ZP2

Chr 16AR

zona pellucida glycoprotein 2

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

NCBI Gene: 7783 ENSG00000103310 UniProt: Q05996 OMIM: 182888

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.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

OMIM ResearchGenerating clinical summary…

DNmechanismARLOEUF 0.731 OMIM phenotype

Clinical Summary— ZP2

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.73LOEUF

pLI 0.000

Z-score 2.84

OE 0.49 (0.34–0.73)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.13Z-score

OE missense 0.98 (0.90–1.07)

402 obs / 409.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.49 (0.34–0.73)

0≤0.351.4

Missense OE?0.98 (0.90–1.07)

0≤0.61.4

Synonymous OE?0.97

0≤1.21.6

LoF obs/exp: 18 / 36.6Missense obs/exp: 402 / 409.6Syn Z: 0.33

This gene — mechanism propensity

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.