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…

Primary Disease Associations & Inheritance

Oocyte/zygote/embryo maturation arrest 6MIM #618353

Clinical highlights

Gene–disease validity

Not independently assessedOMIM lists Oocyte/zygote/embryo maturation arrest 6; no ClinGen or GenCC tier

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.73

LOEUF

Mechanism· predicted

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

Background carrier burden — how many people carry a rare variant somewhere in ZP2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 56

969 rare PASS variants

Rare truncating (LoF)

1 in 1,400

148 rare PASS variants

Rare synonymous (reference)

1 in 130

401 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ZP2. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 86	1 in 1,400
South Asian	~43k	1 in 56	1 in 1,900
Remaining (unassigned)	~30k	1 in 50	1 in 4,300
European (Finnish)	~27k	1 in 150	1 in 880
Admixed American	~22k	1 in 75	1 in 1,000
African / African American	~21k	1 in 53	1 in 1,000
East Asian	~20k	1 in 69	1 in 700
Ashkenazi Jewish	~13k	1 in 480	≈ 1 in 4,200
Middle Eastern	~2,884	1 in 78	≈ 1 in 1,400

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 19 coding exons well covered in gnomAD exomes and genomes.? see exons ↓