ASTL
protein-codingastacin like metalloendopeptidase, the group of Astacins
Gene summary
Predicted to enable aspartic-type peptidase activity; glutamic-type peptidase activity; and metalloendopeptidase activity. Predicted to be involved in several processes, including negative regulation of binding activity of sperm to zona pellucida; positive regulation of protein processing; and prevention of polyspermy. Predicted to be located in cortical granule and plasma membrane. Predicted to be active in obsolete extracellular space. [provided by Alliance of Genome Resources, Jun 2026]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~15.7 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0030490
Submitter: PanelApp Australia
Clinical Genomic Database (CGD)
Manifestation: Obstetric
Intervention: General
Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing
Comments: Attempts at IVF and assisted reproduction were not reported as successful
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to ASTL variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001002036.4. 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 | 1 | 2 | 1 | 4 | ||
| missense | 73 | 10 | 1 | 84 | ||
| nonsense | 1 | 1 | ||||
| start loss | 1 | 1 | ||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 1 | 0 | 76 | 12 | 3 | 92 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001002036.3 | 9 | MANE Select | |
| Ensembl | ENSP00000343674.2 | 9 | MANE Select | |
| Ensembl | ENSP00000537314.1 | 9 | Standard | |
| Ensembl | ENSP00000808074.1 | 9 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- proteolysis
- cell adhesion
- fertilization
- positive regulation of protein processing
- prevention of polyspermy
Molecular Function
- metalloendopeptidase activity
- peptidase activity
- zinc ion binding
- aspartic-type peptidase activity
- glutamic-type peptidase activity
Cellular Component
- cytoplasm
- plasma membrane
- transport vesicle
- cortical granule
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000342380
- Coding exons
- 9
- Length
- 14587
- Individuals with no LoFs
- 125493
- Homozygous LoFs
- 3
- Heterozygous LoFs
- 252
- Defined
- 125748
- p
- 0.00101
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.288 | 257 | 270 | 0.951 | 0.0000164 | 2760 |
| Missense (PolyPhen) | 60 | 80.517 | 0.74519 | 822 | ||
| Synonymous | 0.606 | 104 | 112 | 0.927 | 0.00000712 | 925 |
| Loss of Function | 1.16 | 12 | 17.2 | 0.699 | 9.00e-7 | 170 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0.00020 | 0.00020 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00027 | 0.00027 | rare |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.00016 | 0.00016 | rare |
| South Asian | 0.0071 | 0.0070 | notable |
| Other | 0.0016 | 0.0016 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Oocyte-specific oolemmal receptor involved in sperm and egg adhesion and fertilization. Plays a role in the polyspermy inhibition. Probably acts as a protease for the post-fertilization cleavage of ZP2. Cleaves the sperm-binding ZP2 at the surface of the zona pellucida after fertilization and cortical granule exocytosis, rendering the zona pellucida unable to support further sperm binding (By similarity). {ECO:0000250}.;
Recessive Scores
- pRec
- 0.0962
Intolerance Scores
- LoFtool
- 0.696
- RVIS EVS
- 0.71
- RVIS percentile EVS
- 85.73
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.193
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |