AUTSX2
MCID: ATS366
MIFTS: 42

Autism X-Linked 2 (AUTSX2)

Categories: Genetic diseases, Mental diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Autism X-Linked 2

MalaCards integrated aliases for Autism X-Linked 2:

Name: Autism X-Linked 2 56
Mental Retardation, X-Linked 56 29 13 39 71
Autism, Susceptibility to, X-Linked 2 56 29 6
Autism Susceptibility, X-Linked 2 56 29
X-Linked Mental Retardation 74 36
Autsx2 56 73
Autism, X-Linked 2 73

Characteristics:

OMIM:

56
Inheritance:
isolated cases
multifactorial
x-linked

Miscellaneous:
genetic heterogeneity (see )
onset by 3 years of age
male to female ratio 4:1
occurs in 2-5 per 10,000 individuals
associated with tuberous sclerosis
associated with untreated phenylketonuria


HPO:

31
autism x-linked 2:
Inheritance x-linked inheritance multifactorial inheritance heterogeneous sporadic
Onset and clinical course childhood onset


Classifications:



Summaries for Autism X-Linked 2

OMIM : 56 Autism, the prototypic pervasive developmental disorder (PDD), is usually apparent by 3 years of age. It is characterized by a triad of limited or absent verbal communication, a lack of reciprocal social interaction or responsiveness, and restricted, stereotypic, and ritualized patterns of interests and behavior (Bailey et al., 1996; Risch et al., 1999). 'Autism spectrum disorder,' sometimes referred to as ASD, is a broader phenotype encompassing the less severe disorders Asperger syndrome (see ASPG1; 608638) and pervasive developmental disorder, not otherwise specified (PDD-NOS). 'Broad autism phenotype' includes individuals with some symptoms of autism, but who do not meet the full criteria for autism or other disorders. Mental retardation coexists in approximately two-thirds of individuals with ASD, except for Asperger syndrome, in which mental retardation is conspicuously absent (Jones et al., 2008). Genetic studies in autism often include family members with these less stringent diagnoses (Schellenberg et al., 2006). For a discussion of genetic heterogeneity of autism, see 209850. (300495)

MalaCards based summary : Autism X-Linked 2, also known as mental retardation, x-linked, is related to mental retardation, x-linked, with or without seizures, arx-related and mental retardation, x-linked, syndromic 13. An important gene associated with Autism X-Linked 2 is NLGN4X (Neuroligin 4 X-Linked), and among its related pathways/superpathways is Regulation of actin cytoskeleton. The drugs Lovastatin and Hypolipidemic Agents have been mentioned in the context of this disorder. Affiliated tissues include brain, eye and lung, and related phenotypes are seizures and eeg abnormality

KEGG : 36 X-linked mental retardation (XLMR) is an inherited condition that causes failure to develop cognitive abilities because of mutations in several genes on the X chromosome. XLMR is subdivided into syndromic and non-syndromic forms (NS-XLMR), depending on whether further abnormalities are found on physical examination, laboratory investigation and brain imaging. The majority of genes that are mutated in NS-XLMR encode proteins are involved in three distinct pathways: Rho GTPases pathway modulating neuronal differentiation and synaptic plasticity; Rab GTPases pathway regulating synaptic vesicle cycling; gene expression regulation.

UniProtKB/Swiss-Prot : 73 Autism, X-linked 2: A complex multifactorial, pervasive developmental disorder characterized by impairments in reciprocal social interaction and communication, restricted and stereotyped patterns of interests and activities, and the presence of developmental abnormalities by 3 years of age. Most individuals with autism also manifest moderate mental retardation.

Wikipedia : 74 X-linked intellectual disability (previously known as X-linked mental retardation) refers to forms of... more...

