AUTS2

Chr 7AD

activator of transcription and developmental regulator AUTS2

Also known as: FBRSL2, MRD26

NCBI Gene: 26053ENSG00000158321UniProt: Q8WXX7

This gene has been implicated in neurodevelopment and as a candidate gene for numerous neurological disorders, including autism spectrum disorders, intellectual disability, and developmental delay. Mutations in this gene have also been associated with non-neurological disorders, such as acute lymphoblastic leukemia, aging of the skin, early-onset androgenetic alopecia, and certain cancers. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, May 2014]

Primary Disease Associations & Inheritance

Intellectual developmental disorder, autosomal dominant 26MIM #615834
AD
413
ClinVar variants
52
Pathogenic / LP
1.00
pLI score· haploinsufficient
1
Active trials
Clinical Summary— AUTS2
🧬
Gene-Disease Validity (ClinGen)
syndromic intellectual disability · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
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.
📋
ClinVar Variants
52 Pathogenic / Likely Pathogenic· 201 VUS of 413 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
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?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
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?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.13 (0.08–0.25)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.78 (0.73–0.83)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.08
0≤1.21.6
LoF obs/exp: 7 / 52.0Missense obs/exp: 617 / 793.3Syn Z: -1.17

ClinVar Variant Classifications

413 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic41
Likely Pathogenic11
VUS201
Likely Benign139
Benign16
Conflicting5
41
Pathogenic
11
Likely Pathogenic
201
VUS
139
Likely Benign
16
Benign
5
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
9
1
31
0
41
Likely Pathogenic
7
2
2
0
11
VUS
5
172
23
1
201
Likely Benign
0
12
37
90
139
Benign
0
10
1
5
16
Conflicting
—5
Total211979496413

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in 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.

Gene2Phenotype Curations

AUTS2-related syndromic intellectual disability

definitive
ADLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Intellectual developmental disorder, autosomal dominant 26

MIM #615834

Molecular basis of disorder known

Autosomal dominant
📖
GeneReview available — AUTS2
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
AUTS2-related syndrome: Insights from a large European cohort.
Loberti L et al.·Genet Med
2025Cohort
Cerebral organoids containing an AUTS2 missense variant model microcephaly.
Fair SR et al.·Brain
2023Functional
De Novo Pathogenic Variant in FBRSL1, Non OMIM Gene Paralogue AUTS2, Causes a Novel Recognizable Syndromic Manifestation with Intellectual Disability; An Additional Patient and Review of the Literature.
Bukvic N et al.·Genes (Basel)
2024Review
De novo mutations in FBRSL1 cause a novel recognizable malformation and intellectual disability syndrome.
Ufartes R et al.·Hum Genet
2020Case report
The role of AUTS2 in neurodevelopment and human evolution.
Oksenberg N et al.·Trends Genet
2013Review
Attention Deficit Hyperactivity and Autism Spectrum Disorders as the Core Symptoms of AUTS2 Syndrome: Description of Five New Patients and Update of the Frequency of Manifestations and Genotype-Phenotype Correlation.
Sanchez-Jimeno C et al.·Genes (Basel)
2021Review
Further Delineation of the AUTS2 HX Repeat Domain-Related Phenotype.
Erdogan EN et al.·Am J Med Genet A
2025
Erotomania and phenotypic continuum in a family frameshift variant of AUTS2: a case report and review.
Gauld C et al.·BMC Psychiatry
2021Review
NRF1 association with AUTS2-Polycomb mediates specific gene activation in the brain.
Liu S et al.·Mol Cell
2021
Ancestry of the AUTS2 family-A novel group of polycomb-complex proteins involved in human neurological disease.
Sellers RA et al.·PLoS One
2020
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
16P11.2 Deletion Syndrome16p11.2 Duplications1Q21.1 Deletion

Online Study of People Who Have Genetic Changes and Features of Autism: Simons Searchlight

RECRUITING
NCT01238250Simons SearchlightStarted 2010-10

External Resources

Links to major genomics databases and tools