syndrome. 61 56
19288554 2009
43
Prenatal diagnosis of Costello syndrome using 3D ultrasonography amniocentesis confirmation of the rare HRAS mutation G12D. 56 61
18642361 2009
44
A mouse model for Costello syndrome reveals an Ang II-mediated hypertensive condition. 56 61
18483625 2008
45
Clarification of previously reported Costello syndrome patients. 61 56
18302240 2008
46
Mutation analysis in Costello syndrome: functional and structural characterization of the HRAS p.Lys117Arg mutation. 61 6
17979197 2008
47
Mutation and phenotypic spectrum in patients with cardio-facio-cutaneous and Costello syndrome. 61 56
18042262 2008
48
Expansion of the genotypic and phenotypic spectrum in patients with KRAS germline mutations. 61 56
17056636 2007
49
Further evidence of genetic heterogeneity in Costello syndrome: involvement of the KRAS gene. 56 61
17468812 2007
50
Costello Syndrome 6 61
20301680 2006

Variations for Costello Syndrome

ClinVar genetic disease variations for Costello Syndrome:

6 (show top 50) (show all 122) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 HRAS NM_005343.4(HRAS):c.35G>T (p.Gly12Val)SNV Pathogenic 12600 rs104894230 11:534288-534288 11:534288-534288
2 HRAS NM_005343.4(HRAS):c.34G>A (p.Gly12Ser)SNV Pathogenic 12602 rs104894229 11:534289-534289 11:534289-534289
3 HRAS NM_005343.4(HRAS):c.35G>C (p.Gly12Ala)SNV Pathogenic 12603 rs104894230 11:534288-534288 11:534288-534288
4 HRAS NM_005343.4(HRAS):c.187G>A (p.Glu63Lys)SNV Pathogenic 12608 rs121917756 11:533869-533869 11:533869-533869
5 HRAS NM_005343.4(HRAS):c.34G>T (p.Gly12Cys)SNV Pathogenic 12613 rs104894229 11:534289-534289 11:534289-534289
6 HRAS NM_005343.4(HRAS):c.110_111+1dupduplication Pathogenic 29911 rs398122808 11:534211-534213 11:534211-534213
7 HRAS NM_005343.4(HRAS):c.108_110dup (p.Glu37dup)duplication Pathogenic 29912 rs398122809 11:534213-534215 11:534213-534215
8 HRAS NM_005343.4(HRAS):c.173C>T (p.Thr58Ile)SNV Pathogenic 12610 rs121917758 11:533883-533883 11:533883-533883
9 HRAS NM_005343.4(HRAS):c.35G>A (p.Gly12Asp)SNV Pathogenic 12612 rs104894230 11:534288-534288 11:534288-534288
10 HRAS NM_005343.4(HRAS):c.187_207dup (p.Glu63_Asp69dup)duplication Pathogenic 120223 rs587777239 11:533849-533869 11:533849-533869
11 HRAS NM_005343.4(HRAS):c.450+139dupduplication Pathogenic 522672 rs35613389 11:533309-533309 11:533309-533309
12 HRAS NM_005343.4(HRAS):c.37G>T (p.Gly13Cys)SNV Pathogenic 12606 rs104894228 11:534286-534286 11:534286-534286
13 HRAS NM_005343.4(HRAS):c.350A>G (p.Lys117Arg)SNV Pathogenic 12605 rs104894227 11:533553-533553 11:533553-533553
14 HRAS NM_005343.4(HRAS):c.38G>A (p.Gly13Asp)SNV Pathogenic 12604 rs104894226 11:534285-534285 11:534285-534285
15 HRAS NM_005343.4(HRAS):c.35_36delinsAA (p.Gly12Glu)indel Pathogenic/Likely pathogenic 163690 rs727503094 11:534287-534288 11:534287-534288
16 HRAS NM_005343.4(HRAS):c.38G>T (p.Gly13Val)SNV Pathogenic/Likely pathogenic 180848 rs104894226 11:534285-534285 11:534285-534285
17 HRAS NM_005343.4(HRAS):c.436G>A (p.Ala146Thr)SNV Pathogenic/Likely pathogenic 12607 rs104894231 11:533467-533467 11:533467-533467
18 HRAS NM_005343.4(HRAS):c.175G>A (p.Ala59Thr)SNV Likely pathogenic 40435 rs727503093 11:533881-533881 11:533881-533881
19 HRAS NM_005343.4(HRAS):c.64C>A (p.Gln22Lys)SNV Likely pathogenic 12609 rs121917757 11:534259-534259 11:534259-534259
20 HRAS NM_005343.4(HRAS):c.437C>T (p.Ala146Val)SNV Likely pathogenic 12611 rs121917759 11:533466-533466 11:533466-533466
21 HRAS NM_005343.4(HRAS):c.175_176delinsCT (p.Ala59Leu)indel Likely pathogenic 179260 rs727504747 11:533880-533881 11:533880-533881
22 TNNT2 NM_000364.4(TNNT2):c.853C>T (p.Arg285Cys)SNV Conflicting interpretations of pathogenicity 12411 rs121964857 1:201328373-201328373 1:201359245-201359245
