ZP4

Chr 1

zona pellucida glycoprotein 4

Also known as: ZBP, ZP1, ZP1B, ZPB, ZPB2, Zp-4

ZP4 encodes a glycoprotein component of the zona pellucida, an extracellular matrix surrounding oocytes that mediates sperm binding and prevents polyspermy after fertilization. Mutations cause female infertility due to oocyte maturation defects, inherited in an autosomal recessive pattern. The gene shows tolerance to loss-of-function variants, consistent with its specific role in reproductive function rather than essential developmental processes.

OMIMResearchSummary from RefSeq, UniProt
LOEUF 1.31
Clinical SummaryZP4
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
9 unique Pathogenic / Likely Pathogenic· 78 VUS of 100 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.31LOEUF
pLI 0.000
Z-score 0.21
OE 0.96 (0.711.31)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-1.24Z-score
OE missense 1.20 (1.101.31)
357 obs / 296.8 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.96 (0.711.31)
00.351.4
Missense OE1.20 (1.101.31)
00.61.4
Synonymous OE1.19
01.21.6
LoF obs/exp: 28 / 29.2Missense obs/exp: 357 / 296.8Syn Z: -1.60

ClinVar Variant Classifications

100 submitted variants in ClinVar

Classification Summary

Pathogenic9
VUS78
Likely Benign11
9
Pathogenic
78
VUS
11
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
9
0
9
Likely Pathogenic
0
0
0
0
0
VUS
0
77
1
0
78
Likely Benign
0
10
0
1
11
Benign
0
0
0
0
0
Total08710198

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

View in ClinVar →

Protein Context — Lollipop Plot

ZP4 · 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.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →