ZPBP2
Chr 17zona pellucida binding protein 2
Also known as: ZPBPL
Predicted to be involved in acrosome assembly and binding activity of sperm to zona pellucida. Predicted to act upstream of or within membrane lipid metabolic process and regulation of gene expression. Located in nucleus. [provided by Alliance of Genome Resources, Jul 2025]
Clinical Summary— ZPBP2
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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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ClinVar Variants
8 Pathogenic / Likely Pathogenic· 33 VUS of 45 total submissions
Some data sources returned errors (1)
ensembl: Error: Ensembl fetch failed: 500 for https://rest.ensembl.org/lookup/symbol/homo_sapiens/ZPBP2?content-type=application/json&expand=1
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.26LOEUF
pLI 0.000
Z-score 0.75
OE 0.81 (0.53–1.26)
Highly tolerant — LoF variants common in population
Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.42Z-score
OE missense 0.91 (0.81–1.04)
171 obs / 187.2 exp
Mild missense constraint
Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.81 (0.53–1.26)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.91 (0.81–1.04)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.76
0≤1.21.6
LoF obs/exp: 14 / 17.4Missense obs/exp: 171 / 187.2Syn Z: 1.49
ClinVar Variant Classifications
45 submitted variants in ClinVar
Classification Summary
Pathogenic8
VUS33
Likely Benign2
Benign2
8
Pathogenic
33
VUS
2
Likely Benign
2
Benign
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 0 | 8 | 0 | 8 |
Likely Pathogenic | 0 | 0 | 0 | 0 | 0 |
VUS | 0 | 30 | 3 | 0 | 33 |
Likely Benign | 0 | 2 | 0 | 0 | 2 |
Benign | 0 | 1 | 0 | 1 | 2 |
| Total | 0 | 33 | 11 | 1 | 45 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
ZPBP2 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
OMIM — Genotype-Phenotype Relationships
1 OMIM entry
ZONA PELLUCIDA-BINDING PROTEIN 2; ZPBP2
MIM #608499 · *
External Resources
Links to major genomics databases and tools
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
Hyperuricemia cosegregating with osteogenesis imperfecta is associated with a mutation in GPATCH8.
Kaneko H et al.·Hum Genet
2011
Association of Asthma Risk Alleles With Acute Respiratory Tract Infections and Wheezing Illnesses in Young Children.
Forsström V et al.·J Infect Dis
2023
Exome analysis of patients with concurrent pediatric inflammatory bowel disease and autoimmune disease.
Andreoletti G et al.·Inflamm Bowel Dis
2015Cohort
Identification of the functional variant driving ORMDL3 and GSDMB expression in human chromosome 17q12-21 in primary biliary cholangitis.
Hitomi Y et al.·Sci Rep
2017Functional
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
The Germ Cell-Specific Markers ZPBP2 and PGK2 in Testicular Biopsies Can Predict the Presence as well as the Quality of Sperm in Non-obstructive Azoospermia Patients.
Ghanami Gashti N et al.·Reprod Sci
2021Cohort
Regulatory interaction between the ZPBP2-ORMDL3/Zpbp2-Ormdl3 region and the circadian clock.
Chang ML et al.·PLoS One
2019Open Access
Loss of the zona pellucida-binding protein 2 (Zpbp2) gene in mice impacts airway hypersensitivity and lung lipid metabolism in a sex-dependent fashion.
Kanagaratham C et al.·Mamm Genome
2018
Top 5 resultsSearch Europe PMC ↗
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
Genome-wide search for genes affecting the age at diagnosis of type 1 diabetes
Syreeni A et al.·J Intern Med
2021
Coordinated Transcriptomic and Epigenetic Approach Reveals Molecular Features Underlying Natural Mating Ability in Captive Male Giant Pandas.
Yan Z et al.·Ecol Evol
2025
Sequence variants influencing the regulation of serum IgG subclass levels.
Olafsdottir TA et al.·Nat Commun
2024
Testis-specific serine protease PRSS54 regulates acrosomal granule localization and sperm head morphogenesis in mice .
Shen C et al.·Biol Reprod
2022
Association of Gasdermin B Gene GSDMB Polymorphisms with Risk of Allergic Diseases.
Karunas AS et al.·Biochem Genet
2021
DNA methylation across the tree of life, from micro to macro-organism
Nasrullah et al.·Bioengineered
2022
17q12-21 risk-variants influence cord blood immune regulation and multitrigger-wheeze.
Laubhahn K et al.·Pediatr Allergy Immunol
2022
Top 8 full-text resultsSearch PubTator3 ↗
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools