ASTN2

Chr 9

astrotactin 2

Also known as: bA67K19.1

NCBI Gene: 23245 ENSG00000148219 UniProt: O75129

This protein mediates recycling of the neuronal cell adhesion molecule ASTN1 and selectively binds phosphoinositides, functioning in neuronal migration during brain development. Mutations cause autosomal dominant neurodevelopmental disorders including intellectual disability, autism spectrum disorder, and schizophrenia. The gene is highly constrained against loss-of-function variants, indicating that even heterozygous mutations can cause significant clinical phenotypes.

GeneReviews ResearchSummary from RefSeq, UniProt

This gene encodes a protein that is expressed in the brain and may function in neuronal migration, based on functional studies of the related astrotactin 1 gene in human and mouse. A deletion at this locus has been associated with schizophrenia. Multiple transcript variants encoding different proteins have been found for this locus. [provided by RefSeq, May 2010]

GeneReviews ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.25

Clinical Summary— ASTN2

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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

85 unique Pathogenic / Likely Pathogenic· 591 VUS of 1052 total submissions

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GeneReview available — ASTN2

Authoritative clinical overview · Recommended first read

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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?

0.25LOEUF

pLI 1.000

Z-score 6.12

OE 0.14 (0.08–0.25)

Highly constrained

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

Missense Constraint?

1.16Z-score

OE missense 0.88 (0.82–0.94)

603 obs / 688.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.14 (0.08–0.25)

0≤0.351.4

Missense OE?0.88 (0.82–0.94)

0≤0.61.4

Synonymous OE?1.10

0≤1.21.6

LoF obs/exp: 8 / 58.6Missense obs/exp: 603 / 688.5Syn Z: -1.39

This gene — mechanism propensity

0.3196th %ile

GOF

0.4776th %ile

LOF

0.69top 10%

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

LOFprediction above median · 81% of P/LP variants are LoF · LOEUF 0.25

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

1052 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic51

Likely Pathogenic34

VUS591

Likely Benign270

Benign31

Conflicting51

Pathogenic

Likely Pathogenic

591

VUS

270

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	38	1	12	0	51
Likely Pathogenic	31	2	1	0	34
VUS	6	551	31	3	591
Likely Benign	2	11	6	251	270
Benign	0	5	13	13	31
Conflicting	—				51
Total	77	570	63	267	1,028

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

View in ClinVar →

32 pathogenic / likely-pathogenic (of 150) ClinVar copy-number / structural variants overlap ASTN2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →