AUTS2

Chr 7AD

activator of transcription and developmental regulator AUTS2

Also known as: FBRSL2, MRD26

NCBI Gene: 26053ENSG00000158321UniProt: Q8WXX7OMIM: 607270

The AUTS2 protein localizes to the nucleus and functions in neurodevelopment. Mutations cause intellectual developmental disorder through a loss-of-function mechanism, with autosomal dominant inheritance. The gene is highly intolerant to loss-of-function variants, consistent with haploinsufficiency as the pathogenic mechanism.

OMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
LOFmechanismADLOEUF 0.251 OMIM phenotype
Clinical Summary— AUTS2
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Gene-Disease Validity (ClinGen)
syndromic intellectual disability · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint
0.25LOEUF
pLI 0.999
Z-score 5.78
OE 0.13 (0.08–0.25)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
2.22Z-score
OE missense 0.78 (0.73–0.83)
617 obs / 793.3 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.13 (0.08–0.25)
0≤0.351.4
Missense OE0.78 (0.73–0.83)
0≤0.61.4
Synonymous OE1.08
0≤1.21.6
LoF obs/exp: 7 / 52.0Missense obs/exp: 617 / 793.3Syn Z: -1.17
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveAUTS2-related syndromic intellectual disabilityLOFAD
DN
0.2898th %ile
GOF
0.15100th %ile
LOF
0.90top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · 1 literature citation · LOEUF 0.25

Literature Evidence

LOFHaploinsufficiency of AUTS2 has been associated with neurodevelopmental disorders and dysmorphic features (MIM # 615834).PMID:33577136

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

AUTS2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold
Clinical Literature
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Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Base editing in the AUTS2 gene and high-throughput NGS genotyping of clones: a strategy for generating a cellular model.
Yan AP et al.·Vavilovskii Zhurnal Genet Selektsii
2026Open AccessFunctional
AUTS2 disruption underlies radioulnar synostosis and skeletal dysmorphogenesis: evidence from four unrelated cases.
Liu C et al.·J Med Genet
2025Cohort
Genetic Heterogeneity of Autism Spectrum Disorder: Identification of Five Novel Mutations (RIMS2, FOXG1, AUTS2, ZCCHC17, and SPTBN5) in Iranian Families via Whole-Exome and Whole-Genome Sequencing.
Mirahmadi M et al.·Biochem Genet
2025
The relationship of methylation and mRNA expression profile of AUTS2 with suicidal ideation in adolescents with bipolar depression.
Shen X et al.·BMC Psychiatry
2025Open Access
Parent-of-origin regulation by maternal auts2 shapes neurodevelopment and behavior in fish.
Clément AE et al.·Genome Biol
2025Open Access
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients