CLS
MCID: CFF002
MIFTS: 59

Coffin-Lowry Syndrome (CLS)

Categories: Endocrine diseases, Fetal diseases, Genetic diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Coffin-Lowry Syndrome

MalaCards integrated aliases for Coffin-Lowry Syndrome:

Name: Coffin-Lowry Syndrome 57 12 73 25 20 43 58 72 36 29 13 54 6 44 15 70
Cls 57 20 43 58 72
Mental Retardation with Osteocartilaginous Abnormalities 43
Syndrome, Coffin-Lowry 39
Coffin Lowry Syndrome 53
Coffin Syndrome 20

Characteristics:

Orphanet epidemiological data:

58
coffin-lowry syndrome
Inheritance: X-linked dominant; Prevalence: 1-9/100000 (Europe); Age of onset: Neonatal;

OMIM®:

57 (Updated 05-Apr-2021)
Inheritance:
x-linked dominant

Miscellaneous:
milder expression in female heterozygotes
clinical features in females include mild mental retardation (80%), short stature (50%), prominent forehead, and coarse facies
approximately 70-80% of cases are de novo and sporadic
incidence of 1 in 50,000 to 1 in 100,000


HPO:

31
coffin-lowry syndrome:
Onset and clinical course death in early adulthood
Inheritance sporadic x-linked dominant inheritance


Classifications:

Orphanet: 58  
Rare neurological diseases
Rare endocrine diseases
Developmental anomalies during embryogenesis


Summaries for Coffin-Lowry Syndrome

NINDS : 53 Coffin-Lowry syndrome is a rare genetic disorder characterized by craniofacial (head and facial) and skeletal abnormalities, delayed intellectual development, short stature, and hypotonia. Characteristic facial features may include an underdeveloped upper jaw bone (maxillary hypoplasia), a broad nose, protruding nostrils (nares), an abnormally prominent brow, down-slanting eyelid folds (palpebral fissures), widely spaced eyes (hypertelorism), large low-set ears, and unusually thick eyebrows. Skeletal abnormalities may include abnormal front-to-back and side-to-side curvature of the spine (kyphoscoliosis), unusual prominence of the breastbone (pigeon chest, or pectus carinatum), dental abnormalities, and short, hyperextensible, tapered fingers. Other features may include feeding and respiratory problems, developmental delay, hearing impairment, awkward gait, stimulus-induced drop episodes, and heart and kidney involvement. The disorder affects males and females in equal numbers, but symptoms are usually more severe in males. The disorder is caused by a defective gene, RSK2, which is found in 1996 on the X chromosome (Xp22.2-p22.1). Thus, the syndrome is typically more severe in males because males have only one X chromosome, while females have two. It is unclear how changes (mutations) in the DNA structure of the gene lead to the clinical findings.

MalaCards based summary : Coffin-Lowry Syndrome, also known as cls, is related to learning disability and non-syndromic x-linked intellectual disability, and has symptoms including seizures An important gene associated with Coffin-Lowry Syndrome is RPS6KA3 (Ribosomal Protein S6 Kinase A3), and among its related pathways/superpathways are MAPK signaling pathway and Oocyte meiosis. Affiliated tissues include skeletal muscle, cerebellum and brain, and related phenotypes are intellectual disability and frontal bossing

Disease Ontology : 12 A syndrome that is characterized by skeletal malformations, growth retardation, hearing deficit, paroxysmal movement disorders, and cognitive impairment in affected males and some carrier females, and has material basis in mutation in the RSK2 gene on chromosome Xp22.

MedlinePlus Genetics : 43 Coffin-Lowry syndrome is a condition that affects many parts of the body. The signs and symptoms are usually more severe in males than in females, although the features of this disorder range from very mild to severe in affected women.Males with Coffin-Lowry syndrome typically have severe to profound intellectual disability and delayed development. Affected women may be cognitively normal, or they may have intellectual disability ranging from mild to profound. Beginning in childhood or adolescence, some people with this condition experience brief episodes of collapse when excited or startled by a loud noise. These attacks are called stimulus-induced drop episodes (SIDEs).Most affected males and some affected females have distinctive facial features including a prominent forehead, widely spaced and downward-slanting eyes, a short nose with a wide tip, and a wide mouth with full lips. These features become more pronounced with age. Soft hands with short, tapered fingers are also characteristic of Coffin-Lowry syndrome. Additional features of this condition include short stature, an unusually small head (microcephaly), progressive abnormal curvature of the spine (kyphoscoliosis), and other skeletal abnormalities.

GARD : 20 Coffin-Lowry syndrome is a genetic condition that affects many parts of the body. The signs and symptoms and severity vary from person to person; however, males are typically more severely affected than females. Signs and symptoms may include distinct facial findings, short stature, microcephaly, kyphoscoliosis, other skeletal abnormalities, stimulus-induced drop episodes, intellectual disability and delayed development. Mutations in the RPS6KA3 gene cause the syndrome. It is inherited in an X-linked dominant fashion. Treatment is symptomatic.

OMIM® : 57 Coffin-Lowry syndrome is a rare form of X-linked mental retardation characterized by skeletal malformations, growth retardation, hearing deficit, paroxysmal movement disorders, and cognitive impairment in affected males and some carrier females (Kesler et al., 2007). Hendrich and Bickmore (2001) reviewed human disorders which share in common defects of chromatin structure or modification, including the ATR-X spectrum of disorders (301040), ICF syndrome (242860), Rett syndrome (312750), Rubinstein-Taybi syndrome (180849), and Coffin-Lowry syndrome. Pereira et al. (2010) provided a review of Coffin-Lowry syndrome. Mutation in the RPS6KA3 gene can also cause nonsyndromic X-linked mental retardation-19 (MRX19; 300844), a milder disorder without skeletal anomalies. (303600) (Updated 05-Apr-2021)

KEGG : 36 Coffin-Lowry syndrome (CLS) is a syndromic form of X-linked mental retardation, which is characterized in male patients by psychomotor and growth retardation and various skeletal anomalies. Typical facial changes and specific clinical and radiological signs in the hand are useful aids in the diagnosis. Mutations in the RSK2 (RPS6KA3) gene cause CLS. The RPS6KA3 gene encodes RSK2 that is involved with signaling within cells.

UniProtKB/Swiss-Prot : 72 Coffin-Lowry syndrome: An X-linked mental retardation associated with facial and digital dysmorphisms, progressive skeletal malformations, growth retardation, hearing deficit and paroxysmal movement disorders.

Wikipedia : 73 Coffin-Lowry syndrome is a genetic disorder that is X-linked dominant and which causes severe mental... more...

GeneReviews: NBK1346

Related Diseases for Coffin-Lowry Syndrome

Diseases related to Coffin-Lowry Syndrome via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 149)
# Related Disease Score Top Affiliating Genes
1 learning disability 29.9 RPS6KA3 MECP2 H2AC18
2 non-syndromic x-linked intellectual disability 29.6 RPS6KA3 OPHN1 MECP2 ATRX
3 disease of mental health 27.8 RPS6KA3 RPS6KA1 OPHN1 MECP2 H2AC18 FOS
4 cenani-lenz syndactyly syndrome 11.3
5 symptomatic form of coffin-lowry syndrome in female carriers 11.3
6 coffin syndrome 1 11.2
7 craniosynostosis with fibular aplasia 11.2
8 split-hand with obstructive uropathy, spina bifida, and diaphragmatic defects 10.9
9 alacrima, achalasia, and mental retardation syndrome 10.6
10 hypotonia 10.6
11 hypertelorism 10.5
12 scoliosis 10.4
13 branchiootic syndrome 1 10.4
14 hyperekplexia 10.4
15 quadriplegia 10.4
16 adrenal cortical adenocarcinoma 10.3 RPS6KA6 RPS6KA1
17 aganglionosis, total intestinal 10.2 EDNRB-AS1 EDNRB
18 atrial standstill 1 10.2
19 coffin-siris syndrome 1 10.2
20 sleep apnea 10.2
21 sensorineural hearing loss 10.2
22 microcephaly 10.2
23 hydrocephalus 10.2
24 dilated cardiomyopathy 10.2
25 restrictive cardiomyopathy 10.2
26 congestive heart failure 10.2
27 paraplegia 10.2
28 cardiomyopathy, familial hypertrophic, 4 10.2 RPS6KA3 RPS6KA2 RPS6KA1
29 mitochondrial dna depletion syndrome 12a 10.2 EDNRB-AS1 EDNRB
30 hirschsprung disease 2 10.2 EDNRB-AS1 EDNRB
31 waardenburg syndrome type 4 10.2 EDNRB-AS1 EDNRB
32 cerebral hypoxia 10.2 FOS CREB1
33 dyskeratosis congenita, autosomal dominant 3 10.1 RPS6KA6 RPS6KA3 RPS6KA2 RPS6KA1
34 uveitis 10.1
35 macular retinal edema 10.1
36 apnea, obstructive sleep 10.1
37 hyperglycinuria 10.1
38 hypochondroplasia 10.1
39 pectus excavatum 10.1
40 spondylolisthesis 10.1
41 telecanthus 10.1
42 corpus callosum, agenesis of 10.1
43 hydrops fetalis, nonimmune 10.1
44 iminoglycinuria 10.1
45 johanson-blizzard syndrome 10.1
46 abnormal hair, joint laxity, and developmental delay 10.1
47 body mass index quantitative trait locus 11 10.1
48 opitz-kaveggia syndrome 10.1
49 retinoschisis 1, x-linked, juvenile 10.1
50 body mass index quantitative trait locus 9 10.1

Graphical network of the top 20 diseases related to Coffin-Lowry Syndrome:



Diseases related to Coffin-Lowry Syndrome

Symptoms & Phenotypes for Coffin-Lowry Syndrome

Human phenotypes related to Coffin-Lowry Syndrome:

58 31 (show top 50) (show all 102)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 intellectual disability 58 31 hallmark (90%) Very frequent (99-80%) HP:0001249
2 frontal bossing 58 31 hallmark (90%) Very frequent (99-80%) HP:0002007
3 neurological speech impairment 58 31 hallmark (90%) Very frequent (99-80%) HP:0002167
4 scoliosis 58 31 hallmark (90%) Very frequent (99-80%) HP:0002650
5 kyphosis 58 31 hallmark (90%) Very frequent (99-80%) HP:0002808
6 coarse facial features 58 31 hallmark (90%) Very frequent (99-80%) HP:0000280
7 delayed skeletal maturation 58 31 hallmark (90%) Very frequent (99-80%) HP:0002750
8 craniofacial hyperostosis 58 31 hallmark (90%) Very frequent (99-80%) HP:0004493
9 depressed nasal bridge 58 31 hallmark (90%) Very frequent (99-80%) HP:0005280
10 hypertelorism 58 31 hallmark (90%) Very frequent (99-80%) HP:0000316
11 widely spaced teeth 58 31 hallmark (90%) Very frequent (99-80%) HP:0000687
12 pectus carinatum 58 31 hallmark (90%) Very frequent (99-80%) HP:0000768
13 anteverted nares 58 31 hallmark (90%) Very frequent (99-80%) HP:0000463
14 short stature 58 31 hallmark (90%) Very frequent (99-80%) HP:0004322
15 thick lower lip vermilion 58 31 hallmark (90%) Very frequent (99-80%) HP:0000179
16 thick nasal alae 58 31 hallmark (90%) Very frequent (99-80%) HP:0009928
17 abnormal form of the vertebral bodies 58 31 hallmark (90%) Very frequent (99-80%) HP:0003312
18 everted lower lip vermilion 58 31 hallmark (90%) Very frequent (99-80%) HP:0000232
19 epicanthus 58 31 hallmark (90%) Very frequent (99-80%) HP:0000286
20 pectus excavatum 58 31 hallmark (90%) Very frequent (99-80%) HP:0000767
21 downslanted palpebral fissures 58 31 hallmark (90%) Very frequent (99-80%) HP:0000494
22 open mouth 58 31 hallmark (90%) Very frequent (99-80%) HP:0000194
23 brachydactyly 58 31 hallmark (90%) Very frequent (99-80%) HP:0001156
24 joint hyperflexibility 58 31 hallmark (90%) Very frequent (99-80%) HP:0005692
25 hypodontia 58 31 hallmark (90%) Very frequent (99-80%) HP:0000668
26 abnormality of dental morphology 58 31 hallmark (90%) Very frequent (99-80%) HP:0006482
27 severe global developmental delay 58 31 hallmark (90%) Very frequent (99-80%) HP:0011344
28 abnormal diaphysis morphology 58 31 hallmark (90%) Very frequent (99-80%) HP:0000940
29 large hands 58 31 hallmark (90%) Very frequent (99-80%) HP:0001176
30 tapered finger 58 31 hallmark (90%) Very frequent (99-80%) HP:0001182
31 broad finger 58 31 hallmark (90%) Very frequent (99-80%) HP:0001500
32 hypotonia 31 hallmark (90%) HP:0001252
33 gait disturbance 58 31 frequent (33%) Frequent (79-30%) HP:0001288
34 high palate 58 31 frequent (33%) Frequent (79-30%) HP:0000218
35 narrow palate 58 31 frequent (33%) Frequent (79-30%) HP:0000189
36 pes planus 58 31 frequent (33%) Frequent (79-30%) HP:0001763
37 microcephaly 58 31 frequent (33%) Frequent (79-30%) HP:0000252
38 feeding difficulties in infancy 58 31 frequent (33%) Frequent (79-30%) HP:0008872
39 hyperconvex fingernails 58 31 frequent (33%) Frequent (79-30%) HP:0001812
40 wide mouth 58 31 frequent (33%) Frequent (79-30%) HP:0000154
41 hypoplasia of the maxilla 58 31 frequent (33%) Frequent (79-30%) HP:0000327
42 protruding ear 58 31 frequent (33%) Frequent (79-30%) HP:0000411
43 ventriculomegaly 58 31 frequent (33%) Frequent (79-30%) HP:0002119
44 redundant skin 58 31 frequent (33%) Frequent (79-30%) HP:0001582
45 short distal phalanx of finger 58 31 frequent (33%) Frequent (79-30%) HP:0009882
46 wide nose 58 31 frequent (33%) Frequent (79-30%) HP:0000445
47 hypoplastic fingernail 58 31 frequent (33%) Frequent (79-30%) HP:0001804
48 progressive spasticity 58 31 frequent (33%) Frequent (79-30%) HP:0002191
49 narrow iliac wings 58 31 frequent (33%) Frequent (79-30%) HP:0002868
50 pseudoepiphyses of the metacarpals 58 31 frequent (33%) Frequent (79-30%) HP:0009193

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Neurologic Central Nervous System:
seizures
hypotonia
mental retardation
ventricular dilatation

Head And Neck Mouth:
high palate
narrow palate
thick, everted lower lip
large, open mouth

Head And Neck Eyes:
hypertelorism
downslanting palpebral fissures
arched eyebrows
heavy eyebrows

Head And Neck Head:
microcephaly

Growth Height:
short stature
normal birth length

Head And Neck Teeth:
hypodontia
malocclusion
wide-spaced teeth
large medial incisors

Skeletal Pelvis:
coxa valga
narrow iliac wings

Genitourinary Internal Genitalia Female:
uterine prolapse

Growth Weight:
normal birth weight
weight less than 3rd percentile

Skeletal:
delayed bone age

Head And Neck Ears:
sensorineural hearing loss
prominent ears

Cardiovascular Heart:
mitral insufficiency

Skeletal Limbs:
forearm fullness
extensible joints

Skeletal Spine:
scoliosis
kyphosis
lumbar gibbus deformity

Genitourinary External Genitalia Male:
inguinal hernia

Chest External Features:
pectus carinatum
pectus excavatum

Head And Neck Nose:
anteverted nares
thick nasal septum
broad nose
thick alae nasi

Skin Nails Hair Nails:
hyperconvex fingernails
small fingernails

Abdomen Gastrointestinal:
rectal prolapse

Skin Nails Hair Skin:
cutis marmorata
transverse palmar creases
loose skin
dependent acrocyanosis

Skeletal Feet:
flat feet

Skeletal Hands:
short metacarpals
transverse palmar creases
hyperextensible fingers
tapering fingers
large, soft hands
more
Head And Neck Face:
coarse facies
prominent chin
prominent brow

Skeletal Skull:
delayed closure of anterior fontanel
thick calvarium
hypoplastic sinuses
hypoplastic mastoids

Chest Ribs Sternum Clavicles And Scapulae:
short bifid sternum

Skin Nails Hair Hair:
straight, coarse hair

Clinical features from OMIM®:

303600 (Updated 05-Apr-2021)

UMLS symptoms related to Coffin-Lowry Syndrome:


seizures

GenomeRNAi Phenotypes related to Coffin-Lowry Syndrome according to GeneCards Suite gene sharing:

26 (show all 18)
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased viability GR00055-A-1 10.65 RPS6KA2
2 Decreased viability GR00055-A-2 10.65 RPS6KA2
3 Decreased viability GR00055-A-3 10.65 RPS6KA2
4 Decreased viability GR00106-A-0 10.65 PLD1
5 Decreased viability GR00221-A-1 10.65 PHKA2 PLD1 RPS6KA1 RPS6KA5 RPS6KA6
6 Decreased viability GR00221-A-2 10.65 PHKA2 RPS6KA1 RPS6KA3 RPS6KA5 RPS6KA6
7 Decreased viability GR00221-A-3 10.65 PHKA2 PLD1 RPS6KA1 RPS6KA2
8 Decreased viability GR00221-A-4 10.65 PHKA2 RPS6KA1 RPS6KA6 RPS6KA4
9 Decreased viability GR00249-S 10.65 RPS6KA2 RPS6KA5
10 Decreased viability GR00301-A 10.65 RPS6KA1
11 Decreased viability GR00342-S-1 10.65 PHKA2 RPS6KA1 RPS6KA2 RPS6KA3 RPS6KA5 RPS6KA4
12 Decreased viability GR00342-S-2 10.65 PHKA2 RPS6KA2 RPS6KA6 RPS6KA4
13 Decreased viability GR00342-S-3 10.65 PHKA2 RPS6KA6
14 Decreased viability GR00381-A-1 10.65 RPS6KA2
15 Decreased viability GR00386-A-1 10.65 RPS6KA1
16 Decreased human cytomegalovirus (HCMV) strain AD169 replication GR00248-A 9.46 RPS6KA2 RPS6KA3 RPS6KA4 RPS6KA6
17 Decreased cell viability after pRB stimulation GR00230-A-1 8.96 RPS6KA5
18 Increased telomerase activity GR00156-A 8.32 RPS6KB2

MGI Mouse Phenotypes related to Coffin-Lowry Syndrome:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 cardiovascular system MP:0005385 9.73 ATF4 ATRX CREB1 EDNRB FOS MECP2
2 mortality/aging MP:0010768 9.44 ATF4 ATRX CAMP CREB1 EDNRB FOS

Drugs & Therapeutics for Coffin-Lowry Syndrome

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Chewing and Swallowing Training Program in Coffin-Lowry Syndrome: A Case Report Completed NCT04199546

Search NIH Clinical Center for Coffin-Lowry Syndrome

Cochrane evidence based reviews: coffin-lowry syndrome

Genetic Tests for Coffin-Lowry Syndrome

Genetic tests related to Coffin-Lowry Syndrome:

# Genetic test Affiliating Genes
1 Coffin-Lowry Syndrome 29 RPS6KA3

Anatomical Context for Coffin-Lowry Syndrome

MalaCards organs/tissues related to Coffin-Lowry Syndrome:

40
Skeletal Muscle, Cerebellum, Brain, Bone, Spinal Cord, Lung, Skin

Publications for Coffin-Lowry Syndrome

Articles related to Coffin-Lowry Syndrome:

(show top 50) (show all 231)
# Title Authors PMID Year
1
A female with Coffin-Lowry syndrome and "cataplexy". 54 61 6 57 25
12558110 2002
2
Unreported RSK2 missense mutation in two male sibs with an unusually mild form of Coffin-Lowry syndrome. 25 6 57 54 61
10528858 1999
3
Coffin-Lowry syndrome. 6 57 25 61
19888300 2010
4
Cardiomyopathy in Coffin-Lowry syndrome. 6 57 61 25
15214012 2004
5
A new dominant gene mental retardation syndrome. Association with small stature, tapering fingers, characteristic facies, and possible hydrocephalus. 25 57 6
5581017 1971
6
The historical Coffin-Lowry syndrome family revisited: identification of two novel mutations of RPS6KA3 in three male patients. 61 57 6
25044551 2014
7
The first large duplication of the RSK2 gene identified in a Coffin-Lowry syndrome patient. 54 61 6 25
17717706 2007
8
Altered neurodevelopment associated with mutations of RSK2: a morphometric MRI study of Coffin-Lowry syndrome. 25 57 61 54
17318637 2007
9
Identification of novel mutations in the RSK2 gene (RPS6KA3) in patients with Coffin-Lowry syndrome. 57 25 54 61
16879200 2006
10
A novel RSK2 (RPS6KA3) gene mutation associated with abnormal brain MRI findings in a family with Coffin-Lowry syndrome. 61 57 54 25
16691578 2006
11
Intronic L1 insertion and F268S, novel mutations in RPS6KA3 (RSK2) causing Coffin-Lowry syndrome. 6 25 61 54
14986828 2003
12
Cognitive impairment in Coffin-Lowry syndrome correlates with reduced RSK2 activation. 54 61 25 57
11160957 2001
13
Germline mosaicism in Coffin-Lowry syndrome. 6 25 54 61
9887375 1998
14
Mutations in the kinase Rsk-2 associated with Coffin-Lowry syndrome. 6 61 57
8955270 1996
15
Mutations in the RSK2(RPS6KA3) gene cause Coffin-Lowry syndrome and nonsyndromic X-linked mental retardation. 57 25 61
17100996 2006
16
Coffin-Lowry syndrome: a 20-year follow-up and review of long-term outcomes. 61 25 57
12210291 2002
17
Cognitive function in Coffin-Lowry syndrome. 61 25 57
12030896 2002
18
Adult with an interstitial deletion of chromosome 10 [del(10)(q25. 1q25.3)]: overlap with Coffin-Lowry syndrome. 57 25 61
11078556 2000
19
Cardiac involvement in Coffin-Lowry syndrome. 57 25 61
10342551 1999
20
Mutation analysis of the RSK2 gene in Coffin-Lowry patients: extensive allelic heterogeneity and a high rate of de novo mutations. 6 25 61
9837815 1998
21
Drop episodes in Coffin-Lowry syndrome: exaggerated startle responses treated with clonazepam. 57 25 61
9744638 1998
22
The Coffin-Lowry syndrome. 61 25 57
3290491 1988
23
Unusual splice-site mutations in the RSK2 gene and suggestion of genetic heterogeneity in Coffin-Lowry syndrome. 6 54 61
11992250 2002
24
A missense mutation in RPS6KA3 (RSK2) responsible for non-specific mental retardation. 25 57
10319851 1999
25
Novel mutations in Rsk-2, the gene for Coffin-Lowry syndrome (CLS). 6 54 61
10094187 1999
26
Rapid immunoblot and kinase assay tests for a syndromal form of X linked mental retardation: Coffin-Lowry syndrome. 54 57 61
9832033 1998
27
RSK2 enzymatic assay as a second level diagnostic tool in Coffin-Lowry syndrome. 25 54 61
17586481 2007
28
The movement disorders of Coffin-Lowry syndrome. 54 25 61
15668049 2005
29
RSK2 gene mutations in Coffin-Lowry syndrome with drop episodes. 25 61 54
15668050 2005
30
Delineation of the mechanisms of aberrant splicing caused by two unusual intronic mutations in the RSK2 gene involved in Coffin-Lowry syndrome. 54 61 25
14973203 2004
31
Expression of the RSK2 gene during early human development. 25 54 61
14678837 2004
32
Coffin-Lowry syndrome in a patient from the Cook Islands confirmed by the presence of a unique mutation. 6 61
12439904 2002
33
Expression analysis of RSK gene family members: the RSK2 gene, mutated in Coffin-Lowry syndrome, is prominently expressed in brain structures essential for cognitive function and learning. 61 25 54
12393804 2002
34
X-linked Coffin-Lowry syndrome (CLS, MIM 303600, RPS6KA3 gene, protein product known under various names: pp90(rsk2), RSK2, ISPK, MAPKAP1). 54 25 61
11896450 2002
35
Prenatal diagnosis in Coffin-Lowry syndrome demonstrates germinal mosaicism confirmed by mutation analysis. 25 61 54
11746134 2001
36
Mutations in the X-linked RSK2 gene (RPS6KA3) in patients with Coffin-Lowry syndrome. 61 54 25
11180593 2001
37
A novel ribosomal S6-kinase (RSK4; RPS6KA6) is commonly deleted in patients with complex X-linked mental retardation. 61 54 25
10644430 1999
38
"Cataplexy" in Coffin-Lowry syndrome. 61 57
9719387 1998
39
Crossover analysis in a British family suggests that Coffin-Lowry syndrome maps to a 3.4-cM interval in Xp22. 61 57
8585574 1995
40
The association between Coffin-Lowry syndrome and psychosis: a family study. 61 57
7841685 1994
41
Construction of a high-resolution linkage map for Xp22.1-p22.2 and refinement of the genetic localization of the Coffin-Lowry syndrome gene. 61 57
8001973 1994
42
Pleiotropy in Coffin-Lowry syndrome: sensorineural hearing deficit and premature tooth loss as early manifestations. 57 61
7681250 1993
43
Confirmation and refinement of the genetic localization of the Coffin-Lowry syndrome locus in Xp22.1-p22.2. 57 61
1349200 1992
44
Coffin-Lowry syndrome associated with calcium pyrophosphate crystal deposition in the ligamenta flava. 61 57
1735205 1992
45
Coffin-Lowry syndrome: a multicenter study. 57 61
3069251 1988
46
A family with the Coffin Lowry syndrome revisited: localization of CLS to Xp21-pter. 61 57
3177468 1988
47
Probable localisation of the Coffin-Lowry locus in Xp22.2-p22.1 by multipoint linkage analysis. 57 61
3177469 1988
48
Coffin-Lowry syndrome and schizophrenia: a family report. 61 57
3625766 1987
49
Autopsy findings in two adult siblings with Coffin-Lowry syndrome. 57 61
3130866 1987
50
The Coffin-Lowry syndrome. A study of two new index patients and their families. 61 57
6519116 1984

Variations for Coffin-Lowry Syndrome

ClinVar genetic disease variations for Coffin-Lowry Syndrome:

6 (show top 50) (show all 65)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 RPS6KA3 NM_004586.3(RPS6KA3):c.451_452del (p.Arg151fs) Deletion Pathogenic 11656 rs1603426295 GRCh37: X:20212341-20212342
GRCh38: X:20194223-20194224
2 RPS6KA3 NM_004586.3(RPS6KA3):c.2065C>T (p.Gln689Ter) SNV Pathogenic 11657 rs122454128 GRCh37: X:20174262-20174262
GRCh38: X:20156144-20156144
3 RPS6KA3 NM_004586.3(RPS6KA3):c.566T>A (p.Ile189Lys) SNV Pathogenic 11660 rs122454130 GRCh37: X:20211632-20211632
GRCh38: X:20193514-20193514
4 RPS6KA3 NM_004586.3(RPS6KA3):c.486+3A>G SNV Pathogenic 11661 rs1603426293 GRCh37: X:20212304-20212304
GRCh38: X:20194186-20194186
5 RPS6KA3 RPS6KA3, IVS5, A-G, -11 SNV Pathogenic 11662 GRCh37:
GRCh38:
6 RPS6KA3 NM_004586.3(RPS6KA3):c.2144del (p.Ser715fs) Deletion Pathogenic 11663 rs1603417213 GRCh37: X:20173595-20173595
GRCh38: X:20155477-20155477
7 RPS6KA3 RPS6KA3, IVS12, A-G, -2 SNV Pathogenic 11664 GRCh37:
GRCh38:
8 RPS6KA3 RPS6KA3, IVS3, L1 INS, -8 Insertion Pathogenic 11665 GRCh37:
GRCh38:
9 RPS6KA3 NM_004586.3(RPS6KA3):c.803T>C (p.Phe268Ser) SNV Pathogenic 11666 rs122454131 GRCh37: X:20204456-20204456
GRCh38: X:20186338-20186338
10 RPS6KA3 NM_004586.3(RPS6KA3):c.1428_1430del (p.Ile477del) Deletion Pathogenic 11667 rs1603420690 GRCh37: X:20187533-20187535
GRCh38: X:20169415-20169417
11 RPS6KA3 RPS6KA3, DUP EXONS 17-20, NT1959 Duplication Pathogenic 11668 GRCh37:
GRCh38:
12 RPS6KA3 RPS6KA3, 7.2-KB DEL Deletion Pathogenic 190301 GRCh37:
GRCh38:
13 RPS6KA3 NM_004586.3(RPS6KA3):c.913C>T (p.Arg305Ter) SNV Pathogenic 225519 GRCh37: X:20195135-20195135
GRCh38: X:20177017-20177017
14 RPS6KA3 RPS6KA3, 187-BP DEL, NT406 Deletion Pathogenic 11650 GRCh37:
GRCh38:
15 RPS6KA3 NM_004586.3(RPS6KA3):c.224G>T (p.Gly75Val) SNV Pathogenic 11651 rs122454124 GRCh37: X:20227425-20227425
GRCh38: X:20209307-20209307
16 RPS6KA3 NM_004586.3(RPS6KA3):c.679T>G (p.Ser227Ala) SNV Pathogenic 11652 rs122454125 GRCh37: X:20206041-20206041
GRCh38: X:20187923-20187923
17 RPS6KA3 NM_004586.3(RPS6KA3):c.244G>T (p.Val82Phe) SNV Pathogenic 11653 rs122454126 GRCh37: X:20222221-20222221
GRCh38: X:20204103-20204103
18 RPS6KA3 NM_004586.3(RPS6KA3):c.326-1G>C SNV Pathogenic 11654 rs587776755 GRCh37: X:20213264-20213264
GRCh38: X:20195146-20195146
19 RPS6KA3 NM_004586.3(RPS6KA3):c.327del (p.Arg110fs) Deletion Pathogenic 488448 rs1555943492 GRCh37: X:20213262-20213262
GRCh38: X:20195144-20195144
20 RPS6KA3 NM_004586.3(RPS6KA3):c.328C>T (p.Arg110Ter) SNV Pathogenic 547761 rs1555943484 GRCh37: X:20213261-20213261
GRCh38: X:20195143-20195143
21 RPS6KA3 NM_004586.3(RPS6KA3):c.334C>T (p.Arg112Ter) SNV Pathogenic 547762 rs1555943479 GRCh37: X:20213255-20213255
GRCh38: X:20195137-20195137
22 RPS6KA3 NM_004586.3(RPS6KA3):c.1845del (p.Gly614_Tyr615insTer) Deletion Pathogenic 566835 rs1569190602 GRCh37: X:20179876-20179876
GRCh38: X:20161758-20161758
23 RPS6KA3 NM_004586.3(RPS6KA3):c.932T>G (p.Leu311Ter) SNV Pathogenic 637053 rs1603422403 GRCh37: X:20195116-20195116
GRCh38: X:20176998-20176998
24 RPS6KA3 NM_004586.3(RPS6KA3):c.2196del (p.Ile735fs) Deletion Pathogenic 635336 rs1603417191 GRCh37: X:20173543-20173543
GRCh38: X:20155425-20155425
25 RPS6KA3 NM_004586.3(RPS6KA3):c.727C>T (p.Arg243Ter) SNV Pathogenic 651889 rs1603425345 GRCh37: X:20205993-20205993
GRCh38: X:20187875-20187875
26 RPS6KA3 NM_004586.3(RPS6KA3):c.1996C>T (p.Gln666Ter) SNV Pathogenic 652883 rs1603417440 GRCh37: X:20174331-20174331
GRCh38: X:20156213-20156213