23 HRAS NM_005343.4(HRAS):c.45C>T (p.Gly15=)SNV Conflicting interpretations of pathogenicity 179085 rs727504614 11:534278-534278 11:534278-534278
24 HRAS NM_005343.4(HRAS):c.367C>T (p.Arg123Cys)SNV Conflicting interpretations of pathogenicity 180851 rs369106578 11:533536-533536 11:533536-533536
25 HRAS NM_005343.4(HRAS):c.412G>A (p.Gly138Ser)SNV Conflicting interpretations of pathogenicity 45304 rs397517142 11:533491-533491 11:533491-533491
26 HRAS NM_005343.4(HRAS):c.451-5C>GSNV Conflicting interpretations of pathogenicity 415886 rs370181298 11:532760-532760 11:532760-532760
27 HRAS NM_005343.4(HRAS):c.391C>T (p.Gln131Ter)SNV Uncertain significance 409949 rs376688893 11:533512-533512 11:533512-533512
28 HRAS NM_005343.4(HRAS):c.317C>T (p.Ser106Leu)SNV Uncertain significance 409948 rs730880462 11:533586-533586 11:533586-533586
29 HRAS NM_005343.4(HRAS):c.106A>G (p.Ile36Val)SNV Uncertain significance 409947 rs1060502663 11:534217-534217 11:534217-534217
30 HRAS NM_005343.4(HRAS):c.290+6C>ASNV Uncertain significance 240134 rs878854758 11:533760-533760 11:533760-533760
31 HRAS NM_005343.4(HRAS):c.174_192del (p.Gly60fs)deletion Uncertain significance 240133 rs878854757 11:533864-533882 11:533864-533882
32 HRAS NM_005343.4(HRAS):c.111+6C>TSNV Uncertain significance 240132 rs377130570 11:534206-534206 11:534206-534206
33 HRAS NM_005343.4(HRAS):c.4A>G (p.Thr2Ala)SNV Uncertain significance 240137 rs878854761 11:534319-534319 11:534319-534319
34 HRAS NC_000011.9:g.(?_532631)_(532755_?)dupduplication Uncertain significance 417510 11:532631-532755 11:532631-532755
35 HRAS NM_005343.4(HRAS):c.445C>T (p.Arg149Trp)SNV Uncertain significance 503536 rs1554884750 11:533458-533458 11:533458-533458
36 HRAS NM_005343.4(HRAS):c.552dup (p.Lys185fs)duplication Uncertain significance 531191 rs1554884418 11:532654-532654 11:532654-532654
37 HRAS NM_005343.4(HRAS):c.302A>G (p.Lys101Arg)SNV Uncertain significance 430506 rs1131691997 11:533601-533601 11:533601-533601
38 HRAS NM_005343.4(HRAS):c.518C>T (p.Pro173Leu)SNV Uncertain significance 462156 rs1171786943 11:532688-532688 11:532688-532688
39 HRAS NM_005343.4(HRAS):c.413G>A (p.Gly138Asp)SNV Uncertain significance 462151 rs1554884772 11:533490-533490 11:533490-533490
40 HRAS NM_005343.4(HRAS):c.186_206dup (p.Glu62_Arg68dup)duplication Uncertain significance 462149 rs1554884966 11:533850-533870 11:533850-533870
41 HRAS NM_005343.4(HRAS):c.452G>C (p.Gly151Ala)SNV Uncertain significance 462154 rs1362209698 11:532754-532754 11:532754-532754
42 HRAS NC_000011.9:g.(?_532631)_(534375_?)dupduplication Uncertain significance 179613 11:532631-534375 11:532631-534375
43 HRAS NM_005343.4(HRAS):c.546G>A (p.Met182Ile)SNV Uncertain significance 240138 rs748639813 11:532660-532660 11:532660-532660
44 HRAS NM_005343.4(HRAS):c.498C>A (p.His166Gln)SNV Uncertain significance 240136 rs878854760 11:532708-532708 11:532708-532708
45 HRAS NM_005343.4(HRAS):c.460G>A (p.Asp154Asn)SNV Uncertain significance 40445 rs745497215 11:532746-532746 11:532746-532746
46 HRAS NM_005343.4(HRAS):c.508A>T (p.Lys170Ter)SNV Uncertain significance 40447 rs372936166 11:532698-532698 11:532698-532698
47 HRAS NM_005343.4(HRAS):c.277A>G (p.Ile93Val)SNV Uncertain significance 40439 rs587782949 11:533779-533779 11:533779-533779
48 HRAS NM_005343.4(HRAS):c.368G>C (p.Arg123Pro)SNV Uncertain significance 180852 rs730880464 11:533535-533535 11:533535-533535
49 HRAS NM_005343.4(HRAS):c.506G>A (p.Arg169Gln)SNV Uncertain significance 180856 rs142218590 11:532700-532700 11:532700-532700
50 HRAS NM_005343.4(HRAS):c.31G>A (p.Ala11Thr)SNV Uncertain significance 178860 rs727504496 11:534292-534292 11:534292-534292

UniProtKB/Swiss-Prot genetic disease variations for Costello Syndrome:

73 (show all 14)
# Symbol AA change Variation ID SNP ID
1 HRAS p.Gly12Val VAR_006836 rs104894230
2 HRAS p.Gly12Ser VAR_006837 rs104894229
3 HRAS p.Gly12Ala VAR_026106 rs104894230
4 HRAS p.Gly13Cys VAR_026107 rs104894228
5 HRAS p.Gly13Asp VAR_026108 rs104894226
6 HRAS p.Gly12Cys VAR_045975 rs104894229
7 HRAS p.Gly12Glu VAR_045976
8 HRAS p.Gln22Lys VAR_045977 rs121917757
9 HRAS p.Thr58Ile VAR_045978 rs121917758
10 HRAS p.Glu63Lys VAR_045980 rs121917756
11 HRAS p.Lys117Arg VAR_045981 rs104894227
12 HRAS p.Ala146Thr VAR_045982 rs104894231
13 HRAS p.Ala146Val VAR_045983 rs121917759
14 HRAS p.Gly12Asp VAR_068816 rs104894230

Copy number variations for Costello Syndrome from CNVD:

7
# CNVD ID Chromosome Start End Type Gene Symbol CNVD Disease
1 48338 11 1 2800000 Genomic rearrangement HRAS Costello syndrome

Expression for Costello Syndrome

Search GEO for disease gene expression data for Costello Syndrome.

Pathways for Costello Syndrome

Pathways related to Costello Syndrome according to KEGG:

36
# Name Kegg Source Accession
1 Ras signaling pathway hsa04014

Pathways related to Costello Syndrome according to GeneCards Suite gene sharing:

(show top 50) (show all 200)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
14.2 SOS1 PTPN11 PIK3CA PDGFRB PDGFRA MAP2K2
2
Show member pathways
14.03 VCAN SOS1 PDGFRB PDGFRA MAP2K2 MAP2K1
3
Show member pathways
14.01 SOS1 PDGFRB PDGFRA MAP2K2 MAP2K1 KRAS
4
Show member pathways
13.92 VCAN SOS1 PTPN11 PIK3CA PDGFRB PDGFRA
5
Show member pathways
13.86 SOS1 PDGFRB PDGFRA MAP2K2 MAP2K1 KRAS
6
Show member pathways
13.83 SOS1 PDGFRB PDGFRA MAP2K2 MAP2K1 KRAS
7
Show member pathways
13.75 SOS1 PTPN11 PIK3CA PDGFRB PDGFRA MAP2K2
8
Show member pathways
13.73 SOS1 PDGFRB PDGFRA MAP2K2 MAP2K1 KRAS
9
Show member pathways
13.71 SOS1 PTPN11 PIK3CA PDGFRB PDGFRA MAP2K2
10
Show member pathways
13.64 SOS1 PTPN11 PIK3CA PDGFRB PDGFRA KRAS
11
Show member pathways
13.62 VCAN SOS1 PIK3CA MAP2K2 MAP2K1 KRAS
12
Show member pathways
13.58 SOS1 PTPN11 PIK3CA PDGFRB PDGFRA MAP2K2
13
Show member pathways
13.5 SOS1 PDGFRB PDGFRA MAP2K2 MAP2K1 KRAS
14
Show member pathways
13.49 SOS1 PDGFRB PDGFRA MAP2K2 MAP2K1 KRAS
15
Show member pathways
13.37 SOS1 MAP2K2 MAP2K1 KRAS HRAS EGF
16
Show member pathways
13.33 SOS1 PIK3CA MAP2K2 MAP2K1 KRAS HRAS
17
Show member pathways
13.29 SOS1 PTPN11 PIK3CA PDGFRB PDGFRA INS
18
Show member pathways
13.29 SOS1 PDGFRB PDGFRA MAP2K2 MAP2K1 KRAS
19
Show member pathways
13.23 SOS1 MAP2K2 MAP2K1 KRAS HRAS EGF
20
Show member pathways
13.21 SOS1 PIK3CA PDGFRB PDGFRA MAP2K2 MAP2K1
21
Show member pathways
13.18 VCAN SOS1 PDGFRB PDGFRA MAP2K2 MAP2K1
22
Show member pathways
13.15 SOS1 MAP2K2 MAP2K1 KRAS HRAS BRAF
23
Show member pathways
13.14 SOS1 PIK3CA PDGFRA MAP2K2 MAP2K1 KRAS
24
Show member pathways
13.12 SOS1 PDGFRB PDGFRA MAP2K2 MAP2K1 KRAS
25
Show member pathways
13.11 SOS1 PIK3CA PDGFRB PDGFRA MAP2K2 MAP2K1
26
Show member pathways
13.1 SOS1 PIK3CA MAP2K2 MAP2K1 KRAS HRAS
27
Show member pathways
13.1 SOS1 PTPN11 PIK3CA MAP2K2 MAP2K1 KRAS
28
Show member pathways
13.09 SOS1 PIK3CA PDGFRB PDGFRA MAP2K2 MAP2K1
29
Show member pathways
13.07 MAP2K2 MAP2K1 KRAS INS HRAS BRAF
30
Show member pathways
13.06 SOS1 PIK3CA MAP2K1 KRAS HRAS BRAF
31
Show member pathways
13.06 PIK3CA MAP2K2 MAP2K1 KRAS HRAS FBLN5
32
Show member pathways
13.04 SOS1 PIK3CA PDGFRB PDGFRA MAP2K2 MAP2K1
33
Show member pathways
13.03 SOS1 MAP2K2 MAP2K1 KRAS INS HRAS
34 13.03 SOS1 PIK3CA PDGFRB PDGFRA MAP2K2 MAP2K1
35
Show member pathways
13.01 SOS1 PIK3CA MAP2K2 MAP2K1 KRAS HRAS
36
Show member pathways
13.01 SOS1 PTPN11 PIK3CA MAP2K2 MAP2K1 KRAS
37
Show member pathways
12.98 SOS1 PTPN11 PIK3CA PDGFRB PDGFRA MAP2K2
38
Show member pathways
12.96 SOS1 PTPN11 PIK3CA MAP2K2 MAP2K1 KRAS
39
Show member pathways
12.95 SOS1 PTPN11 PIK3CA PDGFRB PDGFRA KRAS
40
Show member pathways
12.94 PIK3CA MAP2K2 MAP2K1 KRAS HRAS
41
Show member pathways
12.94 VCAN MFAP2 LOX FBN1 FBLN5 ELN
42 12.94 SOS1 PDGFRB PDGFRA MAP2K2 MAP2K1 KRAS
43
Show member pathways
12.91 SOS1 MAP2K2 MAP2K1 KRAS HRAS EGF
44
Show member pathways
12.91 PDGFRB PDGFRA MAP2K2 MAP2K1 KRAS HRAS
45
Show member pathways
12.88 SOS1 PIK3CA MAP2K2 MAP2K1 KRAS HRAS
46
Show member pathways
12.86 SOS1 PIK3CA MAP2K2 MAP2K1 KRAS HRAS
47
Show member pathways
12.85 SOS1 PTPN11 PIK3CA MAP2K2 MAP2K1 KRAS
48
Show member pathways
12.84 SOS1 PTPN11 PIK3CA PDGFRB PDGFRA KRAS
49
Show member pathways
12.84 SOS1 PTPN11 PIK3CA MAP2K2 MAP2K1 KRAS
50
Show member pathways
12.83 SOS1 PIK3CA PDGFRB PDGFRA MAP2K2 MAP2K1

