ZP2
protein-codingzona pellucida glycoprotein 2, the group of Zona pellucida glycoproteins
Gene summary
The zona pellucida is an extracellular matrix that surrounds the oocyte and early embryo. It is composed of three glycoproteins with various functions during fertilization and preimplantation development. The glycosylated mature peptide is one of the structural components of the zona pellucida and functions in secondary binding and penetration of acrosome-reacted spermatozoa. Female mice lacking this gene do not form a stable zona matrix and are sterile. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2014]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~17.1 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0014342
Submitter: Orphanet
Inheritance Pattern: AR
Disease ID:MONDO:0032696
Submitter: PanelApp Australia
Inheritance Pattern: AR
Disease ID:MONDO:0032696
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AD
Disease ID:MONDO:0014769
Submitter: Ambry Genetics
Inheritance Pattern: AR
Disease ID:MONDO:0032696
Submitter: Ambry Genetics
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
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to ZP2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001376232.1. 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 | 10 | 1 | 11 | |||
| missense | 1 | 1 | 120 | 14 | 1 | 137 |
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 2 | 1 | 1 | 4 | ||
| splice donor/acceptor (+/-2bp) | 4 | 1 | 1 | 6 | ||
| Total | 7 | 3 | 123 | 24 | 2 | 159 |
Highest pathogenic variant AF is 0.0000055766022
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001363161.1 | 19 | MANE Select | |
| Ensembl | ENSP00000458991.2 | 19 | MANE Select | |
| RefSeq | NP_001363160.1 | 19 | Standard | |
| RefSeq | NP_001363162.1 | 19 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Ovarian Infertility Genes
- Interaction With The Zona Pellucida
- Fertilization
- Reproduction
Biological Process
- binding of sperm to zona pellucida
- regulation of acrosome reaction
- prevention of polyspermy
Molecular Function
- protein binding
- coreceptor activity
- acrosin binding
- identical protein binding
Cellular Component
- extracellular region
- multivesicular body
- endoplasmic reticulum
- plasma membrane
- integral component of membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000574002
- Coding exons
- 19
- Length
- 17059
- Individuals with no LoFs
- 125699
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 47
- Defined
- 125746
- p
- 0.000187
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.134 | 402 | 410 | 0.981 | 0.0000207 | 4901 |
| Missense (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 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00019 | 0.00018 | rare |
| Latino/Admixed American | 0.00030 | 0.00029 | rare |
| Ashkenazi Jewish | 0.00010 | 0.000099 | rare |
| East Asian | 0.00034 | 0.00033 | rare |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.00019 | 0.00018 | rare |
| South Asian | 0.000098 | 0.000098 | rare |
| Other | 0.00033 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- 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}.;
Recessive Scores
- pRec
- 0.192
Intolerance Scores
- LoFtool
- 0.411
- RVIS EVS
- -0.84
- RVIS percentile EVS
- 11.36
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.119
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |