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GeneBe

AUTS2

activator of transcription and developmental regulator AUTS2

Basic information

Region (hg38): 7:69598295-70793506

Links

ENSG00000158321NCBI:26053OMIM:607270HGNC:14262Uniprot:Q8WXX7AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

Phenotypes

GenCC

Source: genCC

  • autism, susceptibility to, 15 (Definitive), mode of inheritance: AD
  • autism spectrum disorder due to AUTS2 deficiency (Strong), mode of inheritance: AD
  • autism spectrum disorder due to AUTS2 deficiency (Supportive), mode of inheritance: AD
  • syndromic intellectual disability (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Intellectual developmental disorder, autosomal dominant 26ADGeneralGenetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testingCraniofacial; Musculoskeletal; Neurologic22872102; 23332918; 25205402

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the AUTS2 gene.

  • not provided (635 variants)
  • Autism spectrum disorder due to AUTS2 deficiency (107 variants)
  • Inborn genetic diseases (63 variants)
  • AUTS2-related condition (15 variants)
  • not specified (6 variants)
  • Autism spectrum disorder (6 variants)
  • Intellectual disability (5 variants)
  • See cases (4 variants)
  • Autism;Global developmental delay (1 variants)
  • Neurodevelopmental abnormality (1 variants)
  • Developmental disorder (1 variants)
  • Intellectual disability, autosomal dominant 57 (1 variants)
  • 15q11q13 microduplication syndrome (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the AUTS2 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type Pathogenic Likely pathogenic VUS Likely benign Benign Sum
synonymous
4
clinvar
111
clinvar
18
clinvar
133
missense
5
clinvar
281
clinvar
50
clinvar
21
clinvar
357
nonsense
10
clinvar
9
clinvar
2
clinvar
21
start loss
2
clinvar
1
clinvar
3
frameshift
17
clinvar
8
clinvar
6
clinvar
31
inframe indel
1
clinvar
21
clinvar
3
clinvar
1
clinvar
26
splice donor/acceptor (+/-2bp)
5
clinvar
2
clinvar
2
clinvar
9
splice region
?
7
11
6
24
non coding
?
5
clinvar
44
clinvar
82
clinvar
131
Total 34 25 322 208 122

Highest pathogenic variant AF is 0.0000460

Variants in AUTS2

This is a list of pathogenic ClinVar variants found in the AUTS2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position Type Phenotype Significance ClinVar
7-69598633-A-AGCG Benign (Apr 17, 2020)1290296
7-69598673-T-C Likely benign (Jun 24, 2019)1199522
7-69598914-T-G Benign (Jul 26, 2018)1226087
7-69599223-A-G Likely benign (Sep 29, 2019)1195316
7-69599651-A-G Benign (Jul 03, 2018)1178068
7-69599654-A-G Uncertain significance (Sep 17, 2023)2761164
7-69599654-A-T Autism spectrum disorder due to AUTS2 deficiency Pathogenic (Jul 08, 2020)1174542
7-69599655-T-C Autism spectrum disorder due to AUTS2 deficiency Pathogenic (Apr 23, 2018)1033782
7-69599664-C-T Intellectual disability Benign (Oct 01, 2023)975656
7-69599669-C-T Inborn genetic diseases Uncertain significance (Apr 11, 2023)2535839
7-69599681-C-G Uncertain significance (Jan 08, 2021)1212096
7-69599693-C-T Uncertain significance (May 11, 2023)2662364
7-69599693-C-CGGCGGT Uncertain significance (Jul 22, 2019)1307171
7-69599717-C-T Uncertain significance (Apr 20, 2022)1205753
7-69599721-A-G Uncertain significance (Jul 01, 2022)2073845
7-69599731-C-T Likely benign (Feb 01, 2023)2657525
7-69599732-C-T Uncertain significance (Dec 21, 2023)2704710
7-69599742-T-G Inborn genetic diseases Uncertain significance (Jul 03, 2023)2394218
7-69599743-GGGGGCCGGCGCGGCCGGCGGCGGC-G Uncertain significance (Jul 27, 2022)2412924
7-69599744-G-A Autism spectrum disorder due to AUTS2 deficiency Uncertain significance (May 05, 2019)2439437
7-69599745-G-T Uncertain significance (Jul 01, 2022)1701526
7-69599747-G-A Uncertain significance (Oct 04, 2022)1412198
7-69599757-C-CCGG Autism spectrum disorder due to AUTS2 deficiency Uncertain significance (Dec 06, 2022)1314638
7-69599759-G-C Inborn genetic diseases Uncertain significance (Jun 29, 2023)2608320
7-69599761-C-G Likely benign (Oct 17, 2023)748288

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
AUTS2protein_codingprotein_codingENST00000342771 191194150
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
0.9990.000661125742061257480.0000239
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense2.226177930.7780.00005128156
Missense in Polyphen253375.20.674313698
Synonymous-1.173623351.080.00002332614
Loss of Function5.78752.00.1350.00000292553

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.000.00
Ashkenazi Jewish0.000.00
East Asian0.000.00
Finnish0.00004620.0000462
European (Non-Finnish)0.00003580.0000352
Middle Eastern0.000.00
South Asian0.00003270.0000327
Other0.000.00

dbNSFP

Source: dbNSFP

Function
FUNCTION: Component of a Polycomb group (PcG) multiprotein PRC1- like complex, a complex class required to maintain the transcriptionally repressive state of many genes, including Hox genes, throughout development. PcG PRC1 complex acts via chromatin remodeling and modification of histones; it mediates monoubiquitination of histone H2A 'Lys-119', rendering chromatin heritably changed in its expressibility (PubMed:25519132). The PRC1-like complex that contains PCGF5, RNF2, CSNK2B, RYBP and AUTS2 has decreased histone H2A ubiquitination activity, due to the phosphorylation of RNF2 by CSNK2B (PubMed:25519132). As a consequence, the complex mediates transcriptional activation (PubMed:25519132). In the cytoplasm, plays a role in axon and dendrite elongation and in neuronal migration during embryonic brain development. Promotes reorganization of the actin cytoskeleton, lamellipodia formation and neurite elongation via its interaction with RAC guanine nucleotide exchange factors, which then leads to the activation of RAC1 (By similarity). {ECO:0000250|UniProtKB:A0A087WPF7, ECO:0000269|PubMed:25519132}.;
Disease
DISEASE: Mental retardation, autosomal dominant 26 (MRD26) [MIM:615834]: A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. Additional MRD26 features include autism, short stature, microcephaly, cerebral palsy, and facial dysmorphisms. {ECO:0000269|PubMed:23332918}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway
Gene expression (Transcription);RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known;Generic Transcription Pathway;RNA Polymerase II Transcription;Transcriptional regulation by RUNX1 (Consensus)

Recessive Scores

pRec
0.107

Intolerance Scores

loftool
0.317
rvis_EVS
-1.97
rvis_percentile_EVS
1.82

Haploinsufficiency Scores

pHI
0.831
hipred
Y
hipred_score
0.525
ghis
0.577

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
N
essential_gene_gene_trap
N
gene_indispensability_pred
N
gene_indispensability_score
0.0988

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

Mouse Genome Informatics

Gene name
Auts2
Phenotype
growth/size/body region phenotype; endocrine/exocrine gland phenotype; cellular phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); neoplasm; embryo phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); liver/biliary system phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan);

Zebrafish Information Network

Gene name
auts2a
Affected structure
motor neuron
Phenotype tag
abnormal
Phenotype quality
decreased size

Gene ontology

Biological process
neuron migration;biological_process;positive regulation of lamellipodium assembly;forebrain neuron development;actin cytoskeleton reorganization;positive regulation of Rac protein signal transduction;positive regulation of transcription by RNA polymerase II;axon extension;embryonic viscerocranium morphogenesis;positive regulation of histone H3-K4 methylation;righting reflex;neuron cellular homeostasis;dendrite extension;innate vocalization behavior;positive regulation of histone H4-K16 acetylation
Cellular component
cellular_component;nucleus;cytoplasm;actin cytoskeleton;growth cone
Molecular function
molecular_function;chromatin binding;protein binding