ZP2

Chr 16AR

zona pellucida glycoprotein 2

Also known as: OOMD6, OZEMA6, ZPA, Zp-2

NCBI Gene: 7783ENSG00000103310UniProt: Q05996

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]

Primary Disease Associations & Inheritance

Oocyte/zygote/embryo maturation arrest 6MIM #618353
AR
181
ClinVar variants
22
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— ZP2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
22 Pathogenic / Likely Pathogenic· 125 VUS of 181 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.
0.73LOEUF
pLI 0.000
Z-score 2.84
OE 0.49 (0.34–0.73)
Tolerant

Typical tolerance to LoF variation

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.
0.13Z-score
OE missense 0.98 (0.90–1.07)
402 obs / 409.6 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.0.49 (0.34–0.73)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.98 (0.90–1.07)
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.0.97
0≤1.21.6
LoF obs/exp: 18 / 36.6Missense obs/exp: 402 / 409.6Syn Z: 0.33

ClinVar Variant Classifications

181 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic20
Likely Pathogenic2
VUS125
Likely Benign25
Benign7
Conflicting2
20
Pathogenic
2
Likely Pathogenic
125
VUS
25
Likely Benign
7
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
5
1
14
0
20
Likely Pathogenic
1
1
0
0
2
VUS
2
116
7
0
125
Likely Benign
0
12
4
9
25
Benign
0
2
2
3
7
Conflicting
—2
Total81322712181

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

View in ClinVar →

Protein Context — Lollipop Plot

ZP2 · 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 6

MIM #618353

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
ZP2 pathogenic variants cause in vitro fertilization failure and female infertility.
Dai C et al.·Genet Med
2019
A novel homozygous variant in ZP2 causes abnormal zona pellucida formation and female infertility.
Sun Y et al.·J Assist Reprod Genet
2021
Novel variants in ZP1, ZP2 and ZP3 associated with empty follicle syndrome and abnormal zona pellucida.
Sun L et al.·Reprod Biomed Online
2023
Identification of a heterozygous variant of ZP2 as a novel cause of empty follicle syndrome in humans and mice.
Shen Y et al.·Hum Reprod
2022
Identification of zona pellucida defects revealed a novel loss-of-function mutation in ZP2 in humans and rats.
Zeng J et al.·Front Endocrinol (Lausanne)
2023
Gene mutations associated with fertilization failure after in vitro fertilization/intracytoplasmic sperm injection.
Xue Y et al.·Front Endocrinol (Lausanne)
2022Review
A Compound Heterozygous Pathogenic Variant in ZP2 Gene Causes Female Infertility.
Yang S et al.·Reprod Sci
2025Case report
Identification of chromatin remodeling-related gene signature to predict the prognosis in breast cancer.
Feng J et al.·Clin Exp Med
2025Functional
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