ASTN2

protein-coding

astrotactin 2, the group of Fibronectin type III domain containing|Small nucleolar RNA protein coding host genes

Gene summary

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]

MANE transcript

NM_001365068.1

Inheritance

AD, SD

ClinVar variants

U:212B:42

Top phenotype

Bardet-Biedl syndrome

gnomAD constraint

pLI —, LoF o/e 0.14

Max pathogenic AF

—

Genomic locus

chr9:116,423,112-117,415,070

External References & Databases

Ensembl (ENSG00000148219)

Transcript & Mutation Effects

hg38 • Region Span ~992.0 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

autism spectrum disorderLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0005258

Submitter: Ambry Genetics

neurodevelopmental disorderMODERATE

Inheritance Pattern: SD

Disease ID:MONDO:0700092

Submitter: PanelApp Australia

intellectual disabilityLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0001071

Submitter: Ambry Genetics

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ASTN2 variants in ClinVar

16 Conditions Cataloged

Bardet-Biedl syndromeTotal: 567

TRIM32-related disorderTotal: 288

not providedTotal: 264

not specifiedTotal: 249

Sarcotubular myopathyTotal: 217

Bardet-Biedl syndrome 11Total: 210

Inborn genetic diseasesTotal: 80

ASTN2-related disorderTotal: 41

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001365068.1. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			4 clinvar	21 clinvar	9 clinvar	34
missense			202 clinvar	9 clinvar	3 clinvar	214
nonsense			2 clinvar			2
start loss						0
frameshift			2 clinvar			2
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	212	30	12	254

Highest pathogenic variant AF is 0.00007620639

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 22 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001365068.1	RefSeq	NP_001351997.1	23	MANE Select
ENST00000313400.9	Ensembl	ENSP00000314038.4	23	MANE Select
NM_001184734.1	RefSeq	NP_001171663.1	8	Standard
NM_001184735.1	RefSeq	NP_001171664.1	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

protein transport
establishment of body hair planar orientation
negative regulation of protein localization to cell surface

Molecular Function

calcium ion binding
inositol 1,3,4,5 tetrakisphosphate binding

Cellular Component

early endosome
late endosome
cell cortex
integral component of membrane
clathrin-coated vesicle

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000361209
Coding exons: 22
Length: 989845
Individuals with no LoFs: 125734
Homozygous LoFs: 0
Heterozygous LoFs: 14
Defined: 125748
p: 0.0000557

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.16	603	689	0.876	0.0000417	8290
Missense (PolyPhen)		2	1.1962	1.6719		16
Synonymous	-1.39	326	296	1.10	0.0000179	2627
Loss of Function	6.12	8	58.6	0.137	0.00000291	671

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.00018	0.00017	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.000057	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000035	0.000035	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Mediates recycling of the neuronal cell adhesion molecule ASTN1 to the anterior pole of the cell membrane in migrating neurons. Promotes ASTN1 internalization and intracellular transport of endocytosed ASTN1 (By similarity). Selectively binds inositol-4,5-bisphosphate, inositol-3,4,5- trisphosphate and inositol-1,3,4,5-tetrakisphosphate, suggesting it is recruited to membranes that contain lipids with a phosphoinositide headgroup (Ref.6). {ECO:0000250|UniProtKB:Q80Z10, ECO:0000269|Ref.6}.;

Recessive Scores

pRec: 0.110

Intolerance Scores

LoFtool: 0.363
RVIS EVS: -2.27
RVIS percentile EVS: 1.26

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.366

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium