AUTS2

activator of transcription and developmental regulator AUTS2

Basic information

Region (hg38): 7:69598296-70793506

Links

ENSG00000158321 ∙ NCBI:26053 ∙ OMIM:607270 ∙ HGNC:14262 ∙ Uniprot:Q8WXX7 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

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

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Intellectual developmental disorder, autosomal dominant 26	AD	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Craniofacial; Musculoskeletal; Neurologic	22872102; 23332918; 25205402

ClinVar

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

• Autism spectrum disorder due to AUTS2 deficiency (19 variants)
• not provided (19 variants)
• Inborn genetic diseases (4 variants)
• Intellectual disability (1 variants)
• Developmental disorder (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			5	163	15	183
missense		5	325	53	35	418
nonsense	11	9	1	1		22
start loss	2		1			3
frameshift	20	8	7	1		36
inframe indel		1	21	4	1	27
splice donor/acceptor (+/-2bp)	6	2	2			10
splice region			9	17	6	32
non coding			5	57	84	146
Total	39	25	367	279	135

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)
7-69598673-T-C			Likely benign (Jun 24, 2019)
7-69598914-T-G			Benign (Jul 26, 2018)
7-69599223-A-G			Likely benign (Sep 29, 2019)
7-69599651-A-G			Benign (Jul 03, 2018)
7-69599654-A-G			Uncertain significance (Sep 17, 2023)
7-69599654-A-T		Autism spectrum disorder due to AUTS2 deficiency	Pathogenic (Jul 08, 2020)
7-69599655-T-C		Autism spectrum disorder due to AUTS2 deficiency	Pathogenic (Apr 23, 2018)
7-69599664-C-T		Intellectual disability • AUTS2-related disorder	Benign (Apr 01, 2024)
7-69599669-C-T		Inborn genetic diseases	Uncertain significance (Apr 11, 2023)
7-69599679-G-A		Inborn genetic diseases	Uncertain significance (Feb 21, 2024)
7-69599681-C-G			Uncertain significance (Jan 08, 2021)
7-69599693-C-T			Uncertain significance (May 11, 2023)
7-69599693-C-CGGCGGT			Uncertain significance (Jul 22, 2019)
7-69599697-G-T		Inborn genetic diseases	Uncertain significance (Jun 11, 2024)
7-69599717-C-T			Uncertain significance (Apr 20, 2022)
7-69599721-A-G			Uncertain significance (Jul 01, 2022)
7-69599731-C-T			Likely benign (Feb 01, 2023)
7-69599732-C-T			Uncertain significance (Dec 21, 2023)
7-69599740-G-T			Likely benign (Mar 20, 2023)
7-69599742-T-G		Inborn genetic diseases	Uncertain significance (Jul 03, 2023)
7-69599743-GGGGGCCGGCGCGGCCGGCGGCGGC-G			Uncertain significance (Jul 27, 2022)
7-69599744-G-A		Autism spectrum disorder due to AUTS2 deficiency	Uncertain significance (May 05, 2019)
7-69599745-G-T			Uncertain significance (Jul 01, 2022)
7-69599747-G-A			Uncertain significance (Oct 01, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
AUTS2	protein_coding	protein_coding	ENST00000342771	19	1194150

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.999	0.000661	125742	0	6	125748	0.0000239

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.22	617	793	0.778	0.0000512	8156
Missense in Polyphen		253	375.2	0.67431		3698
Synonymous	-1.17	362	335	1.08	0.0000233	2614
Loss of Function	5.78	7	52.0	0.135	0.00000292	553

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.0000358	0.0000352
Middle Eastern	0.00	0.00
South Asian	0.0000327	0.0000327
Other	0.00	0.00

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

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

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