GO Terms for Costello Syndrome

Cellular components related to Costello Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 extracellular region GO:0005576 9.97 VCAN MFAP2 MAP2K2 LOX INS FBN1
2 collagen-containing extracellular matrix GO:0062023 9.55 VCAN MFAP2 FBN1 FBLN5 ELN
3 microfibril GO:0001527 9.26 MFAP2 FBN1
4 extracellular matrix GO:0031012 9.02 VCAN LOX FBN1 FBLN5 ELN
5 elastic fiber GO:0071953 8.96 FBLN5 ELN

Biological processes related to Costello Syndrome according to GeneCards Suite gene sharing:

(show all 50)
# Name GO ID Score Top Affiliating Genes
1 signal transduction GO:0007165 10.32 SOS1 PDGFRB MAP2K1 KRAS INS HRAS
2 phosphorylation GO:0016310 10.15 PIK3CA PDGFRB PDGFRA MAP2K2 MAP2K1 BRAF
3 protein phosphorylation GO:0006468 10.13 PIK3CA PDGFRB PDGFRA MAP2K2 MAP2K1 BRAF
4 positive regulation of cell proliferation GO:0008284 10.1 PDGFRB PDGFRA KRAS INS HRAS EGF
5 positive regulation of gene expression GO:0010628 10 MAP2K1 KRAS INS HRAS EGF BRAF
6 chemotaxis GO:0006935 9.97 PDGFRB PDGFRA MAP2K1 HRAS
7 heart development GO:0007507 9.96 PTPN11 MAP2K2 MAP2K1 LOX FBN1
8 negative regulation of neuron apoptotic process GO:0043524 9.95 PIK3CA KRAS HRAS BRAF
9 animal organ morphogenesis GO:0009887 9.94 PDGFRA HRAS ELN BRAF
10 positive regulation of cell migration GO:0030335 9.93 PDGFRB PDGFRA INS HRAS EGF
11 activation of MAPK activity GO:0000187 9.9 PTPN11 MAP2K2 MAP2K1 EGF
12 cell chemotaxis GO:0060326 9.88 PDGFRB PDGFRA LOX
13 Ras protein signal transduction GO:0007265 9.88 SOS1 KRAS HRAS
14 phosphatidylinositol-mediated signaling GO:0048015 9.85 PIK3CA PDGFRB PDGFRA
15 thymus development GO:0048538 9.84 MAP2K2 MAP2K1 BRAF
16 positive regulation of axonogenesis GO:0050772 9.81 MAP2K2 MAP2K1 BRAF
17 wound healing GO:0042060 9.81 PDGFRB PDGFRA LOX INS
18 positive regulation of phosphatidylinositol 3-kinase signaling GO:0014068 9.8 PIK3CA PDGFRB PDGFRA INS
19 positive regulation of ERK1 and ERK2 cascade GO:0070374 9.8 PTPN11 PDGFRB PDGFRA MAP2K1 HRAS BRAF
20 platelet-derived growth factor receptor signaling pathway GO:0048008 9.77 PTPN11 PDGFRB PDGFRA
21 ERBB2 signaling pathway GO:0038128 9.76 SOS1 PIK3CA EGF
22 positive regulation of MAP kinase activity GO:0043406 9.76 PDGFRB KRAS HRAS EGF
23 ERK1 and ERK2 cascade GO:0070371 9.75 MAP2K2 MAP2K1 EGF
24 positive regulation of mitotic nuclear division GO:0045840 9.74 PDGFRB INS EGF
25 positive regulation of protein kinase B signaling GO:0051897 9.73 PTPN11 PIK3CA PDGFRB PDGFRA INS EGF
26 thyroid gland development GO:0030878 9.72 MAP2K2 MAP2K1 BRAF
