ASXL3

Chr 18AD

ASXL transcriptional regulator 3

Also known as: BRPS, KIAA1713

NCBI Gene: 80816ENSG00000141431UniProt: Q9C0F0

This gene encodes a protein containing a plant homeodomain (PHD) zinc finger domain that plays a role in the regulation of gene transcription. The encoded protein has been shown to negatively regulate lipogenesis by binding to and inhibiting the transcriptional activity of two nuclear hormone receptors, oxysterols receptor LXR-alpha (LXRalpha) and thyroid hormone receptor beta (TRbeta). The encoded protein may also inhibit histone deubiquitination. Mutations in this gene have been identified in human patients with Bainbridge-Ropers syndrome, which is characterized by feeding difficulties, developmental delay and other features. [provided by RefSeq, May 2017]

Primary Disease Associations & Inheritance

Bainbridge-Ropers syndromeMIM #615485
AD
3
Active trials
67
Pathogenic / LP
398
ClinVar variants
23
Pubs (1 yr)
0.6
Missense Z
0.20
LOEUF· LoF intolerant
Clinical Summary— ASXL3
🧬
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
67 Pathogenic / Likely Pathogenic· 243 VUS of 398 total submissions
💊
Clinical Trials
3 active or recruiting trials — potential therapeutic options may be available
📖
GeneReview available — ASXL3
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint
0.20LOEUF
pLI 1.000
Z-score 7.02
OE 0.11 (0.06–0.20)
Highly constrained

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

Missense Constraint
0.61Z-score
OE missense 0.95 (0.90–1.00)
1097 obs / 1155.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.11 (0.06–0.20)
0≤0.351.4
Missense OE0.95 (0.90–1.00)
0≤0.61.4
Synonymous OE1.01
0≤1.21.6
LoF obs/exp: 8 / 72.6Missense obs/exp: 1097 / 1155.1Syn Z: -0.12
LOF
DN
0.2299th %ile
GOF
0.2298th %ile
LOF
0.81top 5%

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

LOFprediction above median · 1 literature citation · 60% of P/LP variants are LoF · LOEUF 0.20

Literature Evidence

LOFDe novo dominant ASXL3 mutations alter H2A deubiquitination and transcription in Bainbridge-Ropers syndromePMID:26647312

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

398 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic26
Likely Pathogenic41
VUS243
Likely Benign80
Benign2
Conflicting6
26
Pathogenic
41
Likely Pathogenic
243
VUS
80
Likely Benign
2
Benign
6
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
15
0
11
0
26
Likely Pathogenic
25
0
16
0
41
VUS
3
223
13
4
243
Likely Benign
0
56
3
21
80
Benign
0
1
1
0
2
Conflicting
—6
Total432804425398

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

View in ClinVar →

ASXL3 · protein map & ClinVar variants

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

Gene2Phenotype Curations

ASXL3-related Bainbridge-Ropers syndrome

strong
ADLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

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

Clinical Literature
Landmark / reviewRecent case evidence
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Phenotypic spectrum and genomics of undiagnosed arthrogryposis multiplex congenita.
Laquerriere A et al.·J Med Genet
2022
Expanding the phenotype of ASXL3-related syndrome: A comprehensive description of 45 unpublished individuals with inherited and de novo pathogenic variants in ASXL3.
Schirwani S et al.·Am J Med Genet A
2021
De novo variants underlying monogenic syndromes with intellectual disability in a neurodevelopmental cohort from India.
Pande S et al.·Eur J Hum Genet
2024Cohort
ASXL3-related disorder: Molecular phenotyping and comprehensive review providing insights into disease mechanism.
Woods E et al.·Clin Genet
2024Review
De novo nonsense variant in ASXL3 in a Chinese girl causing Bainbridge-Ropers syndrome: A case report and review of literature.
Wang Q et al.·Mol Genet Genomic Med
2022Review
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
ASXL3 gene variants causing Bainbridge-Ropers syndrome: clinical and genetic analysis of four Chinese patients.
Yang Q et al.·Front Neurosci
2025Open AccessCohort
Correction: Case Report: Synergistic effects of an ASXL3 mutation and a 15q11.2 BP1-BP2 microdeletion in a severe neurodevelopmental phenotype.
Yang M et al.·Front Genet
2025Open AccessCase report
Case Report: Synergistic effects of an ASXL3 mutation and a 15q11.2 BP1-BP2 microdeletion in a severe neurodevelopmental phenotype.
Yang M et al.·Front Genet
2025Open AccessCase report
A novel ASXL3 gene variant in a Chinese Boy causing Bainbridge.
Dai B et al.·BMC Infect Dis
2025Open Access
Paternal mosaicism in ASXL3-related bainbridge-ropers syndrome: implications for genetic counseling and prenatal diagnosis.
Zhao B et al.·Front Pediatr
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