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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
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ZP1
zona pellucida glycoprotein 1
Chromosome 11 Β· 11q12.2
NCBI Gene: 22917Ensembl: ENSG00000149506.12HGNC: HGNC:13187UniProt: P60852
36PubMed Papers
21Diseases
0Drugs
13Pathogenic Variants
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
protein bindingegg coatstructural constituent of egg coatbinding of sperm to zona pellucidafemale infertility due to zona pellucida defectoocyte maturation defect 3hypertrophic cardiomyopathygenetic disorder
✦AI Summary

ZP1 (zona pellucida glycoprotein 1) is a structural component of the zona pellucida, the extracellular matrix surrounding oocytes that mediates sperm-egg interactions and prevents polyspermy 1. ZP1 is one of three to four glycoproteins (ZP1-4) that assemble into interconnected filaments through a ZP domain 12. The protein ensures structural integrity of the zona pellucida and contributes to acrosome reaction induction; ZP1 binds capacitated spermatozoa and dose-dependently increases acrosome reaction 2. Following fertilization, ZP1 filaments become cross-linked and rigidified as part of the zona reaction, physically blocking supernumerary sperm penetration 3. Mutations in ZP1 cause oocyte maturation arrest and female infertility 4. Pathogenic variants impair ZP protein polymerization or secretion, preventing proper zona pellucida assembly 567. Clinical manifestations include empty follicle syndrome (failure to retrieve oocytes despite normal follicle development) and absence of zona pellucida around oocytes 56. Both homozygous and heterozygous mutations have been identified; some heterozygous cases respond to intracytoplasmic sperm injection (ICSI) 7. Genetic diagnosis of ZP genes enables appropriate reproductive counseling and selection of assisted reproductive technology strategies.

Sources cited
1
ZP1 is one of 3-4 glycoproteins assembling into zona pellucida filaments; ZP domain required for assembly; role in sperm binding and polyspermy prevention
PMID: 40180510
2
ZP1 binds capacitated spermatozoa at head region; induces dose-dependent acrosome reaction; N-linked glycosylation essential for function
PMID: 29853184
3
ZP1 forms type II protofilaments in double helix structure; cross-linking and rigidification following fertilization blocks polyspermy
PMID: 38490181
4
ZP1 mutations cause oocyte maturation arrest and are among 16 genes responsible for early reproductive failure
PMID: 33895934
5
Homozygous ZP1 missense variant prevents zona assembly; causes empty follicle syndrome; absence of ZP1 protein confirmed by immunohistochemistry
PMID: 36529558
6
Compound heterozygous ZP1 mutations (frameshift and missense) associated with empty follicle syndrome and abnormal oocytes
PMID: 30778819
7
Heterozygous ZP1 mutation impedes cross-linking and secretion of ZP proteins; causes zona pellucida formation disorder; amenable to ICSI treatment
PMID: 32573113
Disease Associationsβ“˜21
female infertility due to zona pellucida defectOpen Targets
0.67Moderate
oocyte maturation defect 3Open Targets
0.34Weak
hypertrophic cardiomyopathyOpen Targets
0.29Weak
genetic disorderOpen Targets
0.19Weak
primary ovarian insufficiencyOpen Targets
0.06Suggestive
46,XY complete gonadal dysgenesisOpen Targets
0.05Suggestive
46,XX testicular disorder of sex developmentOpen Targets
0.04Suggestive
Familial hyperprolactinemiaOpen Targets
0.04Suggestive
familial hyperprolactinemiaOpen Targets
0.04Suggestive
aromatase deficiencyOpen Targets
0.04Suggestive
Perrault syndrome 6Open Targets
0.04Suggestive
46,XX ovotesticular disorder of sex developmentOpen Targets
0.04Suggestive
premature ovarian failure 18Open Targets
0.04Suggestive
polycystic ovary syndromeOpen Targets
0.04Suggestive
46,XX gonadal dysgenesisOpen Targets
0.04Suggestive
infertilityOpen Targets
0.03Suggestive
Mayer-Rokitansky-Kuster-Hauser syndromeOpen Targets
0.03Suggestive
Mayer-Rokitansky-KΓΌster-Hauser syndromeOpen Targets
0.03Suggestive
Mayer-Rokitansky-Kuster-Hauser syndrome type 1Open Targets
0.03Suggestive
Xp22.3 microdeletion syndromeOpen Targets
0.03Suggestive
Oocyte/zygote/embryo maturation arrest 1UniProt
Pathogenic Variants13
NM_207341.4(ZP1):c.1113-2A>GPathogenic
Female infertility due to zona pellucida defect
β˜…β˜…β˜†β˜†2023
NM_207341.4(ZP1):c.874C>T (p.Gln292Ter)Pathogenic
Female infertility due to zona pellucida defect
β˜…β˜†β˜†β˜†2023β†’ Residue 292
NM_207341.4(ZP1):c.1708G>A (p.Val570Met)Pathogenic
Female infertility due to zona pellucida defect
β˜…β˜†β˜†β˜†2023β†’ Residue 570
NM_207341.4(ZP1):c.769C>T (p.Gln257Ter)Pathogenic
Oocyte maturation defect 3
β˜…β˜†β˜†β˜†2019β†’ Residue 257
NM_207341.4(ZP1):c.628C>T (p.Gln210Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2017β†’ Residue 210
NM_207341.4(ZP1):c.670C>T (p.Arg224Ter)Pathogenic
ZP1-related disorder|Female infertility due to zona pellucida defect
β˜…β˜†β˜†β˜†β†’ Residue 224
NM_207341.4(ZP1):c.1602C>A (p.Cys534Ter)Pathogenic
Female infertility due to zona pellucida defect
β˜…β˜†β˜†β˜†β†’ Residue 534
NM_207341.4(ZP1):c.1129_1130del (p.Val377fs)Pathogenic
Female infertility due to zona pellucida defect
β˜…β˜†β˜†β˜†β†’ Residue 377
NM_207341.4(ZP1):c.1015-1G>ALikely pathogenic
ZP1-related disorder
β˜†β˜†β˜†β˜†2024
NM_207341.4(ZP1):c.1775-8T>CPathogenic
Female infertility due to zona pellucida defect
β˜†β˜†β˜†β˜†2023
NM_207341.4(ZP1):c.1430+1G>TPathogenic
Female infertility due to zona pellucida defect
β˜†β˜†β˜†β˜†2023
NM_207341.4(ZP1):c.1168del (p.Ile390fs)Likely pathogenic
Female infertility due to zona pellucida defect
β˜†β˜†β˜†β˜†2020β†’ Residue 390
NM_207341.4(ZP1):c.1169_1176del (p.Ile390fs)Pathogenic
Female infertility due to zona pellucida defect
β˜†β˜†β˜†β˜†2014β†’ Residue 390
View on ClinVar β†—
Related Genes
ZP2Protein interaction88%ZP3Protein interaction86%OVGP1Protein interaction83%GDF9Protein interaction82%FIGLAProtein interaction76%ZP4Protein interaction67%
Tissue Expression6 tissues
Brain
100%
Heart
76%
Ovary
22%
Lung
16%
Liver
11%
Bone Marrow
0%
Gene Interaction Network
Click a node to explore
ZP1ZP2ZP3OVGP1GDF9FIGLAZP4
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted Β· UniProt P60852
View on AlphaFold β†—
Constraintβ“˜
LOEUFβ“˜
1.03LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.83 [0.67–1.03]
RankingsWhere ZP1 stands among ~20K protein-coding genes
  • #10,902of 20,598
    Most Researched36
  • #2,630of 5,498
    Most Pathogenic Variants13
  • #10,123of 17,882
    Most Constrained (LOEUF)1.03
Genes detectedZP1
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Genetic factors as potential molecular markers of human oocyte and embryo quality.
PMID: 33895934
J Assist Reprod Genet Β· 2021
1.00
2
The mammalian egg's zona pellucida, fertilization, and fertility.
PMID: 40180510
Curr Top Dev Biol Β· 2025
0.90
3
ZP2 cleavage blocks polyspermy by modulating the architecture of the egg coat.
PMID: 38490181
Cell Β· 2024
0.80
4
A ZP1 gene mutation in a patient with empty follicle syndrome: A case report and literature review.
PMID: 36529558
Eur J Obstet Gynecol Reprod Biol Β· 2023
0.70
5
Novel mutation in the ZP1 gene and clinical implications.
PMID: 30778819
J Assist Reprod Genet Β· 2019
0.60