ZP1

zona pellucida glycoprotein 1, the group of Zona pellucida glycoproteins

Basic information

Region (hg38): 11:60867542-60875693

Links

ENSG00000149506 ∙ NCBI:22917 ∙ OMIM:195000 ∙ HGNC:13187 ∙ Uniprot:P60852 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• female infertility due to zona pellucida defect (Supportive), mode of inheritance: AD
• female infertility due to zona pellucida defect (Moderate), mode of inheritance: AR
• female infertility due to zona pellucida defect (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Oocyte/zygote/embryo maturation arrest 1	AR	General	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	Obstetric	24670168

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ZP1 gene.

• Female infertility due to zona pellucida defect (5 variants)
• Oocyte maturation defect 3 (1 variants)
• ZP1-related disorder (1 variants)
• not provided (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ZP1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	1	4	6
missense	1		66	4	1	72
nonsense	4					4
start loss						0
frameshift	1	1				2
inframe indel						0
splice donor/acceptor (+/-2bp)	1					1
splice region						0
non coding					2	2
Total	7	1	67	5	7

Highest pathogenic variant AF is 0.0000461

Variants in ZP1

This is a list of pathogenic ClinVar variants found in the ZP1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
11-60867575-C-T		Inborn genetic diseases	Uncertain significance (Oct 12, 2021)
11-60867618-T-C			Benign (Jun 09, 2021)
11-60867619-G-A		Inborn genetic diseases	Uncertain significance (Jul 05, 2024)
11-60867626-T-C		Inborn genetic diseases	Uncertain significance (Mar 08, 2024)
11-60867628-G-A		Inborn genetic diseases	Uncertain significance (Jan 19, 2022)
11-60867633-G-A		Female infertility due to zona pellucida defect	Uncertain significance (May 06, 2022)
11-60867674-G-A		Inborn genetic diseases	Uncertain significance (Oct 06, 2024)
11-60867679-A-G		Inborn genetic diseases	Uncertain significance (Jan 07, 2025)
11-60867685-G-A		Inborn genetic diseases	Uncertain significance (Feb 16, 2023)
11-60869159-C-G		Inborn genetic diseases	Uncertain significance (Dec 25, 2024)
11-60869160-G-A		Inborn genetic diseases	Conflicting classifications of pathogenicity (Aug 01, 2022)
11-60869164-T-A		Inborn genetic diseases	Uncertain significance (Jun 23, 2023)
11-60869225-G-A			Likely benign (Oct 01, 2024)
11-60869233-G-A		ZP1-related disorder	Benign (Aug 02, 2017)
11-60869237-G-A			Likely benign (Mar 01, 2025)
11-60869238-A-C		Inborn genetic diseases	Uncertain significance (Apr 04, 2023)
11-60869255-G-A		Inborn genetic diseases	Uncertain significance (Mar 12, 2024)
11-60869255-G-C		Inborn genetic diseases	Uncertain significance (May 03, 2023)
11-60869537-G-A		ZP1-related disorder	Benign (Jan 01, 2025)
11-60869589-G-A		Inborn genetic diseases	Likely benign (Mar 24, 2023)
11-60869609-G-A		Inborn genetic diseases	Likely benign (Mar 23, 2022)
11-60869630-C-T		Inborn genetic diseases	Uncertain significance (Feb 14, 2023)
11-60869637-C-T		Inborn genetic diseases	Uncertain significance (Aug 27, 2024)
11-60869661-T-C		Inborn genetic diseases	Uncertain significance (Jan 29, 2024)
11-60869678-T-G		Inborn genetic diseases	Uncertain significance (Jul 10, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ZP1	protein_coding	protein_coding	ENST00000278853	12	8132

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.87e-21	0.00156	125631	0	117	125748	0.000465

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.185	363	373	0.973	0.0000208	4097
Missense in Polyphen		83	93.022	0.89226		1135
Synonymous	-0.552	166	157	1.06	0.00000910	1356
Loss of Function	0.0515	32	32.3	0.990	0.00000192	312

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00137	0.00136
Ashkenazi Jewish	0.000299	0.000298
East Asian	0.000382	0.000381
Finnish	0.00	0.00
European (Non-Finnish)	0.000323	0.000316
Middle Eastern	0.000382	0.000381
South Asian	0.00111	0.00111
Other	0.000672	0.000652

dbNSFP

Source: dbNSFP

• Function: FUNCTION: The mammalian zona pellucida, which mediates species- specific sperm binding, induction of the acrosome reaction and prevents post-fertilization polyspermy, is composed of three to four glycoproteins, ZP1, ZP2, ZP3, and ZP4. ZP1 ensures the structural integrity of the zona pellucida.
• Disease: DISEASE: Oocyte maturation defect 1 (OOMD1) [MIM:615774]: An infertility disorder caused by defective oocyte maturation that results in abnormal eggs lacking a zona pellucida. Affected females have normal menstrual cycles and sex hormone levels, no obstruction in the fallopian tubes or abnormalities of the uterus or adnexa. {ECO:0000269|PubMed:24670168}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Interaction With The Zona Pellucida;Fertilization;Reproduction (Consensus)

Recessive Scores

• pRec: 0.107

Intolerance Scores

• loftool: 0.442
• rvis_EVS: 0.07
• rvis_percentile_EVS: 59.04

Haploinsufficiency Scores

• pHI: 0.123
• hipred: N
• hipred_score: 0.112

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.0714

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Zp1
• Phenotype: endocrine/exocrine gland phenotype; reproductive system phenotype

Gene ontology

• Biological process: binding of sperm to zona pellucida
• Cellular component: extracellular region;plasma membrane;integral component of membrane;collagen-containing extracellular matrix
• Molecular function: protein binding