ZP2

Chr 16AR

zona pellucida glycoprotein 2

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

ZP2 encodes zona pellucida glycoprotein 2, a structural component of the extracellular matrix surrounding oocytes that mediates sperm binding and prevents polyspermy after fertilization. Biallelic mutations cause oocyte/zygote/embryo maturation arrest 6, an autosomal recessive condition leading to female infertility due to defective zona pellucida formation. The gene shows low constraint to loss-of-function variation, consistent with its specialized reproductive function that does not affect viability.

OMIMResearchSummary from RefSeq, OMIM, UniProt
DNmechanismARLOEUF 0.731 OMIM phenotype
Clinical SummaryZP2
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
23 unique Pathogenic / Likely Pathogenic· 127 VUS of 185 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.73LOEUF
pLI 0.000
Z-score 2.84
OE 0.49 (0.340.73)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.13Z-score
OE missense 0.98 (0.901.07)
402 obs / 409.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.49 (0.340.73)
00.351.4
Missense OE0.98 (0.901.07)
00.61.4
Synonymous OE0.97
01.21.6
LoF obs/exp: 18 / 36.6Missense obs/exp: 402 / 409.6Syn Z: 0.33
DN
0.6841th %ile
GOF
0.5366th %ile
LOF
0.3066th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

185 submitted variants in ClinVar

Classification Summary

Pathogenic20
Likely Pathogenic3
VUS127
Likely Benign24
Benign7
Conflicting3
20
Pathogenic
3
Likely Pathogenic
127
VUS
24
Likely Benign
7
Benign
3
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
5
1
14
0
20
Likely Pathogenic
2
1
0
0
3
VUS
3
118
6
0
127
Likely Benign
0
11
4
9
24
Benign
0
2
2
3
7
Conflicting
3
Total101332612184

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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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