ASTL

astacin like metalloendopeptidase, the group of Astacins

Basic information

Region (hg38): 2:96122818-96138502

Links

ENSG00000188886 ∙ NCBI:431705 ∙ OMIM:608860 ∙ HGNC:31704 ∙ Uniprot:Q6HA08 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Oocyte/zygote/embryo maturation arrest 11	AR	General	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	Obstetric	34704130
Attempts at IVF and assisted reproduction were not reported as successful

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ASTL gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ASTL gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				1	1	2
missense			25	5	1	31
nonsense						0
start loss						0
frameshift					1	1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	25	6	3

Variants in ASTL

This is a list of pathogenic ClinVar variants found in the ASTL region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
2-96123863-AT-A			Benign (Aug 21, 2018)
2-96123872-A-T		not specified	Uncertain significance (Apr 18, 2023)
2-96123911-C-T		not specified	Uncertain significance (Jun 11, 2024)
2-96124091-T-C		not specified	Likely benign (Mar 18, 2024)
2-96124104-A-G		not specified	Likely benign (Mar 26, 2024)
2-96124110-A-G		not specified	Uncertain significance (Oct 13, 2023)
2-96124128-C-T		not specified	Uncertain significance (Aug 17, 2021)
2-96124143-C-T		not specified	Uncertain significance (Dec 18, 2023)
2-96124193-G-A		not specified	Uncertain significance (Mar 07, 2024)
2-96124196-G-A		not specified	Likely benign (Jan 04, 2022)
2-96124221-G-T		not specified	Uncertain significance (Nov 03, 2022)
2-96124234-C-T			Likely benign (Nov 01, 2022)
2-96124235-G-A		not specified	Likely benign (Feb 23, 2023)
2-96124235-G-T		not specified	Uncertain significance (Mar 01, 2023)
2-96124244-C-T		not specified	Uncertain significance (Jan 18, 2022)
2-96129826-C-T			Benign (Jul 13, 2018)
2-96129860-C-T		not specified	Uncertain significance (Jul 27, 2022)
2-96129877-C-T		not specified	Uncertain significance (May 18, 2022)
2-96129925-C-T		not specified	Uncertain significance (Apr 15, 2024)
2-96130092-C-T		not specified	Uncertain significance (Jul 17, 2023)
2-96130114-G-C		not specified	Uncertain significance (Jun 02, 2024)
2-96132549-T-C		not specified	Uncertain significance (Jul 09, 2021)
2-96132552-C-G		not specified	Uncertain significance (Nov 09, 2021)
2-96132567-G-A			Likely benign (Aug 01, 2023)
2-96132647-C-T		not specified	Uncertain significance (Apr 13, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ASTL	protein_coding	protein_coding	ENST00000342380	9	14587

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
6.05e-7	0.691	125493	3	252	125748	0.00101

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.288	257	270	0.951	0.0000164	2760
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000265	0.000265
Ashkenazi Jewish	0.00	0.00
East Asian	0.000272	0.000272
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000159	0.000158
Middle Eastern	0.000272	0.000272
South Asian	0.00706	0.00698
Other	0.00163	0.00163

dbNSFP

Source: dbNSFP

• 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

Haploinsufficiency Scores

• pHI: 0.0802
• hipred: N
• hipred_score: 0.123

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.193

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Astl
• Phenotype: reproductive system phenotype

Gene ontology

• Biological process: proteolysis;cell adhesion;fertilization;positive regulation of protein processing;prevention of polyspermy;negative regulation of binding of sperm to zona pellucida
• Cellular component: cytoplasm;plasma membrane;transport vesicle;cortical granule
• Molecular function: metalloendopeptidase activity;peptidase activity;zinc ion binding;aspartic-type peptidase activity;glutamic-type peptidase activity