ZPBP

protein-coding

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

Gene summary

ZPBP is one of several proteins that are thought to participate in secondary binding between acrosome-reacted sperm and the egg-specific extracellular matrix, the zona pellucida (McLeskey et al., 1998 [PubMed 9378618]).[supplied by OMIM, Aug 2008]

MANE transcript

NM_007009.3

Inheritance

ClinVar variants

P:1U:39B:13

Top phenotype

Spermatogenic failure 66

gnomAD constraint

pLI —, LoF o/e 0.46

Max pathogenic AF

—

Genomic locus

chr7:49,850,421-50,121,329

External References & Databases

Ensembl (ENSG00000042813)

Transcript & Mutation Effects

hg38 • Region Span ~270.9 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

spermatogenic failure 66LIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0030716

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Spermatogenic failure 66AR

Manifestation: Genitourinary

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 31985809

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ZPBP variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 44

ZPBP-related disorderTotal: 10

Spermatogenic failure 66Total: 4

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_007009.3. 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				2 clinvar		2
missense			36 clinvar	8 clinvar	3 clinvar	47
nonsense	1 clinvar		1 clinvar			2
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	1	0	39	10	3	53

Highest pathogenic variant AF is 6.843362e-7

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 21 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_007009.3	RefSeq	NP_008940.2	8	MANE Select
ENST00000046087.7	Ensembl	ENSP00000046087.2	8	MANE Select
NM_001159878.2	RefSeq	NP_001153350.1	8	Standard
ENST00000413331.1	Ensembl	ENSP00000414755.1	1	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

binding of sperm to zona pellucida

Cellular Component

acrosomal membrane
extracellular region
nucleus

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000046087
Coding exons: 8
Length: 270909
Individuals with no LoFs: 125710
Homozygous LoFs: 0
Heterozygous LoFs: 10
Defined: 125720
p: 0.0000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.895	161	196	0.820	0.0000112	2244
Missense (PolyPhen)		51	80.353	0.6347		979
Synonymous	-1.27	82	68.6	1.19	0.00000366	669
Loss of Function	2.23	9	19.7	0.457	0.00000113	228

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000054	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000080	0.000079	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Plays a role in acrosome compaction and sperm morphogenesis (PubMed:21911476). Is implicated in sperm-oocyte interaction during fertilization (By similarity). {ECO:0000250|UniProtKB:Q62522, ECO:0000269|PubMed:21911476}.;

Recessive Scores

pRec: 0.113

Intolerance Scores

LoFtool: 0.574
RVIS EVS: -0.49
RVIS percentile EVS: 22.36

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.233

Gene Damage Prediction

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