ASXL3

Chr 18AD

ASXL transcriptional regulator 3

Also known as: BRPS, KIAA1713

The protein contains a PHD zinc finger domain and regulates gene transcription by binding to and inhibiting nuclear hormone receptors LXRalpha and TRbeta, and may also inhibit histone deubiquitination. Mutations cause Bainbridge-Ropers syndrome, an autosomal dominant condition characterized by feeding difficulties and developmental delay. The gene is highly intolerant to loss-of-function variants, and mutations predominantly cause disease through haploinsufficiency.

OMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
LOFmechanismADLOEUF 0.201 OMIM phenotype
Clinical SummaryASXL3
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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.
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Clinical Trials
3 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.20LOEUF
pLI 1.000
Z-score 7.02
OE 0.11 (0.060.20)
Highly constrained

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

Missense Constraint
0.61Z-score
OE missense 0.95 (0.901.00)
1097 obs / 1155.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.11 (0.060.20)
00.351.4
Missense OE0.95 (0.901.00)
00.61.4
Synonymous OE1.01
01.21.6
LoF obs/exp: 8 / 72.6Missense obs/exp: 1097 / 1155.1Syn Z: -0.12
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongASXL3-related Bainbridge-Ropers syndromeLOFAD
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 · 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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

ASXL3 · 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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