MCID: XLN224
MIFTS: 22

X-Linked Non-Specific Intellectual Disability

Categories: Rare diseases, Neuronal diseases

Aliases & Classifications for X-Linked Non-Specific Intellectual Disability

MalaCards integrated aliases for X-Linked Non-Specific Intellectual Disability:

Name: X-Linked Non-Specific Intellectual Disability 53 59
X-Linked Non-Syndromic Intellectual Disability 53 59

Characteristics:

Orphanet epidemiological data:

59
x-linked non-syndromic intellectual disability
Inheritance: X-linked recessive; Age of onset: Childhood;

Classifications:

Orphanet: 59  
Rare neurological diseases


External Ids:

Orphanet 59 ORPHA777
UMLS via Orphanet 74 C2931498
SNOMED-CT via HPO 69 228156007 247578003 91138005

Summaries for X-Linked Non-Specific Intellectual Disability

NIH Rare Diseases : 53 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 777Disease definitionNonspecific X-linked intellectual deficiencies (MRX) belong to the family of sex-linked intellectual deficiencies (XLMR). In contrast to syndromic or specific X-linked intellectual deficiencies (MRXS), which also present with associated physical, neurological and/or psychiatric manifestations, intellectual deficiency is the only symptom of MRX.EpidemiologyThe incidence of MRX among males is about 1/900 and these conditions represent two thirds of the familial cases of X-linked intellectual deficiency.Clinical descriptionHowever, the natural history, severity and clinical aspect of MRX often vary from one sibling to another in a given family. In addition, a history of minor physical signs (such as mild neonatal hypotonia, hyperreflexia, mild microcephaly, slightly small stature, a few convulsive seizures or secondary arrest of acquisition of verbal skills) may be reported and although they are generally considered as banal they are characteristic for a given family.EtiologySeventeen different genes responsible for MRX have been identified to date. Most of the corresponding proteins are involved, either directly or through a regulatory function, in the growth of nerve cells or in synaptic communication between these cells. These proteins play a role in learning and/or memory. Encephalic function and/or development or neuronal plasticity is impaired in MRX patients. In addition, specific mutations in MRXS genes have been discovered in some MRX families. Finally, additional genes clearly remain to be uncovered as the causative gene has not yet been identified in half the MRX families. However, the identification of the genes involved in many families now makes it possible to perform a clinical study using a gene by gene approach. A fine approach using neurological, psychological and psychiatric tools and high quality medical imaging has allowed certain features, such as an evocative morphological anomaly of the cerebellar vermix (OPHN1 gene) or very specific motor disorders of the hands (ARX gene), to be substantiated. Thus, some forms that were previously classified as `non specific' (MRX) have been progressively shown to have a gene-dependant specificity (MRXS). It might be possible, in the future, to identify a specific phenotype for each MRX gene, which might allow an efficient and economic examination protocol to be designed for male patients suffering from intellectual deficiency. The finding of several signs will orientate the diagnosis towards one form or another of MRX, and hence the linkage to X chromosome may be identified even if only a single boy is affected.Diagnostic methodsAs intellectual deficiency is the key symptom and no specific physical signs are observed during routine examinations, to date the diagnosis of MRX is only considered in cases of typical X-linked familial recurrence. Extensive investigations should be carried to search for a potential recurrence in the families of all male patients presenting with isolated, permanent intellectual deficit for which no cause has been found.Genetic counselingGenetic counselling is the only preventive measure available.Management and treatmentThere is currently no specific treatment.Visit the Orphanet disease page for more resources.

MalaCards based summary : X-Linked Non-Specific Intellectual Disability, also known as x-linked non-syndromic intellectual disability, is related to alacrima, achalasia, and mental retardation syndrome and respiratory system benign neoplasm. An important gene associated with X-Linked Non-Specific Intellectual Disability is RLIM (Ring Finger Protein, LIM Domain Interacting). Related phenotypes are intellectual disability and Decreased viability

Related Diseases for X-Linked Non-Specific Intellectual Disability

Diseases related to X-Linked Non-Specific Intellectual Disability via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 alacrima, achalasia, and mental retardation syndrome 10.2 IL1RAPL1 IQSEC2 MECP2
2 respiratory system benign neoplasm 10.1 ARHGEF6 SYP
3 partington x-linked mental retardation syndrome 10.1 ARX IL1RAPL1 MECP2 RPS6KA3
4 autism 9.7 ARX IL1RAPL1 MECP2 RAB39B UPF3B
5 non-syndromic x-linked intellectual disability 9.4 ARHGEF6 IL1RAPL1 IQSEC2 PAK3 RAB39B RLIM
6 syndromic x-linked intellectual disability 9.3 ARHGEF6 IL1RAPL1 PAK3 RAB39B RLIM SYP

Graphical network of the top 20 diseases related to X-Linked Non-Specific Intellectual Disability:



Diseases related to X-Linked Non-Specific Intellectual Disability

Symptoms & Phenotypes for X-Linked Non-Specific Intellectual Disability

Human phenotypes related to X-Linked Non-Specific Intellectual Disability:

59 32
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 intellectual disability 59 32 hallmark (90%) Very frequent (99-80%) HP:0001249

GenomeRNAi Phenotypes related to X-Linked Non-Specific Intellectual Disability according to GeneCards Suite gene sharing:

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased viability GR00221-A-1 9.4 PAK3
2 Decreased viability GR00221-A-2 9.4 RPS6KA3 PAK3
3 Decreased viability GR00221-A-3 9.4 PAK3
4 Decreased viability GR00342-S-1 9.4 RPS6KA3 AGTR2 PAK3
5 Decreased viability GR00342-S-2 9.4 PAK3
6 Decreased viability GR00342-S-3 9.4 AGTR2
7 Decreased viability GR00402-S-2 9.4 RPS6KA3 AGTR2 PAK3

MGI Mouse Phenotypes related to X-Linked Non-Specific Intellectual Disability:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 nervous system MP:0003631 9.36 TSPAN7 UPF3B USP9X AGTR2 ARHGEF6 ARX

Drugs & Therapeutics for X-Linked Non-Specific Intellectual Disability

Search Clinical Trials , NIH Clinical Center for X-Linked Non-Specific Intellectual Disability

Genetic Tests for X-Linked Non-Specific Intellectual Disability

Anatomical Context for X-Linked Non-Specific Intellectual Disability

Publications for X-Linked Non-Specific Intellectual Disability

Variations for X-Linked Non-Specific Intellectual Disability

ClinVar genetic disease variations for X-Linked Non-Specific Intellectual Disability:

6
(show top 50) (show all 680)
# Gene Variation Type Significance SNP ID Assembly Location
1 NLGN4X NLGN4, 2-BP DEL, 1253AG deletion Pathogenic,risk factor
2 NLGN4X nsv513783 deletion Pathogenic,risk factor
3 RLIM NM_183353.2(RLIM): c.1067A> G (p.Tyr356Cys) single nucleotide variant Pathogenic/Likely pathogenic rs786205133 GRCh37 Chromosome X, 73812083: 73812083
4 RLIM NM_183353.2(RLIM): c.1067A> G (p.Tyr356Cys) single nucleotide variant Pathogenic/Likely pathogenic rs786205133 GRCh38 Chromosome X, 74592248: 74592248
5 BRWD3 NM_153252.4(BRWD3): c.33G> A (p.Glu11=) single nucleotide variant Benign/Likely benign rs139071237 GRCh37 Chromosome X, 80064802: 80064802
6 BRWD3 NM_153252.4(BRWD3): c.33G> A (p.Glu11=) single nucleotide variant Benign/Likely benign rs139071237 GRCh38 Chromosome X, 80809303: 80809303
7 RAB39B NM_171998.3(RAB39B): c.543A> G (p.Thr181=) single nucleotide variant Benign/Likely benign rs369970931 GRCh37 Chromosome X, 154490187: 154490187
8 RAB39B NM_171998.3(RAB39B): c.543A> G (p.Thr181=) single nucleotide variant Benign/Likely benign rs369970931 GRCh38 Chromosome X, 155260902: 155260902
9 SYP NM_003179.2(SYP): c.687C> T (p.Ala229=) single nucleotide variant Conflicting interpretations of pathogenicity rs201427270 GRCh37 Chromosome X, 49048149: 49048149
10 SYP NM_003179.2(SYP): c.687C> T (p.Ala229=) single nucleotide variant Conflicting interpretations of pathogenicity rs201427270 GRCh38 Chromosome X, 49191692: 49191692
11 PAK3 NM_002578.4(PAK3): c.531G> A (p.Glu177=) single nucleotide variant Benign/Likely benign rs56270341 GRCh38 Chromosome X, 111162977: 111162977
12 PAK3 NM_002578.4(PAK3): c.531G> A (p.Glu177=) single nucleotide variant Benign/Likely benign rs56270341 GRCh37 Chromosome X, 110406205: 110406205
13 UPF3B NM_080632.2(UPF3B): c.1121G> A (p.Arg374His) single nucleotide variant Conflicting interpretations of pathogenicity rs143538947 GRCh37 Chromosome X, 118971901: 118971901
14 UPF3B NM_080632.2(UPF3B): c.1121G> A (p.Arg374His) single nucleotide variant Conflicting interpretations of pathogenicity rs143538947 GRCh38 Chromosome X, 119837938: 119837938
15 ARHGEF6 NM_004840.2(ARHGEF6): c.1190C> G (p.Thr397Ser) single nucleotide variant Likely benign rs532348958 GRCh37 Chromosome X, 135770146: 135770146
16 ARHGEF6 NM_004840.2(ARHGEF6): c.1190C> G (p.Thr397Ser) single nucleotide variant Likely benign rs532348958 GRCh38 Chromosome X, 136687987: 136687987
17 ARHGEF6 NM_004840.2(ARHGEF6): c.942C> T (p.His314=) single nucleotide variant Uncertain significance rs34274521 GRCh37 Chromosome X, 135789171: 135789171
18 ARHGEF6 NM_004840.2(ARHGEF6): c.942C> T (p.His314=) single nucleotide variant Uncertain significance rs34274521 GRCh38 Chromosome X, 136707012: 136707012
19 ARHGEF6 NM_004840.2(ARHGEF6): c.685G> A (p.Val229Ile) single nucleotide variant Likely benign rs75329154 GRCh37 Chromosome X, 135814308: 135814308
20 ARHGEF6 NM_004840.2(ARHGEF6): c.685G> A (p.Val229Ile) single nucleotide variant Likely benign rs75329154 GRCh38 Chromosome X, 136732149: 136732149
21 IL1RAPL1 NM_014271.3(IL1RAPL1): c.2067C> G (p.Thr689=) single nucleotide variant Conflicting interpretations of pathogenicity rs140330609 GRCh37 Chromosome X, 29973913: 29973913
22 IL1RAPL1 NM_014271.3(IL1RAPL1): c.2067C> G (p.Thr689=) single nucleotide variant Conflicting interpretations of pathogenicity rs140330609 GRCh38 Chromosome X, 29955796: 29955796
23 ZNF81 NM_007137.3(ZNF81): c.417A> G (p.Ile139Met) single nucleotide variant Conflicting interpretations of pathogenicity rs189835360 GRCh37 Chromosome X, 47774462: 47774462
24 ZNF81 NM_007137.3(ZNF81): c.417A> G (p.Ile139Met) single nucleotide variant Conflicting interpretations of pathogenicity rs189835360 GRCh38 Chromosome X, 47915063: 47915063
25 ZNF81 NM_007137.3(ZNF81): c.1495A> G (p.Ile499Val) single nucleotide variant Conflicting interpretations of pathogenicity rs182239885 GRCh37 Chromosome X, 47775540: 47775540
26 ZNF81 NM_007137.3(ZNF81): c.1495A> G (p.Ile499Val) single nucleotide variant Conflicting interpretations of pathogenicity rs182239885 GRCh38 Chromosome X, 47916141: 47916141
27 BRWD3 NM_153252.4(BRWD3): c.597A> C (p.Ser199=) single nucleotide variant Benign/Likely benign rs142085721 GRCh38 Chromosome X, 80744248: 80744248
28 BRWD3 NM_153252.4(BRWD3): c.597A> C (p.Ser199=) single nucleotide variant Benign/Likely benign rs142085721 GRCh37 Chromosome X, 79999747: 79999747
29 SYP NM_003179.2(SYP): c.868G> T (p.Gly290Trp) single nucleotide variant Conflicting interpretations of pathogenicity rs376222680 GRCh37 Chromosome X, 49047968: 49047968
30 SYP NM_003179.2(SYP): c.868G> T (p.Gly290Trp) single nucleotide variant Conflicting interpretations of pathogenicity rs376222680 GRCh38 Chromosome X, 49191511: 49191511
31 BRWD3 NM_153252.4(BRWD3): c.2325+5G> A single nucleotide variant Benign/Likely benign rs186391561 GRCh38 Chromosome X, 80716152: 80716152
32 BRWD3 NM_153252.4(BRWD3): c.2325+5G> A single nucleotide variant Benign/Likely benign rs186391561 GRCh37 Chromosome X, 79971651: 79971651
33 IL1RAPL1 NM_014271.3(IL1RAPL1): c.-19G> A single nucleotide variant Benign rs6526806 GRCh37 Chromosome X, 28807442: 28807442
34 IL1RAPL1 NM_014271.3(IL1RAPL1): c.-19G> A single nucleotide variant Benign rs6526806 GRCh38 Chromosome X, 28789325: 28789325
35 UPF3B NM_080632.2(UPF3B): c.*395G> A single nucleotide variant Benign rs2239962 GRCh37 Chromosome X, 118968446: 118968446
36 UPF3B NM_080632.2(UPF3B): c.*395G> A single nucleotide variant Benign rs2239962 GRCh38 Chromosome X, 119834483: 119834483
37 UPF3B NM_080632.2(UPF3B): c.*206A> G single nucleotide variant Uncertain significance rs1042421205 GRCh37 Chromosome X, 118968635: 118968635
38 UPF3B NM_080632.2(UPF3B): c.*206A> G single nucleotide variant Uncertain significance rs1042421205 GRCh38 Chromosome X, 119834672: 119834672
39 ARHGEF6 NM_004840.2(ARHGEF6): c.*2126G> A single nucleotide variant Uncertain significance rs1057515774 GRCh38 Chromosome X, 136665903: 136665903
40 ARHGEF6 NM_004840.2(ARHGEF6): c.*2126G> A single nucleotide variant Uncertain significance rs1057515774 GRCh37 Chromosome X, 135748062: 135748062
41 ARHGEF6 NM_004840.2(ARHGEF6): c.*2062T> C single nucleotide variant Likely benign rs142057050 GRCh38 Chromosome X, 136665967: 136665967
42 ARHGEF6 NM_004840.2(ARHGEF6): c.*2062T> C single nucleotide variant Likely benign rs142057050 GRCh37 Chromosome X, 135748126: 135748126
43 ARHGEF6 NM_004840.2(ARHGEF6): c.*1141G> T single nucleotide variant Benign rs147013994 GRCh38 Chromosome X, 136666888: 136666888
44 ARHGEF6 NM_004840.2(ARHGEF6): c.*1141G> T single nucleotide variant Benign rs147013994 GRCh37 Chromosome X, 135749047: 135749047
45 ARHGEF6 NM_004840.2(ARHGEF6): c.*1028A> G single nucleotide variant Uncertain significance rs747024117 GRCh38 Chromosome X, 136667001: 136667001
46 ARHGEF6 NM_004840.2(ARHGEF6): c.*1028A> G single nucleotide variant Uncertain significance rs747024117 GRCh37 Chromosome X, 135749160: 135749160
47 ARHGEF6 NM_004840.2(ARHGEF6): c.*220T> G single nucleotide variant Uncertain significance rs926836865 GRCh38 Chromosome X, 136667809: 136667809
48 ARHGEF6 NM_004840.2(ARHGEF6): c.*220T> G single nucleotide variant Uncertain significance rs926836865 GRCh37 Chromosome X, 135749968: 135749968
49 ARHGEF6 NM_004840.2(ARHGEF6): c.*38C> T single nucleotide variant Likely benign rs747771125 GRCh37 Chromosome X, 135750150: 135750150
50 ARHGEF6 NM_004840.2(ARHGEF6): c.*38C> T single nucleotide variant Likely benign rs747771125 GRCh38 Chromosome X, 136667991: 136667991

Expression for X-Linked Non-Specific Intellectual Disability

Search GEO for disease gene expression data for X-Linked Non-Specific Intellectual Disability.

Pathways for X-Linked Non-Specific Intellectual Disability

GO Terms for X-Linked Non-Specific Intellectual Disability

Biological processes related to X-Linked Non-Specific Intellectual Disability according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 protein K48-linked deubiquitination GO:0071108 9.26 USP27X USP9X
2 regulation of neuron projection development GO:0010975 9.16 IL1RAPL1 PAK3
3 neuron differentiation GO:0030182 9.13 ACSL4 IL1RAPL1 MECP2
4 dendritic spine development GO:0060996 8.62 ACSL4 PAK3

Molecular functions related to X-Linked Non-Specific Intellectual Disability according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 thiol-dependent ubiquitinyl hydrolase activity GO:0036459 9.13 ALG13 USP27X USP9X
2 Lys48-specific deubiquitinase activity GO:1990380 8.62 USP27X USP9X

Sources for X-Linked Non-Specific Intellectual Disability

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
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