Related Diseases for Autism X-Linked 2

Diseases in the Autism X-Linked 2 family:

Autism X-Linked 1 Autism X-Linked 3
Autism X-Linked 4 Autism X-Linked 5
Autism X-Linked 6

Diseases related to Autism X-Linked 2 via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 276)
# Related Disease Score Top Affiliating Genes
1 mental retardation, x-linked, with or without seizures, arx-related 13.1
2 mental retardation, x-linked, syndromic 13 12.9
3 mental retardation, x-linked, syndromic, cabezas type 12.9
4 mental retardation, x-linked 92 12.9
5 mental retardation, x-linked, syndromic, turner type 12.9
6 mental retardation, x-linked 12 12.9
7 mental retardation, x-linked, with cerebellar hypoplasia and distinctive facial appearance 12.9
8 mental retardation, x-linked, with panhypopituitarism 12.8
9 mental retardation, x-linked, syndromic, hedera type 12.8
10 mental retardation, x-linked, syndromic, wu type 12.8
11 mental retardation, x-linked, syndromic, nascimento type 12.8
12 mental retardation, x-linked, syndromic, claes-jensen type 12.8
13 mental retardation, x-linked, syndromic, raymond type 12.8
14 mental retardation, x-linked 97 12.8
15 mental retardation, x-linked, syndromic 32 12.8
16 mental retardation, x-linked, syndromic 34 12.8
17 mental retardation, x-linked, syndromic, martin-probst type 12.8
18 mental retardation, x-linked 96 12.8
19 mental retardation, x-linked 21 12.8
20 mental retardation, x-linked, syndromic, christianson type 12.8
21 mental retardation, x-linked 98 12.8
22 mental retardation, x-linked 99 12.8
23 mental retardation, x-linked 100 12.8
24 mental retardation, x-linked 101 12.8
25 mental retardation, x-linked 102 12.8
26 mental retardation, x-linked, syndromic 33 12.8
27 mental retardation, x-linked, syndromic, 35 12.8
28 mental retardation, x-linked 107 12.8
29 mental retardation, x-linked 99, syndromic, female-restricted 12.8
30 mental retardation, x-linked 103 12.8
31 mental retardation, x-linked 104 12.8
32 mental retardation, x-linked 105 12.8
33 mental retardation, x-linked, syndromic, bain type 12.8
34 mental retardation, x-linked 106 12.8
35 mental retardation, x-linked, syndromic, houge type 12.8
36 mental retardation, x-linked, associated with fragile site fraxe 12.8
37 mental retardation, x-linked, syndromic 17 12.6
38 mental retardation, x-linked, syndromic, chudley-schwartz type 12.6
39 mental retardation, x-linked, syndromic, snyder-robinson type 12.6
40 mental retardation, x-linked, with craniofacial dysmorphism 12.6
41 mental retardation, x-linked, syndromic 9 12.6
42 mental retardation, x-linked 23 12.5
43 mental retardation, x-linked 50 12.5
44 mental retardation, x-linked 53 12.5
45 mental retardation, x-linked 42 12.5
46 mental retardation, x-linked 73 12.5
47 syndromic x-linked mental retardation hough type 12.5
48 pettigrew syndrome 12.4
49 lubs x-linked mental retardation syndrome 12.3
50 wilson-turner x-linked mental retardation syndrome 12.3

Graphical network of the top 20 diseases related to Autism X-Linked 2:



Diseases related to Autism X-Linked 2

Symptoms & Phenotypes for Autism X-Linked 2

Human phenotypes related to Autism X-Linked 2:

31 (show all 12)
# Description HPO Frequency HPO Source Accession
1 seizures 31 frequent (33%) HP:0001250
2 eeg abnormality 31 frequent (33%) HP:0002353
3 increased serum serotonin 31 frequent (33%) HP:0003144
4 intellectual disability 31 HP:0001249
5 delayed speech and language development 31 HP:0000750
6 stereotypy 31 HP:0000733
7 autism 31 HP:0000717
8 impaired use of nonverbal behaviors 31 HP:0000758
9 lack of peer relationships 31 HP:0002332
10 restrictive behavior 31 HP:0000723
11 lack of spontaneous play 31 HP:0000721
12 inflexible adherence to routines or rituals 31 HP:0000732

Symptoms via clinical synopsis from OMIM:

56
Neurologic Central Nervous System:
lack of peer relationships
lack of spontaneous play
inflexible adherence to routines or rituals
mental retardation in 75%
seizures in 15-30%
more
Laboratory Abnormalities:
increased serum serotonin in 25%

Clinical features from OMIM:

300495

Drugs & Therapeutics for Autism X-Linked 2

Drugs for Autism X-Linked 2 (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 14)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Lovastatin Approved, Investigational Phase 4 75330-75-5 53232
2 Hypolipidemic Agents Phase 4
3 Anticholesteremic Agents Phase 4
4 Hydroxymethylglutaryl-CoA Reductase Inhibitors Phase 4
5 Dihydromevinolin Phase 4
6 Lipid Regulating Agents Phase 4
7 L 647318 Phase 4
8 Antimetabolites Phase 4
9
Metformin Approved Phase 2, Phase 3 657-24-9 14219 4091
10 Hypoglycemic Agents Phase 2, Phase 3
11
Formaldehyde Approved, Vet_approved 50-00-0 712
12
Creatine Approved, Investigational, Nutraceutical 57-00-1 586
13 Astragalus
14 Neuroserpin

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Combining Lovastatin and a Parent-Implemented Language Intervention in a Multimodal Treatment for Fragile X Syndrome Completed NCT02642653 Phase 4 Lovastatin
2 A Double-Blind, Placebo-Controlled Trial of Metformin in Individuals With Fragile X Syndrome Recruiting NCT03479476 Phase 2, Phase 3 Placebo Medication;Metformin
3 A Double-Blind, Placebo-Controlled Trial of Metformin in Individuals With Fragile X Syndrome (FXS) Recruiting NCT03862950 Phase 2 Placebo Medication;Metformin
4 Clinical Phenotyping and Characterization of Neural Networks and Cognitive Processes Involved in Mental Retardation X-linked Unknown status NCT02854956
5 Genetic Disease Gene Identification Unknown status NCT00916903
6 Effects of Creatine Supplementation in Rett Syndrome: A Randomized, Placebo-controlled Trial Completed NCT01147575
7 The Seaver Autism Center for Research and Treatment - Assessment Core Recruiting NCT03718910
8 Development of a New Algorithm-based Classification for Glioma Active, not recruiting NCT04194593

Search NIH Clinical Center for Autism X-Linked 2

Genetic Tests for Autism X-Linked 2

Genetic tests related to Autism X-Linked 2:

# Genetic test Affiliating Genes
1 Autism, Susceptibility to, X-Linked 2 29 NLGN4X
2 Mental Retardation, X-Linked 29
3 Autism Susceptibility, X-Linked 2 29

Anatomical Context for Autism X-Linked 2

MalaCards organs/tissues related to Autism X-Linked 2:

40
Brain, Eye, Lung, Bone, Heart, Breast, Testes

Publications for Autism X-Linked 2

Articles related to Autism X-Linked 2:

(show top 50) (show all 89)
# Title Authors PMID Year
1
Familial deletion within NLGN4 associated with autism and Tourette syndrome. 56 6
18231125 2008
2
X-linked mental retardation and autism are associated with a mutation in the NLGN4 gene, a member of the neuroligin family. 56 6
14963808 2004
3
Mutations of the X-linked genes encoding neuroligins NLGN3 and NLGN4 are associated with autism. 56 6
12669065 2003
4
Genetic/familial high-risk assessment: breast and ovarian, version 1.2014. 6
25190698 2014
5
Clinical genetics evaluation in identifying the etiology of autism spectrum disorders: 2013 guideline revisions. 6
23519317 2013
6
Consensus statement: chromosomal microarray is a first-tier clinical diagnostic test for individuals with developmental disabilities or congenital anomalies. 6
20466091 2010
7
Hypothesis: dysregulation of methylation of brain-expressed genes on the X chromosome and autism spectrum disorders. 56
18698615 2008
8
Evidence for multiple loci from a genome scan of autism kindreds. 56
16880825 2006
9
Disorder-associated mutations lead to functional inactivation of neuroligins. 6
15150161 2004
10
A genomic screen of autism: evidence for a multilocus etiology. 56
10417292 1999
11
Xp deletions associated with autism in three females. 56
10071191 1999
12
Autism: towards an integration of clinical, genetic, neuropsychological, and neurobiological perspectives. 56
8655659 1996
13
Global changes in chromatin accessibility and transcription following ATRX inactivation in human cancer cells. 61
31329278 2020
14
Further delineation of the phenotypic spectrum associated with hemizygous loss-of-function variants in NONO. 61
31883306 2019
15
Diffuse leptomeningeal glioneuronal tumor in a Chinese adult: a novel case report and review of literature. 61
31875302 2019
16
ATRX In-Frame Fusion Neuroblastoma Is Sensitive to EZH2 Inhibition via Modulation of Neuronal Gene Signatures. 61
31631027 2019
17
Expression and prognostic impact of alpha thalassemia/mental retardation X-linked and death domain-associated protein in human lung cancer. 61
31374064 2019
18
High frequency of H3K27M immunopositivity in adult thalamic glioblastoma. 61
30937985 2019
19
G-quadruplex DNA drives genomic instability and represents a targetable molecular abnormality in ATRX-deficient malignant glioma. 61
30808951 2019
20
Recurrent Glioma With Lineage Conversion From Oligodendroglioma to Astrocytoma in Two Cases. 61
31508376 2019
21
The Loss of ATRX Increases Susceptibility to Pancreatic Injury and Oncogenic KRAS in Female But Not Male Mice. 61
30510993 2019
22
Daxx Functions Are p53-Independent In Vivo. 61
29903771 2018
23
Evidence for HNRNPH1 being another gene for Bain type syndromic mental retardation. 61
29938792 2018
24
Persistent accumulation of unrepaired DNA damage in rat cortical neurons: nuclear organization and ChIP-seq analysis of damaged DNA. 61
30049290 2018
25
Loss of Chromatin-Remodeling Proteins and/or CDKN2A Associates With Metastasis of Pancreatic Neuroendocrine Tumors and Reduced Patient Survival Times. 61
29486199 2018
26
Ribosomal DNA copy loss and repeat instability in ATRX-mutated cancers. 61
29669917 2018
27
How to Tackle Challenging ChIP-Seq, with Long-Range Cross-Linking, Using ATRX as an Example. 61
30073524 2018
28
DNA repair synthesis and histone deposition partner during homologous recombination. 61
30263950 2018
29
Novel insights into the epigenetics of diffuse glioma. 61
30263940 2018
30
Mechanistic understanding of the role of ATRX in senescence provides new insight for combinatorial therapies with CDK4 inhibitors. 61
29404388 2018
31
Altered Gene-Regulatory Function of KDM5C by a Novel Mutation Associated With Autism and Intellectual Disability. 61
29670509 2018
32
Primary Astrocytic Tumours and Paired Recurrences have Similar Biological Features in IDH1, TP53 and TERTp Mutation and MGMT, ATRX Loss. 61
29026176 2017
33
Deciphering the Molecular Effects of Mutations on ATRX Cause ATRX Syndrome: A Molecular Dynamics Study. 61
28294389 2017
34
Arabidopsis ATRX Modulates H3.3 Occupancy and Fine-Tunes Gene Expression. 61
28684426 2017
35
Alternative lengthening of telomeres and ATRX/DAXX loss can be reliably detected in FNAs of pancreatic neuroendocrine tumors. 61
28371511 2017
36
Dual-Genotype Diffuse Low-Grade Glioma: Is It Really Time to Abandon Oligoastrocytoma As a Distinct Entity? 61
28419269 2017
37
ATRX and DAXX: Mechanisms and Mutations. 61
28062559 2017
38
Identification of epigenetic signature associated with alpha thalassemia/mental retardation X-linked syndrome. 61
28293299 2017
39
Retinal interneuron survival requires non-cell-autonomous Atrx activity. 61
28173139 2016
40
New Genetics and Genomic Data on Pancreatic Neuroendocrine Tumors: Implications for Diagnosis, Treatment, and Targeted Therapies. 61
27456058 2016
41
Effect of ATRX and G-Quadruplex Formation by the VNTR Sequence on α-Globin Gene Expression. 61
26991472 2016
42
Molecular alterations in sporadic pancreatic neuroendocrine microadenomas. 61
26905832 2016
43
Stalled replication forks within heterochromatin require ATRX for protection. 61
27171262 2016
44
Differential nuclear ATRX expression in sarcomas. 61
26291601 2016
45
Detection of ATRX and IDH1-R132H immunohistochemistry in the progression of 211 paired gliomas. 61
26918938 2016
46
Correction: Characterization of the Drosophila Group Ortholog to the Amino-Terminus of the Alpha-Thalassemia and Mental Retardation X-Linked (ATRX) Vertebrate Protein. 61
26863318 2016
47
Volvulus and bowel obstruction in ATR-X syndrome-clinical report and review of literature. 61
26174613 2015
48
Impact of the tumor microenvironment in predicting postoperative hepatic recurrence of pancreatic neuroendocrine tumors. 61
25310565 2014
49
ATRX is required for maintenance of the neuroprogenitor cell pool in the embryonic mouse brain. 61
25395668 2014
50
Characterization of the Drosophila group ortholog to the amino-terminus of the alpha-thalassemia and mental retardation X-Linked (ATRX) vertebrate protein. 61
25437195 2014

Variations for Autism X-Linked 2

ClinVar genetic disease variations for Autism X-Linked 2:

6 ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 NLGN4X NM_181332.3(NLGN4X):c.1252_1253GA[1] (p.Glu418fs)short repeat Pathogenic,risk factor 11051 rs1569118680 X:5821464-5821465 X:5903423-5903424
2 NLGN4X nsv513783deletion Pathogenic,risk factor 11052
3 NLGN4X NM_181332.3(NLGN4X):c.301C>T (p.Arg101Ter)SNV Pathogenic 374392 rs756651509 X:6069207-6069207 X:6151166-6151166
4 NLGN4X NM_181332.3(NLGN4X):c.1185dup (p.Asp396Ter)duplication risk factor 11050 rs1569118853 X:5821533-5821534 X:5903492-5903493
5 NLGN4X NM_181332.3(NLGN4X):c.2259G>C (p.Arg753Ser)SNV Uncertain significance 284715 rs886042929 X:5811050-5811050 X:5893009-5893009
6 NLGN4X NM_181332.3(NLGN4X):c.2428G>A (p.Gly810Arg)SNV Uncertain significance 561066 rs1181689310 X:5810881-5810881 X:5892840-5892840
7 NLGN4X NM_181332.3(NLGN4X):c.1777C>T (p.Leu593Phe)SNV Benign/Likely benign 95980 rs3747333 X:5811532-5811532 X:5893491-5893491

Expression for Autism X-Linked 2

Search GEO for disease gene expression data for Autism X-Linked 2.

Pathways for Autism X-Linked 2

Pathways related to Autism X-Linked 2 according to KEGG:

36
# Name Kegg Source Accession
1 Regulation of actin cytoskeleton hsa04810

GO Terms for Autism X-Linked 2

Sources for Autism X-Linked 2

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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