ASTN1

Chr 1

astrotactin 1

Also known as: ASTN

NCBI Gene: 460 ENSG00000152092 UniProt: O14525

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.

ResearchSummary from RefSeq, UniProt

Astrotactin is a neuronal adhesion molecule required for glial-guided migration of young postmitotic neuroblasts in cortical regions of developing brain, including cerebrum, hippocampus, cerebellum, and olfactory bulb (Fink et al., 1995).[supplied by OMIM, Jun 2009]

ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.21

Clinical Summary— ASTN1

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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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ClinVar Variants

2 unique Pathogenic / Likely Pathogenic· 156 VUS of 192 total submissions

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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 →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.21LOEUF

pLI 1.000

Z-score 6.47

OE 0.11 (0.06–0.21)

Highly constrained

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

Missense Constraint?

1.65Z-score

OE missense 0.83 (0.78–0.89)

644 obs / 773.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.11 (0.06–0.21)

0≤0.351.4

Missense OE?0.83 (0.78–0.89)

0≤0.61.4

Synonymous OE?0.99

0≤1.21.6

LoF obs/exp: 7 / 62.0Missense obs/exp: 644 / 773.2Syn Z: 0.17

This gene — mechanism propensity

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

192 submitted variants in ClinVar

ClinVar

Classification Summary

Likely Pathogenic2

VUS156

Likely Benign14

Conflicting2

Likely Pathogenic

156

VUS

Likely Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0	0
Likely Pathogenic	1	1	0	0	2
VUS	0	156	0	0	156
Likely Benign	0	5	1	8	14
Benign	0	0	0	0	0
Conflicting	—				2
Total	1	162	1	8	174

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

View in ClinVar →

22 pathogenic / likely-pathogenic (of 33) ClinVar copy-number / structural variants overlap ASTN1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →