ASTL

Summary

ASTL (astacin like metalloendopeptidase, HGNC:31704) is a protein-coding gene on chromosome 2q11.2, encoding Astacin-like metalloendopeptidase (Q6HA08). Oocyte-specific oolemmal receptor involved in sperm and egg adhesion and fertilization.

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.

Source: NCBI Gene 431705 — automated summary from GO annotations (Alliance of Genome Resources).

At a glance

• Gene–disease (curated): oocyte maturation defect 11 (Limited, GenCC)
• Clinical variants (ClinVar): 96 total — 1 pathogenic
• GTEx eGene: eQTL in 15 tissues, sQTL in 0 (q < 0.05)
• Phenotypes (HPO): 3
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.02 (unconstrained)
• MANE Select transcript: NM_001002036
• Notable: 96 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:31704
Approved symbol	ASTL
Name	astacin like metalloendopeptidase
Location	2q11.2
Locus type	gene with protein product
Status	Approved
Aliases	ovastacin, SAS1B
Ensembl gene	ENSG00000188886
Ensembl biotype	protein_coding
OMIM	608860
Entrez	431705

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 3 protein_coding, 1 retained_intron

MANE Select: ENST00000342380

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 3: 1

ENST00000342380, ENST00000470582, ENST00000867255, ENST00001142943

RefSeq mRNA: 1 — MANE Select: NM_001002036 NM_001002036

CCDS: CCDS33249

Canonical transcript exons

ENST00000342380 — 9 exons

Exon	Start	End
ENSE00001364407	96129824	96129978
ENSE00001366112	96130064	96130145
ENSE00001369654	96122818	96124271
ENSE00001374492	96133965	96134058
ENSE00001382523	96133425	96133542
ENSE00001384861	96137575	96137700
ENSE00001391218	96132540	96132721
ENSE00001404132	96138382	96138502
ENSE00003563298	96135351	96135412

Expression profiles

Bgee: expression breadth ubiquitous, 101 present calls, max score 72.76.

Highest expression (Bgee): bone marrow, bone marrow cell, primordial germ cell in gonad, olfactory segment of nasal mucosa, blood.

Genetic regulation across tissues (GTEx eQTL / sQTL)

ASTL is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 15 tissues and its splicing (sQTL) in 0 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

15 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Esophagus Mucosa	eqtl	8.1e-14	-0.42	2:96124048:T:C
Skin Sun Exposed Lower leg	eqtl	2.4e-10	-0.22	2:96124048:T:C
Minor Salivary Gland	eqtl	5.6e-08	+1.58	2:96092356:C:T
Artery Aorta	eqtl	3.3e-05	-0.30	2:95857299:A:G
Breast Mammary Tissue	eqtl	5.6e-04	+0.57	2:96082306:A:G
Nerve Tibial	eqtl	5.9e-04	+0.24	2:95897458:A:T
Thyroid	eqtl	1.5e-03	-0.18	2:96580930:T:C
Colon Transverse	eqtl	6.6e-03	+0.17	2:96473570:G:A
Small Intestine Terminal Ileum	eqtl	8.8e-03	-1.41	2:96061621:C:T
Cells EBV-transformed lymphocytes	eqtl	1.0e-02	+0.15	2:96132771:G:A
Esophagus Gastroesophageal Junction	eqtl	1.1e-02	+0.26	2:96251850:T:G
Spleen	eqtl	1.1e-02	+0.26	2:96693499:C:A
Brain Cortex	eqtl	1.8e-02	-1.16	2:96249848:A:G
Brain Cerebellum	eqtl	2.4e-02	+0.43	2:96841990:T:C
Whole Blood	eqtl	3.0e-02	+0.27	2:96781566:C:A

Top tissues by expression

showing 100 of 113 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
bone marrow	UBERON:0002371	72.76	gold quality
bone marrow cell	CL:0002092	72.32	silver quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	62.50	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	61.94	gold quality
blood	UBERON:0000178	59.38	gold quality
skin of abdomen	UBERON:0001416	59.24	gold quality
granulocyte	CL:0000094	58.49	gold quality
zone of skin	UBERON:0000014	58.31	gold quality
skin of leg	UBERON:0001511	57.46	gold quality
spleen	UBERON:0002106	56.06	gold quality
right lung	UBERON:0002167	53.89	gold quality
lymph node	UBERON:0000029	53.32	gold quality
colonic epithelium	UBERON:0000397	52.05	silver quality
lower esophagus mucosa	UBERON:0035834	51.80	gold quality
cerebellar hemisphere	UBERON:0002245	51.29	gold quality
cerebellar cortex	UBERON:0002129	51.28	gold quality
cerebellum	UBERON:0002037	51.19	gold quality
right hemisphere of cerebellum	UBERON:0014890	50.85	gold quality
urinary bladder	UBERON:0001255	50.57	gold quality
vermiform appendix	UBERON:0001154	49.65	gold quality
right frontal lobe	UBERON:0002810	48.93	gold quality
tonsil	UBERON:0002372	48.91	gold quality
small intestine Peyer’s patch	UBERON:0003454	47.79	gold quality
gall bladder	UBERON:0002110	47.68	gold quality
Brodmann (1909) area 9	UBERON:0013540	47.30	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	46.91	gold quality
frontal cortex	UBERON:0001870	46.90	gold quality
small intestine	UBERON:0002108	46.54	gold quality
apex of heart	UBERON:0002098	46.27	gold quality
prefrontal cortex	UBERON:0000451	46.23	gold quality
left uterine tube	UBERON:0001303	45.56	gold quality
leukocyte	CL:0000738	45.16	gold quality
esophagus mucosa	UBERON:0002469	44.87	gold quality
hindlimb stylopod muscle	UBERON:0004252	44.84	gold quality
anterior cingulate cortex	UBERON:0009835	44.48	gold quality
cerebral cortex	UBERON:0000956	44.46	gold quality
omental fat pad	UBERON:0010414	44.22	gold quality
monocyte	CL:0000576	44.16	gold quality
pituitary gland	UBERON:0000007	44.06	gold quality
superior frontal gyrus	UBERON:0002661	43.99	silver quality
adenohypophysis	UBERON:0002196	43.47	gold quality
prostate gland	UBERON:0002367	43.33	gold quality
smooth muscle tissue	UBERON:0001135	43.16	gold quality
ascending aorta	UBERON:0001496	43.03	gold quality
thoracic aorta	UBERON:0001515	42.73	gold quality
upper lobe of left lung	UBERON:0008952	42.73	gold quality
muscle tissue	UBERON:0002385	42.65	silver quality
rectum	UBERON:0001052	42.24	gold quality
transverse colon	UBERON:0001157	41.95	gold quality
brain	UBERON:0000955	41.67	gold quality
fundus of stomach	UBERON:0001160	41.53	gold quality
lung	UBERON:0002048	41.38	gold quality
multicellular organism	UBERON:0000468	40.98	gold quality
cortical plate	UBERON:0005343	40.97	silver quality
fallopian tube	UBERON:0003889	40.76	gold quality
body of stomach	UBERON:0001161	40.58	gold quality
adipose tissue	UBERON:0001013	40.15	gold quality
stomach	UBERON:0000945	39.67	gold quality
right ovary	UBERON:0002118	39.67	gold quality
intestine	UBERON:0000160	39.60	gold quality
descending thoracic aorta	UBERON:0002345	39.41	silver quality
left testis	UBERON:0004533	38.99	gold quality
right coronary artery	UBERON:0001625	38.96	silver quality
testis	UBERON:0000473	38.72	gold quality
duodenum	UBERON:0002114	38.65	silver quality
mucosa of transverse colon	UBERON:0004991	38.54	silver quality
thoracic mammary gland	UBERON:0005200	38.29	gold quality
right testis	UBERON:0004534	38.24	gold quality
esophagus	UBERON:0001043	37.66	gold quality
nucleus accumbens	UBERON:0001882	37.56	gold quality
colon	UBERON:0001155	37.53	gold quality
ovary	UBERON:0000992	37.21	gold quality
left ovary	UBERON:0002119	37.03	gold quality
subcutaneous adipose tissue	UBERON:0002190	37.03	gold quality
temporal lobe	UBERON:0001871	36.92	gold quality
amygdala	UBERON:0001876	36.67	gold quality
right uterine tube	UBERON:0001302	36.55	silver quality
endometrium	UBERON:0001295	36.53	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
muscle of leg	UBERON:0001383	36.45	gold quality
saliva-secreting gland	UBERON:0001044	36.24	gold quality
right atrium auricular region	UBERON:0006631	36.04	gold quality
caudate nucleus	UBERON:0001873	35.82	gold quality
ectocervix	UBERON:0012249	35.67	silver quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
putamen	UBERON:0001874	35.43	gold quality
minor salivary gland	UBERON:0001830	35.21	gold quality
Ammon’s horn	UBERON:0001954	35.08	gold quality
mucosa of stomach	UBERON:0001199	34.68	gold quality
vagina	UBERON:0000996	33.93	gold quality
heart	UBERON:0000948	33.86	gold quality
heart left ventricle	UBERON:0002084	33.46	silver quality
body of uterus	UBERON:0009853	33.36	gold quality
left coronary artery	UBERON:0001626	32.09	silver quality
popliteal artery	UBERON:0002250	31.46	silver quality
tibial artery	UBERON:0007610	31.39	silver quality
muscle layer of sigmoid colon	UBERON:0035805	31.02	gold quality
hypothalamus	UBERON:0001898	30.09	silver quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
placenta	UBERON:0001987	29.81	silver quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	3.31

HPA expression

RNA tissue specificity: Tissue enhanced

27 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM
Bone marrow	tissue	3.7
Hippocampus	tissue	1.1
Ovary	tissue	1.0
Seminal vesicle	tissue	1.0
Skin 1	tissue	0.7
Thymus	tissue	0.7
Pituitary gland	tissue	0.5
Postcentral gyrus	tissue	0.5
Epididymis	tissue	0.4
Lymph node	tissue	0.3
Nucleus accumbens	tissue	0.3
Spleen	tissue	0.3
Appendix	tissue	0.3
Testis	tissue	0.2
Colon	tissue	0.2
Urinary bladder	tissue	0.2
Tonsil	tissue	0.2
Breast	tissue	0.1
Stomach 1	tissue	0.1
Vagina	tissue	0.1
Salivary gland	tissue	0.1
Rectum	tissue	0.1
Endometrium 1	tissue	0.1
Choroid plexus	tissue	0.1
Gallbladder	tissue	0.1
Locus coeruleus	tissue	0.1
Prostate	tissue	0.1

Brain sub-regions (HPA Brain Atlas): detected in 164; highest nTPM — Inferior parietal lobule (5.6), Parietal operculum (3.8), Precentral gyrus, ventral (3.7), Supramarginal gyrus (3.6), Area striata (3.0).

Regulation

Is transcription factor: no

Functional genomics

gnomAD constraint: pLI 2.83e-07, LOEUF 1.02, missense Z 0.806 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000342380 — one region, missense o/e 0.91.

Literature-anchored findings (GeneRIF, showing 4)

• SAS1B protein [ovastacin] shows temporal and spatial restriction to oocytes in several eutherian orders and initiates translation at the primary to secondary follicle transition. (PMID:24038607)
• The SAS1B metalloproteinase is proposed as a prototype cancer-oocyte tumor surface neoantigen for development of targeted immunotherapeutics with limited on-target/off tumor effects predicted to be restricted to the population of growing oocytes. (PMID:26327203)
• The detection of SAS1B in serum provides clues for early diagnosis of thyroid cancer. (PMID:33629311)
• ASTL is mutated in female infertility. (PMID:34704130)

Cross-species orthologs

10 orthologs

Organism	Symbol	Gene ID
danio_rerio	hce2l2	ENSDARG00000070011
mus_musculus	Astl	ENSMUSG00000050468
rattus_norvegicus	Astl	ENSRNOG00000022603
drosophila_melanogaster	CG7631	FBGN0028945
drosophila_melanogaster	CG6696	FBGN0030947
drosophila_melanogaster	CG10280	FBGN0037395
drosophila_melanogaster	CG5715	FBGN0039180
caenorhabditis_elegans		WBGENE00003521
caenorhabditis_elegans		WBGENE00003522
caenorhabditis_elegans		WBGENE00021221

Paralogs (35): NRXN3 (ENSG00000021645), TLL1 (ENSG00000038295), CP (ENSG00000047457), DCBLD2 (ENSG00000057019), HEPH (ENSG00000089472), TLL2 (ENSG00000095587), NRP1 (ENSG00000099250), PCOLCE (ENSG00000106333), CNTNAP3 (ENSG00000106714), CUBN (ENSG00000107611), CNTNAP1 (ENSG00000108797), NRXN2 (ENSG00000110076), MEP1A (ENSG00000112818), NRP2 (ENSG00000118257), CUZD1 (ENSG00000138161), MFGE8 (ENSG00000140545), MEP1B (ENSG00000141434), PDGFC (ENSG00000145431), CNTNAP4 (ENSG00000152910), CNTNAP3B (ENSG00000154529), CNTNAP5 (ENSG00000155052), CDCP2 (ENSG00000157211), PCOLCE2 (ENSG00000163710), EDIL3 (ENSG00000164176), NETO1 (ENSG00000166342), BMP1 (ENSG00000168487), PDGFD (ENSG00000170962), NETO2 (ENSG00000171208), CNTNAP2 (ENSG00000174469), NRXN1 (ENSG00000179915), HEPHL1 (ENSG00000181333), F8 (ENSG00000185010), F5 (ENSG00000198734), MFRP (ENSG00000235718), CNTNAP3C (ENSG00000283378)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:3046414) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 2 distinct phenotype terms.

Mouse phenotype (MP)	Records
reduced female fertility	2
decreased litter size	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Gallus gallus	P0DJJ2	93.2%	Diamond
Coturnix japonica	P42662	93.2%	Diamond
Caenorhabditis briggsae	Q61EX6	93.2%	Diamond
Teladorsagia circumcincta	A0A0C5PRQ1	93.0%	Diamond
Haemonchus contortus	D5FM34	93.0%	Diamond
Oryzias latipes	P31580	90.0%	Diamond
Xenopus laevis	Q8JI28	87.1%	Diamond
Loxosceles intermedia	A0FKN6	86.8%	Diamond
Loxosceles gaucho	P0DM62	86.8%	Diamond
Argiope aurantia	P84748	85.0%	Diamond
Loxosceles laeta	P0DM61	79.0%	Diamond
Strongylocentrotus purpuratus	P98068	71.6%	Diamond
Brugia malayi	A8Q2D1	71.1%	Diamond
Paracentrotus lividus	P42674	71.1%	Diamond
Steinernema carpocapsae	D2KBH9	65.0%	Diamond
Astacus astacus	P07584	48.7%	Diamond
Nematostella vectensis	K7Z9Q9	44.4%	Diamond
Elizabethkingia meningoseptica	Q47899	40.9%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
GPAT2	protein-coding	150763
ADRA2B	protein-coding	151
SNORA112	snoRNA	109623481
DUSP2	protein-coding	1844
STARD7-AS1	ncRNA	285033
STARD7	protein-coding	56910
TMEM127	protein-coding	55654
CIAO1	protein-coding	9391

Protein

Protein identifiers

Astacin-like metalloendopeptidase — Q6HA08 (reviewed: Q6HA08)

Alternative names: Oocyte astacin, Ovastacin, ZP2-proteinase

All UniProt accessions (1): Q6HA08

UniProt curated annotations — full annotation on UniProt →

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.

Subunit / interactions. Interacts (via N-terminal domain) with SPACA3; the interaction occurs during fertilization.

Subcellular location. Cytoplasm. Cell membrane. Cytoplasmic vesicle. Secretory vesicle. Cortical granule.

Disease relevance. Oocyte/zygote/embryo maturation arrest 11 (OZEMA11) [MIM:619643] An autosomal recessive disorder characterized by decreased or absent fertility and poor embryonic outcomes with assisted reproductive technology. The disease may be caused by variants affecting the gene represented in this entry.

Cofactor. Binds 1 zinc ion per subunit.

RefSeq proteins (1): NP_001002036* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001506	Peptidase_M12A	Domain
IPR006026	Peptidase_Metallo	Domain
IPR024079	MetalloPept_cat_dom_sf	Homologous_superfamily

Pfam: PF01400

Enzyme classification (BRENDA)

• EC 3.4.24.21 — astacin (BRENDA: 25 organisms, 107 substrates, 82 inhibitors, 35 Km, 36 kcat entries)

Substrate kinetics (BRENDA)

37 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
DANSYL-GLY-LYS-ASN-ALA-PRO-LEU-VAL	0.4–0.52	2
2-AMINOBENZOYL-ARG-GLY-PRO-PHE-SER-PRO-(4-NITRO)	0.327	1
2-AMINOBENZOYL-ARG-HYP-GLY-PHE-SER-PRO-(4-NITRO)	0.044	1
2-AMINOBENZOYL-ARG-PRO-GLY-ALA-SER-PRO-(4-NITRO)	0.154	1
2-AMINOBENZOYL-ARG-PRO-GLY-GLU-SER-PRO-(4-NITRO)	0.954	1
2-AMINOBENZOYL-ARG-PRO-GLY-LYS-SER-PRO-(4-NITRO)	0.281	1
2-AMINOBENZOYL-ARG-PRO-ILE-PHE-SER-PRO-(4-NITRO)	0.029	1
AC-RE(EDANS)-DRNLEVGDDPYK(DABCYL)-NH2	0.034	1
ARG-PRO-PRO-GLY-(4-NITRO)PHE-ALA-PRO-PHE-ARG	0.306	1
ARG-PRO-PRO-GLY-(4-NITRO)PHE-ARG-PRO-PHE-ARG	0.209	1
ARG-PRO-PRO-GLY-(4-NITRO)PHE-LYS-PRO-PHE-ARG	0.116	1
ARG-PRO-PRO-GLY-(4-NITRO)PHE-PHE-PRO-PHE-ARG	0.194	1
ARG-PRO-PRO-GLY-(4-NITRO)PHE-SER-PRO-PHE-ARG	0.085	1
AZOCASEIN	1.86	1
DANSYL-ALA-ALA-ARG-ALA-PRO-LEU-VAL	0.48	1

UniProt features (17 total): binding site 3, sequence variant 3, disulfide bond 2, region of interest 2, compositionally biased region 2, signal peptide 1, chain 1, helix 1, domain 1, active site 1

Structure

Experimental structures (PDB)

1 structures by resolution:

PDB	Title	Method	Resolution (Å)
7ST8	Crystal structure of 7H2.2 Fab in complex with SAS1B C-terminal region	X-RAY DIFFRACTION	2.75

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6HA08-F1	71.90	0.48

Antibody-complex structures (SAbDab)

1 antibodies co-crystallized with this protein: 7ST8

Human Protein Atlas

Protein class: Predicted intracellular proteins, Disease related genes, Human disease related genes

Protein evidence: Evidence at protein level

Antibody reliability (HPA): IH uncertain

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1)

Position	Role
183

Ligand- & substrate-binding residues (3)

Position	Role
192	Zn(2+)
182	Zn(2+)
186	Zn(2+)

Disulfide bonds (2)

Type	Positions
Disulfide bond	132–281, 153–172

Function

Pathways and Gene Ontology

Reactome pathways

0 curated (TAS) of 0; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

MSigDB gene sets: 67 (showing top): GSE45365_NK_CELL_VS_BCELL_DN, GOBP_POSITIVE_REGULATION_OF_PROTEIN_MATURATION, GOBP_SINGLE_FERTILIZATION, GOBP_NEGATIVE_REGULATION_OF_REPRODUCTIVE_PROCESS, GOMF_METALLOPEPTIDASE_ACTIVITY, GOCC_SECRETORY_GRANULE, GOBP_PROTEIN_MATURATION, GOBP_SPERM_EGG_RECOGNITION, GOBP_REGULATION_OF_REPRODUCTIVE_PROCESS, GOBP_REGULATION_OF_PROTEIN_MATURATION, GOBP_POSITIVE_REGULATION_OF_PROTEOLYSIS, GOBP_FERTILIZATION, GOBP_CELL_CELL_RECOGNITION, GOBP_REGULATION_OF_PROTEOLYSIS, GOBP_BINDING_OF_SPERM_TO_ZONA_PELLUCIDA

GO Biological Process (7): proteolysis (GO:0006508), cell adhesion (GO:0007155), fertilization (GO:0009566), positive regulation of protein processing (GO:0010954), prevention of polyspermy (GO:0060468), negative regulation of binding of sperm to zona pellucida (GO:2000360), single fertilization (GO:0007338)

GO Molecular Function (9): metalloendopeptidase activity (GO:0004222), zinc ion binding (GO:0008270), aspartic-type peptidase activity (GO:0070001), glutamic-type peptidase activity (GO:0070002), protein binding (GO:0005515), peptidase activity (GO:0008233), metallopeptidase activity (GO:0008237), hydrolase activity (GO:0016787), metal ion binding (GO:0046872)

GO Cellular Component (4): cytoplasm (GO:0005737), plasma membrane (GO:0005886), cortical granule (GO:0060473), cytoplasmic vesicle (GO:0031410)

GO top-level categories

31 GO namespaces:

Category	Terms
peptidase activity	3
protein metabolic process	1
cellular process	1
sexual reproduction	1
reproductive process	1
protein processing	1
positive regulation of proteolysis	1
regulation of protein processing	1
positive regulation of protein maturation	1
egg activation	1
negative regulation of fertilization	1
binding of sperm to zona pellucida	1
negative regulation of cellular process	1
negative regulation of reproductive process	1
regulation of binding of sperm to zona pellucida	1
fertilization	1
endopeptidase activity	1
metallopeptidase activity	1
transition metal ion binding	1
binding	1
hydrolase activity	1
catalytic activity, acting on a protein	1
catalytic activity	1
cation binding	1
intracellular anatomical structure	1
cellular anatomical structure	1
membrane	1
cell periphery	1
secretory granule	1
cytoplasm	1
intracellular vesicle	1

Protein interactions and networks

STRING

showing 15 of 419 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ASTL	ZP2	Q05996	758
ASTL	TIMP1	P01033	722
ASTL	ZP1	P60852	621
ASTL	ZP3	P21754	606
ASTL	ZP4	Q12836	606
ASTL	FETUB	Q9UGM5	576
ASTL	SPACA3	Q8IXA5	421
ASTL	LYZL6	O75951	408
ASTL	FAHD2B	Q6P2I3	388
ASTL	IZUMO1	Q8IYV9	385
ASTL	PLCZ1	Q86YW0	383
ASTL	OOSP1	A8MZH6	380
ASTL	FAM178B	Q8IXR5	378
ASTL	CRISP1	P54107	373
ASTL	APBA1	Q02410	370

IntAct

Human interaction partners of ASTL in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

4 partners by confidence:

Partner	Interaction type	MIscore	Records
CYSRT1	physical association	0.560	3
HSPD1	physical association	0.400	1
HSPA5	association	0.350	2
VHL	association	0.350	1

BioGRID (16 interactions; top human partners by supporting records): JMJD8 (Affinity Capture-MS; 3 records), TUBB1 (Affinity Capture-MS; 3 records), VHL (Affinity Capture-MS; 3 records), HSPA5 (Affinity Capture-MS; 2 records), AMD1 (Affinity Capture-MS), CYSRT1 (Two-hybrid), HSPD1 (Affinity Capture-MS), MAPK4 (Affinity Capture-MS), TP53 (Negative Genetic)

Disease & clinical

Genetic variants

Variant evidence for ASTL: 96 ClinVar records (1 pathogenic / likely pathogenic). Per-variant detail is on Sugi Variant.

ClinVar

96 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	72
Likely benign	13
Benign	3

Top pathogenic / likely-pathogenic (1)

Showing all 1 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
1326900	NM_001002036.4(ASTL):c.456-1G>A	Pathogenic	no assertion criteria provided	1

Per-variant reference — Sugi Variant

Explore ASTL’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 23 predictions of 651):

Position(s)	Effect	Δscore	Sites
2:96130146	acceptor_gain	1.0000
2:96130146	acceptor_loss	1.0000
2:96132538–96132539	donor_loss	1.0000	5
2:96132722–96132723	acceptor_loss	1.0000	2
2:96132729	acceptor_gain	1.0000
2:96133963–96133964	donor_loss	1.0000	5
2:96134059–96134060	acceptor_loss	1.0000	3
2:96135350	donor_loss	1.0000
2:96135413	acceptor_gain	1.0000
2:96135413–96135414	acceptor_loss	1.0000	3

AlphaMissense

592 missense substitutions predicted likely pathogenic (of 2,783 scored), across 141 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
H186	8	0.972	0.985
D271	8	0.964	0.985
H192	8	0.962	0.977
H182	8	0.946	0.979
F218	8	0.938	0.992
D77	8	0.926	0.967
F243	8	0.923	0.994
F190	8	0.914	0.987
D198	8	0.899	0.960
F135	8	0.891	0.968
D231	8	0.880	0.941
H237	8	0.853	0.965
C153	7	0.975	0.988
C172	7	0.963	0.979
W94	7	0.957	0.997
F144	7	0.938	0.991
E193	7	0.930	0.982
C132	7	0.929	0.967
E183	7	0.927	0.980
S268	7	0.900	0.987

HPA cancer prognostics

RNA cancer specificity: Cancer enhanced (Ovary Serous Cystadenocarcinoma)

Disease associations

OMIM: gene MIM:608860 | disease phenotypes: MIM:619643

GenCC curated gene-disease

1 curated gene-disease records:

Disease	Classification	Inheritance	Records
oocyte maturation defect 11	Limited	Autosomal recessive

Mondo (1): oocyte maturation defect 11 (MONDO:0030490)

HPO phenotypes

3 phenotypes (HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0008222	Female infertility
HP:0011462	Young adult onset

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

14 total (human), top 14 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	increases expression	1
sodium arsenite	increases expression	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
(+)-JQ1 compound	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Benzo(a)pyrene	decreases methylation	1
Lipopolysaccharides	affects response to substance, increases expression	1
Methapyrilene	increases methylation	1
Plant Extracts	affects cotreatment, decreases expression	1
Thiram	increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Cadmium Chloride	increases expression	1

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.