ZP2

zona pellucida glycoprotein 2, the group of Zona pellucida glycoproteins

Basic information

Region (hg38): 16:21197450-21214510

Links

ENSG00000103310 ∙ NCBI:7783 ∙ OMIM:182888 ∙ HGNC:13188 ∙ Uniprot:Q05996 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• female infertility due to zona pellucida defect (Supportive), mode of inheritance: AD
• oocyte maturation defect 6 (Strong), mode of inheritance: AR
• oocyte maturation defect 6 (Definitive), mode of inheritance: AR
• inherited oocyte maturation defect (Moderate), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Oocyte/zygote/embryo maturation arrest 6	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	29895852; 30810869

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ZP2 gene.

• not_specified (111 variants)
• not_provided (15 variants)
• Oocyte_maturation_defect_6 (8 variants)
• ZP2-related_disorder (7 variants)
• Developmental_and_epileptic_encephalopathy,_4 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ZP2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_001376232.1. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				6	1	7
missense	1		102	13	1	117
nonsense			1			1
start loss						0
frameshift	2					2
splice donor/acceptor (+/-2bp)	3	1	1			5
Total	6	1	104	19	2

Highest pathogenic variant AF is 0.000002736244

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ZP2	protein_coding	protein_coding	ENST00000574002	19	17059

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
6.22e-8	0.999	125699	0	47	125746	0.000187

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.134	402	410	0.981	0.0000207	4901
Missense in Polyphen		76	103.28	0.73588		1318
Synonymous	0.327	150	155	0.967	0.00000864	1436
Loss of Function	2.84	18	36.6	0.492	0.00000169	431

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000489	0.000489
Ashkenazi Jewish	0.0000999	0.0000992
East Asian	0.000336	0.000326
Finnish	0.0000463	0.0000462
European (Non-Finnish)	0.000186	0.000185
Middle Eastern	0.000336	0.000326
South Asian	0.0000980	0.0000980
Other	0.000326	0.000326

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. ZP2 may act as a secondary sperm receptor. {ECO:0000250|UniProtKB:P20239}.
• Pathway: Ovarian Infertility Genes;Interaction With The Zona Pellucida;Fertilization;Reproduction (Consensus)

Recessive Scores

• pRec: 0.192

Intolerance Scores

• loftool: 0.411
• rvis_EVS: -0.84
• rvis_percentile_EVS: 11.36

Haploinsufficiency Scores

• pHI: 0.0755
• hipred: N
• hipred_score: 0.313
• ghis: 0.418

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.119

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Zp2
• Phenotype: reproductive system phenotype; embryo phenotype; endocrine/exocrine gland phenotype; cellular phenotype

Gene ontology

• Biological process: binding of sperm to zona pellucida;regulation of acrosome reaction;prevention of polyspermy
• Cellular component: extracellular region;multivesicular body;endoplasmic reticulum;plasma membrane;integral component of membrane;collagen-containing extracellular matrix
• Molecular function: protein binding;coreceptor activity;acrosin binding;identical protein binding