AUTSX2
MCID: ATS366
MIFTS: 41

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 57
Mental Retardation, X-Linked 57 13 6 39 70
Autism, Susceptibility to, X-Linked 2 57 29 6
Autism Susceptibility, X-Linked 2 57 29
X-Linked Mental Retardation 73 36
Autsx2 57 72
Autism, X-Linked 2 72

Characteristics:

OMIM®:

57 (Updated 20-May-2021)
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® : 57 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) (Updated 20-May-2021)

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 Metformin and Hypoglycemic Agents have been mentioned in the context of this disorder. Affiliated tissues include eye, bone and heart, and related phenotypes are eeg abnormality and increased serum serotonin

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 : 72 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 : 73 X-linked mental retardation refers to medical disorders associated with X-linked recessive inheritance... 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 298)
# Related Disease Score Top Affiliating Genes
1 mental retardation, x-linked, with or without seizures, arx-related 12.0
2 mental retardation, x-linked, syndromic 13 12.0
3 mental retardation, x-linked, syndromic, cabezas type 11.9
4 pettigrew syndrome 11.9
5 mental retardation, x-linked 12 11.9
6 mental retardation, x-linked, syndromic, turner type 11.9
7 lubs x-linked mental retardation syndrome 11.8
8 mental retardation, x-linked, with cerebellar hypoplasia and distinctive facial appearance 11.8
9 mental retardation, x-linked, with panhypopituitarism 11.8
10 mental retardation, x-linked, syndromic, hedera type 11.8
11 mental retardation, x-linked 97 11.8
12 mental retardation, x-linked, syndromic, nascimento type 11.8
13 wilson-turner x-linked mental retardation syndrome 11.8
14 mental retardation, x-linked, syndromic, claes-jensen type 11.8
15 mental retardation, x-linked, syndromic 32 11.8
16 mental retardation, x-linked, syndromic 34 11.8
17 methylmalonic acidemia and homocysteinemia, cblx type 11.8
18 renpenning syndrome 1 11.8
19 mental retardation, x-linked 21 11.8
20 mental retardation, x-linked, syndromic, martin-probst type 11.8
21 mental retardation, x-linked 96 11.8
22 mental retardation, x-linked, syndromic, christianson type 11.8
23 intellectual developmental disorder, x-linked, syndromic, wu type 11.8
24 mental retardation and microcephaly with pontine and cerebellar hypoplasia 11.8
25 mental retardation, x-linked 98 11.8
26 mental retardation, x-linked 99 11.8
27 mental retardation, x-linked 100 11.8
28 mental retardation, x-linked 101 11.8
29 mental retardation, x-linked 92 11.7
30 mental retardation, x-linked, syndromic 33 11.7
31 mental retardation, x-linked 103 11.7
32 mental retardation, x-linked 104 11.7
33 mental retardation, x-linked 105 11.7
34 mental retardation, x-linked, syndromic, 35 11.7
35 intellectual developmental disorder, x-linked 109 11.7
36 raynaud-claes syndrome 11.7
37 mehmo syndrome 11.7
38 intellectual developmental disorder, x-linked, syndromic, raymond type 11.7
39 stocco dos santos x-linked mental retardation syndrome 11.7
40 mental retardation, x-linked 99, syndromic, female-restricted 11.7
41 mental retardation, x-linked, syndromic, bain type 11.7
42 mental retardation, x-linked 106 11.7
43 mental retardation, x-linked 107 11.7
44 corpus callosum, agenesis of, with mental retardation, ocular coloboma, and micrognathia 11.6
45 mental retardation, x-linked, syndromic, houge type 11.6
46 fragile x syndrome 11.6
47 mental retardation, x-linked, syndromic 17 11.6
48 intellectual developmental disorder, x-linked, syndromic, snijders blok type 11.6
49 intellectual developmental disorder, x-linked, syndromic, armfield type 11.6
50 intellectual developmental disorder, x-linked 50 11.6

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 eeg abnormality 31 frequent (33%) HP:0002353
2 increased serum serotonin 31 frequent (33%) HP:0003144
3 seizure 31 frequent (33%) HP:0001250
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 restrictive behavior 31 HP:0000723
10 lack of peer relationships 31 HP:0002332
11 lack of spontaneous play 31 HP:0000721
12 inflexible adherence to routines or rituals 31 HP:0000732

Symptoms via clinical synopsis from OMIM®:

57 (Updated 20-May-2021)
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 (Updated 20-May-2021)

Drugs & Therapeutics for Autism X-Linked 2

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


# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Metformin Approved Phase 2, Phase 3 657-24-9 14219 4091
2 Hypoglycemic Agents Phase 2, Phase 3
3 Astragalus

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 A Double-Blind, Placebo-Controlled Trial of Metformin in Individuals With Fragile X Syndrome Recruiting NCT03479476 Phase 2, Phase 3 Placebo Medication;Metformin
2 A Double-Blind, Placebo-Controlled Trial of Metformin in Individuals With Fragile X Syndrome (FXS) Recruiting NCT03862950 Phase 2 Placebo Medication;Metformin
3 Clinical Phenotyping and Characterization of Neural Networks and Cognitive Processes Involved in Mental Retardation X-linked Unknown status NCT02854956
4 Genetic Disease Gene Identification Unknown status NCT00916903
5 The Seaver Autism Center for Research and Treatment - Assessment Core Recruiting NCT03718910

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 Autism Susceptibility, X-Linked 2 29

Anatomical Context for Autism X-Linked 2

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

40
Eye, Bone, Heart, Lung, Skin, Brain

Publications for Autism X-Linked 2

Articles related to Autism X-Linked 2:

(show top 50) (show all 94)
# Title Authors PMID Year
1
Familial deletion within NLGN4 associated with autism and Tourette syndrome. 6 57
18231125 2008
2
X-linked mental retardation and autism are associated with a mutation in the NLGN4 gene, a member of the neuroligin family. 6 57
14963808 2004
3
Mutations of the X-linked genes encoding neuroligins NLGN3 and NLGN4 are associated with autism. 57 6
12669065 2003
4
Hypothesis: dysregulation of methylation of brain-expressed genes on the X chromosome and autism spectrum disorders. 57
18698615 2008
5
Evidence for multiple loci from a genome scan of autism kindreds. 57
16880825 2006
6
Disorder-associated mutations lead to functional inactivation of neuroligins. 6
15150161 2004
7
A genomic screen of autism: evidence for a multilocus etiology. 57
10417292 1999
8
Xp deletions associated with autism in three females. 57
10071191 1999
9
Autism: towards an integration of clinical, genetic, neuropsychological, and neurobiological perspectives. 57
8655659 1996
10
Generation and characterization of the induced pluripotent stem cell line SHCDNi004-A from a ten-year-old Chinese boy with X-linked mental retardation in IL1RAPL1 deficiency. 61
33774333 2021
11
Main genetic differences in high-grade gliomas may present different MR imaging and MR spectroscopy correlates. 61
32875375 2021
12
Plasma amino acids indicate glioblastoma with ATRX loss. 61
33398522 2021
13
Impact of DAXX and ATRX expression on telomere length and prognosis of breast cancer patients. 61
32856116 2020
14
Alpha Internexin: A Surrogate Marker for 1p/19q Codeletion and Prognostic Marker in Anaplastic (WHO grade III) Gliomas. 61
32859823 2020
15
Mutually suppressive roles of KMT2A and KDM5C in behaviour, neuronal structure, and histone H3K4 methylation. 61
32483278 2020
16
Effects of a postnatal Atrx conditional knockout in neurons on autism-like behaviours in male and female mice. 61
32580781 2020
17
Further delineation of the phenotypic spectrum associated with hemizygous loss-of-function variants in NONO. 61
31883306 2020
18
Diffuse leptomeningeal glioneuronal tumor in a Chinese adult: a novel case report and review of literature. 61
31875302 2020
19
Case Report: Characterization of a Novel NONO Intronic Mutation in a Fetus With X-Linked Syndromic Mental Retardation-34. 61
33304389 2020
20
Global changes in chromatin accessibility and transcription following ATRX inactivation in human cancer cells. 61
31329278 2020
21
ATRX In-Frame Fusion Neuroblastoma Is Sensitive to EZH2 Inhibition via Modulation of Neuronal Gene Signatures. 61
31631027 2019
22
Expression and prognostic impact of alpha thalassemia/mental retardation X-linked and death domain-associated protein in human lung cancer. 61
31374064 2019
23
High frequency of H3K27M immunopositivity in adult thalamic glioblastoma. 61
30937985 2019
24
G-quadruplex DNA drives genomic instability and represents a targetable molecular abnormality in ATRX-deficient malignant glioma. 61
30808951 2019
25
The Loss of ATRX Increases Susceptibility to Pancreatic Injury and Oncogenic KRAS in Female But Not Male Mice. 61
30510993 2019
26
Recurrent Glioma With Lineage Conversion From Oligodendroglioma to Astrocytoma in Two Cases. 61
31508376 2019
27
Evidence for HNRNPH1 being another gene for Bain type syndromic mental retardation. 61
29938792 2018
28
Daxx Functions Are p53-Independent In Vivo. 61
29903771 2018
29
Persistent accumulation of unrepaired DNA damage in rat cortical neurons: nuclear organization and ChIP-seq analysis of damaged DNA. 61
30049290 2018
30
Loss of Chromatin-Remodeling Proteins and/or CDKN2A Associates With Metastasis of Pancreatic Neuroendocrine Tumors and Reduced Patient Survival Times. 61
29486199 2018
31
Ribosomal DNA copy loss and repeat instability in ATRX-mutated cancers. 61
29669917 2018
32
How to Tackle Challenging ChIP-Seq, with Long-Range Cross-Linking, Using ATRX as an Example. 61
30073524 2018
33
Mechanistic understanding of the role of ATRX in senescence provides new insight for combinatorial therapies with CDK4 inhibitors. 61
29404388 2018
34
Novel insights into the epigenetics of diffuse glioma. 61
30263940 2018
35
DNA repair synthesis and histone deposition partner during homologous recombination. 61
30263950 2018
36
Altered Gene-Regulatory Function of KDM5C by a Novel Mutation Associated With Autism and Intellectual Disability. 61
29670509 2018
37
Primary Astrocytic Tumours and Paired Recurrences have Similar Biological Features in IDH1, TP53 and TERTp Mutation and MGMT, ATRX Loss. 61
29026176 2017
38
Deciphering the Molecular Effects of Mutations on ATRX Cause ATRX Syndrome: A Molecular Dynamics Study. 61
28294389 2017
39
Arabidopsis ATRX Modulates H3.3 Occupancy and Fine-Tunes Gene Expression. 61
28684426 2017
40
Alternative lengthening of telomeres and ATRX/DAXX loss can be reliably detected in FNAs of pancreatic neuroendocrine tumors. 61
28371511 2017
41
Dual-Genotype Diffuse Low-Grade Glioma: Is It Really Time to Abandon Oligoastrocytoma As a Distinct Entity? 61
28419269 2017
42
ATRX and DAXX: Mechanisms and Mutations. 61
28062559 2017
43
Identification of epigenetic signature associated with alpha thalassemia/mental retardation X-linked syndrome. 61
28293299 2017
44
Retinal interneuron survival requires non-cell-autonomous Atrx activity. 61
28173139 2016
45
New Genetics and Genomic Data on Pancreatic Neuroendocrine Tumors: Implications for Diagnosis, Treatment, and Targeted Therapies. 61
27456058 2016
46
Molecular alterations in sporadic pancreatic neuroendocrine microadenomas. 61
26905832 2016
47
Effect of ATRX and G-Quadruplex Formation by the VNTR Sequence on α-Globin Gene Expression. 61
26991472 2016
48
Stalled replication forks within heterochromatin require ATRX for protection. 61
27171262 2016
49
Differential nuclear ATRX expression in sarcomas. 61
26291601 2016
50
Detection of ATRX and IDH1-R132H immunohistochemistry in the progression of 211 paired gliomas. 61
26918938 2016

Variations for Autism X-Linked 2

ClinVar genetic disease variations for Autism X-Linked 2:

6 (show all 11)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 NLGN4X NM_181332.3(NLGN4X):c.301C>T (p.Arg101Ter) SNV Pathogenic 374392 rs756651509 GRCh37: X:6069207-6069207
GRCh38: X:6151166-6151166
2 NLGN4X NM_181332.3(NLGN4X):c.1185dup (p.Asp396Ter) Duplication risk factor 11050 rs1569118853 GRCh37: X:5821533-5821534
GRCh38: X:5903492-5903493
3 NLGN4X NM_181332.3(NLGN4X):c.1252_1253GA[1] (p.Glu418fs) Microsatellite risk factor 11051 rs1569118680 GRCh37: X:5821464-5821465
GRCh38: X:5903423-5903424
4 NLGN4X nsv513783 Deletion risk factor 11052 GRCh37:
GRCh38:
5 NLGN4X NM_181332.3(NLGN4X):c.2259G>C (p.Arg753Ser) SNV Uncertain significance 284715 rs886042929 GRCh37: X:5811050-5811050
GRCh38: X:5893009-5893009
6 NLGN4X NM_181332.3(NLGN4X):c.2428G>A (p.Gly810Arg) SNV Uncertain significance 561066 rs1181689310 GRCh37: X:5810881-5810881
GRCh38: X:5892840-5892840
7 NLGN4X NM_181332.3(NLGN4X):c.1661T>C (p.Phe554Ser) SNV Uncertain significance 829851 rs1601840441 GRCh37: X:5811648-5811648
GRCh38: X:5893607-5893607
8 NLGN4X NM_181332.3(NLGN4X):c.2080G>A (p.Ala694Thr) SNV Uncertain significance 976154 GRCh37: X:5811229-5811229
GRCh38: X:5893188-5893188
9 NLGN4X NM_181332.3(NLGN4X):c.872A>G (p.Tyr291Cys) SNV Uncertain significance 1030724 GRCh37: X:5821847-5821847
GRCh38: X:5903806-5903806
10 NLGN4X NM_181332.3(NLGN4X):c.1777C>T (p.Leu593Phe) SNV Likely benign 95980 rs3747333 GRCh37: X:5811532-5811532
GRCh38: X:5893491-5893491
11 EFHC2 NM_025184.4(EFHC2):c.404G>A (p.Arg135Gln) SNV Benign 167032 rs201560745 GRCh37: X:44120523-44120523
GRCh38: X:44261277-44261277

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
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 20-May-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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