MRXSRC
MCID: RYN006
MIFTS: 42

Raynaud-Claes Syndrome (MRXSRC)

Categories: Genetic diseases, Mental diseases, Neuronal diseases, Oral diseases, Rare diseases
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Aliases & Classifications for Raynaud-Claes Syndrome

MalaCards integrated aliases for Raynaud-Claes Syndrome:

Name: Raynaud-Claes Syndrome 57 11 58 73 14 38
Mrx49 57 11 73 5
Mrxsrc 57 11 73
Clcn4-Related X-Linked Intellectual Disability Syndrome 58 5
Mental Retardation, X-Linked 49 57 71
Mrx15 57 11
Mental Retardation, X-Linked 15 57
Mental Retardation, X-Linked-49 12
X-Linked Mental Retardation 15 11
X-Linked Mental Retardation 49 11

Characteristics:


Inheritance:

X-linked dominant 57

Prevelance:

Clcn4-Related X-Linked Intellectual Disability Syndrome: <1/1000000 (Worldwide) 58

Age Of Onset:

Clcn4-Related X-Linked Intellectual Disability Syndrome: Childhood,Infancy 58

OMIM®:

57 (Updated 24-Oct-2022)
Miscellaneous:
some carrier females may be mildly to severely affected
hemizygous females with de novo mutation have been reported to have clinical features similar to that of hemizygous males


Classifications:

Orphanet: 58  
Rare neurological diseases


Summaries for Raynaud-Claes Syndrome

OMIM®: 57 Raynaud-Claes syndrome is an X-linked intellectual developmental disorder characterized by borderline to severe intellectual disability and impaired language development. Additional features include behavioral problems, psychiatric disorders, seizures (variable forms), progressive ataxia, brain abnormalities, and facial dysmorphisms. Some heterozygous females are unaffected, whereas others are affected with a severity spectrum similar to that seen in males (summary by Palmer et al. (2018)). (300114) (Updated 24-Oct-2022)

MalaCards based summary: Raynaud-Claes Syndrome, also known as mrx49, is related to non-syndromic x-linked intellectual disability and syndromic x-linked intellectual disability cabezas type. An important gene associated with Raynaud-Claes Syndrome is CLCN4 (Chloride Voltage-Gated Channel 4), and among its related pathways/superpathways are Mitochondrial complex IV assembly and rRNA processing in the mitochondrion. Affiliated tissues include brain, and related phenotypes are global developmental delay and intellectual disability, severe

Orphanet: 58 A rare X-linked syndromic intellectual disability characterized by intellectual disability of variable degree, behavioral anomalies (including autism, mood disorders, obsessive-compulsive behavior, and hetero- and auto-aggression), and epilepsy. Progressive neurological symptoms like movement disorders and spasticity, as well as subtle dysmorphic features have also been reported. Heterozygous females may be as severely affected as males.

Disease Ontology: 11 A syndromic X-linked intellectual disability characterized by borderline to severe intellectual disability, impaired language development, and variable additional features including; behavioral problems, psychiatric disorders, seizures, progressive ataxia, brain abnormalities, and facial dysmorphisms that has material basis in heterozygous or hemizygous mutation in CLCN4 on chromosome Xp22.2.

UniProtKB/Swiss-Prot: 73 An X-linked syndrome characterized by borderline to severe intellectual disability and impaired language development. Additional features include behavioral problems, psychiatric disorders, seizures, progressive ataxia, brain abnormalities, and facial dysmorphisms.

Related Diseases for Raynaud-Claes Syndrome

Graphical network of the top 20 diseases related to Raynaud-Claes Syndrome:



Diseases related to Raynaud-Claes Syndrome

Symptoms & Phenotypes for Raynaud-Claes Syndrome

Human phenotypes related to Raynaud-Claes Syndrome:

58 30 (show top 50) (show all 56)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 global developmental delay 58 30 Hallmark (90%) Very frequent (99-80%)
HP:0001263
2 intellectual disability, severe 58 30 Frequent (33%) Frequent (79-30%)
HP:0010864
3 cerebral cortical atrophy 58 30 Very rare (1%) Frequent (79-30%)
HP:0002120
4 intellectual disability, moderate 58 30 Frequent (33%) Frequent (79-30%)
HP:0002342
5 macrocephaly 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0000256
6 scoliosis 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0002650
7 self-injurious behavior 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0100716
8 behavioral abnormality 58 30 Occasional (7.5%) Frequent (79-30%)
HP:0000708
9 microcephaly 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0000252
10 gastroesophageal reflux 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0002020
11 myoclonus 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0001336
12 strabismus 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0000486
13 anxiety 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0000739
14 obsessive-compulsive behavior 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0000722
15 ventriculomegaly 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0002119
16 bipolar affective disorder 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0007302
17 infantile spasms 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0012469
18 feeding difficulties 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0011968
19 autistic behavior 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0000729
20 aggressive behavior 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0000718
21 hyperactivity 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0000752
22 hypoplasia of the corpus callosum 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0002079
23 lower limb spasticity 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0002061
24 periventricular leukomalacia 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0006970
25 cerebral visual impairment 58 30 Very rare (1%) Occasional (29-5%)
HP:0100704
26 progressive cerebellar ataxia 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0002073
27 infantile muscular hypotonia 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0008947
28 focal impaired awareness seizure 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0002384
29 delayed myelination 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0012448
30 focal tonic seizure 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0011167
31 eeg with focal spikes 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0011193
32 depression 30 Occasional (7.5%) HP:0000716
33 bilateral tonic-clonic seizure 30 Occasional (7.5%) HP:0002069
34 generalized non-motor (absence) seizure 30 Occasional (7.5%) HP:0002121
35 chorea 58 30 Very rare (1%) Very rare (<4-1%)
HP:0002072
36 inguinal hernia 58 30 Very rare (1%) Very rare (<4-1%)
HP:0000023
37 pes planus 58 30 Very rare (1%) Very rare (<4-1%)
HP:0001763
38 cryptorchidism 58 30 Very rare (1%) Very rare (<4-1%)
HP:0000028
39 long face 58 30 Very rare (1%) Very rare (<4-1%)
HP:0000276
40 pointed chin 58 30 Very rare (1%) Very rare (<4-1%)
HP:0000307
41 midface retrusion 58 30 Very rare (1%) Very rare (<4-1%)
HP:0011800
42 unsteady gait 58 30 Very rare (1%) Very rare (<4-1%)
HP:0002317
43 upper limb spasticity 58 30 Very rare (1%) Very rare (<4-1%)
HP:0006986
44 downslanted palpebral fissures 30 Very rare (1%) HP:0000494
45 epileptic encephalopathy 30 Very rare (1%) HP:0200134
46 seizures 58 Frequent (79-30%)
47 depressivity 58 Occasional (29-5%)
48 coarse facial features 30 HP:0000280
49 mandibular prognathia 30 HP:0000303
50 intellectual disability, mild 30 HP:0001256

Symptoms via clinical synopsis from OMIM®:

57 (Updated 24-Oct-2022)
Neurologic Behavioral Psychiatric Manifestations:
anxiety
obsessive-compulsive behavior
autistic behavior
aggressive behavior
depression
more
Muscle Soft Tissue:
hypotonia

Skeletal Spine:
scoliosis (in some patients)

Growth Other:
lean body habitus (in some adult patients)

Head And Neck Face:
long face
flat midface
prominent chin
coarse facial features (1 family)

Neurologic Central Nervous System:
mental retardation
language delay
delayed psychomotor development
cerebral atrophy (in some patients)
cortical atrophy (in some patients)
more
Head And Neck Eyes:
downslanting palpebral fissures (in some patients)
strabismus (in some patients)
cortical visual impairment (rare)

Head And Neck Nose:
straight nose

Clinical features from OMIM®:

300114 (Updated 24-Oct-2022)

GenomeRNAi Phenotypes related to Raynaud-Claes Syndrome according to GeneCards Suite gene sharing:

25
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 no effect GR00402-S-1 10.11 ARSL CLCN4 COX18 COX20 MRM1 MRM3
2 no effect GR00402-S-2 10.11 ARSL CLCN4 COX18 COX20 MRM1 MRM3

Drugs & Therapeutics for Raynaud-Claes Syndrome

Search Clinical Trials, NIH Clinical Center for Raynaud-Claes Syndrome

Genetic Tests for Raynaud-Claes Syndrome

Anatomical Context for Raynaud-Claes Syndrome

Organs/tissues related to Raynaud-Claes Syndrome:

MalaCards : Brain
ODiseA: Brain

Publications for Raynaud-Claes Syndrome

Articles related to Raynaud-Claes Syndrome:

(show all 15)
# Title Authors PMID Year
1
Regional localization of two genes for nonspecific X-linked mental retardation to Xp22.3-p22.2 (MRX49) and Xp11.3-p11.21 (MRX50). 62 57 5
9415477 1997
2
X-linked mental retardation with neonatal hypotonia in a French family (MRX15): gene assignment to Xp11.22-Xp21.1. 62 57 5
8826458 1996
3
De novo and inherited mutations in the X-linked gene CLCN4 are associated with syndromic intellectual disability and behavior and seizure disorders in males and females. 57 5
27550844 2018
4
X-exome sequencing of 405 unresolved families identifies seven novel intellectual disability genes. 57 5
25644381 2016
5
Exome sequencing reveals new causal mutations in children with epileptic encephalopathies. 57 5
23647072 2013
6
Léri-Weill syndrome as part of a contiguous gene syndrome at Xp22.3. 57
10232745 1999
7
Nomenclature guidelines for X-linked mental retardation. 57
1605216 1992
8
Novel CLCN4 variant associated with syndromic X-linked intellectual disability in a Chinese girl: a case report. 62
34479510 2021
9
Vestiges of the Bacterial Signal Recognition Particle-Based Protein Targeting in Mitochondria. 62
33837778 2021
10
The ribosome receptors Mrx15 and Mba1 jointly organize cotranslational insertion and protein biogenesis in mitochondria. 62
30091672 2018
11
Insertion Defects of Mitochondrially Encoded Proteins Burden the Mitochondrial Quality Control System. 62
30336542 2018
12
Normal intelligence and social interactions in a male patient despite the deletion of NLGN4X and the VCX genes. 62
18194880 2008
13
Absence of learning difficulties in a hyperactive boy with a terminal Xp deletion encompassing the MRX49 locus. 62
11474655 2001
14
A familial X/Y translocation: cytogenetic and molecular study. 62
14564057 2001
15
Mother and daughter with 45,X/46,X,r(X)(p22.3q28) and mental retardation: analysis of the X-inactivation patterns. 62
10766981 2000

Variations for Raynaud-Claes Syndrome

ClinVar genetic disease variations for Raynaud-Claes Syndrome:

5 (show all 31)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 CLCN4 NM_001830.4(CLCN4):c.2191G>C (p.Gly731Arg) SNV Pathogenic
253113 rs1569233549 GRCh37: X:10188916-10188916
GRCh38: X:10220876-10220876
2 CLCN4 NM_001830.4(CLCN4):c.1606G>A (p.Val536Met) SNV Pathogenic
253116 rs1569231897 GRCh37: X:10181750-10181750
GRCh38: X:10213710-10213710
3 CLCN4 NM_001830.4(CLCN4):c.232G>A (p.Gly78Ser) SNV Pathogenic
253114 rs1569226551 GRCh37: X:10155642-10155642
GRCh38: X:10187602-10187602
4 CLCN4 NM_001830.4(CLCN4):c.43_55del (p.Asp15fs) DEL Pathogenic
253112 rs1923775114 GRCh37: X:10153111-10153123
GRCh38: X:10185071-10185083
5 CLCN4 NM_001830.4(CLCN4):c.661C>G (p.Leu221Val) SNV Pathogenic
253115 rs1569230006 GRCh37: X:10174503-10174503
GRCh38: X:10206463-10206463
6 CLCN4 NM_001830.4(CLCN4):c.875G>A (p.Trp292Ter) SNV Pathogenic
1164025 GRCh37: X:10176116-10176116
GRCh38: X:10208076-10208076
7 CLCN4 NM_001830.4(CLCN4):c.112G>T (p.Glu38Ter) SNV Pathogenic
1679299 GRCh37: X:10153184-10153184
GRCh38: X:10185144-10185144
8 CLCN4 NM_001830.4(CLCN4):c.1630G>A (p.Gly544Arg) SNV Pathogenic
100781 rs587777161 GRCh37: X:10181774-10181774
GRCh38: X:10213734-10213734
9 CLCN4 NM_001830.4(CLCN4):c.2152C>T (p.Arg718Trp) SNV Pathogenic
209116 rs879255584 GRCh37: X:10188877-10188877
GRCh38: X:10220837-10220837
10 CLCN4 NM_001830.4(CLCN4):c.1576G>A (p.Gly526Ser) SNV Likely Pathogenic
495273 rs1555976973 GRCh37: X:10180693-10180693
GRCh38: X:10212653-10212653
11 CLCN4 NM_001830.4(CLCN4):c.1399G>A (p.Gly467Ser) SNV Likely Pathogenic
807385 rs1602159841 GRCh37: X:10180516-10180516
GRCh38: X:10212476-10212476
12 CLCN4 NM_001830.4(CLCN4):c.2051C>T (p.Pro684Leu) SNV Likely Pathogenic
827824 rs1246068842 GRCh37: X:10188776-10188776
GRCh38: X:10220736-10220736
13 CLCN4 NM_001830.4(CLCN4):c.373del (p.Asp125fs) DEL Likely Pathogenic
976142 rs1924061524 GRCh37: X:10163078-10163078
GRCh38: X:10195038-10195038
14 CLCN4 NM_001830.4(CLCN4):c.1646T>C (p.Ile549Thr) SNV Likely Pathogenic
976472 rs1924631837 GRCh37: X:10181790-10181790
GRCh38: X:10213750-10213750
15 CLCN4 NM_001830.4(CLCN4):c.1202T>C (p.Leu401Pro) SNV Likely Pathogenic
988775 rs1924450715 GRCh37: X:10176443-10176443
GRCh38: X:10208403-10208403
16 CLCN4 NM_001830.4(CLCN4):c.832del (p.Ser278fs) DEL Likely Pathogenic
983535 rs1924399093 GRCh37: X:10174805-10174805
GRCh38: X:10206765-10206765
17 CLCN4 NM_001830.4(CLCN4):c.740dup (p.Asn248fs) DUP Likely Pathogenic
1320175 GRCh37: X:10174580-10174581
GRCh38: X:10206540-10206541
18 CLCN4 NM_001830.4(CLCN4):c.1909G>C (p.Val637Leu) SNV Uncertain Significance
1321251 GRCh37: X:10182053-10182053
GRCh38: X:10214013-10214013
19 CLCN4 NM_001830.4(CLCN4):c.130G>A (p.Asp44Asn) SNV Uncertain Significance
988758 GRCh37: X:10153202-10153202
GRCh38: X:10185162-10185162
20 CLCN4 NM_001830.4(CLCN4):c.1561G>A (p.Ala521Thr) SNV Uncertain Significance
1030482 rs1924590136 GRCh37: X:10180678-10180678
GRCh38: X:10212638-10212638
21 CLCN4 NM_001830.4(CLCN4):c.2038C>A (p.Pro680Thr) SNV Uncertain Significance
992811 rs142375213 GRCh37: X:10188763-10188763
GRCh38: X:10220723-10220723
22 CLCN4 NM_001830.4(CLCN4):c.2102C>T (p.Pro701Leu) SNV Uncertain Significance
1297055 GRCh37: X:10188827-10188827
GRCh38: X:10220787-10220787
23 CLCN4 NM_001830.4(CLCN4):c.469A>C (p.Ile157Leu) SNV Uncertain Significance
982984 rs913431577 GRCh37: X:10166015-10166015
GRCh38: X:10197975-10197975
24 CLCN4 NM_001830.4(CLCN4):c.1051C>G (p.Arg351Gly) SNV Uncertain Significance
658669 rs763535956 GRCh37: X:10176292-10176292
GRCh38: X:10208252-10208252
25 CLCN4 NM_001830.4(CLCN4):c.1439G>T (p.Gly480Val) SNV Uncertain Significance
1684626 GRCh37: X:10180556-10180556
GRCh38: X:10212516-10212516
26 CLCN4 NM_001830.4(CLCN4):c.10G>T (p.Ala4Ser) SNV Uncertain Significance
625920 rs1015209935 GRCh37: X:10153082-10153082
GRCh38: X:10185042-10185042
27 CLCN4 NM_001830.4(CLCN4):c.1078C>T (p.Arg360Cys) SNV Uncertain Significance
659757 rs1602157389 GRCh37: X:10176319-10176319
GRCh38: X:10208279-10208279
28 CLCN4 NM_001830.4(CLCN4):c.2167C>T (p.Arg723Trp) SNV Uncertain Significance
964595 rs1924842665 GRCh37: X:10188892-10188892
GRCh38: X:10220852-10220852
29 CLCN4 NM_001830.4(CLCN4):c.2153G>A (p.Arg718Gln) SNV Uncertain Significance
521940 rs779824005 GRCh37: X:10188878-10188878
GRCh38: X:10220838-10220838
30 CLCN4 NM_001830.4(CLCN4):c.1849A>G (p.Met617Val) SNV Uncertain Significance
1339128 GRCh37: X:10181993-10181993
GRCh38: X:10213953-10213953
31 CLCN4 NM_001830.4(CLCN4):c.944G>A (p.Arg315His) SNV Uncertain Significance
996971 rs1374813094 GRCh37: X:10176185-10176185
GRCh38: X:10208145-10208145

UniProtKB/Swiss-Prot genetic disease variations for Raynaud-Claes Syndrome:

73 (show all 11)
# Symbol AA change Variation ID SNP ID
1 CLCN4 p.Gly78Ser VAR_077819 rs1569226551
2 CLCN4 p.Leu221Val VAR_077820 rs1569230006
3 CLCN4 p.Val536Met VAR_077821 rs1569231897
4 CLCN4 p.Gly544Arg VAR_077822 rs587777161
5 CLCN4 p.Gly731Arg VAR_077823 rs1569233549
6 CLCN4 p.Val212Gly VAR_083578 rs879255580
7 CLCN4 p.Leu221Pro VAR_083579 rs879255581
8 CLCN4 p.Val275Met VAR_083580 rs879255585
9 CLCN4 p.Ser534Leu VAR_083581 rs879255582
10 CLCN4 p.Ala555Val VAR_083582 rs879255583
11 CLCN4 p.Arg718Trp VAR_083583 rs879255584

Expression for Raynaud-Claes Syndrome

Search GEO for disease gene expression data for Raynaud-Claes Syndrome.

Pathways for Raynaud-Claes Syndrome

Pathways related to Raynaud-Claes Syndrome according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 10.62 TMEM177 COX20 COX18
2
Show member pathways
10 MTERF4 MRM3 MRM1

GO Terms for Raynaud-Claes Syndrome

Cellular components related to Raynaud-Claes Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 mitochondrial inner membrane GO:0005743 10.06 TMEM242 TMEM223 TMEM177 OXA1L MRPS5 MRPL22
2 mitochondrial matrix GO:0005759 10.03 RPUSD4 PTCD1 OXA1L MTERF4 MRM3 MRM1
3 mitochondrion GO:0005739 9.72 TMEM242 TMEM223 TMEM177 RPUSD4 RBFA PTCD1
4 obsolete integral component of mitochondrial inner membrane GO:0031305 9.26 COX18 OXA1L TMEM177 TMEM223

Biological processes related to Raynaud-Claes Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 mitochondrial translation GO:0032543 9.93 PTCD1 MRPS5 MRPL22
2 protein insertion into membrane GO:0051205 9.71 OXA1L COX18
3 ribosome assembly GO:0042255 9.67 MTERF4 MRPL22
4 mitochondrial proton-transporting ATP synthase complex assembly GO:0033615 9.62 TMEM242 OXA1L
5 protein insertion into mitochondrial inner membrane from matrix GO:0032979 9.56 COX18 OXA1L
6 rRNA 2'-O-methylation GO:0000451 9.46 MRM3 MRM1
7 establishment of protein localization to membrane GO:0090150 9.43 OXA1L COX18
8 mitochondrial cytochrome c oxidase assembly GO:0033617 9.43 TMEM223 COX20 COX18
9 rRNA processing GO:0006364 9.17 RPUSD4 RBFA MTERF4 MRM3 MRM1

Molecular functions related to Raynaud-Claes Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 membrane insertase activity GO:0032977 9.56 OXA1L COX18
2 mitochondrial ribosome binding GO:0097177 9.26 TMEM223 OXA1L
3 RNA methyltransferase activity GO:0008173 9.16 MRM3 MRM1
4 rRNA (guanosine-2'-O-)-methyltransferase activity GO:0070039 8.92 MRM3 MRM1

Sources for Raynaud-Claes Syndrome

2 CDC
6 CNVD
8 Cosmic
9 dbSNP
10 DGIdb
16 EFO
17 ExPASy
18 FMA
19 GARD
27 GO
28 GTR
29 HMDB
30 HPO
31 ICD10
32 ICD10 via Orphanet
33 ICD11
34 ICD9CM
35 IUPHAR
36 LifeMap
38 LOVD
40 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
52 NINDS
53 Novoseek
55 ODiseA
56 OMIM via Orphanet
57 OMIM® (Updated 24-Oct-2022)
61 PubChem
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 Tocris
71 UMLS
72 UMLS via Orphanet
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