27 positive regulation of production of miRNAs involved in gene silencing by miRNA GO:1903800 9.71 MAP2K2 MAP2K1
28 epidermal growth factor receptor signaling pathway GO:0007173 9.71 SOS1 PTPN11 PIK3CA EGF
29 regulation of stress-activated MAPK cascade GO:0032872 9.7 MAP2K2 MAP2K1
30 elastic fiber assembly GO:0048251 9.7 LOX FBLN5
31 embryonic eye morphogenesis GO:0048048 9.7 MFAP2 FBN1
32 regulation of protein heterodimerization activity GO:0043497 9.69 MAP2K2 MAP2K1
33 regulation of early endosome to late endosome transport GO:2000641 9.69 MAP2K2 MAP2K1
34 retina vasculature development in camera-type eye GO:0061298 9.69 PDGFRB PDGFRA
35 Bergmann glial cell differentiation GO:0060020 9.68 PTPN11 MAP2K1
36 trachea formation GO:0060440 9.68 MAP2K2 MAP2K1
37 response to isolation stress GO:0035900 9.68 KRAS HRAS
38 platelet-derived growth factor receptor-beta signaling pathway GO:0035791 9.66 PDGFRB LOX
39 regulation of Golgi inheritance GO:0090170 9.65 MAP2K2 MAP2K1
40 face development GO:0060324 9.65 MAP2K2 MAP2K1 BRAF
41 post-embryonic eye morphogenesis GO:0048050 9.64 MFAP2 FBN1
42 peptidyl-tyrosine phosphorylation GO:0018108 9.63 PDGFRB PDGFRA MAP2K2 MAP2K1 EGF BRAF
43 metanephric glomerular capillary formation GO:0072277 9.62 PDGFRB PDGFRA
44 epithelial cell proliferation involved in lung morphogenesis GO:0060502 9.62 MAP2K2 MAP2K1
45 positive regulation of cell proliferation by VEGF-activated platelet derived growth factor receptor signaling pathway GO:0038091 9.61 PDGFRB PDGFRA
46 cerebellar cortex formation GO:0021697 9.61 PTPN11 MAP2K1
47 positive regulation of phospholipase C activity GO:0010863 9.61 PDGFRB PDGFRA HRAS
48 regulation of axon regeneration GO:0048679 9.54 MAP2K2 MAP2K1 BRAF
49 extracellular matrix organization GO:0030198 9.5 VCAN PDGFRA MFAP2 LOX FBN1 FBLN5
50 MAPK cascade GO:0000165 9.28 SOS1 PDGFRB PDGFRA MAP2K2 MAP2K1 KRAS

Molecular functions related to Costello Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 kinase activity GO:0016301 9.73 PIK3CA PDGFRB PDGFRA MAP2K2 MAP2K1 BRAF
2 platelet-derived growth factor binding GO:0048407 9.4 PDGFRB PDGFRA
3 insulin receptor substrate binding GO:0043560 9.37 PTPN11 PIK3CA
4 protein tyrosine kinase activity GO:0004713 9.35 PDGFRB PDGFRA MAP2K2 MAP2K1 BRAF
5 extracellular matrix constituent conferring elasticity GO:0030023 9.33 FBN1 FBLN5 ELN
6 vascular endothelial growth factor binding GO:0038085 9.32 PDGFRB PDGFRA
7 nucleotide binding GO:0000166 9.17 PDGFRB PDGFRA MAP2K2 MAP2K1 KRAS HRAS

Sources for Costello Syndrome

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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