27 RPS6KA3 NM_004586.3(RPS6KA3):c.1959+2dup Duplication Pathogenic 374040 rs1057518853 GRCh37: X:20179759-20179760
GRCh38: X:20161641-20161642
28 RPS6KA3 NM_004586.3(RPS6KA3):c.913C>T (p.Arg305Ter) SNV Pathogenic 225519 GRCh37: X:20195135-20195135
GRCh38: X:20177017-20177017
29 RPS6KA3 NM_004586.3(RPS6KA3):c.632-1G>C SNV Pathogenic 95150 rs398124177 GRCh37: X:20206089-20206089
GRCh38: X:20187971-20187971
30 RPS6KA3 NM_004586.3(RPS6KA3):c.243+1G>A SNV Pathogenic 803734 rs1603428228 GRCh37: X:20227405-20227405
GRCh38: X:20209287-20209287
31 RPS6KA3 NM_004586.3(RPS6KA3):c.1765-2A>C SNV Pathogenic 945691 GRCh37: X:20181160-20181160
GRCh38: X:20163042-20163042
32 RPS6KA3 NM_004586.3(RPS6KA3):c.2186G>A (p.Arg729Gln) SNV Pathogenic 11658 rs28935171 GRCh37: X:20173553-20173553
GRCh38: X:20155435-20155435
33 RPS6KA3 NM_004586.3(RPS6KA3):c.1894C>T (p.Arg632Ter) SNV Pathogenic 426465 rs1085307639 GRCh37: X:20179827-20179827
GRCh38: X:20161709-20161709
34 RPS6KA3 NM_004586.3(RPS6KA3):c.2185C>T (p.Arg729Trp) SNV Pathogenic/Likely pathogenic 547768 rs1555924331 GRCh37: X:20173554-20173554
GRCh38: X:20155436-20155436
35 RPS6KA3 NM_004586.3(RPS6KA3):c.649G>A (p.Glu217Lys) SNV Likely pathogenic 620064 GRCh37: X:20206071-20206071
GRCh38: X:20187953-20187953
36 RPS6KA3 NM_004586.3(RPS6KA3):c.629C>T (p.Thr210Ile) SNV Likely pathogenic 559935 rs1325953089 GRCh37: X:20206617-20206617
GRCh38: X:20188499-20188499
37 RPS6KA3 NM_004586.3(RPS6KA3):c.1823T>G (p.Leu608Arg) SNV Likely pathogenic 973946 GRCh37: X:20181100-20181100
GRCh38: X:20162982-20162982
38 RPS6KA3 NM_004586.3(RPS6KA3):c.1507G>C (p.Asp503His) SNV Likely pathogenic 975768 GRCh37: X:20185802-20185802
GRCh38: X:20167684-20167684
39 RPS6KA3 NM_004586.3(RPS6KA3):c.212T>G (p.Leu71Ter) SNV Likely pathogenic 974962 GRCh37: X:20227437-20227437
GRCh38: X:20209319-20209319
40 RPS6KA3 NM_004586.3(RPS6KA3):c.748G>A (p.Asp250Asn) SNV Likely pathogenic 803733 rs1603425338 GRCh37: X:20205972-20205972
GRCh38: X:20187854-20187854
41 RPS6KA3 NM_004586.3(RPS6KA3):c.774+1G>C SNV Likely pathogenic 547764 rs1555939331 GRCh37: X:20205945-20205945
GRCh38: X:20187827-20187827
42 RPS6KA3 NM_004586.3(RPS6KA3):c.1308C>A (p.Cys436Ter) SNV Likely pathogenic 547766 rs1160828151 GRCh37: X:20190909-20190909
GRCh38: X:20172791-20172791
43 RPS6KA3 NM_004586.3(RPS6KA3):c.1964del (p.Leu655fs) Deletion Likely pathogenic 547767 rs1555924704 GRCh37: X:20174363-20174363
GRCh38: X:20156245-20156245
44 RPS6KA3 NM_004586.3(RPS6KA3):c.646A>G (p.Lys216Glu) SNV Likely pathogenic 522803 rs1555939456 GRCh37: X:20206074-20206074
GRCh38: X:20187956-20187956
45 RPS6KA3 NM_004586.3(RPS6KA3):c.340C>T (p.Arg114Trp) SNV Likely pathogenic 11655 rs122454127 GRCh37: X:20213249-20213249
GRCh38: X:20195131-20195131
46 RPS6KA3 NM_004586.3(RPS6KA3):c.1762G>C (p.Glu588Gln) SNV Likely pathogenic 438301 rs1555927532 GRCh37: X:20183019-20183019
GRCh38: X:20164901-20164901
47 RPS6KA3 NM_004586.3(RPS6KA3):c.764G>A (p.Gly255Asp) SNV Uncertain significance 547763 rs1555939335 GRCh37: X:20205956-20205956
GRCh38: X:20187838-20187838
48 RPS6KA3 NM_004586.3(RPS6KA3):c.894_902del (p.Arg300_Leu302del) Deletion Uncertain significance 547765 rs1555933769 GRCh37: X:20195146-20195154
GRCh38: X:20177028-20177036
49 RPS6KA3 NM_004586.3(RPS6KA3):c.754T>C (p.Trp252Arg) SNV Uncertain significance 570134 rs1569215936 GRCh37: X:20205966-20205966
GRCh38: X:20187848-20187848
50 RPS6KA3 NM_004586.3(RPS6KA3):c.1603-5A>G SNV Uncertain significance 579151 rs1569194162 GRCh37: X:20183183-20183183
GRCh38: X:20165065-20165065

UniProtKB/Swiss-Prot genetic disease variations for Coffin-Lowry Syndrome:

72 (show all 11)
# Symbol AA change Variation ID SNP ID
1 RPS6KA3 p.Gly75Val VAR_006189 rs122454124
2 RPS6KA3 p.Val82Phe VAR_006190 rs122454126
3 RPS6KA3 p.Arg114Trp VAR_006191 rs122454127
4 RPS6KA3 p.His127Gln VAR_006192
5 RPS6KA3 p.Asp154Tyr VAR_006193
6 RPS6KA3 p.Ala225Val VAR_006194 rs879027948
7 RPS6KA3 p.Ser227Ala VAR_006195 rs122454125
8 RPS6KA3 p.Gly431Asp VAR_006196
9 RPS6KA3 p.Arg729Gln VAR_006197 rs28935171
10 RPS6KA3 p.Ile189Lys VAR_065894 rs122454130
11 RPS6KA3 p.Phe268Ser VAR_065896 rs122454131

Expression for Coffin-Lowry Syndrome

Search GEO for disease gene expression data for Coffin-Lowry Syndrome.

Pathways for Coffin-Lowry Syndrome

Pathways related to Coffin-Lowry Syndrome according to KEGG:

36
# Name Kegg Source Accession
1 MAPK signaling pathway hsa04010
2 Oocyte meiosis hsa04114

Pathways related to Coffin-Lowry Syndrome according to GeneCards Suite gene sharing:

(show top 50) (show all 60)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
13.86 RPS6KA6 RPS6KA5 RPS6KA4 RPS6KA3 RPS6KA2 RPS6KA1
2
Show member pathways
13.83 RPS6KA6 RPS6KA5 RPS6KA4 RPS6KA3 RPS6KA2 RPS6KA1
3
Show member pathways
13.54 RPS6KA5 RPS6KA4 RPS6KA3 RPS6KA2 RPS6KA1 FOS
4
Show member pathways
13.5 RPS6KA6 RPS6KA5 RPS6KA4 RPS6KA3 RPS6KA2 RPS6KA1
5
Show member pathways
13.41 RPS6KB2 RPS6KA6 RPS6KA3 RPS6KA2 RPS6KA1 PDHA1
6
Show member pathways
13.3 RPS6KB2 RPS6KA6 RPS6KA5 RPS6KA4 RPS6KA3 RPS6KA2
7
Show member pathways
13.23 RPS6KA6 RPS6KA4 RPS6KA3 RPS6KA2 RPS6KA1 FOS
8
Show member pathways
13.08 RPS6KA6 RPS6KA4 RPS6KA3 RPS6KA2 RPS6KA1 PLD1
9
Show member pathways
12.93 RPS6KB2 RPS6KA5 RPS6KA1 PHKA2 PDHA1 FOS
10
Show member pathways
12.87 RPS6KA3 RPS6KA2 RPS6KA1 FOS EDNRB CREB1
11
Show member pathways
12.86 RPS6KB2 PLD1 FOS CREB1 ATF4
12 12.83 RPS6KB2 RPS6KA5 PLD1 FOS EDNRB
13 12.82 RPS6KA6 RPS6KA5 RPS6KA4 RPS6KA3 RPS6KA2 RPS6KA1
14
Show member pathways
12.77 RPS6KA6 RPS6KA5 RPS6KA3 RPS6KA2 RPS6KA1 FOS
15
Show member pathways
12.76 RPS6KA5 PLD1 FOS CREB1 ATF4
16
Show member pathways
12.62 RPS6KB2 RPS6KA6 RPS6KA5 RPS6KA4 RPS6KA3 RPS6KA2
17
Show member pathways
12.61 RPS6KB2 PLD1 FOS ATF4
18
Show member pathways
12.54 RPS6KB2 RPS6KA6 RPS6KA3 RPS6KA2 RPS6KA1
19
Show member pathways
12.52 RPS6KA5 EDNRB CREB1 ATF4
20
Show member pathways
12.49 RPS6KB2 RPS6KA6 RPS6KA5 RPS6KA4 RPS6KA3 RPS6KA2
21
Show member pathways
12.47 RPS6KA2 RPS6KA1 FOS CREB1
22
Show member pathways
12.44 RPS6KB2 FOS CREB1 ATF4
23
Show member pathways
12.43 RPS6KA6 RPS6KA3 RPS6KA2 RPS6KA1
24
Show member pathways
12.43 RPS6KA3 RPS6KA2 RPS6KA1 FOS CREB1
25
Show member pathways
12.41 RPS6KA3 RPS6KA2 RPS6KA1 PLD1
26
Show member pathways
12.38 RPS6KA5 RPS6KA4 RPS6KA3 RPS6KA2 RPS6KA1 CREB1
27
Show member pathways
12.36 RPS6KA6 RPS6KA3 RPS6KA2 RPS6KA1
28
Show member pathways
12.27 RPS6KA6 RPS6KA3 RPS6KA2 RPS6KA1 CREB1
29
Show member pathways
12.26 RPS6KB2 RPS6KA6 RPS6KA2 CREB1 ATF4
30
Show member pathways
12.19 RPS6KA6 RPS6KA3 RPS6KA2 RPS6KA1
31 12.16 RPS6KA5 RPS6KA3 RPS6KA1 FOS CREB1
32 12.13 RPS6KA6 RPS6KA3 RPS6KA2 RPS6KA1 FOS
33 12.13 RPS6KA5 RPS6KA3 RPS6KA2 RPS6KA1 PLD1 FOS
34
Show member pathways
12.1 RPS6KA6 RPS6KA5 RPS6KA4 RPS6KA3 RPS6KA2 RPS6KA1
35
Show member pathways
12.08 RPS6KA6 RPS6KA3 RPS6KA2 RPS6KA1 FOS
36
Show member pathways
12.06 RPS6KA3 RPS6KA2 RPS6KA1 CREB1
37 12.04 RPS6KA5 RPS6KA4 RPS6KA3 RPS6KA2 RPS6KA1 FOS
38 12.03 RPS6KA5 RPS6KA4 FOS CREB1 ATF4
39
Show member pathways
12.01 RPS6KB2 RPS6KA6 RPS6KA3 RPS6KA2 RPS6KA1 CREB1
40 11.99 PHKA2 PDHA1 CREB1 ATF4
41
Show member pathways
11.99 RPS6KA6 RPS6KA3 RPS6KA2 RPS6KA1 CREB1 ATF4
42
Show member pathways
11.99 RPS6KA6 RPS6KA4 RPS6KA3 RPS6KA2 RPS6KA1 FOS
43
Show member pathways
11.99 RPS6KB2 RPS6KA6 RPS6KA5 RPS6KA4 RPS6KA3 RPS6KA2
44
Show member pathways
11.98 FOS CREB1 ATF4
45 11.98 PLD1 FOS CREB1 ATF4
46 11.94 RPS6KA5 RPS6KA4 RPS6KA3 PLD1 FOS CREB1
47
Show member pathways
11.91 RPS6KA6 RPS6KA5 RPS6KA4 RPS6KA3 RPS6KA2 RPS6KA1
48
Show member pathways
11.9 RPS6KA5 RPS6KA4 CREB1
49 11.9 RPS6KA5 RPS6KA4 CREB1 ATF4
50
Show member pathways
11.9 RPS6KA5 RPS6KA3 RPS6KA2 RPS6KA1 FOS CREB1

GO Terms for Coffin-Lowry Syndrome

Cellular components related to Coffin-Lowry Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 nucleus GO:0005634 10 RPS6KB2 RPS6KA6 RPS6KA5 RPS6KA4 RPS6KA3 RPS6KA2
2 nucleoplasm GO:0005654 9.4 RPS6KB2 RPS6KA6 RPS6KA5 RPS6KA4 RPS6KA3 RPS6KA2
3 ATF4-CREB1 transcription factor complex GO:1990589 8.96 CREB1 ATF4

Biological processes related to Coffin-Lowry Syndrome according to GeneCards Suite gene sharing:

(show all 12)
# Name GO ID Score Top Affiliating Genes
1 signal transduction GO:0007165 10.11 RPS6KB2 RPS6KA6 RPS6KA3 RPS6KA2 RPS6KA1 OPHN1
2 positive regulation of transcription by RNA polymerase II GO:0045944 9.81 RPS6KA5 RPS6KA4 RPS6KA3 RPS6KA1 MECP2 FOS
3 intracellular signal transduction GO:0035556 9.8 RPS6KA6 RPS6KA5 RPS6KA4 RPS6KA3 RPS6KA2 RPS6KA1
4 phosphorylation GO:0016310 9.8 RPS6KB2 RPS6KA6 RPS6KA5 RPS6KA4 RPS6KA3 RPS6KA2
5 protein phosphorylation GO:0006468 9.61 RPS6KB2 RPS6KA6 RPS6KA5 RPS6KA4 RPS6KA3 RPS6KA2
6 histone phosphorylation GO:0016572 9.49 RPS6KA5 RPS6KA4
7 positive regulation of histone phosphorylation GO:0033129 9.48 RPS6KA5 RPS6KA4
8 regulation of DNA-templated transcription in response to stress GO:0043620 9.46 RPS6KA3 RPS6KA1
9 histone H3-S28 phosphorylation GO:0043988 9.43 RPS6KA5 RPS6KA4
10 histone H3-S10 phosphorylation GO:0043987 9.4 RPS6KA5 RPS6KA4
11 regulation of translation in response to stress GO:0043555 9.37 RPS6KA3 RPS6KA1
12 peptidyl-serine phosphorylation GO:0018105 9.17 RPS6KB2 RPS6KA6 RPS6KA5 RPS6KA4 RPS6KA3 RPS6KA2

Molecular functions related to Coffin-Lowry Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 nucleotide binding GO:0000166 10.01 RPS6KB2 RPS6KA6 RPS6KA5 RPS6KA4 RPS6KA3 RPS6KA2
2 ATP binding GO:0005524 9.97 RPS6KB2 RPS6KA6 RPS6KA5 RPS6KA4 RPS6KA3 RPS6KA2
3 kinase activity GO:0016301 9.87 RPS6KB2 RPS6KA6 RPS6KA5 RPS6KA4 RPS6KA3 RPS6KA2
4 protein kinase activity GO:0004672 9.8 RPS6KB2 RPS6KA6 RPS6KA5 RPS6KA4 RPS6KA3 RPS6KA2
5 protein serine/threonine kinase activity GO:0004674 9.7 RPS6KB2 RPS6KA6 RPS6KA5 RPS6KA4 RPS6KA3 RPS6KA2
6 magnesium ion binding GO:0000287 9.43 RPS6KA6 RPS6KA5 RPS6KA4 RPS6KA3 RPS6KA2 RPS6KA1
7 ribosomal protein S6 kinase activity GO:0004711 9.1 RPS6KB2 RPS6KA6 RPS6KA4 RPS6KA3 RPS6KA2 RPS6KA1

Sources for Coffin-Lowry Syndrome

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Apr-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
Content
Loading form....