ASTN1

Chr 1

astrotactin 1

Also known as: ASTN

Astrotactin is a neuronal adhesion molecule that mediates glial-guided migration of postmitotic neuroblasts during brain development, particularly in the cerebrum, hippocampus, cerebellum, and olfactory bulb. Mutations cause autosomal dominant cortical dysplasia-complex with other brain malformations, typically manifesting as developmental abnormalities affecting multiple brain regions. The gene is highly constrained against loss-of-function variants, indicating that even heterozygous disruption can cause significant neurodevelopmental phenotypes.

OMIMResearchSummary from RefSeq, UniProt
LOFmechanismLOEUF 0.21
Clinical SummaryASTN1
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

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.21LOEUF
pLI 1.000
Z-score 6.47
OE 0.11 (0.060.21)
Highly constrained

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

Missense Constraint
1.65Z-score
OE missense 0.83 (0.780.89)
644 obs / 773.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.11 (0.060.21)
00.351.4
Missense OE0.83 (0.780.89)
00.61.4
Synonymous OE0.99
01.21.6
LoF obs/exp: 7 / 62.0Missense obs/exp: 644 / 773.2Syn Z: 0.17
DN
0.3395th %ile
GOF
0.5268th %ile
LOF
0.66top 25%

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

LOFprediction above median · LOEUF 0.21

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

ASTN1 · 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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