ZP3

zona pellucida glycoprotein 3, the group of Zona pellucida glycoproteins

Basic information

Region (hg38): 7:76397518-76442071

Previous symbols: [ "ZP3A", "ZP3B" ]

Links

ENSG00000188372 ∙ NCBI:7784 ∙ OMIM:182889 ∙ HGNC:13189 ∙ Uniprot:P21754 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• oocyte maturation defect 3 (Strong), mode of inheritance: AD
• female infertility due to zona pellucida defect (Supportive), mode of inheritance: AD
• oocyte maturation defect 3 (Moderate), mode of inheritance: AD
• inherited oocyte maturation defect (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Oocyte/zygote/embryo maturation arrest 3	AD	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	28886344

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ZP3 gene.

• not provided (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ZP3 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			47	3	7	57
nonsense						0
start loss						0
frameshift		1				1
inframe indel						0
splice donor/acceptor (+/-2bp)	1					1
splice region				3		3
non coding			20	2	1	23
Total	1	1	67	6	9

Variants in ZP3

This is a list of pathogenic ClinVar variants found in the ZP3 region.

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

Position	Type	Phenotype	Significance	ClinVar
7-76397674-C-G		not specified	Uncertain significance (Sep 30, 2021)
7-76397677-C-G		not specified	Uncertain significance (Sep 30, 2021)
7-76397679-A-C		not specified	Uncertain significance (Jun 11, 2021)
7-76397688-C-T		not specified	Uncertain significance (Dec 16, 2022)
7-76397695-C-G		not specified	Uncertain significance (Sep 03, 2024)
7-76397715-G-C		not specified	Uncertain significance (Feb 16, 2023)
7-76397779-C-G		not specified	Uncertain significance (Oct 07, 2024)
7-76398734-A-G		not specified	Likely benign (Jun 29, 2023)
7-76400342-C-T		not specified	Uncertain significance (May 29, 2024)
7-76400348-C-T		not specified	Uncertain significance (Sep 18, 2024)
7-76400405-G-A		not specified	Uncertain significance (Nov 09, 2022)
7-76400420-C-A		not specified	Uncertain significance (Jan 04, 2022)
7-76400439-G-A		not specified	Uncertain significance (Feb 13, 2023)
7-76400442-C-T		not specified	Uncertain significance (Jun 22, 2021)
7-76400518-G-T		not specified	Uncertain significance (Aug 08, 2023)
7-76400539-C-T		not specified	Uncertain significance (Oct 14, 2023)
7-76404361-C-T		not specified	Likely benign (Aug 28, 2023)
7-76404377-C-A		not specified	Uncertain significance (Oct 26, 2022)
7-76404384-C-A		not specified	Uncertain significance (Feb 28, 2023)
7-76404386-C-G		not specified	Uncertain significance (Oct 17, 2023)
7-76404427-C-T		not specified	Uncertain significance (Sep 30, 2024)
7-76424968-G-A		not specified	Uncertain significance (Oct 26, 2021)
7-76424969-A-T		not specified	Uncertain significance (Oct 26, 2021)
7-76424977-T-G		ZP3-related disorder • not specified	Uncertain significance (Aug 30, 2022)
7-76425002-T-C		not specified	Uncertain significance (Jun 09, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ZP3	protein_coding	protein_coding	ENST00000394857	8	44554

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000285	0.943	125718	0	30	125748	0.000119

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.0164	240	239	1.00	0.0000132	2743
Missense in Polyphen		57	69.098	0.82492		875
Synonymous	-2.27	127	98.3	1.29	0.00000595	860
Loss of Function	1.70	8	15.2	0.528	7.02e-7	172

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000244	0.000243
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000524	0.0000462
European (Non-Finnish)	0.000159	0.000158
Middle Eastern	0.00	0.00
South Asian	0.000197	0.000196
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: The mammalian zona pellucida, which mediates species- specific sperm binding, induction of the acrosome reaction and prevents post-fertilization polyspermy, is composed of three to four glycoproteins, ZP1, ZP2, ZP3, and ZP4. ZP3 is essential for sperm binding and zona matrix formation.
• Disease: DISEASE: Oocyte maturation defect 3 (OOMD3) [MIM:617712]: An autosomal dominant infertility disorder characterized by abnormal oocytes that lack the zona pellucida, and oocytes degeneration. {ECO:0000269|PubMed:28886344}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Ovarian Infertility Genes;Interaction With The Zona Pellucida;Fertilization;Reproduction (Consensus)

Recessive Scores

• pRec: 0.202

Intolerance Scores

• loftool: 0.238
• rvis_EVS: 0.78
• rvis_percentile_EVS: 87.14

Haploinsufficiency Scores

• pHI: 0.240
• hipred: N
• hipred_score: 0.112

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.0208

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Zp3
• Phenotype: cellular phenotype; endocrine/exocrine gland phenotype; reproductive system phenotype; embryo phenotype

Gene ontology

• Biological process: positive regulation of type IV hypersensitivity;blastocyst formation;humoral immune response mediated by circulating immunoglobulin;positive regulation of leukocyte migration;positive regulation of humoral immune response;binding of sperm to zona pellucida;regulation of signaling receptor activity;positive regulation of phosphatidylinositol biosynthetic process;positive regulation of interferon-gamma production;positive regulation of interleukin-4 production;egg coat formation;positive regulation of T cell proliferation;negative regulation of transcription, DNA-templated;positive regulation of transcription, DNA-templated;phosphatidylinositol-mediated signaling;oocyte development;positive regulation of inflammatory response;positive regulation of acrosome reaction;negative regulation of binding of sperm to zona pellucida;positive regulation of acrosomal vesicle exocytosis;positive regulation of ovarian follicle development;positive regulation of antral ovarian follicle growth
• Cellular component: extracellular region;extracellular space;plasma membrane;integral component of membrane;collagen-containing extracellular matrix
• Molecular function: extracellular matrix structural constituent;protein binding;carbohydrate binding;acrosin binding;structural constituent of egg coat;identical protein binding;receptor ligand activity