ZPBP2

protein-coding

zona pellucida binding protein 2, the group of Immunoglobulin like domain containing

Gene summary

Predicted to be involved in acrosome assembly and binding activity of sperm to zona pellucida. Predicted to act upstream of or within obsolete membrane lipid catabolic process; regulation of gene expression; and sphingolipid metabolic process. Located in nucleus. Implicated in asthma and childhood-onset asthma. Biomarker of lung squamous cell carcinoma and type 1 diabetes mellitus. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_199321.3

Inheritance

—

ClinVar variants

U:32B:4

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.81

Max pathogenic AF

—

Genomic locus

chr17:39,868,202-39,877,896

External References & Databases

Ensembl (ENSG00000186075)

Transcript & Mutation Effects

hg38 • Region Span ~9.7 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ZPBP2 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 31

not providedTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_199321.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous					1 clinvar	1
missense			31 clinvar	2 clinvar	1 clinvar	34
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	32	2	2	36

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 11 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_199321.3	RefSeq	NP_955353.1	8	MANE Select
ENST00000348931.9	Ensembl	ENSP00000335384.5	8	MANE Select
NM_198844.3	RefSeq	NP_942141.2	7	Standard
ENST00000377940.3	Ensembl	ENSP00000367174.3	7	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

acrosome assembly
binding of sperm to zona pellucida

Cellular Component

acrosomal vesicle
zona pellucida receptor complex
extracellular region
nucleus
cell body

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000348931
Coding exons: 8
Length: 9733
Individuals with no LoFs: 125717
Homozygous LoFs: 0
Heterozygous LoFs: 31
Defined: 125748
p: 0.000123

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.421	171	187	0.913	0.0000101	2228
Missense (PolyPhen)		48	66.27	0.72431		827
Synonymous	1.49	49	64.2	0.763	0.00000348	602
Loss of Function	0.751	14	17.4	0.806	9.45e-7	211

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00050	0.00049	rare
Latino/Admixed American	0.00012	0.00012	rare
Ashkenazi Jewish	0.00040	0.00030	rare
East Asian	0.00022	0.00022	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000091	0.000088	rare
South Asian	0.000066	0.000065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Is implicated in sperm-oocyte interaction during fertilization. {ECO:0000250|UniProtKB:Q6X786}.;

Intolerance Scores

LoFtool: 0.953
RVIS EVS: 0.37
RVIS percentile EVS: 75.43

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.187

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	High
Cancer	Medium	Medium	Medium