ZP1
protein-codingzona pellucida glycoprotein 1, 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 primarily of three or four glycoproteins with various functions during fertilization and preimplantation development. The protein encoded by this gene ensures the structural integrity of the zona pellucida. Mutations in this gene are a cause of oocyte maturation defect and infertility. [provided by RefSeq, May 2014]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~8.2 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0014342
Submitter: Ambry Genetics
Inheritance Pattern: AD
Disease ID:MONDO:0014342
Submitter: PanelApp Australia
Inheritance Pattern: AR
Disease ID:MONDO:0014342
Submitter: PanelApp Australia
Inheritance Pattern: AR
Disease ID:MONDO:0014342
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AD
Disease ID:MONDO:0014342
Submitter: Orphanet
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 ZP1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_207341.4. 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 | 1 | 4 | 2 | 7 | ||
| missense | 1 | 1 | 113 | 9 | 1 | 125 |
| nonsense | 6 | 3 | 9 | |||
| start loss | 0 | |||||
| frameshift | 2 | 3 | 5 | |||
| splice donor/acceptor (+/-2bp) | 1 | 3 | 4 | |||
| Total | 10 | 10 | 114 | 13 | 3 | 150 |
Highest pathogenic variant AF is 0.00008358304
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_997224.2 | 12 | MANE Select | |
| Ensembl | ENSP00000278853.5 | 12 | MANE Select | |
| RefSeq | NP_001378872.1 | 8 | Standard | |
| RefSeq | NP_001378873.1 | 6 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Interaction With The Zona Pellucida
- Fertilization
- Reproduction
Biological Process
- binding of sperm to zona pellucida
Molecular Function
- protein binding
Cellular Component
- extracellular region
- plasma membrane
- integral component of membrane
- collagen-containing extracellular matrix
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000278853
- Coding exons
- 12
- Length
- 8132
- Individuals with no LoFs
- 125631
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 117
- Defined
- 125748
- p
- 0.000465
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.185 | 363 | 373 | 0.973 | 0.0000208 | 4097 |
| Missense (PolyPhen) | 83 | 93.022 | 0.89226 | 1135 | ||
| Synonymous | -0.552 | 166 | 157 | 1.06 | 0.00000910 | 1356 |
| Loss of Function | 0.0515 | 32 | 32.3 | 0.990 | 0.00000192 | 312 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00075 | 0.00074 | rare |
| Latino/Admixed American | 0.00062 | 0.00061 | rare |
| Ashkenazi Jewish | 0.00030 | 0.00030 | rare |
| East Asian | 0.00038 | 0.00038 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00032 | 0.00032 | rare |
| South Asian | 0.0011 | 0.0011 | notable |
| Other | 0.00067 | 0.00065 | 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. ZP1 ensures the structural integrity of the zona pellucida.;
- Disease
- DISEASE: Oocyte maturation defect 1 (OOMD1) [MIM:615774]: An infertility disorder caused by defective oocyte maturation that results in abnormal eggs lacking a zona pellucida. Affected females have normal menstrual cycles and sex hormone levels, no obstruction in the fallopian tubes or abnormalities of the uterus or adnexa. {ECO:0000269|PubMed:24670168}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Recessive Scores
- pRec
- 0.107
Intolerance Scores
- LoFtool
- 0.442
- RVIS EVS
- 0.07
- RVIS percentile EVS
- 59.04
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.0714
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |