ZP1

Chr 11

zona pellucida glycoprotein 1

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

NCBI Gene: 22917 ENSG00000149506 UniProt: P60852

The ZP1 protein is a glycoprotein component of the zona pellucida that ensures the structural integrity of this extracellular matrix surrounding oocytes during fertilization and early embryonic development. Autosomal recessive mutations cause oocyte/zygote/embryo maturation arrest, leading to female infertility. This gene is not highly constrained against loss-of-function variants and primarily affects reproductive function rather than pediatric neurological development.

ResearchSummary from RefSeq, OMIM, UniProt

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]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtOocyte/zygote/embryo maturation arrest 1

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.33

LOEUF

—

Mechanism

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

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?

0.18Z-score

OE missense 0.97 (0.89–1.06)

363 obs / 373.0 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.99 (0.75–1.33)

0≤0.351.4

Missense OE?0.97 (0.89–1.06)

0≤0.61.4

Synonymous OE?1.06

0≤1.21.6

LoF obs/exp: 32 / 32.3Missense obs/exp: 363 / 373.0Syn Z: -0.55

Background carrier burden — how many people carry a rare variant somewhere in ZP1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 73

810 rare PASS variants

Rare truncating (LoF)

1 in 720

156 rare PASS variants

Rare synonymous (reference)

1 in 180

352 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ZP1. 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 93	1 in 740
South Asian	~43k	1 in 46	1 in 350
Remaining (unassigned)	~30k	1 in 75	1 in 1,100
European (Finnish)	~27k	1 in 250	1 in 3,300
Admixed American	~22k	1 in 56	1 in 540
African / African American	~21k	1 in 46	1 in 760
East Asian	~20k	1 in 78	1 in 840
Ashkenazi Jewish	~13k	1 in 450	1 in 1,600
Middle Eastern	~2,884	1 in 83	1 in 580

Each group is summed over the variants that are rare in that group. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 12 coding exons well covered in gnomAD exomes and genomes.? see exons ↓