ZP1

Chr 11AR

zona pellucida glycoprotein 1

Also known as: HEL163, OOMD, OOMD1, OZEMA1, ZPB1

NCBI Gene: 22917ENSG00000149506UniProt: P60852

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]

Primary Disease Associations & Inheritance

Oocyte/zygote/embryo maturation arrest 1MIM #615774
AR
160
ClinVar variants
23
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— ZP1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
23 Pathogenic / Likely Pathogenic· 117 VUS of 160 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.33LOEUF
pLI 0.000
Z-score 0.05
OE 0.99 (0.75–1.33)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.18Z-score
OE missense 0.97 (0.89–1.06)
363 obs / 373.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.99 (0.75–1.33)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.97 (0.89–1.06)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.06
0≤1.21.6
LoF obs/exp: 32 / 32.3Missense obs/exp: 363 / 373.0Syn Z: -0.55

ClinVar Variant Classifications

160 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic16
Likely Pathogenic7
VUS117
Likely Benign10
Benign8
Conflicting2
16
Pathogenic
7
Likely Pathogenic
117
VUS
10
Likely Benign
8
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
3
1
12
0
16
Likely Pathogenic
3
0
4
0
7
VUS
0
113
3
1
117
Likely Benign
0
7
0
3
10
Benign
0
2
2
4
8
Conflicting
—2
Total6123218160

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

ZP1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Oocyte/zygote/embryo maturation arrest 1

MIM #615774

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Genetic factors as potential molecular markers of human oocyte and embryo quality.
Sang Q et al.·J Assist Reprod Genet
2021Review
Immunology and fertilization.
De Placido G et al.·Acta Eur Fertil
1991Review
A ZP1 gene mutation in a patient with empty follicle syndrome: A case report and literature review.
Pujalte M et al.·Eur J Obstet Gynecol Reprod Biol
2023Review
Novel mutation in the ZP1 gene and clinical implications.
Yuan P et al.·J Assist Reprod Genet
2019
Novel variants in ZP1, ZP2 and ZP3 associated with empty follicle syndrome and abnormal zona pellucida.
Sun L et al.·Reprod Biomed Online
2023
A recurrent ZP1 variant is responsible for oocyte maturation defect with degenerated oocytes in infertile females.
Loeuillet C et al.·Clin Genet
2022
Heterozygous mutations in ZP1 and ZP3 cause formation disorder of ZP and female infertility in human.
Cao Q et al.·J Cell Mol Med
2020
A compound heterozygous mutation in ZP1 and two novel heterozygous cis mutations in ZP3 causes infertility in women presenting with empty follicle syndrome.
Wang X et al.·J Ovarian Res
2025
Gene mutations impede oocyte maturation, fertilization, and early embryonic development.
Fei CF et al.·Bioessays
2022Review
Association of Zona Pellucida Gene Variants With Female Infertility: A Retrospective Genetic Analysis.
Sa SW et al.·BJOG
2025
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools